CA1268051A - Controlled release powder and process for its preparation - Google Patents
Controlled release powder and process for its preparationInfo
- Publication number
- CA1268051A CA1268051A CA000494130A CA494130A CA1268051A CA 1268051 A CA1268051 A CA 1268051A CA 000494130 A CA000494130 A CA 000494130A CA 494130 A CA494130 A CA 494130A CA 1268051 A CA1268051 A CA 1268051A
- Authority
- CA
- Canada
- Prior art keywords
- active ingredient
- controlled release
- particles
- release powder
- polymer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
- A23G4/00—Chewing gum
- A23G4/18—Chewing gum characterised by shape, structure or physical form, e.g. aerated products
- A23G4/20—Composite products, e.g. centre-filled, multi-layer, laminated
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5138—Organic macromolecular compounds; Dendrimers obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5161—Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
- Y10T428/2989—Microcapsule with solid core [includes liposome]
Abstract
A B S T R A C
CONTROLLED RELEASE POWDER AND PROCESS FOR ITS PREPARATION
A controlled release powder containing discrete microparticles for use in edible, pharmaceutical and other controlled release compositions. The microparticles have an average size in the range 0.1 to 125 µ m, each of the microparticles being in the form of a micromatrix of an active ingredient uniformly distributed in at least one non-toxic polymer. The microparticles have a predetermined release of active ingredient when the dissolution rate thereof is measured according to the Paddle method of U.S.
Pharmacopoeia XX at 37°C and 75 r.p.m.
CONTROLLED RELEASE POWDER AND PROCESS FOR ITS PREPARATION
A controlled release powder containing discrete microparticles for use in edible, pharmaceutical and other controlled release compositions. The microparticles have an average size in the range 0.1 to 125 µ m, each of the microparticles being in the form of a micromatrix of an active ingredient uniformly distributed in at least one non-toxic polymer. The microparticles have a predetermined release of active ingredient when the dissolution rate thereof is measured according to the Paddle method of U.S.
Pharmacopoeia XX at 37°C and 75 r.p.m.
Description
This invention relates to controlled release formulations and, in particular, to sustained release powders consisting of discrete micro-particles.
Many types of controlled or sustained release pellets are known which are loaded into capsules for oral administration. These pellets can be described as macro-particles and invariably have an average size greater than 400 ~m. Such pellets are the subject, for example, of the Applicants' EP-A- 0 122 077, EP-A- 0 123 470, ~P-A- 0 156 077 and EP-A- 0 149 920.
Sustained release pellets cannot be readily formulated as liquids. Sustained release liquids are desirable for use as geriatric and paediatric formulations.
Various processes are known for the production of micro-spheres using solvent evaporation emulsion techniques.
Known micro-encapsulation techniques are generally employed for phase transformation, such as for the conversion of liquids to solids. Alternatively, such techniques may be used for protecting an active material, such as coating aspirin to mask its stomach irritant properties.
Sustained release liquids are known which contain ion exchange resins. In such sustained release liquids the active ingredient is bound to an ion exchange resin in the form of a reversible complex and is displaced therefrom in vivo. Such sustained release liquids are described, for example, in French Patent Publication No. 2 278 325.
It is an object of the present invention to provide a controlled release powder of discrete micro-particles which can be readily formulated in liqu~d form but which can also be formuIated in other sustained release forms such as tablets`which have improved properties relative to the known forms.
......
, 12~
Accordingly, the invention provides a controlled release powder containing discrete micro-particles for use in controlled release compositions, said powder comprising particles containing an active ingredient and optionally an excipient in intimiate admixture with at least one non-toxic polymer, each of said particles being in the form of a micromatrix with active ingredient and the excipient, if present, uni~ormly distributed throughout the matrix, said particles having an average size o~
between 0.1 and 125 ~m and having a predetermined release of active ingredient when the dissolution rate thereof is measured according to the Paddle Method of U.S.
Pharmacopoeia XX at 37C and 75 r.p.m., said dissolution rate being substantially proportional to the square root of time.
Pre~erably~ the particles have a~ ave~age size o~
between 5 and 100 ~m.
The Applicants have coined the term "pharmasomes" ~or the micro-particles of the powder according to the invention and which term is used hereinafter in the Specification.
The controlled release powders according to the invention can permit a sustained release of active ingredient as hereinafter demonstrated.
Further preferably, the active ingredient is a drug, a nutrient, a colouring agent, a fragrance, a herbic.ide, a pesticide, a flavouring agent or a sweetening agent.
The powder can be dispersed or suspended in a liquid vehicle and will maintain its sustained release characteristics for a useful period of time. Such dispersions or suspensions have both chemical stability and stability in terms of dissolution rate.
The polymer may be soluble, insoluble, permeable, impermeable or biodegradable. The polymers may be polymers or co-polymers. The polymer may be a natural or synthetic polymer. Natural polymers include polypeptides, polysaccharides and alginic acid. A suitable polypeptide is zein and a suitable polysaccharide is cellulose.
Representative synthetic polymers include alkyl celluloses, hydroxyalkyl celluloses r cellulose ethers, `! ,`;
' ~
5~
cellulose esters, nitro cellulose~, ~olymer~ of acrylic and methacrylic acids and esters thereof, polyamides, poly-carbonates, polyalkylenes, polyalkylene glycols, poly-alkylene oxides, polyalkylene terephthalates, polyvinyl alcohols, polyvinyl ethers, polyvinyl esters, polyvinyl halides, polyvinylpyrrolidone, polyglycolides, polysiloxanes and polyurethanes and co-polymers thereo~.
Particularly suitable polymers include: methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxy~utyl methyl cellulose, cellulose acetate, cellulose propionate ~lower, medium or higher molecular weight), cellulose ace~ate propionate, cellulose acetate butyrate, cellulose acetate phthalate, carboxymethyl cellulose, cellulose triacetate, cellulose sulphate sodium salt, poly(methyl methacrylate), poly(ethyl methacrylate), poly(butyl methacrylate~, polytisQbutyl methacrylate), poly(hexyl methacrylate), poly(isodecyl methacrylate~, poly(lauryl methacryla~e), poly(phenyl methacrylate~, poly(methyl acrylate), poly(isopropyl acrylate), poly(iso~utyl acrylate), poly(octadecyl acrylate), poly(ethylene~, poly(ethylene) low density, poly(ethylene) high density, poly~propylene~, poly(ethylene glycol), poly(ethylené oxide), polylethylene terephthalate), poly(vinyl alcohol3, poly(vinyl i80~utyl ether), poly(vinyl acetate), poly~vinyl chloride) and polyvinylpyrrolidone.
Especially suitable co-polymers include: butyl methacrylate/isobutyl methacrylate co-polymer, high molecular weight, methylvinyl ether/m~leic acid co-polymer, methylvinyl ether/m~leic acid, monoethyl ester co-polymer, methylvinyl ether/maleic anhydride co-polymer and vinyl alcohol/vinyl acetate co-polymer.
Representative biodegradable pol~mers include, poly glycolides, ~oly(ethylene terephthalate) and polyurethane.
Representative acrylates and methacrylate~ are polymers sold under the Trade ~ark Eudragit.
When t~e active ingredient is a drug there is essentially no limitation on the type o drug which may be used.
: ~,:, : ~. :
0~1 Representative active ingredients include antacids, anti-inflammatory substances, coronary dilator6, cerebral dilators, peripheral vasodilators, anti-infectives, psychotropics, anti-manics, stimulants, anti-hi~tamines, laxatives, decongestants, vitamins, gastro-intestina-sedatives, anti-diarrheal preparations, anti-anginal drugs, vasodilators, anti-arrhythmics, anti-hypertensive drugs, vasoconstrictors and mi~raine treatments, anti-coagulants and anti-thrombotic drugs, analgesics, anti-pyretics, hypno~ics, sedatives, anti emetics, anti-nauseants, anti-convulsants, neuromuscular drugs, hyper- and hypo~lycaemic agents, thyroid and anti-thyroid preparati.ons, diuretics, anti-spasmodics, uterine rela~ants, mineral and nutritional additives, anti-obesity drugs, anabolic drugs, erythropoietic drugs, anti-asthmatics, bronchodilators, expectorants, cough suppressants, mucolytics and anti-uricemic dru~s.
~ ypical active ingredients include gastro-intestinal sedatives such as meto~lopramide and propantheline bromide, antacids such as aluminium trisilicate, aluminium hydroxide and cimetidine, anti-inflammatory drugs such as phenylbutazone, indomethacin, naproxen, ibuprofen, flurbiprofen, diclofenac, dexamethasone, prednisone and prednisolone, coronary vasodilator drugs such as slyceryl trinitrate, isosorbide dinitrate and penta~rythritol tetranitrate, peripheral and cere~ral vasodilators ~uch as soloctidilum, vincamine, naftidrofuryl oxalate, co-dergocrine mesylate, cyclandelate, papaverine and nicotinic acid, anti-infective substances such as erythromycin s~earate, cephalexin, nalidixic acid, tetracycline hydrochlorid~, ampicillin, flucloxacillin sodium, hexamine mandela~e and hexamine hippurate, neuroleptic drugs such as 1urazepam, diazepam, temazepam, amitryptyline, doxepin, lithium carbonate, lithium sulfate, chlorpromazine, th oridazine, trifluperazine, fluphenazine/ piperothiazine, haloperidol, maprotiline hydrochloride, imipramine and desmethylimipramine, central nervous stimulants such a~
methylphenida~e, ephedrine, epinephrine, isoproterenol, '.:
..
S~
amphetamine sulfate and amphetamine hydr~chloride, anti-histamic drugs such as diphenhydramine, diphenylpyraline, chlorpheniramine and brompheniramine, anti-diarrheal drugs such as bisacodyl and magnesium hydroxide, the laxative 5 drug, dioctyl ~odium sulfosuccinate, nutritional supplements such as ascorbic acid, alpha tocopherol, thiamine an~
pyridoxine, anti-spasmodic drugs such as dicyclomine and diphenoxylate, drugs affecting the rhythm of the heart such as verapamil, ni.edipine, diltiazem, procainamide, disopyramide, bretylium tosylate, quinidine sulfate and quinidine gluconate, drugs used in the treatment o~
hypertension such as propranolol hydrochloride, guanethidine monosulpha~e, methyldopa, oxprenolol hydrochloride, captopril and hydralazine, drugs used in the trea~ment of migraine such as ergotamine, drugs affecting coagulability of blood such as epsilon aminocaproic acid and protamine sulfate, analgesic drugs such as acetylsalicylic acid, acetaminophen, codeine phosphate, codeine sulfate, oxycodone, dihydrocodeine tartrate, oxycodeinone, morphine, heroin, nal~uphine, butorphanol tartrate, penta~ocine hydrochloride, cyclazacine, pethidine, buprenorphine, scopolamine and mefenamic acid, anti-epileptic drugs such as phenytoin sodium and sodium valproate, neuromuscular drugs such as dantrolene sodium, substances used in the treatment of diabetes such as tolbutamide, disbenase glucagon and insu~in, dru~s used in the trea~ment of thyroid gland disfunction such as triiodothyronine, thyroxine and propylthiouracil, diuretic drugs such as furosemide, chlorthalidone, hydrochlorthiaæide, spironolactone and triamterene, the uterine relaxant drug ritodrine, appetite suppressants such as fenfluramine hydrochloride, phentermine and diethylproprion hydrochloride, anti-asthmatic and bronchodilator drugs such as aminophylline, theop~lylline, salbutamol, orciprenaline sulphate and terbutaline ~ulphate, expectorant drugs such as guaiphenesin, cough suppressants such as dextromethorphan and noscapine, mucolytic drugs such as carbocisteine, anti-septics such as cetylpyridinium .
805~
chloride, tyrothricin and chlorhexidine, decongestant drugs such as phenylpropanolamine and p~eudoephedrine, hypnotic drugs such as dichloralphenazone and nitrazepam, anti-nauseant dru~s such as promethazine theoclate, haemopoietic drugs such as ~errous sulphate, folic acid and calcium gluconate, uricosuric drugs such as sulphinpyra~one, allopurinol and probenecid.
Particularly preferred active ingredients are:
ibuprofen, paracetamol, 5-amino-salicylic acid, dextromethorphan, propranolol, theophylline, dil~ia7em, methyldopa, pseudoephedrine, cimetidine, cephalexin, cephaclor, cephradine, naproxen, piroxicam, diazepam, diclofenac, indomethacin, amoxycillin, pivampicillin, bacampicillin, dicioxacillin, erythromycin, erythromycin stearate, lincomycin, co-dergocrine mesylate, d~xycycline, dipyridamole, frusemide, triamterene, sulindac, nifedipine, atenolol, lora7.epam, glibenclamide, sal~utamol, trimethoprimtsulphamethoxazole, spironolactone, carbinoxamine maleate, guaiphenesin, potassium chloride and metoprolol tartrate.
Especially preferred active ingredients include theophylline, paracetamol an~ potassium chloride.
The active ingredient may also be a saccharin for use in edible compositions wherein it is desired to obtained a controlled release of saccharin, such as, for e~ample in chewing gums. The active ingredient may also be other sweetening agents, such asl for example, aspartame which is especially suitable for use in chewing gums.
The invention alsv provides a process for preparing the controlled release powder according to the invention which comprises:
a) orming a solution of the polym~r or polymers in a solvent;
b) dissolving or dispersing the active ingredient in said polymer solution so as to form a uniform mixture; and c) r~moving the solvent from the mi~ture so as to `- obtain micro-particles having an average si~e in the range 0 1 to 125~ m.
~. . ;,; .
: : ' ' .
~. , : ', 12~ 5~L
The solvent is selected from water, alcohols, Xetones, halogenated aliphatic compounds, halogenated aromatic hydrocarbon compounds, aromatic hydrocarbon compounds and cyclic ethers or a mixture thereof.
Especially preferred solvents inc~ude, water, hexane, heptane, methanol, ethanol, acetone, methylethyl ketone, methylisobutyl ketone, methylene chloride, chloroform, carbon tetrachloride, toluene, ~ylene and ~etrahydro~uran.
The choice of solvent or solvents will be dictated by the particular polymer or polymers selected. For example, suitable solvents for use with the celluloses are acetone or a mixture of methanol and methylene chloride.
The concentration of the polymer in the solvent will normally be less than 75% by weight. Normally the concentration will be in the range of 10-30% by weight.
If the active ingredient is not soluble in the polymer solution the particle size of the active ingredient is reduced to less than lQ ~ m. The reduction of particle size may be achieved ~y milling, for example, by ball milling or jet milling.
The active ingredient may, of cour~e, be a liquid.
~ he ratio of drug to polymer will vary within w~de limits, such as within the range 0.1:10 to 10:1.
The uniform mixture of the active ingredient in the polymer solution may be achieved by rapid and continuous mixing.
The removal of the solvent and the formation of particles of the desired si~e may be achieved in a number of ways.
1. SPRAY ~RYI~G.
The mixture of active ingredient and polymer in the solvent i~ sprayed into a stream of hot air in conventionat manner. This causes the solvent ~o evaporate and the powder is collected in the spray drying vessel.
The size of the particles may be controlled in a number of ways, for example, by pre-~electing the inle~ and outlet - temperature of the ~pray drying vessel; the rate of .;, : . , - :
~2~i~305:~
introduction of the spray, the size of the spray tip or the ratio of the concentration of active ingredient to polymer.
Many types of controlled or sustained release pellets are known which are loaded into capsules for oral administration. These pellets can be described as macro-particles and invariably have an average size greater than 400 ~m. Such pellets are the subject, for example, of the Applicants' EP-A- 0 122 077, EP-A- 0 123 470, ~P-A- 0 156 077 and EP-A- 0 149 920.
Sustained release pellets cannot be readily formulated as liquids. Sustained release liquids are desirable for use as geriatric and paediatric formulations.
Various processes are known for the production of micro-spheres using solvent evaporation emulsion techniques.
Known micro-encapsulation techniques are generally employed for phase transformation, such as for the conversion of liquids to solids. Alternatively, such techniques may be used for protecting an active material, such as coating aspirin to mask its stomach irritant properties.
Sustained release liquids are known which contain ion exchange resins. In such sustained release liquids the active ingredient is bound to an ion exchange resin in the form of a reversible complex and is displaced therefrom in vivo. Such sustained release liquids are described, for example, in French Patent Publication No. 2 278 325.
It is an object of the present invention to provide a controlled release powder of discrete micro-particles which can be readily formulated in liqu~d form but which can also be formuIated in other sustained release forms such as tablets`which have improved properties relative to the known forms.
......
, 12~
Accordingly, the invention provides a controlled release powder containing discrete micro-particles for use in controlled release compositions, said powder comprising particles containing an active ingredient and optionally an excipient in intimiate admixture with at least one non-toxic polymer, each of said particles being in the form of a micromatrix with active ingredient and the excipient, if present, uni~ormly distributed throughout the matrix, said particles having an average size o~
between 0.1 and 125 ~m and having a predetermined release of active ingredient when the dissolution rate thereof is measured according to the Paddle Method of U.S.
Pharmacopoeia XX at 37C and 75 r.p.m., said dissolution rate being substantially proportional to the square root of time.
Pre~erably~ the particles have a~ ave~age size o~
between 5 and 100 ~m.
The Applicants have coined the term "pharmasomes" ~or the micro-particles of the powder according to the invention and which term is used hereinafter in the Specification.
The controlled release powders according to the invention can permit a sustained release of active ingredient as hereinafter demonstrated.
Further preferably, the active ingredient is a drug, a nutrient, a colouring agent, a fragrance, a herbic.ide, a pesticide, a flavouring agent or a sweetening agent.
The powder can be dispersed or suspended in a liquid vehicle and will maintain its sustained release characteristics for a useful period of time. Such dispersions or suspensions have both chemical stability and stability in terms of dissolution rate.
The polymer may be soluble, insoluble, permeable, impermeable or biodegradable. The polymers may be polymers or co-polymers. The polymer may be a natural or synthetic polymer. Natural polymers include polypeptides, polysaccharides and alginic acid. A suitable polypeptide is zein and a suitable polysaccharide is cellulose.
Representative synthetic polymers include alkyl celluloses, hydroxyalkyl celluloses r cellulose ethers, `! ,`;
' ~
5~
cellulose esters, nitro cellulose~, ~olymer~ of acrylic and methacrylic acids and esters thereof, polyamides, poly-carbonates, polyalkylenes, polyalkylene glycols, poly-alkylene oxides, polyalkylene terephthalates, polyvinyl alcohols, polyvinyl ethers, polyvinyl esters, polyvinyl halides, polyvinylpyrrolidone, polyglycolides, polysiloxanes and polyurethanes and co-polymers thereo~.
Particularly suitable polymers include: methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxy~utyl methyl cellulose, cellulose acetate, cellulose propionate ~lower, medium or higher molecular weight), cellulose ace~ate propionate, cellulose acetate butyrate, cellulose acetate phthalate, carboxymethyl cellulose, cellulose triacetate, cellulose sulphate sodium salt, poly(methyl methacrylate), poly(ethyl methacrylate), poly(butyl methacrylate~, polytisQbutyl methacrylate), poly(hexyl methacrylate), poly(isodecyl methacrylate~, poly(lauryl methacryla~e), poly(phenyl methacrylate~, poly(methyl acrylate), poly(isopropyl acrylate), poly(iso~utyl acrylate), poly(octadecyl acrylate), poly(ethylene~, poly(ethylene) low density, poly(ethylene) high density, poly~propylene~, poly(ethylene glycol), poly(ethylené oxide), polylethylene terephthalate), poly(vinyl alcohol3, poly(vinyl i80~utyl ether), poly(vinyl acetate), poly~vinyl chloride) and polyvinylpyrrolidone.
Especially suitable co-polymers include: butyl methacrylate/isobutyl methacrylate co-polymer, high molecular weight, methylvinyl ether/m~leic acid co-polymer, methylvinyl ether/m~leic acid, monoethyl ester co-polymer, methylvinyl ether/maleic anhydride co-polymer and vinyl alcohol/vinyl acetate co-polymer.
Representative biodegradable pol~mers include, poly glycolides, ~oly(ethylene terephthalate) and polyurethane.
Representative acrylates and methacrylate~ are polymers sold under the Trade ~ark Eudragit.
When t~e active ingredient is a drug there is essentially no limitation on the type o drug which may be used.
: ~,:, : ~. :
0~1 Representative active ingredients include antacids, anti-inflammatory substances, coronary dilator6, cerebral dilators, peripheral vasodilators, anti-infectives, psychotropics, anti-manics, stimulants, anti-hi~tamines, laxatives, decongestants, vitamins, gastro-intestina-sedatives, anti-diarrheal preparations, anti-anginal drugs, vasodilators, anti-arrhythmics, anti-hypertensive drugs, vasoconstrictors and mi~raine treatments, anti-coagulants and anti-thrombotic drugs, analgesics, anti-pyretics, hypno~ics, sedatives, anti emetics, anti-nauseants, anti-convulsants, neuromuscular drugs, hyper- and hypo~lycaemic agents, thyroid and anti-thyroid preparati.ons, diuretics, anti-spasmodics, uterine rela~ants, mineral and nutritional additives, anti-obesity drugs, anabolic drugs, erythropoietic drugs, anti-asthmatics, bronchodilators, expectorants, cough suppressants, mucolytics and anti-uricemic dru~s.
~ ypical active ingredients include gastro-intestinal sedatives such as meto~lopramide and propantheline bromide, antacids such as aluminium trisilicate, aluminium hydroxide and cimetidine, anti-inflammatory drugs such as phenylbutazone, indomethacin, naproxen, ibuprofen, flurbiprofen, diclofenac, dexamethasone, prednisone and prednisolone, coronary vasodilator drugs such as slyceryl trinitrate, isosorbide dinitrate and penta~rythritol tetranitrate, peripheral and cere~ral vasodilators ~uch as soloctidilum, vincamine, naftidrofuryl oxalate, co-dergocrine mesylate, cyclandelate, papaverine and nicotinic acid, anti-infective substances such as erythromycin s~earate, cephalexin, nalidixic acid, tetracycline hydrochlorid~, ampicillin, flucloxacillin sodium, hexamine mandela~e and hexamine hippurate, neuroleptic drugs such as 1urazepam, diazepam, temazepam, amitryptyline, doxepin, lithium carbonate, lithium sulfate, chlorpromazine, th oridazine, trifluperazine, fluphenazine/ piperothiazine, haloperidol, maprotiline hydrochloride, imipramine and desmethylimipramine, central nervous stimulants such a~
methylphenida~e, ephedrine, epinephrine, isoproterenol, '.:
..
S~
amphetamine sulfate and amphetamine hydr~chloride, anti-histamic drugs such as diphenhydramine, diphenylpyraline, chlorpheniramine and brompheniramine, anti-diarrheal drugs such as bisacodyl and magnesium hydroxide, the laxative 5 drug, dioctyl ~odium sulfosuccinate, nutritional supplements such as ascorbic acid, alpha tocopherol, thiamine an~
pyridoxine, anti-spasmodic drugs such as dicyclomine and diphenoxylate, drugs affecting the rhythm of the heart such as verapamil, ni.edipine, diltiazem, procainamide, disopyramide, bretylium tosylate, quinidine sulfate and quinidine gluconate, drugs used in the treatment o~
hypertension such as propranolol hydrochloride, guanethidine monosulpha~e, methyldopa, oxprenolol hydrochloride, captopril and hydralazine, drugs used in the trea~ment of migraine such as ergotamine, drugs affecting coagulability of blood such as epsilon aminocaproic acid and protamine sulfate, analgesic drugs such as acetylsalicylic acid, acetaminophen, codeine phosphate, codeine sulfate, oxycodone, dihydrocodeine tartrate, oxycodeinone, morphine, heroin, nal~uphine, butorphanol tartrate, penta~ocine hydrochloride, cyclazacine, pethidine, buprenorphine, scopolamine and mefenamic acid, anti-epileptic drugs such as phenytoin sodium and sodium valproate, neuromuscular drugs such as dantrolene sodium, substances used in the treatment of diabetes such as tolbutamide, disbenase glucagon and insu~in, dru~s used in the trea~ment of thyroid gland disfunction such as triiodothyronine, thyroxine and propylthiouracil, diuretic drugs such as furosemide, chlorthalidone, hydrochlorthiaæide, spironolactone and triamterene, the uterine relaxant drug ritodrine, appetite suppressants such as fenfluramine hydrochloride, phentermine and diethylproprion hydrochloride, anti-asthmatic and bronchodilator drugs such as aminophylline, theop~lylline, salbutamol, orciprenaline sulphate and terbutaline ~ulphate, expectorant drugs such as guaiphenesin, cough suppressants such as dextromethorphan and noscapine, mucolytic drugs such as carbocisteine, anti-septics such as cetylpyridinium .
805~
chloride, tyrothricin and chlorhexidine, decongestant drugs such as phenylpropanolamine and p~eudoephedrine, hypnotic drugs such as dichloralphenazone and nitrazepam, anti-nauseant dru~s such as promethazine theoclate, haemopoietic drugs such as ~errous sulphate, folic acid and calcium gluconate, uricosuric drugs such as sulphinpyra~one, allopurinol and probenecid.
Particularly preferred active ingredients are:
ibuprofen, paracetamol, 5-amino-salicylic acid, dextromethorphan, propranolol, theophylline, dil~ia7em, methyldopa, pseudoephedrine, cimetidine, cephalexin, cephaclor, cephradine, naproxen, piroxicam, diazepam, diclofenac, indomethacin, amoxycillin, pivampicillin, bacampicillin, dicioxacillin, erythromycin, erythromycin stearate, lincomycin, co-dergocrine mesylate, d~xycycline, dipyridamole, frusemide, triamterene, sulindac, nifedipine, atenolol, lora7.epam, glibenclamide, sal~utamol, trimethoprimtsulphamethoxazole, spironolactone, carbinoxamine maleate, guaiphenesin, potassium chloride and metoprolol tartrate.
Especially preferred active ingredients include theophylline, paracetamol an~ potassium chloride.
The active ingredient may also be a saccharin for use in edible compositions wherein it is desired to obtained a controlled release of saccharin, such as, for e~ample in chewing gums. The active ingredient may also be other sweetening agents, such asl for example, aspartame which is especially suitable for use in chewing gums.
The invention alsv provides a process for preparing the controlled release powder according to the invention which comprises:
a) orming a solution of the polym~r or polymers in a solvent;
b) dissolving or dispersing the active ingredient in said polymer solution so as to form a uniform mixture; and c) r~moving the solvent from the mi~ture so as to `- obtain micro-particles having an average si~e in the range 0 1 to 125~ m.
~. . ;,; .
: : ' ' .
~. , : ', 12~ 5~L
The solvent is selected from water, alcohols, Xetones, halogenated aliphatic compounds, halogenated aromatic hydrocarbon compounds, aromatic hydrocarbon compounds and cyclic ethers or a mixture thereof.
Especially preferred solvents inc~ude, water, hexane, heptane, methanol, ethanol, acetone, methylethyl ketone, methylisobutyl ketone, methylene chloride, chloroform, carbon tetrachloride, toluene, ~ylene and ~etrahydro~uran.
The choice of solvent or solvents will be dictated by the particular polymer or polymers selected. For example, suitable solvents for use with the celluloses are acetone or a mixture of methanol and methylene chloride.
The concentration of the polymer in the solvent will normally be less than 75% by weight. Normally the concentration will be in the range of 10-30% by weight.
If the active ingredient is not soluble in the polymer solution the particle size of the active ingredient is reduced to less than lQ ~ m. The reduction of particle size may be achieved ~y milling, for example, by ball milling or jet milling.
The active ingredient may, of cour~e, be a liquid.
~ he ratio of drug to polymer will vary within w~de limits, such as within the range 0.1:10 to 10:1.
The uniform mixture of the active ingredient in the polymer solution may be achieved by rapid and continuous mixing.
The removal of the solvent and the formation of particles of the desired si~e may be achieved in a number of ways.
1. SPRAY ~RYI~G.
The mixture of active ingredient and polymer in the solvent i~ sprayed into a stream of hot air in conventionat manner. This causes the solvent ~o evaporate and the powder is collected in the spray drying vessel.
The size of the particles may be controlled in a number of ways, for example, by pre-~electing the inle~ and outlet - temperature of the ~pray drying vessel; the rate of .;, : . , - :
~2~i~305:~
introduction of the spray, the size of the spray tip or the ratio of the concentration of active ingredient to polymer.
2. USE OF ~N EXTERMAL LIQUID PHASE.
The mi~ture of active ingredient and polymer, which is in the form of a solution or ~uspension, is p~ured into a liquid external phase. The liquid external phase comprises a solvent which is immiscible or partially immuscible with the active ingredient/polymer mixture.
The choice of external liquid phase will be determined by the particular combination of active ingredient and polymer selected. Suitable liquids for the external li~uid phase include water, aqueous solutions, for example, sugar solutions, organic solvents, mineral oil, vegeta~le oils, fixed oils, syrups or silicones. The aqueous s~lution may include a thickening agent, such as xanthan gum, to increase the viscosity thereof. Oils may be made more viscous ~y ~he addition ~f substances such as magnesium stearate. The external liquid pha~e may also c~mprise a solution of a different pH, for example, a buffer.
The ratio of external liquid phase to poly~Pr mixture will be at least 2:1.
Following addition of the active ingredient~polymer mixture to the external liquid phase, the two phase mixture obtained is emulsified, for e~ample, by rapid ~i~ing. The emulsion formed may be either stable or unstable. Globules of the active ingredient/polymer are thereby formed in the emulsion.
The solvent may be removea in a number of ways. If the solvent is volatile it can ~e removed passively. For example, if the solvent is aoetone it would normally be removed by evaporation duri~g the mixing step. The particles form~d are ~hen harvested by filtration or centrifugation.
The solvent can also be removed ~y heàting while mixing the two phase mi~ture. For egample, the solvent may ~e removed on a rotary film evaporator. The solvent may also be removed under vacuum wi~h or without heating. Microwave .
:, . .
:- ..
. ~ . ,~-, ,. .:
~2~i8~5~
drying may al60 be employed with or without the application of a vacuum. Ano~her mode of ~ol~ent removal is free~e drying.
After harvesting of the micro-particles, they will 5 normally be given successive washings with a suitable solvent, follGwed by drying.
For e~ample, when the solvent used is acetone and the external liquid phase is mineral oil, then the m1cro-particles will be given successive washings with hexane and dried at 45C.
On a commercial scale emulsification of the mixture may be achieved by emulsification with an in-line mixer or mixers.
The particle size may be controlled in a number of ways For example, the particle size may be controlled b~
the rate of mixing, the viscosity of the external liquid phase, the ViSGosity of the internal phase, the active ingredient particle si~e or the volatility of the solvent.
The mi~ture of active ingredient and polymer, which is in the form of a solution or ~uspension, is p~ured into a liquid external phase. The liquid external phase comprises a solvent which is immiscible or partially immuscible with the active ingredient/polymer mixture.
The choice of external liquid phase will be determined by the particular combination of active ingredient and polymer selected. Suitable liquids for the external li~uid phase include water, aqueous solutions, for example, sugar solutions, organic solvents, mineral oil, vegeta~le oils, fixed oils, syrups or silicones. The aqueous s~lution may include a thickening agent, such as xanthan gum, to increase the viscosity thereof. Oils may be made more viscous ~y ~he addition ~f substances such as magnesium stearate. The external liquid pha~e may also c~mprise a solution of a different pH, for example, a buffer.
The ratio of external liquid phase to poly~Pr mixture will be at least 2:1.
Following addition of the active ingredient~polymer mixture to the external liquid phase, the two phase mixture obtained is emulsified, for e~ample, by rapid ~i~ing. The emulsion formed may be either stable or unstable. Globules of the active ingredient/polymer are thereby formed in the emulsion.
The solvent may be removea in a number of ways. If the solvent is volatile it can ~e removed passively. For example, if the solvent is aoetone it would normally be removed by evaporation duri~g the mixing step. The particles form~d are ~hen harvested by filtration or centrifugation.
The solvent can also be removed ~y heàting while mixing the two phase mi~ture. For egample, the solvent may ~e removed on a rotary film evaporator. The solvent may also be removed under vacuum wi~h or without heating. Microwave .
:, . .
:- ..
. ~ . ,~-, ,. .:
~2~i8~5~
drying may al60 be employed with or without the application of a vacuum. Ano~her mode of ~ol~ent removal is free~e drying.
After harvesting of the micro-particles, they will 5 normally be given successive washings with a suitable solvent, follGwed by drying.
For e~ample, when the solvent used is acetone and the external liquid phase is mineral oil, then the m1cro-particles will be given successive washings with hexane and dried at 45C.
On a commercial scale emulsification of the mixture may be achieved by emulsification with an in-line mixer or mixers.
The particle size may be controlled in a number of ways For example, the particle size may be controlled b~
the rate of mixing, the viscosity of the external liquid phase, the ViSGosity of the internal phase, the active ingredient particle si~e or the volatility of the solvent.
3. Other methods for the removal of the solvent include phase separation, interfacial polymer deposition and coacervation.
The optional excipient u~ed in association with the or each active ingredient will frequently have an active role to play following administration. For example, the excipien~ may be a surface-active agent which facilitates the transport of water into the particles, for example, sodium lauryl sulphate or a surface-active agent sold under the Trade MarX Tween. The e~cipient may also be an active transport agent such as, for example, glucose or one or more 3Q amino acids.
The e~cipient may comprise one or more organic acids which facilitate the dissolution of drugs which are poorly soluble in alkaline media. Such acids include, for example, ascorbic acid, citric acid, fumaric acid, malic acid, 35 succinic acid and tartaric acid. Bimilarly, the excipient may compris~ one or more basic materials which facilitate the aissolution of drugs which are poorly solu~le in acid media. Such basic material~ include sodium carbonate, ,:
~ ,',~ - ' ~ , .: :, . ::: : ~ .
o~
sodium citrate and sodium bicarbonate.
When the active ingredient is a drug, ~he micro-particle~ according to the invention may be formulated in a wide variety of forms. Pharmaceutical formulations according to the invention include pill6 and ta~lets, or example, coated tablets, effervescent tablets, chewable tablets, moulded tablets and melt tablets. The particles according to the invention may be compressed into tablets and optionally coated without any substantial change occurring in the particles. Furthermore, because of the micro-particulate nature of the particles they are unlikely to be significantly degraded or ground by any che~ing action.
Powder formulations according to the invention include dusting powders and douche powders.
The particles according to the invention may also be loaded into capsules which may be either soft gelatin capsules or hard gelatin capsules.
Other solid dosage forms include pessaries, rectal suppositories, vaginal tablets and vaginal inserts.
The particles according to the invention may also be used in implants and ocular inserts.
The powders can also be formulated in form~s ~uitable for topical application, such as, for example, as creams or ointments and for ,ransdermal delivery, for e2~mp1e, in the form of transdermal patches.
The micro-particlate powders according to the invention may also be used in the form of foams, gels, pastes, gums, mucilages and jellies~
Other suitable formulations incorporating the micro-particles according to the invention include inhalants, magmas, intrauterine devices, patches, biodegradable wound dressings and other topical dressings.
~he micro-particulate powders according to the invention are Pspecially ~uitable ~or formulation as liquids for oral, local or parenteral admini6tration. Thus, they can be formulated in liqu~d form for use as eye drops, nasal drops, ear drop~, suspensions, syrups, infusion ana ,"; . ~; , , .. ,, ,,, .. ,.~ ~ " .
' :~,' ,.' :.' ' , or ~
injectable ~olutions. The powders can also be formulated as nasal sprays. The injectable solutions i~clude intravenous, subcutaneous and intramuscular injectable solutions.
The oral suspensions and syrups according to the 5 invention are particularly suitable for use in geriatric and paediatric ~edicine. The liquids formed hav~ good mouth feel. Furthermore, because the polymer substantially coats the active ingredient, the coating masks any unpleasant taste.
A characteristic of good mouth feel also applies to chewable and effervescent tablets. Because of the micro-particulate nature of the powder one does not e~perience a granular sensation.
Preferred paediatric liquids according to the invention are suspensions or syrups of bronchial rela~ants, analgesics, anti-pyretics, anti-tussives~ anti-spa~modics, anti-nauseants, anti-histamines, anti-epileptics and antibiotics.
Other especially suitable liquid formulations according to th~ invention are non-aqueous suspensions ~f highly water soluble or water insoluble active ingredients. Suitable drugs for formulating in this way include de~tro~e~horphan, guaiphenesin and pseudoephedrine or a salt thereof or potassium chloride.
The liquid formulations have good shelf life and demonstrate stability both in chemical t~rms and in terms of dissolution rates up to thirty days~ It i~ e~t~mated that the shelf life can be as long as five year~.
In the liquid formulations according to the iQvention one can achieve a concentration of active ingredient of up to 1 g per 5 ml.
Heretofore many drugs have not been sta~le in liquid form, for example, analgesic~, necessita~ing a dosa~e regimen of every 4-6 hours. The liquids accoxding to the invention offer versatility and the possibili~y of twice daily administra~ion for a medicament such as, for example, analgesics, anti-histamine~ and bronc~ial relasant~
The taste masking ~ea~ure of ~he powders according to the invention is of significant importance in the area of : .,: ~.
- . :
S~L
paediatric medicine. However, this feature is of e~ual importance in veterinary medicine. For example, in the case of antibiotics such as erythromycin which have an extremely unpleasant bitter taste it is virtually impossible to administer such antibiotics orally to animals because it is not possible to successfully mask the bitter taste.
Accordingly, such known oral formulations are re]ected by anlmals .
The present invention therefore in one important aspect provides controlled release antibiotic formulations substantially free from the taste of said antibiotic for pharmaceutical or veterinary use which:
a) are in the form of powders according to the invention;
b) are in the form of non-aqueous suspensions of the powders according to the invention; or c) are in the form of reconstitutable aqueous suspensions of the powders according to the invention.
The powders according to the invention can be used in pre-mixes for animal feedstuffs and other feed additives.
In addition to drugs, nutritional supplements such as vitamins can be administered orally to animals using the powders according to the invention.
Suitable veterinary preparations according to the invention include veterinary feeds, boluses, drenches and washes.
In the agricultural field the powders according to the invention can also be used for preparation of controlled release herbicides and pesticides.
In the cosmetics field one use of the controlled release powders according to the invention is as sustained release fragrance particles for use in talcum powders, creams, lotions and other cosmetic preparations.
:, . -~i8~
- 13a -BRIEF DESCRIPTION OF THE FIGURES
-In the accompanying Figures:
Fig. 1 is an electron micrograph of microparticles according to the invention;
Fig. 2 is an electron micrograph of microparticles of the type depicted in Fig. 1 but from which the active ingredient has been leached by dissolution in water for 24 hours;
Fig. 3 is a graph of plasma levels t~g/ml) versus time after administration (hours) for a syrup according to the invention;
Fig. 4 is a graph representing percentage dissolution of a suspension according to the invention versus time over a fifteen week period;
Fig. 5 is a graph comparing plasma levels (~g/ml) versus time after administration (hours) of a syrup according to the invention (curve a) with a conventional syrup (curve b);
Fig. 6 is a graph comparing plasma levels (~g/ml) versus time after administration (hours) of two suspensions according to the invention (curves a and b) with a conventional syrup (curve c);
Fig. 7 is a graph comparing three suspensions according to the invention in terms of percentage dissolution versus time (hours~;
Fig. 8 is a graph representing percentage dissolution of a suspension according to the invention versus time over a tbirty ~eek period;
Fig. 9 is a graph comparing plasma levels (~g/ml) versus time after administration (hours) of a suspension according to the invention (curve a) with a conventional syrup (curve b);
Fig. 10 is a graph comparing plasma levels (~g~ml) versus time after administration (hours) of a :" '' " ,:
:- , ::: , ~2~5~
- 13b -suspension according to the invention (curve a) with a conventional syrup (curve b);
Fig. 11 is a graph comparing plasma levels (~g/ml~
versus time after administration (hours) of a suspension according to the invention (curve a~ with a conventional syrup (curve b);
Fig. 12 is a graph of percentage dissolution versus time (hours) for three suspensions according to the invention;
Fig. 13 is a graphic representation of observed sweetness for a chewing gum containing aspartame~
containing microparticles according to the invention with a conventional aspartame-containing chewing gum;
Fig. 14 is a graphic representation of percentage dissolution versus time (hours) of microparticles according to the invention ~curve a) relative to chewable tablets prepared therefrom ~curve b);
Fig. 15 is a graphic representation of percentage dissolution versus time ~hours) of microparticles according to the invention ~curve a) relative to melt tablets prepared therefrom (curve b); and Fig. 16 is a graphic representation of percentage dissolution versus time (hours) of microparticles according to the invention (curve a) relative to capsules prepared therefrom ~curve b).
Each of the particles of the controlled release powder accord7ng to the invention represents a true micromatrix with the active ingredient and optionally one or more excipients uniformly distributed therethrough as depicted in ' ~ . .- : ': ' ': : .
i8~
Fig. 1 of ~e accompanying drawings which is a half-tone drawing prepared from an electron micrograph of "pharmasomes"
containing theophylline and prepared as described in Example 1 below. The theophylline can be observed to form veins or a labyrinth throughout the polymeric material of the "pharmasome". Fig. 2 is a half-tone drawing prepared from an electron micrograph of the "pharmasomes" after the theophylline has been leached out by dissolution in water for 24 hours. One is left with a matrix structure of polymeric material.
The micromatrix nature of the particles can also be demonstrated by their dissolution profile. Referring, for example, to Examples 1 and 2 hereinbelow, it is found that the dissolution rate (D) is directly proportional to the square root of time (t) according to the following equation:
D a ~ t after an initial burst of release of active ingredient which is considered to be active ingredient lying close to the surface of the particles. The dissolution rate is dependent on the amount of active ingredient remaining in the particle matrix at any given time. Theoretically the last molecule of ac.ive ingredient never leaches out. The dissolution rate is assumed to reach 100~ at infinity.
The particles according to the invention also have a degree of p~rosity which can be calculated from the absolute density of the particles measured on a pycnometer. ~le dissolution rate of the particles according to the invention is also found to relate to the degree of porosity of said particles.
The microparticles according to the invention are to be distinguished from microcapsules in that in the la~ter the active ingredient is encapsulated by a polymer coating, , ~ ,, i8~353 whereas in the former the active ingredient i~ uniformly distributed throug~out the polymeric material as described above and as indicated in Figs. 1 and 2 of the accompanying drawings.
The invention will be further illustrated by the 5/ following e~amples. In the e~amples the dissolution rate o~
the various pharmaceutical formulations is measured by the Paddle Method of U.S. Pharmacopoeia XX at 37~C and 75 r.p.m., using 200 mg of sample per 900 ml of simulated intestinal fluid excluding enzymes~
Preparation of micro-particles containing theop~ylline Theophylline was ground in a motorised ball mill and then sieYed through a 38 ~m mesh sieve.
Cellulose acetate butyrate (CAB) was dissolved in acetone so as to give a concentration of CAB in acetone o~
15~ w/v.
Hexane (20 ml) was added to an aliquot of the CAB
solution (100 g) with constant stirring.
A portion of the sieved theophylline ~10 9~ was then ~0 added to the polymer solution under constant agitation to ensure an even dispersion of the theophylline. ~his product constituted an internal phase for the su~sequent emulsification step.
Magnesium stearate was dissolved in heavy mineral oil U.S. Pharmacopoeia so as to achieve a concentration of 1.5% w/v. This solution was used as an e~ternal liquid phase. 150 ml of the external liquid phase was decanted into a tall 600 ml beaker and the internal phase prepared above was added thereto. Emulsification was achieved using a Silverson mixer (Silverson is a Trade Mar~ a~ full speed for 2 minutes and thsn dropping the speed as re~uired to achieve the desired particle size.
The suspension of particles in the e~t~rnal phase was then introduced into a rotary evaporatvr and the acetone 35 removed under vacu~m. The suspension now consisted solely , ~
of polymer coated theophylline or "pharmasomes" suspended in the external liquid phase. On microscopic examination particle size was found to range from 10 to 180 ~m.
The particles were centrifuged down and the external phase decanted. The particles were then washed repeatedly with heptane to remove the external liquid phase. The final product was then filtered and dried at 45C for two hours.
The particles were then sieved with mesh sizes of 50, 90, 125 and 180 ~m. The major proportion of particles were retained by the 90 ~m sieve.
The dissolution rate of the 90-125 ~m fraction of the particles was estimated using the Paddle Method of U.S.
Pharmacopoeia XX as indicated above. The results were as follows:
15 Time (h) ~ Release 0.5 42
The optional excipient u~ed in association with the or each active ingredient will frequently have an active role to play following administration. For example, the excipien~ may be a surface-active agent which facilitates the transport of water into the particles, for example, sodium lauryl sulphate or a surface-active agent sold under the Trade MarX Tween. The e~cipient may also be an active transport agent such as, for example, glucose or one or more 3Q amino acids.
The e~cipient may comprise one or more organic acids which facilitate the dissolution of drugs which are poorly soluble in alkaline media. Such acids include, for example, ascorbic acid, citric acid, fumaric acid, malic acid, 35 succinic acid and tartaric acid. Bimilarly, the excipient may compris~ one or more basic materials which facilitate the aissolution of drugs which are poorly solu~le in acid media. Such basic material~ include sodium carbonate, ,:
~ ,',~ - ' ~ , .: :, . ::: : ~ .
o~
sodium citrate and sodium bicarbonate.
When the active ingredient is a drug, ~he micro-particle~ according to the invention may be formulated in a wide variety of forms. Pharmaceutical formulations according to the invention include pill6 and ta~lets, or example, coated tablets, effervescent tablets, chewable tablets, moulded tablets and melt tablets. The particles according to the invention may be compressed into tablets and optionally coated without any substantial change occurring in the particles. Furthermore, because of the micro-particulate nature of the particles they are unlikely to be significantly degraded or ground by any che~ing action.
Powder formulations according to the invention include dusting powders and douche powders.
The particles according to the invention may also be loaded into capsules which may be either soft gelatin capsules or hard gelatin capsules.
Other solid dosage forms include pessaries, rectal suppositories, vaginal tablets and vaginal inserts.
The particles according to the invention may also be used in implants and ocular inserts.
The powders can also be formulated in form~s ~uitable for topical application, such as, for example, as creams or ointments and for ,ransdermal delivery, for e2~mp1e, in the form of transdermal patches.
The micro-particlate powders according to the invention may also be used in the form of foams, gels, pastes, gums, mucilages and jellies~
Other suitable formulations incorporating the micro-particles according to the invention include inhalants, magmas, intrauterine devices, patches, biodegradable wound dressings and other topical dressings.
~he micro-particulate powders according to the invention are Pspecially ~uitable ~or formulation as liquids for oral, local or parenteral admini6tration. Thus, they can be formulated in liqu~d form for use as eye drops, nasal drops, ear drop~, suspensions, syrups, infusion ana ,"; . ~; , , .. ,, ,,, .. ,.~ ~ " .
' :~,' ,.' :.' ' , or ~
injectable ~olutions. The powders can also be formulated as nasal sprays. The injectable solutions i~clude intravenous, subcutaneous and intramuscular injectable solutions.
The oral suspensions and syrups according to the 5 invention are particularly suitable for use in geriatric and paediatric ~edicine. The liquids formed hav~ good mouth feel. Furthermore, because the polymer substantially coats the active ingredient, the coating masks any unpleasant taste.
A characteristic of good mouth feel also applies to chewable and effervescent tablets. Because of the micro-particulate nature of the powder one does not e~perience a granular sensation.
Preferred paediatric liquids according to the invention are suspensions or syrups of bronchial rela~ants, analgesics, anti-pyretics, anti-tussives~ anti-spa~modics, anti-nauseants, anti-histamines, anti-epileptics and antibiotics.
Other especially suitable liquid formulations according to th~ invention are non-aqueous suspensions ~f highly water soluble or water insoluble active ingredients. Suitable drugs for formulating in this way include de~tro~e~horphan, guaiphenesin and pseudoephedrine or a salt thereof or potassium chloride.
The liquid formulations have good shelf life and demonstrate stability both in chemical t~rms and in terms of dissolution rates up to thirty days~ It i~ e~t~mated that the shelf life can be as long as five year~.
In the liquid formulations according to the iQvention one can achieve a concentration of active ingredient of up to 1 g per 5 ml.
Heretofore many drugs have not been sta~le in liquid form, for example, analgesic~, necessita~ing a dosa~e regimen of every 4-6 hours. The liquids accoxding to the invention offer versatility and the possibili~y of twice daily administra~ion for a medicament such as, for example, analgesics, anti-histamine~ and bronc~ial relasant~
The taste masking ~ea~ure of ~he powders according to the invention is of significant importance in the area of : .,: ~.
- . :
S~L
paediatric medicine. However, this feature is of e~ual importance in veterinary medicine. For example, in the case of antibiotics such as erythromycin which have an extremely unpleasant bitter taste it is virtually impossible to administer such antibiotics orally to animals because it is not possible to successfully mask the bitter taste.
Accordingly, such known oral formulations are re]ected by anlmals .
The present invention therefore in one important aspect provides controlled release antibiotic formulations substantially free from the taste of said antibiotic for pharmaceutical or veterinary use which:
a) are in the form of powders according to the invention;
b) are in the form of non-aqueous suspensions of the powders according to the invention; or c) are in the form of reconstitutable aqueous suspensions of the powders according to the invention.
The powders according to the invention can be used in pre-mixes for animal feedstuffs and other feed additives.
In addition to drugs, nutritional supplements such as vitamins can be administered orally to animals using the powders according to the invention.
Suitable veterinary preparations according to the invention include veterinary feeds, boluses, drenches and washes.
In the agricultural field the powders according to the invention can also be used for preparation of controlled release herbicides and pesticides.
In the cosmetics field one use of the controlled release powders according to the invention is as sustained release fragrance particles for use in talcum powders, creams, lotions and other cosmetic preparations.
:, . -~i8~
- 13a -BRIEF DESCRIPTION OF THE FIGURES
-In the accompanying Figures:
Fig. 1 is an electron micrograph of microparticles according to the invention;
Fig. 2 is an electron micrograph of microparticles of the type depicted in Fig. 1 but from which the active ingredient has been leached by dissolution in water for 24 hours;
Fig. 3 is a graph of plasma levels t~g/ml) versus time after administration (hours) for a syrup according to the invention;
Fig. 4 is a graph representing percentage dissolution of a suspension according to the invention versus time over a fifteen week period;
Fig. 5 is a graph comparing plasma levels (~g/ml) versus time after administration (hours) of a syrup according to the invention (curve a) with a conventional syrup (curve b);
Fig. 6 is a graph comparing plasma levels (~g/ml) versus time after administration (hours) of two suspensions according to the invention (curves a and b) with a conventional syrup (curve c);
Fig. 7 is a graph comparing three suspensions according to the invention in terms of percentage dissolution versus time (hours~;
Fig. 8 is a graph representing percentage dissolution of a suspension according to the invention versus time over a tbirty ~eek period;
Fig. 9 is a graph comparing plasma levels (~g/ml) versus time after administration (hours) of a suspension according to the invention (curve a) with a conventional syrup (curve b);
Fig. 10 is a graph comparing plasma levels (~g~ml) versus time after administration (hours) of a :" '' " ,:
:- , ::: , ~2~5~
- 13b -suspension according to the invention (curve a) with a conventional syrup (curve b);
Fig. 11 is a graph comparing plasma levels (~g/ml~
versus time after administration (hours) of a suspension according to the invention (curve a~ with a conventional syrup (curve b);
Fig. 12 is a graph of percentage dissolution versus time (hours) for three suspensions according to the invention;
Fig. 13 is a graphic representation of observed sweetness for a chewing gum containing aspartame~
containing microparticles according to the invention with a conventional aspartame-containing chewing gum;
Fig. 14 is a graphic representation of percentage dissolution versus time (hours) of microparticles according to the invention ~curve a) relative to chewable tablets prepared therefrom ~curve b);
Fig. 15 is a graphic representation of percentage dissolution versus time ~hours) of microparticles according to the invention ~curve a) relative to melt tablets prepared therefrom (curve b); and Fig. 16 is a graphic representation of percentage dissolution versus time (hours) of microparticles according to the invention (curve a) relative to capsules prepared therefrom ~curve b).
Each of the particles of the controlled release powder accord7ng to the invention represents a true micromatrix with the active ingredient and optionally one or more excipients uniformly distributed therethrough as depicted in ' ~ . .- : ': ' ': : .
i8~
Fig. 1 of ~e accompanying drawings which is a half-tone drawing prepared from an electron micrograph of "pharmasomes"
containing theophylline and prepared as described in Example 1 below. The theophylline can be observed to form veins or a labyrinth throughout the polymeric material of the "pharmasome". Fig. 2 is a half-tone drawing prepared from an electron micrograph of the "pharmasomes" after the theophylline has been leached out by dissolution in water for 24 hours. One is left with a matrix structure of polymeric material.
The micromatrix nature of the particles can also be demonstrated by their dissolution profile. Referring, for example, to Examples 1 and 2 hereinbelow, it is found that the dissolution rate (D) is directly proportional to the square root of time (t) according to the following equation:
D a ~ t after an initial burst of release of active ingredient which is considered to be active ingredient lying close to the surface of the particles. The dissolution rate is dependent on the amount of active ingredient remaining in the particle matrix at any given time. Theoretically the last molecule of ac.ive ingredient never leaches out. The dissolution rate is assumed to reach 100~ at infinity.
The particles according to the invention also have a degree of p~rosity which can be calculated from the absolute density of the particles measured on a pycnometer. ~le dissolution rate of the particles according to the invention is also found to relate to the degree of porosity of said particles.
The microparticles according to the invention are to be distinguished from microcapsules in that in the la~ter the active ingredient is encapsulated by a polymer coating, , ~ ,, i8~353 whereas in the former the active ingredient i~ uniformly distributed throug~out the polymeric material as described above and as indicated in Figs. 1 and 2 of the accompanying drawings.
The invention will be further illustrated by the 5/ following e~amples. In the e~amples the dissolution rate o~
the various pharmaceutical formulations is measured by the Paddle Method of U.S. Pharmacopoeia XX at 37~C and 75 r.p.m., using 200 mg of sample per 900 ml of simulated intestinal fluid excluding enzymes~
Preparation of micro-particles containing theop~ylline Theophylline was ground in a motorised ball mill and then sieYed through a 38 ~m mesh sieve.
Cellulose acetate butyrate (CAB) was dissolved in acetone so as to give a concentration of CAB in acetone o~
15~ w/v.
Hexane (20 ml) was added to an aliquot of the CAB
solution (100 g) with constant stirring.
A portion of the sieved theophylline ~10 9~ was then ~0 added to the polymer solution under constant agitation to ensure an even dispersion of the theophylline. ~his product constituted an internal phase for the su~sequent emulsification step.
Magnesium stearate was dissolved in heavy mineral oil U.S. Pharmacopoeia so as to achieve a concentration of 1.5% w/v. This solution was used as an e~ternal liquid phase. 150 ml of the external liquid phase was decanted into a tall 600 ml beaker and the internal phase prepared above was added thereto. Emulsification was achieved using a Silverson mixer (Silverson is a Trade Mar~ a~ full speed for 2 minutes and thsn dropping the speed as re~uired to achieve the desired particle size.
The suspension of particles in the e~t~rnal phase was then introduced into a rotary evaporatvr and the acetone 35 removed under vacu~m. The suspension now consisted solely , ~
of polymer coated theophylline or "pharmasomes" suspended in the external liquid phase. On microscopic examination particle size was found to range from 10 to 180 ~m.
The particles were centrifuged down and the external phase decanted. The particles were then washed repeatedly with heptane to remove the external liquid phase. The final product was then filtered and dried at 45C for two hours.
The particles were then sieved with mesh sizes of 50, 90, 125 and 180 ~m. The major proportion of particles were retained by the 90 ~m sieve.
The dissolution rate of the 90-125 ~m fraction of the particles was estimated using the Paddle Method of U.S.
Pharmacopoeia XX as indicated above. The results were as follows:
15 Time (h) ~ Release 0.5 42
4 69 The particles were found to be tasteless with complete masking of the normally bitter taste of theophylline.
Preparation of Micro-particles containing paracetamol Example 1 was repeated except that 20 g of paracetamol was used in place of 10 g of theophylline. In the external liquid phase heavy mineral oil was replaced by light mineral oil. A major proportion of the particles had an average size of 90 ~m.
1~8~35~
The dissolution rate of the particles was determined and waS found to be as foll~s:
Time (h)% Release O O
0.5 43 ~9 The particles were found to be tasteless.
EXA~IPLF. 3 Preparation of micro-particles containing nifedipine.
Example 1 was repeated except that 16 g of nifedipine was used in place of theophylline. The inter~al phase consisted of Eudra~it RS 100 (Eudragit RS 100 is a Trade Mark~ in me~hanol at a concentration of 33% w/v. The external phase consisted o magnesium stearate in light mineral oil at a concentr~tion of 2.5 ~ w/v.
The dissolution rate of the particles formed was determined and was found to be as follows:
Time ~h) ~ Release 0.5 25 --~ 30 4 70 The particles were found to be ta6teless~
:. , -, :~. .
~ ' ',' ,"'',1,.,'~,' ' `'"' .. " ' ~L2 f~
EXAMPL~ 4 Preparation of micro-particles containing dextromethorphan hydrobromide.
Example 1 was repeated except that 10 g of theophylline was replaced by 10 g of dextromethorphan hydrobromide.
The dissolution rate of the particles was determined and was found to be as follows:
Time (h ) ~ Release 0.5 4S
6 9o Preparation of micro-particles containing 6acchari~ 60dium.
Example 1 was repeated except that theophylline was replaced by 6~5 g o saccharin sodium. The internal phase consisted of Ethocel (e~hyl cellulose~ ~Ethocel is a Trade Mark) 45 cps dissolved in ethanol so as to give a concentration vf 15% w/v. Saccharin sodium was added to 50 g of the polymer solution. The external liquid phase consisted of heavy mineral oil ~.S. Pharmacopoeia.
The dissolution rate of the particles was determlned and was found to be as follGws:
Time (sec.) ~ Release 3~ 15 8~
' " ~' - . :
'', ., ~ ' :
~' ': `
Preparation of micro-particles containing pseudephedrine hydrochloride.
The procedure of Example 1 was repeated except that the theophylline was replaced by 10 g of pseudoephedrine hydrochloride. 50 g of CAB was used which was dissolved in 20 ml of hexane so as to form the polymer solution.
The dissolution rate of the particles was determined and found to be as follows:
Time (h) % Release 0.5 35 ~ EXAMPLE 7 Preparation of micro-particles containing carbinoxamine maleate Example 1 was repeated llsing carbinoxamine maleate in place of theophylline. The dissolution rate of the particles was determined and found to be as follows:
Time (h) ; % Release 0.5 20 2 30 :-~!`
... .
:' ' ,, .: ;
- , .,. : : ~ - :
~;-: . :
. :-.
.,.,. . .: ,.
-: -:: . ::
Preparation of micro-particles containing guaiphenesin Example 1 was repeated except that theophylline was replaced by guaiphenesin (12.5 g). The polymer solution S consisted of Ethocel (Ethocel is a Trade Mark) (ethyl cellulose) 4 cps dissolved in ether so as to give a concentration of 25% w/v.
The external phase consisted of an aqueous solution of sorbitol 7Q% w/w (sorbitol solution B.P.) Upon removal of the solvent of the internal phase the particles or "pharmasomes" remained suspended in the sorbitol solution. The particles were harvested ~y decanting the sorbitol solution. The dissolution rate of the particles was determined and was found to be as follows:
Time ~h) % Release 0.5 50 ~ 61 ~ 76 Example 8 was rep~ated without decanting the ~orbitol solution. The suspension thereby obtained was flavoured and made up to the required strength for use as an oral suspension.
. . . : .
", ~ ; , ,-, ~: , :
- ~ : :
~i8~)5~
Preparation of micro-particles containing erythromycin base Example 1 was repeated except that theophylline was replaced by erythromycin base. .The polymer used was a mixture of cellulose acetate butyrate and cellulose acetate phthalate in a ratio of 2:1. The dissolution rate of the particles was determlned and was found to be as follows:
Time (h) % Release 0.5 20 l 30 Other mixed polymers were used in the internal phase and proved successful in achieving a 100% release o~ the active inyredient from the particles ~ormed. ~xamples of mi~ed polymers used were as foll~ws:
Polymer Ratio Cellulose acetate butyrate/
polyvinylpyrrolidone 9:1 Cellulose acetate butyrate/
polyvinylpyrrolidone 4Ol Cellulose acetate butyrate/
Poly~methyl methacrylic acid) l:l ; Cellulose acetate butyrate/
Poly(methyl methacrylic acid) 3:1 .. :................... .
.. .. ... . .
., ~'..~ ' ~ ' '. ;.
.: , ". "' ' ' Polymer Ratio Eudragit RS/Eudragit RL 9:1 Ethocel/polyvinylpyrrolidone 9:1 -Preparation of theophylline syrup.
Particles prepared according to Example 1 were suspended in a sugar solution in water (65%) so as to obtain a theophyl}ine syrup containing 200 mg of theophylline per 5 ml of syrup. When administered orally the normally bitter taste of theophylline was completely masked.
P~ARMACOLOGICAL DATA
The plasma level profile of theophylline was obtained from the mean values obtained for tWQ subjects according to the data listed in Tables 1 and 2. Fig. 3 is a graph of plasma levels (mcg~ml) versus time after administration (hours~ for the 6yrup prepared according to Example 11 ba~ed on the values indicated ir Tables ~ and 2.
It will be ob6erved from the accompanying Fig. 3 and Tables 1 and 2 that the plasma level~ after 10 hour~ are'not significan~ly different from the plasma levels after one hour. Accordingly, the graph shows a prolonged absorption phase with the minimum of fluctuation of plasma levels over 10 hours. Normally, theophylline (rapid or i~mediate release) peaks at 2 hours. The apparent biolo~ical half-life of theophylline has been found to range from 4-9 hours.
One would normally expect half the peak pla~ma levels by 7 hours and appro~imately one third of the peak plasma levels by 10 hours.
These results suggest that the syrup prepared according ~o Example 11 could potentially be dosed quite safely at intervals of 12 hours i.e. twice daily. This is half the ~, dosage frequency of conventional non-sus~ained or immediat~
release theophylline.
~: - . ~ . - - .
:: : ~ .
rj~L
TABL~: 1 BLOOD LEVEL STUDY RESUL - SUM~Y OF P~ RMACOKI~ETIC DATA
THEOP~YLLI~E - S00 mg S . D.
PL~SMA L~TELS mcg/ml HOURS AFTER ADMINISTRATIO~
SUBJ 0.00 1.00 2.00 4.00 6.00 8.00 10.00 0.00 3.15 4.~5 4.70 3.45 3.00 2~85 2 0.00 2.90 4.85 5.05 5.00 4.30 4.~5 MEAN 0.00 3.03 4.55 4.88 4.23 3.65 3.55 ST DEV 0.00 0.18 0.42 0.25 1.10 0.92 0.99 * CV (96) 0.00 5.84 9.32 5.08 25.94 2s.la 27.89 ~X 0.00 3.15 4.85 5.05 5.00 4.30 4.25 MI~ 0.00 2.90 4.25 4~70 3.45 3.00 2.85 * Coefficient of varia ion :. , ~2~i80S~
- 2~ -THEOPHYLLINE - 600 mg S.D.
PHARMACOKINETIC PARAMETERS
AUC* PEAKING PEAK C(max)/C(min~ ELIMINATIO~ HALF-LIFE
(0.00- TIME HEIGHTAT 10.00 HOURSRATE ~ 1/2 10.00 H) T(ma~) C(max) K EL
134.67 4.00 4.70 1.65 0.Q5 14.51 243.13 4.00 5.05 1.19 0.03 ~0.74 ~EAN38.90 4.00 4.88 1.42 0.04 17.o2 ST DEV 5.98 0.00 0.25 0.33 0~01 4.41 CV (%) 15.3~ 0.00 5.08 22.~1 ~5.00 25.00 ~ASED ON MEA~ BLOOD LEVEL CURVE
MEA~ 4.00 4.88 1.37 * Area under curve 1~;80~jl Theophylline Suspension Theophylline microparticles "Pharmasomes" (prepared as per Example 1) were suspended in a liquid vehicle consisting of:
70~ Sorbitol Solution89.9~ by weight Glycerin 10.0~ by weight Polysorbate-800.1% by weight (Trade Mark) 0 60 as to give a suspension containing 200 mg th~ophylline per 5 ml.
Samples of the suspension were stored at room temperature and tested at intervals to determine the stability of the "pharmasomes" in suspension.
At the time of preparation the assayed content of theophylline was 18B.4 m~/5 ml and after 15 weeks it was 190.5 mg/5 ml indicating that there had ~een no chemical breakdown of th~ drug.
The dissolution rate was also tested over a 15 week period and the results are ~ummarised in Table 3 and Fig. 4.
In summary the data shows that the suspension retains its potency and dissolution characteristics for at least 15 weeks after preparation.
PHARMACOLCGICAL DA~A
The suspension prepared as per Example 1~ was tested in a 6iX subject bioava.ilability study at a dose o 720 mg ~18 ml~ versus a conventional ~yrup (Somop~ylline) given as ~wo doses of 360 mg at 0 and 6 hours. The results are summ~rised in Table 4 and Fig. 5~ In ~ig. 5 the curve (a~
represents the suspension of E~ample 12 and curve (b) ~he Somophylline syrup used as reference.
:,, .. ,, ,;
. : ; : :- ; ::
. ~ : :: -: ,. ,,, ,., :
TABL~ 3 THEOPHYLLI~ SUSPE~SIO~ OF EXAMPLE 12 (200 mg/5ml ) STABILITY OF DISSOLUTIO~
Percentage Disolution TIME ( HOURS ) 0.00 1.00 2.00 3.00 4.00 5 ~ 00 6.00 24.00 O Wks 0.00 43.30 59.~0 7S.~0 80.00 84.30 87.70 100.0Q3 WXs 0~00 39.50 S9.10 70.70 77.~0 84.~0 87.70 99.50
Preparation of Micro-particles containing paracetamol Example 1 was repeated except that 20 g of paracetamol was used in place of 10 g of theophylline. In the external liquid phase heavy mineral oil was replaced by light mineral oil. A major proportion of the particles had an average size of 90 ~m.
1~8~35~
The dissolution rate of the particles was determined and waS found to be as foll~s:
Time (h)% Release O O
0.5 43 ~9 The particles were found to be tasteless.
EXA~IPLF. 3 Preparation of micro-particles containing nifedipine.
Example 1 was repeated except that 16 g of nifedipine was used in place of theophylline. The inter~al phase consisted of Eudra~it RS 100 (Eudragit RS 100 is a Trade Mark~ in me~hanol at a concentration of 33% w/v. The external phase consisted o magnesium stearate in light mineral oil at a concentr~tion of 2.5 ~ w/v.
The dissolution rate of the particles formed was determined and was found to be as follows:
Time ~h) ~ Release 0.5 25 --~ 30 4 70 The particles were found to be ta6teless~
:. , -, :~. .
~ ' ',' ,"'',1,.,'~,' ' `'"' .. " ' ~L2 f~
EXAMPL~ 4 Preparation of micro-particles containing dextromethorphan hydrobromide.
Example 1 was repeated except that 10 g of theophylline was replaced by 10 g of dextromethorphan hydrobromide.
The dissolution rate of the particles was determined and was found to be as follows:
Time (h ) ~ Release 0.5 4S
6 9o Preparation of micro-particles containing 6acchari~ 60dium.
Example 1 was repeated except that theophylline was replaced by 6~5 g o saccharin sodium. The internal phase consisted of Ethocel (e~hyl cellulose~ ~Ethocel is a Trade Mark) 45 cps dissolved in ethanol so as to give a concentration vf 15% w/v. Saccharin sodium was added to 50 g of the polymer solution. The external liquid phase consisted of heavy mineral oil ~.S. Pharmacopoeia.
The dissolution rate of the particles was determlned and was found to be as follGws:
Time (sec.) ~ Release 3~ 15 8~
' " ~' - . :
'', ., ~ ' :
~' ': `
Preparation of micro-particles containing pseudephedrine hydrochloride.
The procedure of Example 1 was repeated except that the theophylline was replaced by 10 g of pseudoephedrine hydrochloride. 50 g of CAB was used which was dissolved in 20 ml of hexane so as to form the polymer solution.
The dissolution rate of the particles was determined and found to be as follows:
Time (h) % Release 0.5 35 ~ EXAMPLE 7 Preparation of micro-particles containing carbinoxamine maleate Example 1 was repeated llsing carbinoxamine maleate in place of theophylline. The dissolution rate of the particles was determined and found to be as follows:
Time (h) ; % Release 0.5 20 2 30 :-~!`
... .
:' ' ,, .: ;
- , .,. : : ~ - :
~;-: . :
. :-.
.,.,. . .: ,.
-: -:: . ::
Preparation of micro-particles containing guaiphenesin Example 1 was repeated except that theophylline was replaced by guaiphenesin (12.5 g). The polymer solution S consisted of Ethocel (Ethocel is a Trade Mark) (ethyl cellulose) 4 cps dissolved in ether so as to give a concentration of 25% w/v.
The external phase consisted of an aqueous solution of sorbitol 7Q% w/w (sorbitol solution B.P.) Upon removal of the solvent of the internal phase the particles or "pharmasomes" remained suspended in the sorbitol solution. The particles were harvested ~y decanting the sorbitol solution. The dissolution rate of the particles was determined and was found to be as follows:
Time ~h) % Release 0.5 50 ~ 61 ~ 76 Example 8 was rep~ated without decanting the ~orbitol solution. The suspension thereby obtained was flavoured and made up to the required strength for use as an oral suspension.
. . . : .
", ~ ; , ,-, ~: , :
- ~ : :
~i8~)5~
Preparation of micro-particles containing erythromycin base Example 1 was repeated except that theophylline was replaced by erythromycin base. .The polymer used was a mixture of cellulose acetate butyrate and cellulose acetate phthalate in a ratio of 2:1. The dissolution rate of the particles was determlned and was found to be as follows:
Time (h) % Release 0.5 20 l 30 Other mixed polymers were used in the internal phase and proved successful in achieving a 100% release o~ the active inyredient from the particles ~ormed. ~xamples of mi~ed polymers used were as foll~ws:
Polymer Ratio Cellulose acetate butyrate/
polyvinylpyrrolidone 9:1 Cellulose acetate butyrate/
polyvinylpyrrolidone 4Ol Cellulose acetate butyrate/
Poly~methyl methacrylic acid) l:l ; Cellulose acetate butyrate/
Poly(methyl methacrylic acid) 3:1 .. :................... .
.. .. ... . .
., ~'..~ ' ~ ' '. ;.
.: , ". "' ' ' Polymer Ratio Eudragit RS/Eudragit RL 9:1 Ethocel/polyvinylpyrrolidone 9:1 -Preparation of theophylline syrup.
Particles prepared according to Example 1 were suspended in a sugar solution in water (65%) so as to obtain a theophyl}ine syrup containing 200 mg of theophylline per 5 ml of syrup. When administered orally the normally bitter taste of theophylline was completely masked.
P~ARMACOLOGICAL DATA
The plasma level profile of theophylline was obtained from the mean values obtained for tWQ subjects according to the data listed in Tables 1 and 2. Fig. 3 is a graph of plasma levels (mcg~ml) versus time after administration (hours~ for the 6yrup prepared according to Example 11 ba~ed on the values indicated ir Tables ~ and 2.
It will be ob6erved from the accompanying Fig. 3 and Tables 1 and 2 that the plasma level~ after 10 hour~ are'not significan~ly different from the plasma levels after one hour. Accordingly, the graph shows a prolonged absorption phase with the minimum of fluctuation of plasma levels over 10 hours. Normally, theophylline (rapid or i~mediate release) peaks at 2 hours. The apparent biolo~ical half-life of theophylline has been found to range from 4-9 hours.
One would normally expect half the peak pla~ma levels by 7 hours and appro~imately one third of the peak plasma levels by 10 hours.
These results suggest that the syrup prepared according ~o Example 11 could potentially be dosed quite safely at intervals of 12 hours i.e. twice daily. This is half the ~, dosage frequency of conventional non-sus~ained or immediat~
release theophylline.
~: - . ~ . - - .
:: : ~ .
rj~L
TABL~: 1 BLOOD LEVEL STUDY RESUL - SUM~Y OF P~ RMACOKI~ETIC DATA
THEOP~YLLI~E - S00 mg S . D.
PL~SMA L~TELS mcg/ml HOURS AFTER ADMINISTRATIO~
SUBJ 0.00 1.00 2.00 4.00 6.00 8.00 10.00 0.00 3.15 4.~5 4.70 3.45 3.00 2~85 2 0.00 2.90 4.85 5.05 5.00 4.30 4.~5 MEAN 0.00 3.03 4.55 4.88 4.23 3.65 3.55 ST DEV 0.00 0.18 0.42 0.25 1.10 0.92 0.99 * CV (96) 0.00 5.84 9.32 5.08 25.94 2s.la 27.89 ~X 0.00 3.15 4.85 5.05 5.00 4.30 4.25 MI~ 0.00 2.90 4.25 4~70 3.45 3.00 2.85 * Coefficient of varia ion :. , ~2~i80S~
- 2~ -THEOPHYLLINE - 600 mg S.D.
PHARMACOKINETIC PARAMETERS
AUC* PEAKING PEAK C(max)/C(min~ ELIMINATIO~ HALF-LIFE
(0.00- TIME HEIGHTAT 10.00 HOURSRATE ~ 1/2 10.00 H) T(ma~) C(max) K EL
134.67 4.00 4.70 1.65 0.Q5 14.51 243.13 4.00 5.05 1.19 0.03 ~0.74 ~EAN38.90 4.00 4.88 1.42 0.04 17.o2 ST DEV 5.98 0.00 0.25 0.33 0~01 4.41 CV (%) 15.3~ 0.00 5.08 22.~1 ~5.00 25.00 ~ASED ON MEA~ BLOOD LEVEL CURVE
MEA~ 4.00 4.88 1.37 * Area under curve 1~;80~jl Theophylline Suspension Theophylline microparticles "Pharmasomes" (prepared as per Example 1) were suspended in a liquid vehicle consisting of:
70~ Sorbitol Solution89.9~ by weight Glycerin 10.0~ by weight Polysorbate-800.1% by weight (Trade Mark) 0 60 as to give a suspension containing 200 mg th~ophylline per 5 ml.
Samples of the suspension were stored at room temperature and tested at intervals to determine the stability of the "pharmasomes" in suspension.
At the time of preparation the assayed content of theophylline was 18B.4 m~/5 ml and after 15 weeks it was 190.5 mg/5 ml indicating that there had ~een no chemical breakdown of th~ drug.
The dissolution rate was also tested over a 15 week period and the results are ~ummarised in Table 3 and Fig. 4.
In summary the data shows that the suspension retains its potency and dissolution characteristics for at least 15 weeks after preparation.
PHARMACOLCGICAL DA~A
The suspension prepared as per Example 1~ was tested in a 6iX subject bioava.ilability study at a dose o 720 mg ~18 ml~ versus a conventional ~yrup (Somop~ylline) given as ~wo doses of 360 mg at 0 and 6 hours. The results are summ~rised in Table 4 and Fig. 5~ In ~ig. 5 the curve (a~
represents the suspension of E~ample 12 and curve (b) ~he Somophylline syrup used as reference.
:,, .. ,, ,;
. : ; : :- ; ::
. ~ : :: -: ,. ,,, ,., :
TABL~ 3 THEOPHYLLI~ SUSPE~SIO~ OF EXAMPLE 12 (200 mg/5ml ) STABILITY OF DISSOLUTIO~
Percentage Disolution TIME ( HOURS ) 0.00 1.00 2.00 3.00 4.00 5 ~ 00 6.00 24.00 O Wks 0.00 43.30 59.~0 7S.~0 80.00 84.30 87.70 100.0Q3 WXs 0~00 39.50 S9.10 70.70 77.~0 84.~0 87.70 99.50
5 Wks 0.00 40.00 ~0.10 69.80 78.20 85.10 ~5.90 g9.00 7 Wks 0.00 42.00 63.00 79.20 8~.20 90.00 90.60 100.0 15 Wks 0.00 45.80 60.90 72.5~ 80.70 8~.90 88.00 99~90 . , , ,. ~ : ~ :
~: . . : :
~. :
MEAN THEOPHYLLI~E PLASMA CONCENTRATIO~ (mcg/ml) T~EOPHYLLI~E
TIME ~h) SOMOPHYLLI~E SUSPE~SION
0.0 0.0 0.0 0-5 7.9~ 1.38 1.0 10.24 3.57 1.5 8.68 6.09 2.0 8.17 7.31 10 3.0 7.68 8.81 4.0 5.93 9.75
~: . . : :
~. :
MEAN THEOPHYLLI~E PLASMA CONCENTRATIO~ (mcg/ml) T~EOPHYLLI~E
TIME ~h) SOMOPHYLLI~E SUSPE~SION
0.0 0.0 0.0 0-5 7.9~ 1.38 1.0 10.24 3.57 1.5 8.68 6.09 2.0 8.17 7.31 10 3.0 7.68 8.81 4.0 5.93 9.75
6.0 5.25 g.l7 6.5 10.94 9.75
7.0 11.20 9.~8 15 7.5 11.75 ~.84
8.0 12.37 9.14
9.0 11.98 8.37
10.0 10.7~ 7.52 12.0 8.~9 6.26 _ The data clearly sh~ws that although the theophylline suspension of ~xample 12 is slightly less bioavailable (~7%) than the refer~nce, the time to peak and the duration of significant blood levels is indicative of a twice dail~
dosage regimen. the usual dosage regimen for theophylline is four times per aay.
.; , :
, :: ~. " ~ :;
. . ,: ~ , - , , ~XAMPLES 13 and 14 Theophylline microparticles "phaxmasomes" were prepared according to Example 1 and screened into two fractions:
Example 13 - microparticles having an average particle size of less than 30 microns Example 14 - microparticles havin~ an average particle siæe of greater than 90 microns.
The "pharmasomes" were suspended in a vehi~le made up o:
~ b~ welght 70~ Sorbitol Solution 85.3 Avicel RC 591 (Trade Mark~ 0.7 Potassium Sorbate 0.3 Titanium Dioxide 25% 2.7 (in 70% Sorbitol) Simethicone (Trade Mark) 10~ Emulsion 0.01 Glycerin 10.8 Citric Acid 0.3 Soaium Lauryl Sulphate 0.04 so as to produce a suspension containing 300 mg Theophylline per 5 ml.
PHARMACOLOGI~AL DATA
The suspensions of Examples 13 and 14 were tested for bioavailability in four subjects at a dose of 690 mg ~11.5 ml) for the syrups of Example~ 13 and 14 ver~us a conventional syrup (Somophylline) given as two do~e~ of 320 mg ~t 0 and 6 hours. The results are ~ummarised in Tahle 5 and Fig. ~. The Fig. 6, the curve (a) represents the suspension of Example 13, the curve ~b) the suspen~ion ~f Example 14 and the curve (c) the Somophylline ~yrup used as reference.
, - ,, - .. : .; :~' ~.
~2~(35~
MEAN THEOPHYLLINE PLASMA CO~CENTRATIONS - mcg/ml Suspension Suspension - o~ of Time (h) Somophylline Example 13 Example 14 0.5 ~.53 2.65 l.g8 1 10.14 5.08 ~.07 1.5 9.~1 6.94 6.~5 2 8.64 7.16 ~.81 3 7.74 6.93 7~67 4 ~.82 7.7~ 7.~g 6 5.21 6.4~ 7.08 6.5 8.79 7 1~.00 6.74 ~.g3 7.5 1~.01 - -8 12.11 6.03 6~47 9 11.61 - ~
10.17 5~5 5.82 12 8.07 4.06 5.02 -2.77 4.04 18 -2.22 ~.67 21 2.44 1.79 1.95 2~ 1.55 1.2~ 1.59 The results confirm the finding~ for Example 12 as ~5 indicated in Fig. 7, wherein cu~ve (a) represents the suspension of Example 12, curve ~b) the ~uspension of Example 13 and curve ~c~ the suspension of Example 14.
.f ~2~
.
PARACETAMO~ SUSPE~SIO~
Paracetamol "pharmasomes" prepared as per E~ample 2 were suspended in a liquid vehicle prepared a6 per Example 12 to give a suspension containing 300 mg of Paracetamol per 5 ml.
The suspension was stored at room temperature and tested at intervals for 30 weeks.
At the time of preparation the assayed content was 299.8 mg (paracetamol) per 5 ml and after 30 weeks was 2~7.9 mg/5 ml indicating that there was no significant loss of activity.
During the above time period the dissolution was also tested and the results are ~iven in Table 6.
PERCENTAGE DISSOLUTIO~
TIME (h) 0.00 1.00 2.00 3.00 4.00 5.00 6000 O Wks O.O0 56.50 70.60 7~.O0 81.30 83.80 86 D 3 0 202 Wks 0.00 58.40 71.80 80~40 ~31.70 B5.40 87.90 5 WXs 0.00 5~.90 72.50 77.20 80.40 ~3.~0 ~4.40 0.00 5~.30 69.10 7~.~0 ~0.30 82.90 84.7~
15Wks 0.00 58.90 69.30 76.78 80.60 8~.80 84.30 30W~s 0.00 58.10 71.50 76.90 81.90 84.70 87.30 .
A graphic representation of these results is shown in Fig. 8.
,..,~
.. -- - . - - ,.:- ::
:-~-.
35~L
The ~u pen~ion was tested or bioavailability i~ 6 subject~ a~ a do~e o 1000 mg versus a reference solution (Do~ol-Eli~ir (Dozol is a Trade Mark)) which wa~ given as two divided do~es of 500 mg. The results are given in Table 7.
MEAN PARACETAMOL PLASMA CONCENTRATIONS (mcg/ml) Reference Suspension of Time (h) (DOZOL) Example 15 0.0 -0.5 7~74 3.44 1.0 6.49 6~05 2.0 4.14 7.36 3.0 3.04 5.80 4.0 2.04 4.60 6.~ 1.08 3.15 6.5 5.33 2.~5 7.0 5.88 2.26 8.0 ~.79 1.~
9.0 4.C0 1.63 10.0 3.05 1.44 1~.0 1.81 1.06 14.0 1.10 0.72 16.0 0.69 0.49 24.0 0.18 0.14 A graphic representation is given in Fig. 9, wherein curve (a~ represents the suspension of ~xample 15 and curve (b). the conv~ntional Ellxir.
The data shows ~hat although the suspension of ~xample 15 is slightly less bioavailable (90~) than the reference, the blood level is maintained for almost twice a~ long equating ~o halving of the dosage frequency.
, , ' : ,, :
., '' . ~ : ' :
~2~
EX~MPLE 16 "Pharmasomes" were prepared a~ per Example 2 and suspended in liquid as per Example 1~ sc a~ to give a suspension cont.aining 320 mg per 5 ml. This suspension was tested fGr bioavailability in 6 su~jects using a conventional (Tylenol (Trade Mark)) Elixir as reference. A single dose of paracetamol "pharmasomes" 2000 mg (31.25 ml) was administered and two doses of Tylenol (1000 mg) at 0 and 6 hours. The results are given in Table 8.
TABhE 8 MEA~ PARACETAMOL PLASMA CONCE~TRATIO~S (mcg/ml) Reference Suspension of TIME (~) ~Tylenol Elixir) Example 16 -0.0 0.0 0.0 0.5 14.~3 ~.27 1.0 14.05 15.09 2.0 6.69 14.34 3.0 6.95 13.~4 4.0 ~.43 11.53 4.5 15.53 9.52 5.0 14.67 8.08 6.0 12.72 6.10 7.~ 8.92 4.43 8.0 6.61 3.54 ~5 10.0 3.64 2.~3 12.0 2.17 1.10 14.0 1.31 1.10 16.0 0.77 0.68 24~0 0.02 ~.17 os~ ~
The results are presented graphically in Figure 10 wherein curve (a) corresponds to the suspen~ion of Example 16 and curve (b) corresponds to the reference Eli~ir. The prolonged absorption profile again can be seen with no significant loss in bioavailability, indicating a reduced dosage frequency.
"Pharmasomes" were prepared as per Example 2 with cellulose acetate being substituted for the cellulose acetate butyrate. The suspension was prepared as per Example 16. The suspension was tested in a 6 subject bioavailability study at a single dose of 2000 mg against a reference solution (Tylen~l Elixir) giv~n as two 1000 mg doses. The results are given in Table 9.
MEA~ PARACETAMOL PLAS~A CO~CENTRATIO~S (mcg/ml~
Tylenol Eli~ir Suspension of TIME ~h)1 g x 2 Example 17 2 9 x 1 r 0.0 0.00 0.0 0.5 12.30 5.11 0.75 12.88 7.07 1.0 12.~9 9.1 1.5 10.17 12.01 2.0 8.19 12.47 3.0 6.00 11~1 4.0 ~.35 4,5 13.S4 ~.37 4.75 1~.00 8.
5.0 13.02 7.55 5.5 13.09 6.57 ~L268051 TABLE 9 (contd) Tylenol Eli2ir ~uspension of TIME (h) 1 9 ~ 2 Example 17 2 g ~ 1 6.0 11.20 ~.71 7.0 ~.17 4.54 8.0 5.98 3.76 10.0 3.4~ 6 12.0 1.98 1.6 14.0 1.~4 l.Q3 16.0 0.82 0.83 2~.0 0.~6 0.39 The figures given in Table ~ and accompanying Figs. 11 and 12 again demonstrate the prolonged absorption nature of the product. In Fig. 11 curve (a) corresp~nds to the ~uspension of Example 19 and curve (b) the reference Tylenol Elixir. In Fig. 12 curve (a) corresponds to the suspension of Example 15, curve (h) to the suspension of Example 16 and curve (c) to the suspension of Example 17.
EX~MPLE 18 Chewing gum containing microparticles of Aspartame were prepared in the following manner.
An internal phase was prepared by dissolving ethylcellulose (45 cps~ in sufficient ethanol to produce ~00 g of ~olution. 100 9 o~ Aspartame (Particle si~e less than 60 microns) was di~persed in 300 9 of acetone. The two liquids were t~en mi~ed by mechanical a~itation. The external phase was prepared according to E~ample 1, 2 litres ~, being required. The internal a~d external phase were mixed , ., ~
: .
~268~91 by mechanical agitation and then passed through an emulsifier. The emulsion was placed in a vacuum and the solvents tacetone and ethanol) evaporated. The Aspartame/
ethylcellulose microparticles were harvested by centrifugation.
To evaluate the Aspartame-containing "pharmasomes", unsweetened chewing gum was used. Pure Aspartame powder and the prepared "pharmasomes" were folded into the gum so as to give a 0.2~ concentration of Aspartame. Both types of gum were chewed by a panel of 24 volunteers in a blind, crossover manner. The volunteers were asked to report their perception of the intensity (on a scale of 0 to 10) and duration of sweetness. On average the duration of sweetness for the pure Aspartame-containing gum was 10 minute~. The gum containing the "pharmasomes" was perceived as being less intensely sweet but observably sweet for 30 minutes on average. The results are indicated in Fig. 13 which is a graphic representation of the Aspartame sweetnes~ test giving mean values for the testing panel of 24 volunieers.
CHEWABLE TABLET CO~TAI~I~G PARACETAMOL
The following materials were mixad together:
1000 g Paracetamol "pharmasomes" - as per Example 2 (equivalent to 500 g of Paracetamol) 250 g Dipac (Trade Mark) (Sucrose 97~, Dextrins 3%) 250 g Mannitol S g Colloidal Silicon Dioxide 25 g Maize Starch 20 g Magneqiu~l Stearate 15 g Orange Flavour 35 g Orange Colour , ': :. ,, : :
~X~i8~35~
The blend was compressed at a weight of 960 ~9 into tablets each containing 300 mg of Paracetamol. The tablets were pleasant to chew and the dissolution characteristics of the "pharma~omes" were unchanged as shcwn in Table 10 and Fig. 14.
DISSOLUTI0~ RATE
TIME (h) "PHARMASOMES" TABLE~S
1 58.7% 59.
3 79.~ 80.7 6 9~.6% 95.
-In Fig. 14 curve ~a) corresponds to the dissolution pattern of the "pharmasomes" of B~ample 19 and curve (b) to the chewable tablets prepared therefrom.
EXAMPL~ 20 "MELT" TABLETS CO~TAI~l~G PA~ACETAMOL
Melt tablets are similar to chewable table~s except that they disintegrate rapidly in the mouth and do not need to be chewed. Such tablets were prepared as foll~ws:
' ~
,.
' " ' ' -~26l~
- 3~ -1000 g Paracetamol "pharmasomes" ~a~ per E~ample 2) (equivalent to 500 g Paracetamol) 50 g Mannitol 250 g Microcrystalline Cellulose 30 9 Strawberry Flavour 15 g Red Colour 60 g Cross-Povidone 5 g Sodium Lauryl Sulphate 30 g Carboxymethyl starch 15 g Magnesium Stearate 15 9 Talc The blend was compressed at a weight of 8~2 mg to give tablets each containing 300 mg o Paracetamol. ~he disintegration time of the tablets was less than 30 saconds and the dissolution rate of the "pharmasomes" was unchanged as indicated in Table 11 and Fig. 15.
-DISSOLUTIO~ RATE
TIME ~h) ~P~ARMhSOMES" TABLETS
1 58.7% ~0.1 3 79.8~ 81.2 6 95.6~ 95.5~
In Fig. 15 curve (a) corresponds to the dissolution pattern for the "pharmasomes" of Example 20 and curve (b) to the melt tablets prepared therefrom.
~2~i8~5~
EY~MPLE 21 CAPSULES CONTAINI~G NIFEDIPI~E
"Pharmasomes" were prepared as per Example 3. By nature they were free flowing and only 0.5% magnesium stearate needed to be added to prevent sticking during capsule filling. The equivalent of 20 mg of ~ifedipine was encapsulated into si~e ~o. 4, two piece hard gelatin capsules. The dissolution rate xemained unchan~ed as shown in Table 12 and Fiy. 16. In Figure 16 curve (a) corresporlds to the dissolution pattern for the "pharmasomes" of E~ample 21 and curve (b) to the capsules prepared thereÇrom.
TAB~E 1~
DISSOLUTIO~ ~TE
-15 TIM~ (h) ~'PHA~MASO~ES" _ CAPS~LES
0.5 42.6% 41.7%
1 56.1% 54~3%
3 7~.6% 73.6 85.9% ~ %
8 . ~8.7% 97.~%
Although not wishing to be bound by any theoretical explanation of the invention, it i8 believed tha~ the polymer ~ubstantially but not entirely coats the active ingredient, because a 100% release of active in~redient can 25 be achieved even when an insoluble polymer is used.
.
: .
- . ~
~6805~
NO~-AQ~EOUS SUSPE~5ION OF POTASSIUM CHLORIDE
A non aqueous suspension of potassium chloride -containing "pharmasomes" was prepared, having a 5 concentration of potassium chloride of 300 mg/~ ml and which in addition to the "pharmasomes" contained the following ingredients:
Oil ~SP (Soy, cotton seed) 425.00 ml Sorbitol Powder USP 100.00 g 10 Aerosil R 972 (Trade Mark) 12.50 g Tenox GT 1 (Trade Mark) 0.20 g Citric acid 0.025 g Chocolate flavour # 3~6676 0.52 ml Chocolate mint flavour ~ 395496 0.37 ml 15 Flavour enhancer l.G0 g Br~wn Lake dye 0.05 Titanium dioxide 0.10 g The total volume of the suspension without the "pharmasomes" was 500 ml.
The Sorbitol powder USP and Aerosil R 972 (Trade Mark~
were dry blended and t~em ball milled with t~e oil mi~ ~o produce an even dispersion. The Tenox GT 1 (Trade Mark) which is an anti-oxidant and the citric acid were dry blended and th~n di~persed with constant agitatior. into the - 25 oil mixture~ The chocolate and chocolate mint flavour~ and the flavour enhancer were then dlspersed into the oil mixture. ~inally, the Brown La~e dye and ~he titanium dioxide were adaed to the oil mixture and the resultant mixture was agitated for one hour to ensure even dispersion of the various ingredients. An amount of potassium chloride - con~aining "pharmasomes", prepared according to the procedure described in Example 1 but substi~uti~g potassium chloride for theophylline, and e~uivalent to 300 mg potassium chloride per 5 ml was blended tog~ther with the 3`5 oil mixture re~ulting in an evenly mixed su~pension.
"" . .
dosage regimen. the usual dosage regimen for theophylline is four times per aay.
.; , :
, :: ~. " ~ :;
. . ,: ~ , - , , ~XAMPLES 13 and 14 Theophylline microparticles "phaxmasomes" were prepared according to Example 1 and screened into two fractions:
Example 13 - microparticles having an average particle size of less than 30 microns Example 14 - microparticles havin~ an average particle siæe of greater than 90 microns.
The "pharmasomes" were suspended in a vehi~le made up o:
~ b~ welght 70~ Sorbitol Solution 85.3 Avicel RC 591 (Trade Mark~ 0.7 Potassium Sorbate 0.3 Titanium Dioxide 25% 2.7 (in 70% Sorbitol) Simethicone (Trade Mark) 10~ Emulsion 0.01 Glycerin 10.8 Citric Acid 0.3 Soaium Lauryl Sulphate 0.04 so as to produce a suspension containing 300 mg Theophylline per 5 ml.
PHARMACOLOGI~AL DATA
The suspensions of Examples 13 and 14 were tested for bioavailability in four subjects at a dose of 690 mg ~11.5 ml) for the syrups of Example~ 13 and 14 ver~us a conventional syrup (Somophylline) given as two do~e~ of 320 mg ~t 0 and 6 hours. The results are ~ummarised in Tahle 5 and Fig. ~. The Fig. 6, the curve (a) represents the suspension of Example 13, the curve ~b) the suspen~ion ~f Example 14 and the curve (c) the Somophylline ~yrup used as reference.
, - ,, - .. : .; :~' ~.
~2~(35~
MEAN THEOPHYLLINE PLASMA CO~CENTRATIONS - mcg/ml Suspension Suspension - o~ of Time (h) Somophylline Example 13 Example 14 0.5 ~.53 2.65 l.g8 1 10.14 5.08 ~.07 1.5 9.~1 6.94 6.~5 2 8.64 7.16 ~.81 3 7.74 6.93 7~67 4 ~.82 7.7~ 7.~g 6 5.21 6.4~ 7.08 6.5 8.79 7 1~.00 6.74 ~.g3 7.5 1~.01 - -8 12.11 6.03 6~47 9 11.61 - ~
10.17 5~5 5.82 12 8.07 4.06 5.02 -2.77 4.04 18 -2.22 ~.67 21 2.44 1.79 1.95 2~ 1.55 1.2~ 1.59 The results confirm the finding~ for Example 12 as ~5 indicated in Fig. 7, wherein cu~ve (a) represents the suspension of Example 12, curve ~b) the ~uspension of Example 13 and curve ~c~ the suspension of Example 14.
.f ~2~
.
PARACETAMO~ SUSPE~SIO~
Paracetamol "pharmasomes" prepared as per E~ample 2 were suspended in a liquid vehicle prepared a6 per Example 12 to give a suspension containing 300 mg of Paracetamol per 5 ml.
The suspension was stored at room temperature and tested at intervals for 30 weeks.
At the time of preparation the assayed content was 299.8 mg (paracetamol) per 5 ml and after 30 weeks was 2~7.9 mg/5 ml indicating that there was no significant loss of activity.
During the above time period the dissolution was also tested and the results are ~iven in Table 6.
PERCENTAGE DISSOLUTIO~
TIME (h) 0.00 1.00 2.00 3.00 4.00 5.00 6000 O Wks O.O0 56.50 70.60 7~.O0 81.30 83.80 86 D 3 0 202 Wks 0.00 58.40 71.80 80~40 ~31.70 B5.40 87.90 5 WXs 0.00 5~.90 72.50 77.20 80.40 ~3.~0 ~4.40 0.00 5~.30 69.10 7~.~0 ~0.30 82.90 84.7~
15Wks 0.00 58.90 69.30 76.78 80.60 8~.80 84.30 30W~s 0.00 58.10 71.50 76.90 81.90 84.70 87.30 .
A graphic representation of these results is shown in Fig. 8.
,..,~
.. -- - . - - ,.:- ::
:-~-.
35~L
The ~u pen~ion was tested or bioavailability i~ 6 subject~ a~ a do~e o 1000 mg versus a reference solution (Do~ol-Eli~ir (Dozol is a Trade Mark)) which wa~ given as two divided do~es of 500 mg. The results are given in Table 7.
MEAN PARACETAMOL PLASMA CONCENTRATIONS (mcg/ml) Reference Suspension of Time (h) (DOZOL) Example 15 0.0 -0.5 7~74 3.44 1.0 6.49 6~05 2.0 4.14 7.36 3.0 3.04 5.80 4.0 2.04 4.60 6.~ 1.08 3.15 6.5 5.33 2.~5 7.0 5.88 2.26 8.0 ~.79 1.~
9.0 4.C0 1.63 10.0 3.05 1.44 1~.0 1.81 1.06 14.0 1.10 0.72 16.0 0.69 0.49 24.0 0.18 0.14 A graphic representation is given in Fig. 9, wherein curve (a~ represents the suspension of ~xample 15 and curve (b). the conv~ntional Ellxir.
The data shows ~hat although the suspension of ~xample 15 is slightly less bioavailable (90~) than the reference, the blood level is maintained for almost twice a~ long equating ~o halving of the dosage frequency.
, , ' : ,, :
., '' . ~ : ' :
~2~
EX~MPLE 16 "Pharmasomes" were prepared a~ per Example 2 and suspended in liquid as per Example 1~ sc a~ to give a suspension cont.aining 320 mg per 5 ml. This suspension was tested fGr bioavailability in 6 su~jects using a conventional (Tylenol (Trade Mark)) Elixir as reference. A single dose of paracetamol "pharmasomes" 2000 mg (31.25 ml) was administered and two doses of Tylenol (1000 mg) at 0 and 6 hours. The results are given in Table 8.
TABhE 8 MEA~ PARACETAMOL PLASMA CONCE~TRATIO~S (mcg/ml) Reference Suspension of TIME (~) ~Tylenol Elixir) Example 16 -0.0 0.0 0.0 0.5 14.~3 ~.27 1.0 14.05 15.09 2.0 6.69 14.34 3.0 6.95 13.~4 4.0 ~.43 11.53 4.5 15.53 9.52 5.0 14.67 8.08 6.0 12.72 6.10 7.~ 8.92 4.43 8.0 6.61 3.54 ~5 10.0 3.64 2.~3 12.0 2.17 1.10 14.0 1.31 1.10 16.0 0.77 0.68 24~0 0.02 ~.17 os~ ~
The results are presented graphically in Figure 10 wherein curve (a) corresponds to the suspen~ion of Example 16 and curve (b) corresponds to the reference Eli~ir. The prolonged absorption profile again can be seen with no significant loss in bioavailability, indicating a reduced dosage frequency.
"Pharmasomes" were prepared as per Example 2 with cellulose acetate being substituted for the cellulose acetate butyrate. The suspension was prepared as per Example 16. The suspension was tested in a 6 subject bioavailability study at a single dose of 2000 mg against a reference solution (Tylen~l Elixir) giv~n as two 1000 mg doses. The results are given in Table 9.
MEA~ PARACETAMOL PLAS~A CO~CENTRATIO~S (mcg/ml~
Tylenol Eli~ir Suspension of TIME ~h)1 g x 2 Example 17 2 9 x 1 r 0.0 0.00 0.0 0.5 12.30 5.11 0.75 12.88 7.07 1.0 12.~9 9.1 1.5 10.17 12.01 2.0 8.19 12.47 3.0 6.00 11~1 4.0 ~.35 4,5 13.S4 ~.37 4.75 1~.00 8.
5.0 13.02 7.55 5.5 13.09 6.57 ~L268051 TABLE 9 (contd) Tylenol Eli2ir ~uspension of TIME (h) 1 9 ~ 2 Example 17 2 g ~ 1 6.0 11.20 ~.71 7.0 ~.17 4.54 8.0 5.98 3.76 10.0 3.4~ 6 12.0 1.98 1.6 14.0 1.~4 l.Q3 16.0 0.82 0.83 2~.0 0.~6 0.39 The figures given in Table ~ and accompanying Figs. 11 and 12 again demonstrate the prolonged absorption nature of the product. In Fig. 11 curve (a) corresp~nds to the ~uspension of Example 19 and curve (b) the reference Tylenol Elixir. In Fig. 12 curve (a) corresponds to the suspension of Example 15, curve (h) to the suspension of Example 16 and curve (c) to the suspension of Example 17.
EX~MPLE 18 Chewing gum containing microparticles of Aspartame were prepared in the following manner.
An internal phase was prepared by dissolving ethylcellulose (45 cps~ in sufficient ethanol to produce ~00 g of ~olution. 100 9 o~ Aspartame (Particle si~e less than 60 microns) was di~persed in 300 9 of acetone. The two liquids were t~en mi~ed by mechanical a~itation. The external phase was prepared according to E~ample 1, 2 litres ~, being required. The internal a~d external phase were mixed , ., ~
: .
~268~91 by mechanical agitation and then passed through an emulsifier. The emulsion was placed in a vacuum and the solvents tacetone and ethanol) evaporated. The Aspartame/
ethylcellulose microparticles were harvested by centrifugation.
To evaluate the Aspartame-containing "pharmasomes", unsweetened chewing gum was used. Pure Aspartame powder and the prepared "pharmasomes" were folded into the gum so as to give a 0.2~ concentration of Aspartame. Both types of gum were chewed by a panel of 24 volunteers in a blind, crossover manner. The volunteers were asked to report their perception of the intensity (on a scale of 0 to 10) and duration of sweetness. On average the duration of sweetness for the pure Aspartame-containing gum was 10 minute~. The gum containing the "pharmasomes" was perceived as being less intensely sweet but observably sweet for 30 minutes on average. The results are indicated in Fig. 13 which is a graphic representation of the Aspartame sweetnes~ test giving mean values for the testing panel of 24 volunieers.
CHEWABLE TABLET CO~TAI~I~G PARACETAMOL
The following materials were mixad together:
1000 g Paracetamol "pharmasomes" - as per Example 2 (equivalent to 500 g of Paracetamol) 250 g Dipac (Trade Mark) (Sucrose 97~, Dextrins 3%) 250 g Mannitol S g Colloidal Silicon Dioxide 25 g Maize Starch 20 g Magneqiu~l Stearate 15 g Orange Flavour 35 g Orange Colour , ': :. ,, : :
~X~i8~35~
The blend was compressed at a weight of 960 ~9 into tablets each containing 300 mg of Paracetamol. The tablets were pleasant to chew and the dissolution characteristics of the "pharma~omes" were unchanged as shcwn in Table 10 and Fig. 14.
DISSOLUTI0~ RATE
TIME (h) "PHARMASOMES" TABLE~S
1 58.7% 59.
3 79.~ 80.7 6 9~.6% 95.
-In Fig. 14 curve ~a) corresponds to the dissolution pattern of the "pharmasomes" of B~ample 19 and curve (b) to the chewable tablets prepared therefrom.
EXAMPL~ 20 "MELT" TABLETS CO~TAI~l~G PA~ACETAMOL
Melt tablets are similar to chewable table~s except that they disintegrate rapidly in the mouth and do not need to be chewed. Such tablets were prepared as foll~ws:
' ~
,.
' " ' ' -~26l~
- 3~ -1000 g Paracetamol "pharmasomes" ~a~ per E~ample 2) (equivalent to 500 g Paracetamol) 50 g Mannitol 250 g Microcrystalline Cellulose 30 9 Strawberry Flavour 15 g Red Colour 60 g Cross-Povidone 5 g Sodium Lauryl Sulphate 30 g Carboxymethyl starch 15 g Magnesium Stearate 15 9 Talc The blend was compressed at a weight of 8~2 mg to give tablets each containing 300 mg o Paracetamol. ~he disintegration time of the tablets was less than 30 saconds and the dissolution rate of the "pharmasomes" was unchanged as indicated in Table 11 and Fig. 15.
-DISSOLUTIO~ RATE
TIME ~h) ~P~ARMhSOMES" TABLETS
1 58.7% ~0.1 3 79.8~ 81.2 6 95.6~ 95.5~
In Fig. 15 curve (a) corresponds to the dissolution pattern for the "pharmasomes" of Example 20 and curve (b) to the melt tablets prepared therefrom.
~2~i8~5~
EY~MPLE 21 CAPSULES CONTAINI~G NIFEDIPI~E
"Pharmasomes" were prepared as per Example 3. By nature they were free flowing and only 0.5% magnesium stearate needed to be added to prevent sticking during capsule filling. The equivalent of 20 mg of ~ifedipine was encapsulated into si~e ~o. 4, two piece hard gelatin capsules. The dissolution rate xemained unchan~ed as shown in Table 12 and Fiy. 16. In Figure 16 curve (a) corresporlds to the dissolution pattern for the "pharmasomes" of E~ample 21 and curve (b) to the capsules prepared thereÇrom.
TAB~E 1~
DISSOLUTIO~ ~TE
-15 TIM~ (h) ~'PHA~MASO~ES" _ CAPS~LES
0.5 42.6% 41.7%
1 56.1% 54~3%
3 7~.6% 73.6 85.9% ~ %
8 . ~8.7% 97.~%
Although not wishing to be bound by any theoretical explanation of the invention, it i8 believed tha~ the polymer ~ubstantially but not entirely coats the active ingredient, because a 100% release of active in~redient can 25 be achieved even when an insoluble polymer is used.
.
: .
- . ~
~6805~
NO~-AQ~EOUS SUSPE~5ION OF POTASSIUM CHLORIDE
A non aqueous suspension of potassium chloride -containing "pharmasomes" was prepared, having a 5 concentration of potassium chloride of 300 mg/~ ml and which in addition to the "pharmasomes" contained the following ingredients:
Oil ~SP (Soy, cotton seed) 425.00 ml Sorbitol Powder USP 100.00 g 10 Aerosil R 972 (Trade Mark) 12.50 g Tenox GT 1 (Trade Mark) 0.20 g Citric acid 0.025 g Chocolate flavour # 3~6676 0.52 ml Chocolate mint flavour ~ 395496 0.37 ml 15 Flavour enhancer l.G0 g Br~wn Lake dye 0.05 Titanium dioxide 0.10 g The total volume of the suspension without the "pharmasomes" was 500 ml.
The Sorbitol powder USP and Aerosil R 972 (Trade Mark~
were dry blended and t~em ball milled with t~e oil mi~ ~o produce an even dispersion. The Tenox GT 1 (Trade Mark) which is an anti-oxidant and the citric acid were dry blended and th~n di~persed with constant agitatior. into the - 25 oil mixture~ The chocolate and chocolate mint flavour~ and the flavour enhancer were then dlspersed into the oil mixture. ~inally, the Brown La~e dye and ~he titanium dioxide were adaed to the oil mixture and the resultant mixture was agitated for one hour to ensure even dispersion of the various ingredients. An amount of potassium chloride - con~aining "pharmasomes", prepared according to the procedure described in Example 1 but substi~uti~g potassium chloride for theophylline, and e~uivalent to 300 mg potassium chloride per 5 ml was blended tog~ther with the 3`5 oil mixture re~ulting in an evenly mixed su~pension.
"" . .
Claims (30)
1. A controlled release powder containing discrete micro-particles for use in controlled release compositions, said powder comprising particles containing an active ingredient in intimate admixture with at least one non-toxic polymer, each of said particles being in the form of a micromatrix with the active ingredient uniformly distributed throughout the polymer, said particles having an average size in the range 0.1 to 125 µm, and having a predetermined release of active ingredient when the dissolution rate thereof is measured according to the Paddle Method of U.S. Pharmacopoeia XX at 37°C and 75 r.p.m., said dissolution rate being substantially proportional to the square root of time.
2. A controlled release powder according to Claim 1, wherein the particles include an excipient in addition to the active ingredient and the polymer.
3. A controlled release powder according to claim 1, wherein the particles have an average size in the range 5 to 100 µm.
4. A controlled release powder according to any one of claims 1 to 3, wherein the active ingredient is a drug, a nutrient, a flavouring agent or a sweetening agent.
5. A controlled release powder according to any one of claims 1 to 3, wherein the active ingredient is a colouring agent, a fragrance, a herbicide or a pesticide.
6. A controlled release powder according to any one of claims 1 to 3, wherein the polymer is selected from:
alkyl celluloses, hydroxyalkyl celluloses, cellulose ethers, cellulose esters, nitro celluloses, polymers of acrylic and methacrylic acids and esters therof, polya-mides, polycarbonates, polyalkylenes, polyalkylene glycols, polyalkylene oxides, polyalkylene terephthalates, polyvinyl alcohols, polyvinyl ethers, polyvinyl esters, polyvinyl halides, polyvinylpyrrolidone, polyglycolides, polysiloxanes and polyurethanes and co-polymers therof.
alkyl celluloses, hydroxyalkyl celluloses, cellulose ethers, cellulose esters, nitro celluloses, polymers of acrylic and methacrylic acids and esters therof, polya-mides, polycarbonates, polyalkylenes, polyalkylene glycols, polyalkylene oxides, polyalkylene terephthalates, polyvinyl alcohols, polyvinyl ethers, polyvinyl esters, polyvinyl halides, polyvinylpyrrolidone, polyglycolides, polysiloxanes and polyurethanes and co-polymers therof.
7. A process for preparing a controlled release powder according to claim 1, which comprises the steps of:
a) forming a solution of the polymer or polymers in solvent;
b) dissolving or dispersing the active ingredient in said polymer solution so as to form a uniform mixture; and c) removing the solvent from the mixture so as to obtain micro-particles having an average size in the range 0.1 to 125 µm.
a) forming a solution of the polymer or polymers in solvent;
b) dissolving or dispersing the active ingredient in said polymer solution so as to form a uniform mixture; and c) removing the solvent from the mixture so as to obtain micro-particles having an average size in the range 0.1 to 125 µm.
8. A process according to claim 7, wherein the particles obtained have an average size in the range 5 to 100 µm.
9. A process according to claim 7 or 8 wherein the solvent is selected from the group consisting of: water, alcohols, ketones, halogenated aliphatic compounds, halogenated aromatic hydrocarbon compounds, aromatic hydrocarbon compounds and cyclic ethers or a mixture thereof, and the solvent is removed in step (c) by spray drying, use of an external liquid phase, phase separation, interfacial polymer deposition or coacervation.
10. A pharmaceutical composition comprising a therapeutically effective amount of a controlled release powder according to claim 1 in admixture with a pharmaceutically acceptable carrier or diluent.
11. A pharmaceutical composition containing a controlled release powder according to claim 1, and which is in the form of tablets, capsules, suppositories, implants or ocular inserts.
12. A pharmaceutical composition according to claim 10, which is in the form of chewable tablets or melt tablets.
13. A pharmaceutical composition containing a controlled release powder according to claim l, and which is in the form of a cream, an ointment or a formulation suitable for transdermal delivery.
14. A pharmaceutical composition containing a controlled release powder according to claim l, and which is in the form of a liquid for oral, local or parenteral administration.
15. A pharmaceutical composition according to claim 13 , which is in the form of eye drops, nasal drops, ear drops, a suspension, a syrup, or an infusion or injectable solution.
16. A pharmaceutical composition according to claim wherein the active ingredient is selected from:
ibuprofen, paracetamol, 5-amino-salicylic acid, dextro-methorpha, propranolol, theophylline, diltiazem, methyldopar pseudoephedrine, cimetidine, cephalexin, cephaclor, cephradine, naproxen, piroxican, diazepam, diclofenacr indomethacin, amoxycillin, pivampicillin, bacampicillin, dicloxacillin, erythromycin, lincomycin, codergocrine mesylate, doxycycline, dipyridamole, frusemide, triamterene, sulindac, nifedipine, atenolol, erythromycin stearate, lorazepam, glibenclamide, salbutamol, trimethoprim/sulpha-methoxazole, spironolactone, carbinoxamine maleate, guaiphenesin and metoprolol tartrate.
ibuprofen, paracetamol, 5-amino-salicylic acid, dextro-methorpha, propranolol, theophylline, diltiazem, methyldopar pseudoephedrine, cimetidine, cephalexin, cephaclor, cephradine, naproxen, piroxican, diazepam, diclofenacr indomethacin, amoxycillin, pivampicillin, bacampicillin, dicloxacillin, erythromycin, lincomycin, codergocrine mesylate, doxycycline, dipyridamole, frusemide, triamterene, sulindac, nifedipine, atenolol, erythromycin stearate, lorazepam, glibenclamide, salbutamol, trimethoprim/sulpha-methoxazole, spironolactone, carbinoxamine maleate, guaiphenesin and metoprolol tartrate.
17. A pharmaceutical composition according to claim 10 for oral administration, wherein the active ingredient is theophylline.
18. A pharmaceutical composition according to claim 10for oral administration, wherein the active ingredient is paracetamol.
19. A pharmaceutical composition according to claim 10for oral administration, wherein the active ingredient is potassium chloride.
20. An oral formulation for administration to human and non-human animals which is substantially free of the taste of the active ingredient comprising an effective amount of a controlled release powder according to claim 1 in admixture with a carrier or diluent.
21. An oral formulation according to claim 20 which is in the form of a liquid, chewable tablet, melt tablet, foam, gel or gum.
22. A chewable gum which comprises microparticles according to claim 1, which microparticles contain an effective sweetening amount of aspartame as active ingredient.
23. A non-aqueous suspension of a highly water-soluble or water-insoluble active ingredient, wherein the active ingredient is in the form of microparticles of a controlled release powder according to claim 1.
24. A non-aqueous suspension according to claim 23, wherein the highly water-soluble active ingredient is selected from: dextromethorphan, guaiphenesin and pseudoephedrine and salts therof and potassium chloride.
25. A controlled release antibiotic formulation substantially free from the taste of said antibiotic for pharmaceutical or veterinary use which comprises a controlled release powder according to claim 1 containing a therapeutically effective amount of said antibiotic as active ingredient in admixture with a carrier or diluent.
26. An antibiotic formulation according to claim 25, wherein the powder is in the form of a non-aqueous suspension.
27. An antibiotic formulation according to claim 25, which is in the form of a reconstitutable aqueous suspension.
28. A controlled release powder containing discrete micro-particles for use in controlled release compositions, said powder comprising particles containing an active ingredient in intimate admixture with at least one non-toxic polymer, each of said particles being in the form of a micromatrix with the active ingredient uniformly distributed throughout the matrix, said particles having an average size from 0.1 to 125 µm, said micromatrix remaining substantially intact following release of the active ingredient.
29. An oral formulation containing a controlled release powder according to claim 28 and which is in the form of chewable tablets or gum wherein said micromatrix has sufficient mechanical and chemical stability to resist degradation by any chewing action.
30. A topical formulation containing a controlled release powder according to claim 28 and which is in the form of a cream, ointment, foam, gel, paste, gum, mucilage, jelly, lotion, talcum powder or a formulation suitable for transdermal delivery.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IE278884A IE58110B1 (en) | 1984-10-30 | 1984-10-30 | Controlled release powder and process for its preparation |
IE2788/84 | 1984-10-30 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA1268051A true CA1268051A (en) | 1990-04-24 |
Family
ID=11036490
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA000494130A Expired - Lifetime CA1268051A (en) | 1984-10-30 | 1985-10-29 | Controlled release powder and process for its preparation |
Country Status (16)
Country | Link |
---|---|
US (3) | US4952402A (en) |
JP (1) | JP2820239B2 (en) |
AU (1) | AU579415B2 (en) |
BE (2) | BE903541Q (en) |
CA (1) | CA1268051A (en) |
CH (1) | CH669728A5 (en) |
DE (1) | DE3538429C2 (en) |
DK (1) | DK175329B1 (en) |
FR (1) | FR2572282B1 (en) |
GB (1) | GB2166651B (en) |
HK (1) | HK44091A (en) |
IE (1) | IE58110B1 (en) |
IT (1) | IT1185831B (en) |
NL (1) | NL193582C (en) |
SE (1) | SE8505099L (en) |
ZA (1) | ZA858300B (en) |
Families Citing this family (1300)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL72381A (en) * | 1983-07-20 | 1988-03-31 | Sanofi Sa | Pharmaceutical composition based on valproic acid |
US5288498A (en) * | 1985-05-01 | 1994-02-22 | University Of Utah Research Foundation | Compositions of oral nondissolvable matrixes for transmucosal administration of medicaments |
IT1178511B (en) * | 1984-09-14 | 1987-09-09 | Pharmatec Spa | PROCEDURE FOR THE PREPARATION OF A SOLID FORM FOR ORAL USE BASED ON NIFEDIPINE WITH RELEASE |
IE58110B1 (en) * | 1984-10-30 | 1993-07-14 | Elan Corp Plc | Controlled release powder and process for its preparation |
JPS63500175A (en) * | 1985-05-22 | 1988-01-21 | リポソ−ム テクノロジ−,インコ−ポレイテツド | Liposome inhalation method and inhalation system |
US5286489A (en) * | 1985-08-26 | 1994-02-15 | The Procter & Gamble Company | Taste masking compositions |
CH669523A5 (en) * | 1986-06-25 | 1989-03-31 | Mepha Ag | |
CA1311686C (en) * | 1986-06-25 | 1992-12-22 | John Weldon Shell | Controlled release bioerodible drug delivery system |
ES2053549T3 (en) * | 1986-08-11 | 1994-08-01 | Innovata Biomed Ltd | A PROCESS FOR THE PREPARATION OF AN APPROPRIATE PHARMACEUTICAL FORMULATION FOR INHALATION. |
US5030632A (en) * | 1986-09-23 | 1991-07-09 | Sandoz Pharm. Corp. | Low dose temazepam |
US5629310A (en) * | 1986-09-23 | 1997-05-13 | Sterling; William R. | Low dose temazepam |
US5211954A (en) * | 1986-09-23 | 1993-05-18 | Sandoz Ltd. | Low dose temazepam |
GB8624628D0 (en) * | 1986-10-14 | 1986-11-19 | Scras | Soluble/splitable tablets |
NL194638C (en) * | 1986-12-19 | 2002-10-04 | Novartis Ag | Hydrosol containing solid particles of a pharmaceutically active substance and pharmaceutical preparation containing this hydrosol. |
SE8605515D0 (en) * | 1986-12-22 | 1986-12-22 | Astra Laekemedel Ab | A LIQUID DOSAGE FORM FOR ORAL ADMINISTRATION OF A PHARMACEUTICALLY ACTIVE SUBSTANCE |
US5283067A (en) * | 1987-01-30 | 1994-02-01 | Ciba-Geigy Corporation | Parenteral suspensions |
CH673395A5 (en) * | 1987-01-30 | 1990-03-15 | Ciba Geigy Ag | |
GB8702411D0 (en) * | 1987-02-03 | 1987-03-11 | Zyma Sa | Swellable pellets |
US4975270A (en) * | 1987-04-21 | 1990-12-04 | Nabisco Brands, Inc. | Elastomer encased active ingredients |
US5601835A (en) * | 1987-04-29 | 1997-02-11 | Massachusetts Institute Of Technology | Polymeric device for controlled drug delivery to the CNS |
IE59934B1 (en) * | 1987-06-19 | 1994-05-04 | Elan Corp Plc | Liquid suspension for oral administration |
EP0297866A3 (en) * | 1987-07-01 | 1989-12-13 | The Boots Company PLC | Therapeutic agents |
US4820522A (en) * | 1987-07-27 | 1989-04-11 | Mcneilab, Inc. | Oral sustained release acetaminophen formulation and process |
NZ226822A (en) * | 1987-11-16 | 1990-03-27 | Mcneil Consumer Prod | Chewable medicament tablet containing means for taste masking |
US5095054A (en) * | 1988-02-03 | 1992-03-10 | Warner-Lambert Company | Polymer compositions containing destructurized starch |
ZA892859B (en) * | 1988-04-22 | 1989-12-27 | Advanced Polymer Systems Inc | Porous particles in preparations involving immiscible phases |
US5296236A (en) * | 1988-09-16 | 1994-03-22 | Recordati S.A., Chemical And Pharmaceutical Company | Controlled release therapeutic system for a liquid pharmaceutical formulations |
DE3834944A1 (en) * | 1988-10-13 | 1990-04-26 | Ars Japan Kk | Drug-release device |
US5840293A (en) * | 1988-11-16 | 1998-11-24 | Advanced Polymer Systems, Inc. | Ionic beads for controlled release and adsorption |
US5241925A (en) * | 1988-12-27 | 1993-09-07 | Dermamed | Apparatus and techniques for administering veterinary medicaments |
US5332577A (en) * | 1988-12-27 | 1994-07-26 | Dermamed | Transdermal administration to humans and animals |
US5139787A (en) * | 1989-01-19 | 1992-08-18 | Wm. Wrigley Jr. Company | Gum composition containing dispersed porous beads containing active chewing gum ingredients and method |
IT1229203B (en) * | 1989-03-22 | 1991-07-25 | Bioresearch Spa | USE OF 5 METHYLTHETRAHYDROPHOLIC ACID, 5 FORMYLTHETRAHYDROPHOLIC ACID AND THEIR PHARMACEUTICALLY ACCEPTABLE SALTS FOR THE PREPARATION OF PHARMACEUTICAL COMPOSITIONS IN THE FORM OF CONTROLLED RELEASE ACTIVE IN THE THERAPY OF MENTAL AND ORGANIC DISORDERS. |
GB8909793D0 (en) * | 1989-04-28 | 1989-06-14 | Beecham Group Plc | Pharmaceutical formulation |
US5206022A (en) * | 1989-05-30 | 1993-04-27 | Moleculon, Inc. | Insect repellent compositions |
US5206019A (en) * | 1989-05-30 | 1993-04-27 | Moleculon, Inc. | Soap compositions containing liquid-loaded powders |
US5290570A (en) * | 1989-05-30 | 1994-03-01 | Purepac, Inc. | Lotions containing liquid-loaded powder |
US5223267A (en) * | 1989-05-30 | 1993-06-29 | Purepac, Inc. | Analgesic compositions |
US5209923A (en) * | 1989-05-30 | 1993-05-11 | Moleculon, Inc. | Sunscreen composition |
US5209932A (en) * | 1989-05-30 | 1993-05-11 | Moleculon, Inc. | Foot care compositions |
US5176132A (en) * | 1989-05-31 | 1993-01-05 | Fisons Plc | Medicament inhalation device and formulation |
FR2649888B1 (en) * | 1989-07-18 | 1994-08-26 | Exsymol Sa | PRODUCTS FOR SKIN APPLICATIONS, WITH COSMETIC OR / AND THERAPEUTIC EFFECTS |
CA2063141C (en) * | 1989-08-04 | 1997-03-04 | Edward J. Roche | Rotogranulations and taste masking coatings for preparation of chewable pharmaceutical tablets |
NZ234587A (en) * | 1989-08-04 | 1991-11-26 | Mcneil Ppc Inc | A chewable pharmaceutical tablet of compressed coated granules |
US5000962A (en) * | 1989-08-25 | 1991-03-19 | Schering Corporation | Long acting diltiazem formulation |
US4992277A (en) * | 1989-08-25 | 1991-02-12 | Schering Corporation | Immediate release diltiazem formulation |
US5112604A (en) * | 1989-09-01 | 1992-05-12 | Riker Laboratories, Inc. | Oral suspension formulation |
IT1256651B (en) * | 1992-12-11 | 1995-12-12 | Giancarlo Santus | PHARMACEUTICAL COMPOSITION WITH CONTROLLED RELEASE IN LIQUID SUSPENSION |
US5527545A (en) * | 1989-09-18 | 1996-06-18 | Recordati S.A. Chemical And Pharmaceutical Company | Liquid-suspension controlled-release pharmaceutical composition |
US5178878A (en) * | 1989-10-02 | 1993-01-12 | Cima Labs, Inc. | Effervescent dosage form with microparticles |
AU634606B2 (en) * | 1989-11-06 | 1993-02-25 | Alkermes Controlled Therapeutics, Inc. | Method for producing protein microspheres |
US5271961A (en) * | 1989-11-06 | 1993-12-21 | Alkermes Controlled Therapeutics, Inc. | Method for producing protein microspheres |
JP2571874B2 (en) * | 1989-11-06 | 1997-01-16 | アルカーメス コントロールド セラピューティクス,インコーポレイテッド | Protein microsphere composition |
FR2655266B1 (en) * | 1989-12-05 | 1992-04-03 | Smith Kline French Lab | CIMETIDINE PHARMACEUTICAL COMPOSITIONS. |
US5215756A (en) * | 1989-12-22 | 1993-06-01 | Gole Dilip J | Preparation of pharmaceutical and other matrix systems by solid-state dissolution |
US5660851A (en) * | 1989-12-26 | 1997-08-26 | Yissum Research Development Company Of The Hebrew Univ. Of Jerusalem | Ocular inserts |
JPH0674206B2 (en) * | 1989-12-28 | 1994-09-21 | 田辺製薬株式会社 | Controlled release formulation and process for producing |
ATE131042T1 (en) * | 1990-04-25 | 1995-12-15 | Hoechst Ag | PHARMACOLOGICAL PREPARATION CONTAINING POLYELECTROLYTE COMPLEXES IN MICROPARTICULAR FORM AND AT LEAST ONE ACTIVE INGREDIENT. |
FR2661683A1 (en) * | 1990-05-02 | 1991-11-08 | Rhone Poulenc Chimie | MATERIAL CONTROLLED DELIVERY SYSTEM COMPRISING A DISPERSE HYDROSOLUBLE ACTIVE PRINCIPLE IN A MATRIX CONSISTING OF A THERMOPLASTIC SILICONE COPOLYMER |
US5460825A (en) * | 1990-05-23 | 1995-10-24 | Mcneil-Ppc, Inc. | Taste mask coatings for preparing chewable pharmaceutical tablets |
US5075114A (en) * | 1990-05-23 | 1991-12-24 | Mcneil-Ppc, Inc. | Taste masking and sustained release coatings for pharmaceuticals |
GB9015822D0 (en) * | 1990-07-18 | 1990-09-05 | Beecham Group Plc | Compositions |
US5260072A (en) * | 1990-08-30 | 1993-11-09 | Mcneil-Ppc, Inc. | Rotogranulations and taste masking coatings for preparation of chewable pharmaceutical tablets |
FR2669222B1 (en) | 1990-11-15 | 1995-03-03 | Oreal | COSMETIC COMPOSITIONS IN THE FORM OF CAST POWDERS COMPRISING HOLLOW MICROSPHERES, AND THEIR PREPARATION. |
CA2041774C (en) * | 1990-11-27 | 1994-04-19 | Mircea A. Mateescu | Use of cross-linked amylose as a matrix for the slow release of biologically active compounds |
US5603956A (en) * | 1990-11-27 | 1997-02-18 | Labopharm Inc. | Cross-linked enzymatically controlled drug release |
ZA919510B (en) * | 1990-12-05 | 1992-10-28 | Smithkline Beecham Corp | Pharmaceutical compositions |
US5562914A (en) * | 1990-12-06 | 1996-10-08 | Zeneca Inc. | Impregnated porous granules and a polyurethane matrix held within the pores thereof and holding a liquid material for controlled release of liquid material and process therefor |
GB9026682D0 (en) * | 1990-12-07 | 1991-01-23 | Walker Bryan J | Lightweight aggregate |
US5275820A (en) * | 1990-12-27 | 1994-01-04 | Allergan, Inc. | Stable suspension formulations of bioerodible polymer matrix microparticles incorporating drug loaded ion exchange resin particles |
US5378475A (en) * | 1991-02-21 | 1995-01-03 | University Of Kentucky Research Foundation | Sustained release drug delivery devices |
US5116627A (en) * | 1991-03-07 | 1992-05-26 | International Flavors & Fragrances Inc. | Chewing gum containing compositions for controlled release of flavor bearing substances and process for producing same |
US5629013A (en) * | 1991-04-04 | 1997-05-13 | The Procter & Gamble Company | Chewable calcium carbonate antacid tablet compositions |
US5993805A (en) * | 1991-04-10 | 1999-11-30 | Quadrant Healthcare (Uk) Limited | Spray-dried microparticles and their use as therapeutic vehicles |
US5380535A (en) * | 1991-05-28 | 1995-01-10 | Geyer; Robert P. | Chewable drug-delivery compositions and methods for preparing the same |
DE69233130T2 (en) * | 1991-05-28 | 2005-06-02 | Mcneil-Ppc, Inc. | COUGAR COMPOSITION FOR MEDICINAL RELEASE |
DE4120918A1 (en) * | 1991-06-25 | 1993-01-07 | Basf Ag | POWDERED PREPARATIONS FROM A WATER-INSOLUBLE CORE SUBSTANCE AND A PROTECTIVE COVER |
US5288505A (en) * | 1991-06-26 | 1994-02-22 | Galephar P.R., Inc., Ltd. | Extended release form of diltiazem |
ATE122228T1 (en) * | 1991-07-01 | 1995-05-15 | Gergely Gerhard | METHOD FOR PRODUCING A PHARMACEUTICAL PREPARATION WITH AT LEAST TWO DIFFERENT ACTIVE INGREDIENTS AND USE OF SUCH A PREPARATION. |
DE4122217C2 (en) * | 1991-07-04 | 1997-02-13 | Merz & Co Gmbh & Co | Process for the preparation of mechanically stable, well decomposing compressed products from small active substance-containing moldings |
ES2034891B1 (en) * | 1991-08-08 | 1993-12-16 | Cusi Lab | CONTINUOUS ELABORATION PROCEDURE OF SCATTERED COLLOID SYSTEMS, IN THE FORM OF NANOCAPSULES OR NANOPARTICLES. |
US5300305A (en) * | 1991-09-12 | 1994-04-05 | The Procter & Gamble Company | Breath protection microcapsules |
FR2681248B1 (en) * | 1991-09-13 | 1995-04-28 | Oreal | COMPOSITION FOR A LONG-TERM COSMETIC AND / OR PHARMACEUTICAL TREATMENT OF THE TOP LAYERS OF THE EPIDERMIS BY TOPICAL APPLICATION TO THE SKIN. |
CA2125483A1 (en) * | 1991-12-11 | 1993-06-24 | Mary Ann Hunter | Cetylpyridinium chloride and domiphen bromide in organic solvent |
US5478577A (en) * | 1993-11-23 | 1995-12-26 | Euroceltique, S.A. | Method of treating pain by administering 24 hour oral opioid formulations exhibiting rapid rate of initial rise of plasma drug level |
ATE146359T1 (en) * | 1992-01-21 | 1997-01-15 | Stanford Res Inst Int | IMPROVED METHOD FOR PRODUCING MICRONIZED POLYPEPTIDE DRUGS |
US5296228A (en) * | 1992-03-13 | 1994-03-22 | Allergan, Inc. | Compositions for controlled delivery of pharmaceutical compounds |
ZA932273B (en) * | 1992-03-30 | 1993-11-26 | Alza Corp | Additives for bioerodible polymers to regulate degradation |
MX9301823A (en) * | 1992-03-30 | 1994-01-31 | Alza Corp | COMPOSITION FOR THE SUPPLY OF CONTROLLED RELEASE OF A BIOLOGICALLY ACTIVE AGENT. |
US5294433A (en) * | 1992-04-15 | 1994-03-15 | The Procter & Gamble Company | Use of H-2 antagonists for treatment of gingivitis |
ES2099438T3 (en) * | 1992-04-30 | 1997-05-16 | Schering Corp | DRY AND STABLE POWDER OF HYDRATED CEPHALOSPORIN FOR ORAL SUSPENSION FORMULATION. |
US5560921A (en) * | 1992-06-01 | 1996-10-01 | The Procter & Gamble Company | Chewable decongestant compositions |
EP0572731A1 (en) * | 1992-06-01 | 1993-12-08 | The Procter & Gamble Company | Chewable preparation containing a decongestant |
US6582728B1 (en) | 1992-07-08 | 2003-06-24 | Inhale Therapeutic Systems, Inc. | Spray drying of macromolecules to produce inhaleable dry powders |
DE69332105T2 (en) | 1992-09-29 | 2003-03-06 | Inhale Therapeutic Systems San | PULMONAL DELIVERY OF ACTIVE FRAGMENT OF PARATHORMON |
EP0595030A3 (en) * | 1992-10-01 | 1995-06-07 | Tanabe Seiyaku Co | Sustained release multi-core microsphere preparation and method for producing the same. |
HU221308B1 (en) * | 1992-10-26 | 2002-09-28 | Sanol Arznei Schwarz Gmbh | Process for producing microcapsules |
US5883115A (en) * | 1992-11-09 | 1999-03-16 | Pharmetrix Division Technical Chemicals & Products, Inc. | Transdermal delivery of the eutomer of a chiral drug |
KR100333115B1 (en) * | 1992-11-17 | 2002-12-02 | 미츠비시 파마 코포레이션 | Sustained-release microsphere containing antipsychotic and process for producing the same |
US5354553A (en) * | 1992-12-08 | 1994-10-11 | Church & Dwight Co., Inc | Antiperspirant-deodorant cosmetic stick products |
US5651983A (en) * | 1993-02-26 | 1997-07-29 | The Procter & Gamble Company | Bisacodyl dosage form for colonic delivery |
US5914132A (en) * | 1993-02-26 | 1999-06-22 | The Procter & Gamble Company | Pharmaceutical dosage form with multiple enteric polymer coatings for colonic delivery |
US5843479A (en) * | 1993-02-26 | 1998-12-01 | The Procter & Gamble Company | Bisacodyl dosage form with multiple enteric polymer coatings for colonic delivery |
AU6251094A (en) * | 1993-02-26 | 1994-09-14 | Procter & Gamble Company, The | Bisacodyl dosage form |
US5616343A (en) * | 1993-03-25 | 1997-04-01 | Labopharm, Inc. | Cross-linked amylose as a binder/disintegrant in tablets |
US5456917A (en) * | 1993-04-12 | 1995-10-10 | Cambridge Scientific, Inc. | Method for making a bioerodible material for the sustained release of a medicament and the material made from the method |
US5415877A (en) * | 1993-04-23 | 1995-05-16 | Church & Dwight Co., Inc. | Bicarbonate fungicide product with a combination of surfactant ingredients |
US6440457B1 (en) * | 1993-05-27 | 2002-08-27 | Alza Corporation | Method of administering antidepressant dosage form |
US5520924A (en) * | 1993-07-09 | 1996-05-28 | Mizu Systems Corporation | Methods and articles for administering drug to the oral cavity |
ZA945944B (en) * | 1993-08-13 | 1996-02-08 | Eurand America Inc | Procedure for encapsulating nsaids |
US6204243B1 (en) | 1993-09-01 | 2001-03-20 | Novatis Ag | Pharmaceutical preparations for the targeted treatment of crohn's disease and ulcerative colitis |
US6818229B1 (en) | 1993-09-20 | 2004-11-16 | Kos Pharmaceuticals, Inc. | Intermediate release nicotinic acid compositions for treating hyperlipidemia |
US6676967B1 (en) | 1993-09-20 | 2004-01-13 | Kos Pharmaceuticals, Inc. | Methods for reducing flushing in individuals being treated with nicotinic acid for hyperlipidemia |
US6129930A (en) | 1993-09-20 | 2000-10-10 | Bova; David J. | Methods and sustained release nicotinic acid compositions for treating hyperlipidemia at night |
US6746691B2 (en) | 1993-09-20 | 2004-06-08 | Kos Pharmaceuticals, Inc. | Intermediate release nicotinic acid compositions for treating hyperlipidemia having unique biopharmaceutical characteristics |
US6080428A (en) | 1993-09-20 | 2000-06-27 | Bova; David J. | Nicotinic acid compositions for treating hyperlipidemia and related methods therefor |
GB2281861B (en) * | 1993-09-21 | 1997-08-20 | Johnson & Johnson Medical | Bioabsorbable wound implant materials containing microspheres |
ES2236700T3 (en) * | 1993-11-19 | 2005-07-16 | Janssen Pharmaceutica N.V. | 1,2-MICROENCAPSULATED BENZAZOLS. |
US5516524A (en) * | 1993-12-20 | 1996-05-14 | The Procter & Gamble Company | Laxative compositions containing bulk fiber |
US5897858A (en) | 1994-02-03 | 1999-04-27 | Schering-Plough Healthcare Products, Inc. | Nasal spray compositions exhibiting increased retention in the nasal cavity |
US7077822B1 (en) * | 1994-02-09 | 2006-07-18 | The University Of Iowa Research Foundation | Stereotactic hypothalamic obesity probe |
US5763416A (en) * | 1994-02-18 | 1998-06-09 | The Regent Of The University Of Michigan | Gene transfer into bone cells and tissues |
US6074840A (en) | 1994-02-18 | 2000-06-13 | The Regents Of The University Of Michigan | Recombinant production of latent TGF-beta binding protein-3 (LTBP-3) |
US5962427A (en) * | 1994-02-18 | 1999-10-05 | The Regent Of The University Of Michigan | In vivo gene transfer methods for wound healing |
US5942496A (en) * | 1994-02-18 | 1999-08-24 | The Regent Of The University Of Michigan | Methods and compositions for multiple gene transfer into bone cells |
US6051256A (en) | 1994-03-07 | 2000-04-18 | Inhale Therapeutic Systems | Dispersible macromolecule compositions and methods for their preparation and use |
MX9603936A (en) * | 1994-03-07 | 1997-05-31 | Inhale Therapeutic Syst | Methods and compositions for pulmonary delivery of insulin. |
US6551618B2 (en) | 1994-03-15 | 2003-04-22 | University Of Birmingham | Compositions and methods for delivery of agents for neuronal regeneration and survival |
US5672358A (en) * | 1994-06-21 | 1997-09-30 | Ascent Pharmaceuticals, Inc. | Controlled release aqueous emulsion |
US5460826A (en) * | 1994-06-27 | 1995-10-24 | Alza Corporation | Morphine therapy |
US5938990A (en) * | 1994-07-01 | 1999-08-17 | Roche Vitamins Inc. | Encapsulation of oleophilic substances and compositions produced thereby |
US5626862A (en) | 1994-08-02 | 1997-05-06 | Massachusetts Institute Of Technology | Controlled local delivery of chemotherapeutic agents for treating solid tumors |
US6290991B1 (en) | 1994-12-02 | 2001-09-18 | Quandrant Holdings Cambridge Limited | Solid dose delivery vehicle and methods of making same |
US5543099A (en) * | 1994-09-29 | 1996-08-06 | Hallmark Pharmaceutical, Inc. | Process to manufacture micronized nifedipine granules for sustained release medicaments |
NL9401703A (en) * | 1994-10-14 | 1996-05-01 | Rijksuniversiteit | Chewing gum. |
US6555098B1 (en) | 1994-12-09 | 2003-04-29 | Church & Dwight Co., Inc. | Cosmetic deodorant products containing encapsulated bicarbonate and fragrance ingredients |
CN1132070A (en) * | 1994-12-21 | 1996-10-02 | 麦克尼尔-Ppc公司 | Aqueous suspension formulation for pharmaceutical applications |
US6429221B1 (en) * | 1994-12-30 | 2002-08-06 | Celgene Corporation | Substituted imides |
US5686107A (en) * | 1995-01-30 | 1997-11-11 | Fmc Corporation | Chewable pharmaceutical tablets |
US6165988A (en) * | 1995-02-10 | 2000-12-26 | Christian Noe | Medicament in particulate form |
AU4775896A (en) * | 1995-03-08 | 1996-09-23 | Church & Dwight Company, Inc. | Encapsulated bicarbonate-containing agrochemical compositions |
DE19516787A1 (en) * | 1995-05-08 | 1996-11-14 | Bayer Ag | (Co) polycarbonates stabilized against gamma radiation |
TW493991B (en) * | 1995-05-08 | 2002-07-11 | Novartis Ag | Pharmaceutical composition for oral administration of active agent having low water solubility and process for preparation of the same |
WO1997013503A1 (en) * | 1995-10-13 | 1997-04-17 | The Penn State Research Foundation | Synthesis of drug nanoparticles by spray drying |
US6270795B1 (en) | 1995-11-09 | 2001-08-07 | Microbiological Research Authority | Method of making microencapsulated DNA for vaccination and gene therapy |
US5837653A (en) * | 1995-12-21 | 1998-11-17 | Basf Corporation | Encapsulated plant growth regulator formulations |
US5861360A (en) * | 1995-12-21 | 1999-01-19 | Basf Corporation | Encapsulated plant growth regulator formulations and applications |
US6858589B2 (en) | 1996-01-25 | 2005-02-22 | Pharmacy And Therapeutic Advisory Consultancy Pty Ltd | Methods of and compositions for potentiating the action of agents active on cell wall sites of the susceptible bacteria |
US5773031A (en) * | 1996-02-27 | 1998-06-30 | L. Perrigo Company | Acetaminophen sustained-release formulation |
AU751497B2 (en) * | 1996-04-23 | 2002-08-15 | Mayne Pharma International Pty Ltd | Taste masked pharmaceutical compositions |
AUPO637197A0 (en) * | 1997-04-23 | 1997-05-15 | F.H. Faulding & Co. Limited | Taste-masked pharmaceutical compositions |
US5792477A (en) * | 1996-05-07 | 1998-08-11 | Alkermes Controlled Therapeutics, Inc. Ii | Preparation of extended shelf-life biodegradable, biocompatible microparticles containing a biologically active agent |
AUPN969796A0 (en) * | 1996-05-07 | 1996-05-30 | F.H. Faulding & Co. Limited | Taste masked liquid suspensions |
GB9614902D0 (en) * | 1996-07-16 | 1996-09-04 | Rhodes John | Sustained release composition |
NZ334148A (en) * | 1996-08-12 | 2001-12-21 | Celgene Corp | 3-Substituted phenyl-ethyl or ethenyl derivatives terminated with a nitrile, alkane, carboxyl or carbamoyl group useful to reduce cytokine levels |
US6488961B1 (en) | 1996-09-20 | 2002-12-03 | Ethypharm, Inc. | Effervescent granules and methods for their preparation |
US6649186B1 (en) | 1996-09-20 | 2003-11-18 | Ethypharm | Effervescent granules and methods for their preparation |
US6071539A (en) * | 1996-09-20 | 2000-06-06 | Ethypharm, Sa | Effervescent granules and methods for their preparation |
IT1284604B1 (en) * | 1996-09-27 | 1998-05-21 | Roberto Valducci | CONTROLLED RELEASE PHARMACEUTICAL COMPOSITIONS FOR ORAL ADMINISTRATION CONTAINING NIFEDIPINE AS THE ACTIVE SUBSTANCE |
WO1998021960A1 (en) * | 1996-11-22 | 1998-05-28 | Rhone-Poulenc Agrochimie | Novel solid compositions with base of insoluble cellulose derivative and 1-aryl-pyrazole derivative |
AU5571598A (en) * | 1996-11-22 | 1998-06-10 | Rhone-Poulenc Agrochimie | Novel solid compositions based on an insoluble cellulose derivative and a 1-arylpyrazole derivative |
FR2764775A1 (en) * | 1997-06-20 | 1998-12-24 | Rhone Poulenc Agrochimie | Solid insecticidal composition effective against termites |
US20030203036A1 (en) | 2000-03-17 | 2003-10-30 | Gordon Marc S. | Systems and processes for spray drying hydrophobic drugs with hydrophilic excipients |
US20020182258A1 (en) * | 1997-01-22 | 2002-12-05 | Zycos Inc., A Delaware Corporation | Microparticles for delivery of nucleic acid |
US5837379A (en) * | 1997-01-31 | 1998-11-17 | Andrx Pharmaceuticals, Inc. | Once daily pharmaceutical tablet having a unitary core |
US5922352A (en) * | 1997-01-31 | 1999-07-13 | Andrx Pharmaceuticals, Inc. | Once daily calcium channel blocker tablet having a delayed release core |
GB9703673D0 (en) * | 1997-02-21 | 1997-04-09 | Bradford Particle Design Ltd | Method and apparatus for the formation of particles |
US5948787A (en) * | 1997-02-28 | 1999-09-07 | Alza Corporation | Compositions containing opiate analgesics |
US6024981A (en) | 1997-04-16 | 2000-02-15 | Cima Labs Inc. | Rapidly dissolving robust dosage form |
US6020004A (en) * | 1997-04-17 | 2000-02-01 | Amgen Inc. | Biodegradable microparticles for the sustained delivery of therapeutic drugs |
US6433154B1 (en) | 1997-06-12 | 2002-08-13 | Bristol-Myers Squibb Company | Functional receptor/kinase chimera in yeast cells |
DE19726195A1 (en) | 1997-06-20 | 1998-12-24 | Bayer Ag | Use of saccharin to stabilize thermoplastic, aromatic polycarbonates |
FR2766089B1 (en) * | 1997-07-21 | 2000-06-02 | Prographarm Lab | IMPROVED MULTIPARTICULAR TABLET WITH RAPID DELIVERY |
US7923250B2 (en) | 1997-07-30 | 2011-04-12 | Warsaw Orthopedic, Inc. | Methods of expressing LIM mineralization protein in non-osseous cells |
EP1007673B1 (en) | 1997-07-30 | 2008-12-17 | Emory University | Novel bone mineralization proteins, dna, vectors, expression systems |
US5902598A (en) * | 1997-08-28 | 1999-05-11 | Control Delivery Systems, Inc. | Sustained release drug delivery devices |
US6309623B1 (en) | 1997-09-29 | 2001-10-30 | Inhale Therapeutic Systems, Inc. | Stabilized preparations for use in metered dose inhalers |
US6565885B1 (en) | 1997-09-29 | 2003-05-20 | Inhale Therapeutic Systems, Inc. | Methods of spray drying pharmaceutical compositions |
US20060165606A1 (en) | 1997-09-29 | 2006-07-27 | Nektar Therapeutics | Pulmonary delivery particles comprising water insoluble or crystalline active agents |
WO1999017742A2 (en) * | 1997-10-03 | 1999-04-15 | Elan Corporation, Plc | Taste masked formulations |
US6485748B1 (en) | 1997-12-12 | 2002-11-26 | Andrx Pharmaceuticals, Inc. | Once daily pharmaceutical tablet having a unitary core |
FI105074B (en) * | 1997-12-31 | 2000-06-15 | Leiras Oy | Process for the preparation of a pharmaceutical formulation |
US7101575B2 (en) * | 1998-03-19 | 2006-09-05 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Production of nanocapsules and microcapsules by layer-wise polyelectrolyte self-assembly |
US6974590B2 (en) | 1998-03-27 | 2005-12-13 | Cima Labs Inc. | Sublingual buccal effervescent |
US20030118645A1 (en) * | 1998-04-29 | 2003-06-26 | Pather S. Indiran | Pharmaceutical compositions for rectal and vaginal administration |
US20030091629A1 (en) * | 1998-03-27 | 2003-05-15 | Cima Labs Inc. | Sublingual buccal effervescent |
TR200103759T2 (en) | 1998-06-15 | 2002-06-21 | Sepracor Inc. | The use of optically pure (-) norcisapride to treat apnea, bulimia and other disorders |
TR200103058T2 (en) | 1998-06-15 | 2002-06-21 | Sepracor Inc. | The use of optically pure (+) - norcisapride for treating apnea, bulimia and other disorders. |
SK262001A3 (en) * | 1998-07-08 | 2001-09-11 | Kirin Amgen Inc | Powdery preparation for mucosal administration containing polymeric medicine |
US6524620B2 (en) | 1998-07-20 | 2003-02-25 | Andrx Pharmaceuticals, Inc. | Diltiazem controlled release formulation and method of manufacture |
GB9816724D0 (en) * | 1998-08-01 | 1998-09-30 | Boots Co Plc | Therapeutic agents |
US6365182B1 (en) | 1998-08-12 | 2002-04-02 | Cima Labs Inc. | Organoleptically pleasant in-mouth rapidly disintegrable potassium chloride tablet |
US6153225A (en) * | 1998-08-13 | 2000-11-28 | Elan Pharma International Limited | Injectable formulations of nanoparticulate naproxen |
US6238677B1 (en) * | 1998-08-18 | 2001-05-29 | The United States Of America As Represented By The Secretary Of Agriculture | Starch microcapsules for delivery of active agents |
US6331571B1 (en) | 1998-08-24 | 2001-12-18 | Sepracor, Inc. | Methods of treating and preventing attention deficit disorders |
US6339106B1 (en) | 1999-08-11 | 2002-01-15 | Sepracor, Inc. | Methods and compositions for the treatment and prevention of sexual dysfunction |
US6974838B2 (en) * | 1998-08-24 | 2005-12-13 | Sepracor Inc. | Methods of treating or preventing pain using sibutramine metabolites |
US6476078B2 (en) * | 1999-08-11 | 2002-11-05 | Sepracor, Inc. | Methods of using sibutramine metabolites in combination with a phosphodiesterase inhibitor to treat sexual dysfunction |
US6254891B1 (en) | 1998-09-03 | 2001-07-03 | Ascent Pediatrics, Inc. | Extended release acetaminophen |
US6126967A (en) * | 1998-09-03 | 2000-10-03 | Ascent Pediatrics | Extended release acetaminophen particles |
US6165506A (en) * | 1998-09-04 | 2000-12-26 | Elan Pharma International Ltd. | Solid dose form of nanoparticulate naproxen |
WO2000016742A1 (en) * | 1998-09-24 | 2000-03-30 | The Procter & Gamble Company | Chewable compositions containing dextromethorphan |
US8293277B2 (en) | 1998-10-01 | 2012-10-23 | Alkermes Pharma Ireland Limited | Controlled-release nanoparticulate compositions |
US20090149479A1 (en) * | 1998-11-02 | 2009-06-11 | Elan Pharma International Limited | Dosing regimen |
US20090297597A1 (en) * | 1998-11-02 | 2009-12-03 | Gary Liversidge | Modified Release Ticlopidine Compositions |
US20060240105A1 (en) * | 1998-11-02 | 2006-10-26 | Elan Corporation, Plc | Multiparticulate modified release composition |
US20070122481A1 (en) * | 1998-11-02 | 2007-05-31 | Elan Corporation Plc | Modified Release Compositions Comprising a Fluorocytidine Derivative for the Treatment of Cancer |
DK1126826T6 (en) * | 1998-11-02 | 2019-06-24 | Alkermes Pharma Ireland Ltd | Multiparticulate modified release of methylphenidate |
US20070160675A1 (en) * | 1998-11-02 | 2007-07-12 | Elan Corporation, Plc | Nanoparticulate and controlled release compositions comprising a cephalosporin |
JP3141107B2 (en) * | 1998-11-16 | 2001-03-05 | 工業技術院長 | Human-derived bradion protein, DNA encoding the same, and uses thereof |
US6902898B2 (en) * | 1998-11-16 | 2005-06-07 | National Institute Of Advanced Industrial Science And Technology | Human derived bradeion proteins, DNA coding for the proteins, and uses thereof |
SA99191255B1 (en) | 1998-11-30 | 2006-11-25 | جي دي سيرل اند كو | celecoxib compounds |
US6342533B1 (en) * | 1998-12-01 | 2002-01-29 | Sepracor, Inc. | Derivatives of (−)-venlafaxine and methods of preparing and using the same |
UA74141C2 (en) * | 1998-12-09 | 2005-11-15 | Дж.Д. Сірл Енд Ко. | Oral pharmaceutical compositions comprising micronized eplerenone (variants), method for its production and method for treating aldosterone-mediated states (variants) |
US6194006B1 (en) * | 1998-12-30 | 2001-02-27 | Alkermes Controlled Therapeutics Inc. Ii | Preparation of microparticles having a selected release profile |
US7919109B2 (en) | 1999-02-08 | 2011-04-05 | Intarcia Therapeutics, Inc. | Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicles |
US7258869B1 (en) * | 1999-02-08 | 2007-08-21 | Alza Corporation | Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicle |
US6274168B1 (en) * | 1999-02-23 | 2001-08-14 | Mylan Pharmaceuticals Inc. | Phenytoin sodium pharmaceutical compositions |
US6337328B1 (en) | 1999-03-01 | 2002-01-08 | Sepracor, Inc. | Bupropion metabolites and methods of use |
JP2002538102A (en) | 1999-03-01 | 2002-11-12 | セプラコア インコーポレーテッド | Method of treating apnea and apnea disorder using optically pure R (+) ondansetron |
US6353005B1 (en) | 1999-03-02 | 2002-03-05 | Sepracor, Inc. | Method and compositions using (+) norcisapride in combination with proton pump inhibitors or H2 receptor antagonist |
US6362202B1 (en) | 1999-03-02 | 2002-03-26 | Sepracor Inc. | Methods and compositions using (−) norcisapride in combination with proton pump inhibitors or H2 receptor antagonists |
US20040121014A1 (en) * | 1999-03-22 | 2004-06-24 | Control Delivery Systems, Inc. | Method for treating and/or preventing retinal diseases with sustained release corticosteroids |
US6217895B1 (en) * | 1999-03-22 | 2001-04-17 | Control Delivery Systems | Method for treating and/or preventing retinal diseases with sustained release corticosteroids |
US6428818B1 (en) | 1999-03-30 | 2002-08-06 | Purdue Research Foundation | Tea catechin formulations and processes for making same |
US6410052B1 (en) | 1999-03-30 | 2002-06-25 | Purdue Research Foundation | Tea catechins in sustained release formulations as cancer specific proliferation inhibitors |
DE60039132D1 (en) * | 1999-04-06 | 2008-07-17 | Sepracor Inc | O-desmethylvenlafaxine succinate |
US6261600B1 (en) | 1999-04-30 | 2001-07-17 | Drugtech Corporation | Folic acid supplement |
US6399826B1 (en) | 1999-08-11 | 2002-06-04 | Sepracor Inc. | Salts of sibutramine metabolites, methods of making sibutramine metabolites and intermediates useful in the same, and methods of treating pain |
US20030083383A1 (en) * | 1999-08-16 | 2003-05-01 | Spallholz Julian E. | Method of using synthetic L-Se-methylselenocysteine as a nutriceutical and a method of its synthesis |
ES2256032T3 (en) * | 1999-09-03 | 2006-07-16 | Apbi Holdings, Llc | USE OF DAPOXETINE, A SELECTIVE INHIBITOR OF RECOVERY OF SEROTONINE, FOR THE TREATMENT OF A SEXUAL DYSFUNCTION. |
JP2003509439A (en) * | 1999-09-14 | 2003-03-11 | スミスクライン・ビーチャム・コーポレイション | How to make water-coated beadlets |
NZ529928A (en) | 1999-10-29 | 2005-10-28 | Euro Celtique Sa | Controlled release hydrocodone formulations |
US10179130B2 (en) | 1999-10-29 | 2019-01-15 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
US6705757B2 (en) * | 1999-11-12 | 2004-03-16 | Alkermes Controlled Therapeutics, Inc. Ii | Method and apparatus for preparing microparticles using in-line solvent extraction |
US6495166B1 (en) | 1999-11-12 | 2002-12-17 | Alkermes Controlled Therapeutics Inc. | Apparatus and method for preparing microparticles using in-line solvent extraction |
US6331317B1 (en) | 1999-11-12 | 2001-12-18 | Alkermes Controlled Therapeutics Ii Inc. | Apparatus and method for preparing microparticles |
US20050037086A1 (en) * | 1999-11-19 | 2005-02-17 | Zycos Inc., A Delaware Corporation | Continuous-flow method for preparing microparticles |
US20060153914A1 (en) * | 1999-12-10 | 2006-07-13 | Biovail Laboratories International S.R.L. | Chronotherapeutic diltiazem formulations and the administration thereof |
US7108866B1 (en) | 1999-12-10 | 2006-09-19 | Biovall Laboratories International Srl | Chronotherapeutic diltiazem formulations and the administration thereof |
US7182953B2 (en) | 1999-12-15 | 2007-02-27 | Celgene Corporation | Methods and compositions for the prevention and treatment of atherosclerosis restenosis and related disorders |
JP2003518485A (en) | 1999-12-23 | 2003-06-10 | ファイザー・プロダクツ・インク | Pharmaceutical composition giving improved drug concentration |
CN1420776A (en) * | 2000-03-31 | 2003-05-28 | 塞尔基因公司 | Inhibition of cyclooxygenase-2 activity |
US6375972B1 (en) | 2000-04-26 | 2002-04-23 | Control Delivery Systems, Inc. | Sustained release drug delivery devices, methods of use, and methods of manufacturing thereof |
US8404217B2 (en) | 2000-05-10 | 2013-03-26 | Novartis Ag | Formulation for pulmonary administration of antifungal agents, and associated methods of manufacture and use |
AU6124601A (en) | 2000-05-10 | 2001-11-20 | Alliance Pharmaceutical Corporation | Phospholipid-based powders for drug delivery |
US7871598B1 (en) | 2000-05-10 | 2011-01-18 | Novartis Ag | Stable metal ion-lipid powdered pharmaceutical compositions for drug delivery and methods of use |
DE60135455D1 (en) | 2000-05-16 | 2008-10-02 | Univ Minnesota | IT OF MULTI-NOZZLE ARRANGEMENT |
US6264987B1 (en) | 2000-05-19 | 2001-07-24 | Alkermes Controlled Therapeutics Inc. Ii | Method for preparing microparticles having a selected polymer molecular weight |
US6495164B1 (en) * | 2000-05-25 | 2002-12-17 | Alkermes Controlled Therapeutics, Inc. I | Preparation of injectable suspensions having improved injectability |
WO2001091730A1 (en) | 2000-05-31 | 2001-12-06 | Drugtech Corporation | Mineral supplement |
EP1292285A4 (en) * | 2000-06-02 | 2009-07-22 | Eisai Corp North America | Delivery systems for bioactive agents |
US7259152B2 (en) | 2000-06-07 | 2007-08-21 | Alfa Wasserman, Inc. | Methods and compositions using sulodexide for the treatment of diabetic nephropathy |
US7575761B2 (en) * | 2000-06-30 | 2009-08-18 | Novartis Pharma Ag | Spray drying process control of drying kinetics |
US7223421B2 (en) * | 2000-06-30 | 2007-05-29 | Mcneil-Ppc, Inc. | Teste masked pharmaceutical particles |
US8512718B2 (en) | 2000-07-03 | 2013-08-20 | Foamix Ltd. | Pharmaceutical composition for topical application |
JP2004502708A (en) * | 2000-07-06 | 2004-01-29 | デルシス ファーマシューティカル コーポレイション | Improved thyroid hormone preparation |
JP2002037727A (en) * | 2000-07-26 | 2002-02-06 | Eisai Co Ltd | Lipid-soluble medicine-formulated rapid disintegrable solid pharmaceutical preparation and method for producing the same |
AU2001277230A1 (en) * | 2000-08-01 | 2002-02-13 | Inhale Therapeutic Systems, Inc. | Apparatus and process to produce particles having a narrow size distribution andparticles made thereby |
AU2001281304B2 (en) | 2000-08-15 | 2006-05-25 | Surmodics, Inc. | Medicament incorporation matrix |
US6824822B2 (en) * | 2001-08-31 | 2004-11-30 | Alkermes Controlled Therapeutics Inc. Ii | Residual solvent extraction method and microparticles produced thereby |
US7198795B2 (en) | 2000-09-21 | 2007-04-03 | Elan Pharma International Ltd. | In vitro methods for evaluating the in vivo effectiveness of dosage forms of microparticulate of nanoparticulate active agent compositions |
US7276249B2 (en) | 2002-05-24 | 2007-10-02 | Elan Pharma International, Ltd. | Nanoparticulate fibrate formulations |
US6471995B1 (en) | 2000-09-27 | 2002-10-29 | Alkermes Controlled Therapeutics, Inc. Ii | Apparatus and method for preparing microparticles using liquid-liquid extraction |
KR101045144B1 (en) | 2000-10-30 | 2011-06-30 | 유로-셀티크 소시에떼 아노뉨 | Controlled release hydrocodone formulations |
US20070208087A1 (en) * | 2001-11-02 | 2007-09-06 | Sanders Virginia J | Compounds, compositions and methods for the treatment of inflammatory diseases |
WO2002036077A2 (en) * | 2000-11-06 | 2002-05-10 | Andrx Pharmaceuticals, Inc. | Once a day antihistamine and decongestant formulation |
GB0027357D0 (en) | 2000-11-09 | 2000-12-27 | Bradford Particle Design Plc | Particle formation methods and their products |
ES2290091T3 (en) * | 2000-11-30 | 2008-02-16 | The Children's Medical Center Corporation | SYNTHESIS OF ENANTIOMERS OF 4-AMINO-TALIDOMIDE. |
US20020114843A1 (en) * | 2000-12-27 | 2002-08-22 | Ramstack J. Michael | Preparation of microparticles having improved flowability |
US20050192220A1 (en) * | 2001-02-05 | 2005-09-01 | Gevys Pharmaceuticas Ltd. | Composition and method for potentiating drugs |
US6833377B2 (en) | 2001-02-05 | 2004-12-21 | Gevys Pharmaceuticals Ltd. | Composition and method for potentiating drugs |
PT1360169E (en) * | 2001-02-12 | 2007-10-29 | Wyeth Corp | Succinate salt of o-desmethyl-venlafaxine |
WO2002067966A1 (en) | 2001-02-22 | 2002-09-06 | Purdue Research Foundation | Compositions based on vanilloid-catechin synergies for prevention and treatment of cancer |
US7192612B2 (en) * | 2001-02-22 | 2007-03-20 | Purdue Research Foundation | Compositions and methods based on synergies between capsicum extracts and tea catechins for prevention and treatment of cancer |
SE0100824D0 (en) * | 2001-03-09 | 2001-03-09 | Astrazeneca Ab | Method III to obtain microparticles |
WO2002076228A1 (en) * | 2001-03-23 | 2002-10-03 | Gumlink A/S | Degradable resin substitute for chewing gum |
DE60230020D1 (en) * | 2001-03-23 | 2009-01-08 | Gumlinck As | COATED, DEVELOPABLE RUBBER WITH IMPROVED DURABILITY AND METHOD FOR THE PRODUCTION THEREOF |
US20040156949A1 (en) * | 2001-03-23 | 2004-08-12 | Lone Andersen | Degradable elastomers for chewing gum base |
DE60223659T2 (en) * | 2001-03-23 | 2008-10-30 | Gumlink A/S | One-step process for the production of chewing gum |
ES2554389T3 (en) * | 2001-03-23 | 2015-12-18 | Gumlink A/S | Biodegradable chewing gum and method of manufacturing such chewing gum |
WO2002083631A1 (en) | 2001-04-13 | 2002-10-24 | Sepracor Inc. | Methods of preparing didesmethylsibutramine and other sibutramine derivatives |
US7247338B2 (en) * | 2001-05-16 | 2007-07-24 | Regents Of The University Of Minnesota | Coating medical devices |
US20040173146A1 (en) * | 2001-06-07 | 2004-09-09 | Figueroa Iddys D. | Application of a bioactive agent to a delivery substrate |
US20040173147A1 (en) * | 2001-06-07 | 2004-09-09 | Figueroa Iddys D. | Application of a bioactive agent to a delivery substrate |
US6962715B2 (en) * | 2001-10-24 | 2005-11-08 | Hewlett-Packard Development Company, L.P. | Method and dosage form for dispensing a bioactive substance |
GB0114532D0 (en) * | 2001-06-14 | 2001-08-08 | Jagotec Ag | Novel compositions |
US7758890B2 (en) | 2001-06-23 | 2010-07-20 | Lyotropic Therapeutics, Inc. | Treatment using dantrolene |
US20040247696A1 (en) * | 2001-07-05 | 2004-12-09 | Antelman Marvin S. | Methods of using electron active compounds for managing conditions afflicting mammals |
PT1411899E (en) * | 2001-08-01 | 2009-04-24 | Novartis Ag | Taste masking composition |
US20030060422A1 (en) | 2001-08-31 | 2003-03-27 | Balaji Venkataraman | Tannate compositions and methods of treatment |
US20030050620A1 (en) * | 2001-09-07 | 2003-03-13 | Isa Odidi | Combinatorial type controlled release drug delivery device |
US20030087963A1 (en) | 2001-09-13 | 2003-05-08 | Senanayake Chris H. | Methods of preparing and using 2-hydroxy derivatives of sibutramine and its metabolites |
US8101209B2 (en) | 2001-10-09 | 2012-01-24 | Flamel Technologies | Microparticulate oral galenical form for the delayed and controlled release of pharmaceutical active principles |
US8765167B2 (en) | 2001-10-12 | 2014-07-01 | Monosol Rx, Llc | Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions |
US20190328679A1 (en) | 2001-10-12 | 2019-10-31 | Aquestive Therapeutics, Inc. | Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions |
US10285910B2 (en) | 2001-10-12 | 2019-05-14 | Aquestive Therapeutics, Inc. | Sublingual and buccal film compositions |
US11207805B2 (en) | 2001-10-12 | 2021-12-28 | Aquestive Therapeutics, Inc. | Process for manufacturing a resulting pharmaceutical film |
US7357891B2 (en) | 2001-10-12 | 2008-04-15 | Monosol Rx, Llc | Process for making an ingestible film |
US20110033542A1 (en) | 2009-08-07 | 2011-02-10 | Monosol Rx, Llc | Sublingual and buccal film compositions |
US8603514B2 (en) | 2002-04-11 | 2013-12-10 | Monosol Rx, Llc | Uniform films for rapid dissolve dosage form incorporating taste-masking compositions |
US7815936B2 (en) * | 2001-10-30 | 2010-10-19 | Evonik Degussa Gmbh | Use of granular materials based on pyrogenically produced silicon dioxide in pharmaceutical compositions |
EP1446104B2 (en) * | 2001-11-01 | 2011-08-03 | Novartis AG | Spray drying methods |
EP1542719A4 (en) | 2001-12-05 | 2006-06-21 | Baylor College Medicine | Methods and compositions for control of bone formation via modulation of sympathetic tone |
JP2005514393A (en) | 2001-12-19 | 2005-05-19 | ネクター セラピューティクス | Supplying aminoglycosides to the lung |
DE10163142A1 (en) * | 2001-12-20 | 2003-07-10 | Henkel Kgaa | Polymeric fragrance capsules and their manufacture |
US20040009953A1 (en) * | 2002-01-10 | 2004-01-15 | Comper Wayne D. | Antimicrobial charged polymers that exhibit resistance to lysosomal degradation during kidney filtration and renal passage, compositions and method of use thereof |
US20030181416A1 (en) * | 2002-01-10 | 2003-09-25 | Comper Wayne D. | Antimicrobial charged polymers that exhibit resistance to lysosomal degradation during kidney filtration and renal passage, compositions and method of use thereof |
WO2003059319A1 (en) * | 2002-01-14 | 2003-07-24 | Dow Global Technologies Inc. | Drug nanoparticles from template emulsions |
ES2345044T3 (en) | 2002-02-01 | 2010-09-14 | Euro-Celtique S.A. | 2-PIPERAZIN-PIRIDINES USEFUL TO TREAT THE PAIN. |
CA2475092C (en) | 2002-02-04 | 2012-05-01 | Christian F. Wertz | Nanoparticulate compositions having lysozyme as a surface stabilizer |
US7927613B2 (en) | 2002-02-15 | 2011-04-19 | University Of South Florida | Pharmaceutical co-crystal compositions |
US7790905B2 (en) | 2002-02-15 | 2010-09-07 | Mcneil-Ppc, Inc. | Pharmaceutical propylene glycol solvate compositions |
US7446107B2 (en) * | 2002-02-15 | 2008-11-04 | Transform Pharmaceuticals, Inc. | Crystalline forms of conazoles and methods of making and using the same |
US7078526B2 (en) * | 2002-05-31 | 2006-07-18 | Transform Pharmaceuticals, Inc. | CIS-itraconazole crystalline forms and related processes, pharmaceutical compositions and methods |
AU2003213719A1 (en) | 2002-03-01 | 2003-09-16 | Regents Of The University Of Michigan | Multiple-component solid phases containing at least one active pharmaceutical ingredient |
US20030190343A1 (en) * | 2002-03-05 | 2003-10-09 | Pfizer Inc. | Palatable pharmaceutical compositions for companion animals |
US6962940B2 (en) | 2002-03-20 | 2005-11-08 | Celgene Corporation | (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione: methods of using and compositions thereof |
US7893101B2 (en) | 2002-03-20 | 2011-02-22 | Celgene Corporation | Solid forms comprising (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, compositions thereof, and uses thereof |
US7022342B2 (en) | 2002-03-28 | 2006-04-04 | Andrx Corporation, Inc. | Controlled release oral dosage form of beta-adrenergic blocking agents |
AU2003230805A1 (en) * | 2002-04-05 | 2003-10-27 | Penwest Pharmaceuticals Co. | Sustained release metoprolol formulations |
WO2003084517A2 (en) * | 2002-04-09 | 2003-10-16 | Flamel Technologies | Oral suspension of amoxicillin capsules |
US6958161B2 (en) | 2002-04-12 | 2005-10-25 | F H Faulding & Co Limited | Modified release coated drug preparation |
GB0216562D0 (en) | 2002-04-25 | 2002-08-28 | Bradford Particle Design Ltd | Particulate materials |
EP1499300B1 (en) * | 2002-04-29 | 2009-03-18 | Supernus Pharmaceuticals, Inc. | Pharmaceutical formulations with improved bioavailability |
US7205413B2 (en) * | 2002-05-03 | 2007-04-17 | Transform Pharmaceuticals, Inc. | Solvates and polymorphs of ritonavir and methods of making and using the same |
US9339459B2 (en) | 2003-04-24 | 2016-05-17 | Nektar Therapeutics | Particulate materials |
US8871241B2 (en) * | 2002-05-07 | 2014-10-28 | Psivida Us, Inc. | Injectable sustained release delivery devices |
US20100129363A1 (en) * | 2002-05-17 | 2010-05-27 | Zeldis Jerome B | Methods and compositions using pde4 inhibitors for the treatment and management of cancers |
US7393862B2 (en) | 2002-05-17 | 2008-07-01 | Celgene Corporation | Method using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for treatment of certain leukemias |
USRE48890E1 (en) | 2002-05-17 | 2022-01-11 | Celgene Corporation | Methods for treating multiple myeloma with 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione after stem cell transplantation |
EP1556033A4 (en) * | 2002-05-17 | 2006-05-31 | Celgene Corp | Methods and compositions using selective cytokine inhibitory drugs for treatment and management of cancers and other diseases |
EP2915533B1 (en) | 2002-05-17 | 2017-09-13 | Celgene Corporation | Pharmaceutical compositions for treating cancer |
US7968569B2 (en) | 2002-05-17 | 2011-06-28 | Celgene Corporation | Methods for treatment of multiple myeloma using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione |
US7323479B2 (en) * | 2002-05-17 | 2008-01-29 | Celgene Corporation | Methods for treatment and management of brain cancer using 1-oxo-2-(2,6-dioxopiperidin-3-yl)-4-methylisoindoline |
US6995168B2 (en) * | 2002-05-31 | 2006-02-07 | Euro-Celtique S.A. | Triazaspiro compounds useful for treating or preventing pain |
PT1511710E (en) | 2002-05-31 | 2014-02-26 | Proteotech Inc | Compounds, compositions and methods for the treatment of amyloid diseases and synucleinopathies such as alzheimer s disease, type 2 diabetes, and parkinson s disease |
US8829198B2 (en) * | 2007-10-31 | 2014-09-09 | Proteotech Inc | Compounds, compositions and methods for the treatment of beta-amyloid diseases and synucleinopathies |
US20070059356A1 (en) * | 2002-05-31 | 2007-03-15 | Almarsson Oern | Pharmaceutical co-crystal compositions of drugs such as carbamazepine, celecoxib, olanzapine, itraconazole, topiramate, modafinil, 5-fluorouracil, hydrochlorothiazide, acetaminophen, aspirin, flurbiprofen, phenytoin and ibuprofen |
AU2003243699B2 (en) * | 2002-06-21 | 2009-01-15 | Transform Pharmaceuticals, Inc. | Pharmaceutical compositions with improved dissolution |
US20040005359A1 (en) * | 2002-06-27 | 2004-01-08 | Cheng Xiu Xiu | Controlled release oral dosage form |
EA010882B1 (en) * | 2002-07-02 | 2008-12-30 | Гумлинк А/С | Compressed chewing gum tablet ii |
ES2280557T3 (en) * | 2002-07-02 | 2007-09-16 | Gumlink A/S | Compressed chewing gum. |
US20050175733A1 (en) * | 2002-07-02 | 2005-08-11 | Bitten Thorengaard | Compressed resin moderated chewing gum |
US6673792B1 (en) | 2002-07-11 | 2004-01-06 | Upchuck, Llc | Broad-spectrum anti-emetic compositions and associated methods |
GB0216413D0 (en) * | 2002-07-15 | 2002-08-21 | Nestle Sa | Tabletted chewing gum sweet |
GB0217056D0 (en) * | 2002-07-23 | 2002-08-28 | Ass Octel | Use |
CA2493458A1 (en) | 2002-07-24 | 2004-01-29 | Ptc Therapeutics, Inc. | Ureido substituted benzoic acid compounds, their use for nonsense suppression and the treatment of diseases caused by such mutations |
DE10234165B4 (en) * | 2002-07-26 | 2008-01-03 | Advanced Micro Devices, Inc., Sunnyvale | A method of filling a trench formed in a substrate with an insulating material |
EP1545468A4 (en) * | 2002-09-20 | 2007-06-20 | Alpharma Inc | Sustained-release opioid formulations and methods of use |
EP1549154A1 (en) * | 2002-09-24 | 2005-07-06 | Gumlink A/S | Degradable chewing gum polymer |
CN1668206A (en) * | 2002-09-24 | 2005-09-14 | 古木林科有限公司 | Chewing gum having improved release of chewing gum ingredients |
ATE407568T1 (en) * | 2002-09-24 | 2008-09-15 | Gumlink As | LOW MOISTURE CHEWING GUM |
JP2006500041A (en) * | 2002-09-24 | 2006-01-05 | ガムリンク エー/エス | Chewing gum containing at least two different biodegradable polymers |
CA2500022C (en) * | 2002-09-24 | 2011-02-22 | Gumlink A/S | Biodegradable chewing gum comprising at least one high molecular weight biodegradable polymer |
WO2004029059A1 (en) | 2002-09-25 | 2004-04-08 | Euro-Celtique S.A. | N-substituted hydromorphones and the use thereof |
AU2003276987B2 (en) * | 2002-09-27 | 2009-07-30 | Bioenvision, Inc. | Methods and compositions for the treatment of lupus using clofarabine |
GB0222522D0 (en) | 2002-09-27 | 2002-11-06 | Controlled Therapeutics Sct | Water-swellable polymers |
AU2003276988B2 (en) * | 2002-09-27 | 2009-11-05 | Bioenvision, Inc. | Methods and compositions for the treatment of autoimmune disorders using clofarabine |
US20080220074A1 (en) * | 2002-10-04 | 2008-09-11 | Elan Corporation Plc | Gamma radiation sterilized nanoparticulate docetaxel compositions and methods of making same |
WO2004033448A2 (en) * | 2002-10-11 | 2004-04-22 | Proteotech, Inc. | Isolation, purification and synthesis of procyanidin b2 and uses thereof |
US7189740B2 (en) * | 2002-10-15 | 2007-03-13 | Celgene Corporation | Methods of using 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for the treatment and management of myelodysplastic syndromes |
US8404717B2 (en) * | 2002-10-15 | 2013-03-26 | Celgene Corporation | Methods of treating myelodysplastic syndromes using lenalidomide |
EP1900369A1 (en) | 2002-10-15 | 2008-03-19 | Celgene Corporation | Methods of using and compositions comprising immunomodulatory compounds for the treatment and management of myelodysplastic syndromes |
US11116782B2 (en) | 2002-10-15 | 2021-09-14 | Celgene Corporation | Methods of treating myelodysplastic syndromes with a combination therapy using lenalidomide and azacitidine |
AU2003228509B2 (en) * | 2002-10-15 | 2008-06-26 | Celgene Corporation | Selective cytokine inhibitory drugs for treating myelodysplastic syndrome |
US8404716B2 (en) | 2002-10-15 | 2013-03-26 | Celgene Corporation | Methods of treating myelodysplastic syndromes with a combination therapy using lenalidomide and azacitidine |
IL152486A0 (en) | 2002-10-25 | 2003-05-29 | Meir Eini | Alcohol-free cosmetic and pharmaceutical foam carrier |
US20040087558A1 (en) * | 2002-10-24 | 2004-05-06 | Zeldis Jerome B. | Methods of using and compositions comprising selective cytokine inhibitory drugs for treatment, modification and management of pain |
US20050203142A1 (en) * | 2002-10-24 | 2005-09-15 | Zeldis Jerome B. | Methods of using and compositions comprising immunomodulatory compounds for treatment, modification and management of pain |
US9211259B2 (en) | 2002-11-29 | 2015-12-15 | Foamix Pharmaceuticals Ltd. | Antibiotic kit and composition and uses thereof |
US7820145B2 (en) | 2003-08-04 | 2010-10-26 | Foamix Ltd. | Oleaginous pharmaceutical and cosmetic foam |
US7700076B2 (en) | 2002-10-25 | 2010-04-20 | Foamix, Ltd. | Penetrating pharmaceutical foam |
MXPA05004278A (en) | 2002-10-25 | 2005-10-05 | Foamix Ltd | Cosmetic and pharmaceutical foam. |
US9265725B2 (en) | 2002-10-25 | 2016-02-23 | Foamix Pharmaceuticals Ltd. | Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof |
US20080138296A1 (en) | 2002-10-25 | 2008-06-12 | Foamix Ltd. | Foam prepared from nanoemulsions and uses |
US7645803B2 (en) | 2005-05-09 | 2010-01-12 | Foamix Ltd. | Saccharide foamable compositions |
US8486376B2 (en) | 2002-10-25 | 2013-07-16 | Foamix Ltd. | Moisturizing foam containing lanolin |
US8900554B2 (en) | 2002-10-25 | 2014-12-02 | Foamix Pharmaceuticals Ltd. | Foamable composition and uses thereof |
US9668972B2 (en) | 2002-10-25 | 2017-06-06 | Foamix Pharmaceuticals Ltd. | Nonsteroidal immunomodulating kit and composition and uses thereof |
US8119109B2 (en) | 2002-10-25 | 2012-02-21 | Foamix Ltd. | Foamable compositions, kits and methods for hyperhidrosis |
US8119150B2 (en) | 2002-10-25 | 2012-02-21 | Foamix Ltd. | Non-flammable insecticide composition and uses thereof |
US7704518B2 (en) | 2003-08-04 | 2010-04-27 | Foamix, Ltd. | Foamable vehicle and pharmaceutical compositions thereof |
US10117812B2 (en) | 2002-10-25 | 2018-11-06 | Foamix Pharmaceuticals Ltd. | Foamable composition combining a polar solvent and a hydrophobic carrier |
US7776907B2 (en) * | 2002-10-31 | 2010-08-17 | Celgene Corporation | Methods for the treatment and management of macular degeneration using cyclopropyl-N-{2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-3-oxoisoindoline-4-yl}carboxamide |
AU2003226361B2 (en) * | 2002-11-06 | 2009-01-22 | Celgene Corporation | Methods of using and compositions comprising selective cytokine inhibitory drugs for the treatment and management of myeloproliferative diseases |
BR0316057A (en) | 2002-11-06 | 2005-09-20 | Celgene Corp | Methods of treating, controlling or preventing specific cancer and a disease associated with unwanted angiogenesis and of reducing or preventing an adverse effect associated with the administration of a second active ingredient and with radiation therapy, hormone therapy, biological therapy or immunotherapy in a patient suffering from a specific cancer, pharmaceutical composition and kit |
US7563810B2 (en) | 2002-11-06 | 2009-07-21 | Celgene Corporation | Methods of using 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione for the treatment and management of myeloproliferative diseases |
US8092831B2 (en) * | 2002-11-08 | 2012-01-10 | Andrx Pharmaceuticals, Llc | Antihistamine and decongestant system |
MXPA05005161A (en) * | 2002-11-18 | 2005-07-22 | Celgene Corp | Methods of usig and compositions comprising (-)-3- (3, 4- dimethoxy -phenyl)-3 -(1-oxo-1, 3-dihydro- isoindol- 2-yl)- propionamide. |
CN1738613A (en) * | 2002-11-18 | 2006-02-22 | 细胞基因公司 | Methods of using and compositions comprising (+)-3-(3,4-dimethoxy-phenyl)-3-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide |
US7202259B2 (en) * | 2002-11-18 | 2007-04-10 | Euro-Celtique S.A. | Therapeutic agents useful for treating pain |
US7988993B2 (en) * | 2002-12-09 | 2011-08-02 | Andrx Pharmaceuticals, Inc. | Oral controlled release dosage form |
AU2003283688A1 (en) * | 2002-12-11 | 2004-06-30 | Pfizer Products Inc. | Controlled-release of an active substance into a high fat environment |
CL2003002653A1 (en) * | 2002-12-18 | 2005-04-22 | Wyeth Corp | PHARMACEUTICAL COMPOSITION THAT INCLUDES (A) AN NON-STEROID ANTI-INFLAMMATORY (NSAID), PREFERREDLY IBUPROFEN, (B) A DECONGESTIONANT, PREFERENTIALLY PSEUDOEFEDRINE AND (C) AN ANTIHISTAMINIC, PREFERENTLY CHLORINE; METHOD FOR YOUR PREPARATION |
US20040253311A1 (en) * | 2002-12-18 | 2004-12-16 | Roger Berlin | Multi-layer tablet comprising non-steroidal anti-inflammatory drugs, decongestants and non-sedating antihist amines |
US7731947B2 (en) | 2003-11-17 | 2010-06-08 | Intarcia Therapeutics, Inc. | Composition and dosage form comprising an interferon particle formulation and suspending vehicle |
US7582635B2 (en) | 2002-12-24 | 2009-09-01 | Purdue Pharma, L.P. | Therapeutic agents useful for treating pain |
EP2339328A3 (en) | 2002-12-30 | 2011-07-13 | Transform Pharmaceuticals, Inc. | Pharmaceutical co-crystal compositions of celecoxib |
MXPA05007154A (en) | 2002-12-30 | 2005-09-21 | Nektar Therapeutics | Prefilming atomizer. |
US8183290B2 (en) | 2002-12-30 | 2012-05-22 | Mcneil-Ppc, Inc. | Pharmaceutically acceptable propylene glycol solvate of naproxen |
US20040170686A1 (en) * | 2003-01-31 | 2004-09-02 | Fredrickson Jennifer K. | Suspension vehicle for coated drug particles |
AU2003214016A1 (en) * | 2003-02-04 | 2004-08-30 | Gumlink A/S | Compressed chewing gum tablet |
WO2004068965A1 (en) * | 2003-02-04 | 2004-08-19 | Gumlink A/S | Compressed chewing gum tablet |
US20040156893A1 (en) * | 2003-02-11 | 2004-08-12 | Irwin Klein | Method for treating hypothyroidism |
AU2003272270A1 (en) | 2003-02-28 | 2004-09-28 | The Regents Of The University Of Michigan | Pharmaceutical co-crystal compositions of drugs such as carbamazeptine, celecoxib, olanzapine, itraconazole, topiramate, modafinil, 5-fluorouracil, hydrochlorothiazide, acetaminophen, aspirin, flurbiprofen, phenytoin and ibuprofen |
WO2004080918A1 (en) * | 2003-03-13 | 2004-09-23 | Jan Prochazka | Manufacturing of photocatalytic, antibacterial, selfcleaning and optically non-interfering surfaces on tiles and glazed ceramic products |
US20040186180A1 (en) * | 2003-03-21 | 2004-09-23 | Gelotte Cathy K. | Non-steroidal anti-inflammatory drug dosing regimen |
EP1462801A3 (en) * | 2003-03-24 | 2005-01-05 | Tepnel Lifecodes | Methods for determining the negative control value for multi-analyte assays |
US20050152967A1 (en) * | 2003-03-28 | 2005-07-14 | Pfab, Lp | Dynamic variable release |
US20040191326A1 (en) * | 2003-03-31 | 2004-09-30 | Reo Joseph P. | Taste-masking vehicle for coated oxazolidinone particles |
ES2535045T3 (en) | 2003-04-10 | 2015-05-04 | Vanderbilt Royalty Sub L.P. | Uses and compositions for capsaicin administration |
HUE059464T2 (en) | 2003-04-11 | 2022-11-28 | Ptc Therapeutics Inc | 1,2,4-oxadiazole benzoic acid compounds and their use for nonsense suppression and the treatment of disease |
WO2004091278A2 (en) * | 2003-04-11 | 2004-10-28 | Transform Pharmaceuticals, Inc. | Gabapentin compositions |
US7575739B2 (en) | 2003-04-28 | 2009-08-18 | Foamix Ltd. | Foamable iodine composition |
EP1474995B1 (en) * | 2003-05-06 | 2012-11-14 | Gumlink A/S | A method for producing chewing gum granules, a gum composition extruder and granulating system, and a chewing gum product |
ES2312741T3 (en) * | 2003-05-06 | 2009-03-01 | Gumlink A/S | PROCEDURE FOR PRODUCING CHEMICAL RUBBER GRANULES AND COMPRESSED RUBBER GRANULES, AND AN EQUIPMENT FOR GRANULAR GUM RUBBER. |
US8158149B2 (en) * | 2004-05-12 | 2012-04-17 | Chelsea Therapeutics, Inc. | Threo-DOPS controlled release formulation |
WO2004100929A1 (en) | 2003-05-12 | 2004-11-25 | Synergia Pharma, Inc. | Threo-dops controlled release formulation |
WO2005000786A1 (en) * | 2003-05-23 | 2005-01-06 | Transform Pharmaceuticals, Inc. | Sertraline compositions |
US8916598B2 (en) | 2003-05-30 | 2014-12-23 | Proteotech Inc | Compounds, compositions, and methods for the treatment of β-amyloid diseases and synucleinopathies |
US20100331380A1 (en) * | 2009-06-29 | 2010-12-30 | Esposito Luke A | Compounds, Compositions, and Methods for the Treatment of Beta-Amyloid Diseases and Synucleinopathies |
US7438903B2 (en) * | 2003-06-06 | 2008-10-21 | Nbty, Inc. | Methods and compositions that enhance bioavailability of coenzyme-Q10 |
AR044688A1 (en) * | 2003-06-12 | 2005-09-21 | Euro Celtique Sa | USEFUL THERAPEUTIC AGENTS FOR THE TREATMENT OF PAIN |
DE10326899A1 (en) | 2003-06-14 | 2004-12-30 | Beiersdorf Ag | Cosmetic preparations with stabilized preservatives |
US7605194B2 (en) | 2003-06-24 | 2009-10-20 | Ppg Industries Ohio, Inc. | Aqueous dispersions of polymer-enclosed particles, related coating compositions and coated substrates |
US20080112909A1 (en) * | 2003-06-24 | 2008-05-15 | Ppg Industries Ohio, Inc. | Compositions for providing color to animate objects and related methods |
US8802139B2 (en) | 2003-06-26 | 2014-08-12 | Intellipharmaceutics Corp. | Proton pump-inhibitor-containing capsules which comprise subunits differently structured for a delayed release of the active ingredient |
ES2322707T3 (en) * | 2003-07-03 | 2009-06-25 | Euro-Celtique S.A. | USED ALKIN 2-PYRIDINE DERIVATIVES TO TREAT PAIN. |
WO2005004882A1 (en) * | 2003-07-09 | 2005-01-20 | Monash University | Antiviral charged polymers that exhibit resistance to lysosomal degradation during kidney filtration and renal passage, compositions and methods of use thereof |
US7314640B2 (en) * | 2003-07-11 | 2008-01-01 | Mongkol Sriwongjanya | Formulation and process for drug loaded cores |
US7632521B2 (en) * | 2003-07-15 | 2009-12-15 | Eurand, Inc. | Controlled release potassium chloride tablets |
KR20060058092A (en) | 2003-07-23 | 2006-05-29 | 신타 파마슈티칼스 코프. | Compounds for inflammation and immune-related uses |
PL1867644T3 (en) | 2003-07-24 | 2009-10-30 | Euro Celtique Sa | Heteroaryl-tetrahydropiperidyl compounds useful for treating or preventing pain |
CN101914088A (en) | 2003-07-24 | 2010-12-15 | 尤罗塞尔蒂克股份有限公司 | Piperidine compounds and pharmaceutical compositions containing them |
EP2080757A1 (en) * | 2003-07-24 | 2009-07-22 | Euro-Celtique S.A. | Heteroaryl-tetrahydropiperidyl compounds useful for treating or preventing pain |
WO2005011707A1 (en) * | 2003-07-25 | 2005-02-10 | Warner Chilcott Company, Inc. | A doxycycline metal complex in a solid dosage form |
CN1832935A (en) | 2003-08-01 | 2006-09-13 | 欧洲凯尔特公司 | Therapeutic agents useful for treating pain |
US8795693B2 (en) | 2003-08-04 | 2014-08-05 | Foamix Ltd. | Compositions with modulating agents |
US8486374B2 (en) | 2003-08-04 | 2013-07-16 | Foamix Ltd. | Hydrophilic, non-aqueous pharmaceutical carriers and compositions and uses |
US7282217B1 (en) | 2003-08-29 | 2007-10-16 | Kv Pharmaceutical Company | Rapidly disintegrable tablets |
WO2005020954A2 (en) * | 2003-09-03 | 2005-03-10 | Agi Therapeutics Limited | Proton pump inhibitor formulations, and methods of preparing and using such formulations |
UA83504C2 (en) | 2003-09-04 | 2008-07-25 | Селджин Корпорейшн | Polymorphic forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione |
ATE412646T1 (en) * | 2003-09-22 | 2008-11-15 | Euro Celtique Sa | THERAPEUTIC AGENTS SUITABLE FOR THE TREATMENT OF PAIN |
DK1664041T3 (en) * | 2003-09-22 | 2008-10-27 | Euro Celtique Sa | Phenylcarboxamide compounds suitable for the treatment of pain |
US7612096B2 (en) * | 2003-10-23 | 2009-11-03 | Celgene Corporation | Methods for treatment, modification and management of radiculopathy using 1-oxo-2-(2,6-dioxopiperidin-3yl)-4-aminoisoindoline |
US20050089558A1 (en) * | 2003-10-28 | 2005-04-28 | Alamo Pharmaceuticals, Llc | Compositions and methods for the co-formulation and administration of tramadol and propoxyphene |
US20050095299A1 (en) * | 2003-10-30 | 2005-05-05 | Wynn David W. | Controlled release analgesic suspensions |
US20050113410A1 (en) * | 2003-11-03 | 2005-05-26 | Mark Tawa | Pharmaceutical salts of zafirlukast |
JP5610663B2 (en) | 2003-11-04 | 2014-10-22 | スパーナス ファーマシューティカルズ インコーポレイテッド | Trospium once a day dosage form |
WO2005046663A1 (en) | 2003-11-04 | 2005-05-26 | Shire Laboratories, Inc. | Compositions of quaternary ammonium containing bioavailability enhancers |
CN1901911A (en) * | 2003-11-06 | 2007-01-24 | 细胞基因公司 | Methods and compositions using thalidomide for the treatment and management of cancers and other diseases |
US7470435B2 (en) * | 2003-11-17 | 2008-12-30 | Andrx Pharmaceuticals, Llc | Extended release venlafaxine formulation |
NZ547689A (en) | 2003-11-19 | 2009-05-31 | Signal Pharm Llc | Indazole compounds and methods of use thereof as protein kinase inhibitors |
CA2546601A1 (en) | 2003-11-19 | 2005-06-09 | Metabasis Therapeutics, Inc. | Novel phosphorus-containing thyromimetics |
US8389032B2 (en) * | 2005-05-23 | 2013-03-05 | Kraft Foods Global Brands Llc | Delivery system for active components as part of an edible composition having selected particle size |
US8591968B2 (en) | 2005-05-23 | 2013-11-26 | Kraft Foods Global Brands Llc | Edible composition including a delivery system for active components |
US8597703B2 (en) | 2005-05-23 | 2013-12-03 | Kraft Foods Global Brands Llc | Delivery system for active components as part of an edible composition including a ratio of encapsulating material and active component |
US8591973B2 (en) | 2005-05-23 | 2013-11-26 | Kraft Foods Global Brands Llc | Delivery system for active components and a material having preselected hydrophobicity as part of an edible composition |
US8591972B2 (en) | 2005-05-23 | 2013-11-26 | Kraft Foods Global Brands Llc | Delivery system for coated active components as part of an edible composition |
US20050112236A1 (en) | 2003-11-21 | 2005-05-26 | Navroz Boghani | Delivery system for active components as part of an edible composition having preselected tensile strength |
US8591974B2 (en) * | 2003-11-21 | 2013-11-26 | Kraft Foods Global Brands Llc | Delivery system for two or more active components as part of an edible composition |
US7201920B2 (en) | 2003-11-26 | 2007-04-10 | Acura Pharmaceuticals, Inc. | Methods and compositions for deterring abuse of opioid containing dosage forms |
US20050137262A1 (en) * | 2003-12-22 | 2005-06-23 | Hu Patrick C. | Highly concentrated pourable aqueous solutions of potassium ibuprofen, their preparation and their uses |
DE60334162D1 (en) * | 2003-12-30 | 2010-10-21 | Gumlink As | COMPRESSIBLE BIODEGRADABLE CHEWING GUM |
AU2004312398B8 (en) * | 2003-12-30 | 2008-10-09 | Euro-Celtique S.A. | Piperazines useful for treating pain |
JP2007525146A (en) * | 2003-12-30 | 2007-09-06 | ガムリンク エー/エス | Chewing gum containing a biodegradable polymer and promoting degradability |
CA2548915C (en) * | 2003-12-31 | 2012-10-16 | Cima Labs Inc. | Generally linear effervescent oral fentanyl dosage form and methods of administering |
US7862833B2 (en) | 2003-12-31 | 2011-01-04 | Cima Labs, Inc. | Effervescent oral opiate dosage forms and methods of administering opiates |
WO2005065317A2 (en) * | 2003-12-31 | 2005-07-21 | Cima Labs Inc. | Effervescent oral fentanyl dosage form |
EP2292213A1 (en) | 2004-02-06 | 2011-03-09 | Cephalon, Inc. | Compositions comprising a polymorphic form of armodafinil |
EP1722758A1 (en) * | 2004-02-11 | 2006-11-22 | Athpharma Limited | Chronotherapeutic compositions and methods of their use |
CA2555811A1 (en) | 2004-02-18 | 2005-08-25 | Gpc Biotech Ag | Methods for treating resistant or refractory tumors |
US20090246288A1 (en) * | 2004-02-25 | 2009-10-01 | Pharmaceutical Industry Technology And Development Center | Taste-masking oral dosage form and method of preparing the same |
TWI335227B (en) | 2004-02-25 | 2011-01-01 | Medical & Pharm Ind Tech & Dev | Pharmaceutical composition of taste masking and rapidly dissolving drug and method of preparing the same |
US20050202051A1 (en) * | 2004-03-15 | 2005-09-15 | Chinea Vanessa I. | Pharmaceutical vehicle |
US20050203482A1 (en) * | 2004-03-15 | 2005-09-15 | Chinea Vanessa I. | Pharmaceutical dispensing apparatus and method |
DE102004013637A1 (en) * | 2004-03-19 | 2005-10-13 | Capsulution Nanoscience Ag | Process for the preparation of CS particles and microcapsules using porous templates as well as CS particles and microcapsules |
JP2007530544A (en) | 2004-03-22 | 2007-11-01 | セルジーン・コーポレーション | Methods of using immunomodulatory compounds for treating and managing skin diseases or disorders and compositions containing the same |
US20060004037A1 (en) * | 2004-03-25 | 2006-01-05 | Transform Pharmaceuticals, Inc. | Novel tricyclic compounds and related methods of treatment |
FR2868426B1 (en) * | 2004-04-05 | 2006-06-02 | Rhodia Chimie Sa | COMPOSITION COMPRISING A POLYMER AND A VOLATILE COMPOUND, AND ITS USE FOR THE CONTROLLED RELEASE OF VOLATILE COMPOUND |
CA2563207A1 (en) * | 2004-04-14 | 2005-11-24 | Celgene Corporation | Use of selective cytokine inhibitory drugs in myelodysplastic syndromes |
EP1744749A4 (en) * | 2004-04-14 | 2009-04-22 | Celgene Corp | Methods of using and compositions comprising immunomodulatory compounds for the treatment and management of myelodysplastic syndromes |
CN1968700A (en) * | 2004-04-15 | 2007-05-23 | 阿尔克姆斯有限公司 | Polymer-based sustained release device |
WO2005102317A1 (en) * | 2004-04-23 | 2005-11-03 | Celgene Corporation | Methods of using and compositions comprising pde4 modulators for the treatment and management of pulmonary hypertension |
US7351739B2 (en) * | 2004-04-30 | 2008-04-01 | Wellgen, Inc. | Bioactive compounds and methods of uses thereof |
US7803366B2 (en) * | 2004-05-07 | 2010-09-28 | Nbty, Inc. | Methods and compositions that enhance bioavailability of coenzyme-Q10 |
EP1600210A1 (en) * | 2004-05-25 | 2005-11-30 | Cognis IP Management GmbH | Charged microspheres |
WO2005117585A1 (en) | 2004-05-28 | 2005-12-15 | Transform Pharmaceuticals, Inc. | Mixed co-crystals and pharmaceutical compositions comprising the same |
US20060009425A1 (en) * | 2004-05-28 | 2006-01-12 | Leticia Delgado-Herrera | Oral formulations of paricalcitol |
WO2005120584A2 (en) * | 2004-06-03 | 2005-12-22 | The Trustees Of Columbia University In The City Of New York | Radiolabeled arylsulfonyl compounds and uses thereof |
JP5017103B2 (en) * | 2004-06-17 | 2012-09-05 | トランスフオーム・フアーマシユーチカルズ・インコーポレーテツド | Pharmaceutical co-crystal composition and related methods of use |
US8394409B2 (en) | 2004-07-01 | 2013-03-12 | Intellipharmaceutics Corp. | Controlled extended drug release technology |
DK1765304T4 (en) | 2004-07-06 | 2019-06-03 | Fertin Pharma As | Compressed chewing gum tablet |
EP1768651A4 (en) * | 2004-07-13 | 2008-09-10 | Altairnano Inc | Ceramic structures for prevention of drug diversion |
WO2006012536A2 (en) | 2004-07-22 | 2006-02-02 | Ritter Andrew J | Methods and compositions for treating lactose intolerance |
GB0417401D0 (en) | 2004-08-05 | 2004-09-08 | Controlled Therapeutics Sct | Stabilised prostaglandin composition |
DK200401195A (en) * | 2004-08-06 | 2004-08-06 | Gumlink As | Layered chewing gum tablet has layer comprising gum base in compressed gum granules having specified average diameter |
AU2005271407A1 (en) * | 2004-08-06 | 2006-02-16 | Transform Pharmaceuticals, Inc. | Novel fenofibrate formulations and related methods of treatment |
CA2576196A1 (en) * | 2004-08-06 | 2006-02-16 | Transform Pharmaceuticals, Inc. | Novel statin pharmaceutical compositions and related methods of treatment |
US20090042979A1 (en) * | 2004-08-06 | 2009-02-12 | Transform Pharmaceuticals Inc. | Novel Statin Pharmaceutical Compositions and Related Methods of Treatment |
US10624858B2 (en) | 2004-08-23 | 2020-04-21 | Intellipharmaceutics Corp | Controlled release composition using transition coating, and method of preparing same |
CZ2004945A3 (en) * | 2004-09-08 | 2006-01-11 | Pliva - Lachema A. S. | Pharmaceutical composition for rectal or vaginal administration, process for its preparation and this composition used as a medicament |
DK1803447T3 (en) * | 2004-09-09 | 2009-10-12 | Psicofarma S A De C V | Pharmaceutical composition for sustained release of hydralazine and its use as a support for cancer treatment |
NZ588431A (en) | 2004-09-17 | 2012-02-24 | Whitehead Biomedical Inst | Using Benzimidazole or Indole compounds with a 1,2-diazole group to Inhibit Alpha-Synuclein Toxicity |
CN101083985A (en) | 2004-09-21 | 2007-12-05 | 幸讬制药公司 | Compounds for inflammation and immune-related uses |
EP1811992A2 (en) * | 2004-10-28 | 2007-08-01 | Celgene Corporation | Methods and compositions using pde4 modulators for treatment and management of central nervous system injury |
US20060093630A1 (en) * | 2004-10-29 | 2006-05-04 | Buehler Gail K | Dye-free pharmaceutical suspensions and related methods |
US20060093631A1 (en) * | 2004-10-29 | 2006-05-04 | Buehler Gail K | Dye-free pharmaceutical suspensions and related methods |
WO2006053184A2 (en) * | 2004-11-10 | 2006-05-18 | The Trustees Of Columbia University In The City Of New York | Methods for treating or preventing a vascular disease |
CN101072759B (en) | 2004-11-18 | 2013-06-19 | Synta医药公司 | Triazole compounds that modulate HSP90 activity |
US20060121112A1 (en) * | 2004-12-08 | 2006-06-08 | Elan Corporation, Plc | Topiramate pharmaceutical composition |
ES2401285T3 (en) | 2004-12-16 | 2013-04-18 | The Regents Of The University Of California | Drugs with lung as target |
CN102504001B (en) | 2004-12-17 | 2015-02-25 | 安那迪斯药品股份有限公司 | 3, 5-disubstituted and 3,5,7-trisubstituted-3h-oxazolo and 3h-thiazolo [4,5-d]pyrimidin-2-one compounds and prodrugs thereof |
ATE422823T1 (en) * | 2004-12-22 | 2009-03-15 | Gumlink As | DEGRADABLE POLYMER FOR CHEWING GUM |
WO2006066572A2 (en) * | 2004-12-22 | 2006-06-29 | Gumlink A/S | Biodegradable chewing gum comprising biodegradable polymer with high glass transition temperature |
ATE432921T1 (en) | 2004-12-23 | 2009-06-15 | Gpc Biotech Ag | SQUARE ACID DERIVATIVES WITH ANTIPROLIFERATIVE EFFECT |
US20060160783A1 (en) * | 2004-12-30 | 2006-07-20 | Transform Pharmaceuticals, Inc. | Novel omeprazole forms and related methods |
TWI441819B (en) * | 2005-01-07 | 2014-06-21 | Synta Pharmaceuticals Corp | Compounds for inflammation and immune-related uses |
CN101128206A (en) * | 2005-01-21 | 2008-02-20 | 沃纳奇尔科特公司 | Tetracycline metal complex in a solid dosage form |
TWI422376B (en) | 2005-01-25 | 2014-01-11 | Synta Pharmaceuticals Corp | Compounds for inflammation and immune-related uses |
US11246913B2 (en) | 2005-02-03 | 2022-02-15 | Intarcia Therapeutics, Inc. | Suspension formulation comprising an insulinotropic peptide |
WO2006083761A2 (en) | 2005-02-03 | 2006-08-10 | Alza Corporation | Solvent/polymer solutions as suspension vehicles |
CN101189000A (en) * | 2005-02-14 | 2008-05-28 | 纽罗吉斯克斯公司 | Device for delivery of TRPV1 agonists |
US20070298098A1 (en) * | 2005-02-16 | 2007-12-27 | Elan Pharma International Limited | Controlled Release Compositions Comprising Levetiracetam |
CA2599951A1 (en) * | 2005-03-04 | 2006-09-14 | Altairnano, Inc. | Ceramic structures for controlled release of biologically active substances |
EP1700824A1 (en) * | 2005-03-09 | 2006-09-13 | Degussa AG | Granules based on pyrogenically prepared silicon dioxide, method for their preparation and use thereof |
WO2006105481A1 (en) * | 2005-03-30 | 2006-10-05 | Neurogesx, Inc. | Low-concentration capsaicin patch and methods for treating neuropathic pain |
US20090156545A1 (en) * | 2005-04-01 | 2009-06-18 | Hostetler Karl Y | Substituted Phosphate Esters of Nucleoside Phosphonates |
US8222257B2 (en) | 2005-04-01 | 2012-07-17 | The Regents Of The University Of California | Phosphono-pent-2-en-1-yl nucleosides and analogs |
WO2006110807A1 (en) * | 2005-04-12 | 2006-10-19 | Elan Pharma International Limited | Controlled release compositions comprising a cephalosporin for the treatment of a bacterial infection |
JP2008539731A (en) | 2005-05-02 | 2008-11-20 | コールド スプリング ハーバー ラボラトリー | Compositions and methods for diagnosis and treatment of cancer |
US20070041944A1 (en) * | 2005-05-05 | 2007-02-22 | The Trustees Of Columbia University In The City Of New York | Treating tumors by ENH dislocation of ID proteins |
US20060270707A1 (en) * | 2005-05-24 | 2006-11-30 | Zeldis Jerome B | Methods and compositions using 4-[(cyclopropanecarbonylamino)methyl]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione for the treatment or prevention of cutaneous lupus |
US20100136106A1 (en) * | 2005-06-08 | 2010-06-03 | Gary Liversidge | Modified Release Famciclovir Compositions |
US20070054868A1 (en) * | 2005-06-20 | 2007-03-08 | The Trustees Of Columbia University In The City Of New York | Synergistic polyphenol compounds, compositions thereof, and uses thereof |
WO2007002109A2 (en) * | 2005-06-20 | 2007-01-04 | The Regents Of The University Of California | Multidentate pyrone-derived chelators for medicinal imaging and chelation |
JP5095615B2 (en) * | 2005-06-27 | 2012-12-12 | バリアント・インターナショナル・(バルバドス)・ソサイアティーズ・ウィズ・リストリクティッド・ライアビリティ | Modified release of bupropion salt |
MX2008000249A (en) * | 2005-07-06 | 2008-03-18 | Sepracor Inc | Combinations of eszopiclone and o-desmethylvenlafaxine, and methods of treatment of menopause and mood, anxiety, and cognitive disorders. |
US20090214643A1 (en) * | 2005-07-19 | 2009-08-27 | Franklin Amie E | Improved pharmacokinetic profile of beta-adrenergic inverse agonists for the treatment of pulmonary airway diseases |
US8394812B2 (en) | 2005-08-24 | 2013-03-12 | Penwest Pharmaceuticals Co. | Sustained release formulations of nalbuphine |
WO2007025005A2 (en) | 2005-08-24 | 2007-03-01 | Penwest Pharmaceuticals Co. | Sustained release formulations of nalbuphine |
US20080058282A1 (en) | 2005-08-30 | 2008-03-06 | Fallon Joan M | Use of lactulose in the treatment of autism |
CA2899923A1 (en) | 2005-08-31 | 2007-03-08 | Celgene Corporation | Isoindole-imide compounds and compositions comprising and methods of using the same |
US20070053983A1 (en) * | 2005-09-06 | 2007-03-08 | Girish Jain | Extended release compositions of metoprolol succinate |
HK1081802A2 (en) * | 2005-09-09 | 2006-05-19 | Jacky Lam Chi Sum | Intelligent crossroad |
US20070066512A1 (en) | 2005-09-12 | 2007-03-22 | Dominique Verhelle | Methods and compositions using immunomodulatory compounds for the treatment of disorders associated with low plasma leptin levels |
US20080138295A1 (en) * | 2005-09-12 | 2008-06-12 | Celgene Coporation | Bechet's disease using cyclopropyl-N-carboxamide |
WO2008051197A2 (en) * | 2005-09-20 | 2008-05-02 | Mayo Foundation For Medical Education And Research | Small-molecule botulinum toxin inhibitors |
WO2007050631A2 (en) * | 2005-10-25 | 2007-05-03 | Cima Labs Inc. | Dosage form with coated active |
WO2007056155A1 (en) | 2005-11-03 | 2007-05-18 | Chembridge Research Laboratories, Inc. | Heterocyclic compounds as tyrosine kinase modulators |
EP2289497A1 (en) | 2005-11-10 | 2011-03-02 | Circ Pharma Research and Development Limited | Once-daily administration of central nervous system drugs |
NZ568430A (en) * | 2005-11-21 | 2011-02-25 | Purdue Pharma Lp | 4-oxadiazolyl-piperidine compounds and use thereof |
RU2008124805A (en) * | 2005-11-21 | 2009-12-27 | Шеринг-Плоу Лтд. (CH) | PHARMACEUTICAL COMPOSITIONS CONTAINING BUPRENORPHIN |
JP2009516589A (en) * | 2005-11-22 | 2009-04-23 | アルテアナノ インコーポレイテッド | Method for producing high surface area nanoporous catalyst and catalyst support structure |
US10064828B1 (en) | 2005-12-23 | 2018-09-04 | Intellipharmaceutics Corp. | Pulsed extended-pulsed and extended-pulsed pulsed drug delivery systems |
WO2007076160A2 (en) * | 2005-12-28 | 2007-07-05 | Acidophil Llc | C-10 carbamates of taxanes |
US20070155791A1 (en) * | 2005-12-29 | 2007-07-05 | Zeldis Jerome B | Methods for treating cutaneous lupus using aminoisoindoline compounds |
EP1981525B1 (en) * | 2005-12-30 | 2015-01-21 | Zensun (Shanghai) Science and Technology Limited | Extended release of neuregulin for improved cardiac function |
EP1998612A4 (en) | 2006-01-25 | 2010-11-24 | Synta Pharmaceuticals Corp | Substituted biaryl compounds for inflammation and immune-related uses |
US8455658B2 (en) * | 2006-01-25 | 2013-06-04 | Synta Pharmaceuticals Corp. | Thiazole and thiadiazole compounds for inflammation and immune-related uses |
US7816535B2 (en) | 2006-01-25 | 2010-10-19 | Synta Pharmaceuticals Corp. | Vinyl-phenyl derivatives for inflammation and immune-related uses |
AU2007211276B2 (en) * | 2006-01-31 | 2013-06-06 | Synta Pharmaceuticals Corp. | Pyridylphenyl compounds for inflammation and immune-related uses |
US9108217B2 (en) | 2006-01-31 | 2015-08-18 | Nanocopoeia, Inc. | Nanoparticle coating of surfaces |
EP2529761B1 (en) | 2006-01-31 | 2017-06-14 | Nanocopoeia, Inc. | Nanoparticle coating of surfaces |
CA2637883C (en) | 2006-01-31 | 2015-07-07 | Regents Of The University Of Minnesota | Electrospray coating of objects |
US7518017B2 (en) | 2006-02-17 | 2009-04-14 | Idexx Laboratories | Fenicol compounds and methods synthesizing 2-trifluoroacetamido-3-substituted propiophenone compounds |
EP1996162A2 (en) * | 2006-03-13 | 2008-12-03 | Encysive Pharmaceuticals, Inc | Methods and compositions for treatment of diastolic heart failure |
PL2383271T3 (en) * | 2006-03-13 | 2013-12-31 | Kyorin Seiyaku Kk | Aminoquinolones as GSK-3 Inhibitors |
MX2008011844A (en) * | 2006-03-13 | 2008-10-02 | Encysive Pharmaceuticals Inc | Formulations of sitaxsentan sodium. |
CN101400343B (en) | 2006-03-16 | 2012-01-11 | 特瑞斯制药股份有限公司 | Modified release formulations containing drug-ion exchange resin complexes |
BRPI0709699A2 (en) * | 2006-03-29 | 2011-07-26 | Foldrx Pharmaceuticals Inc | inhibition of alpha synuclein toxicity |
US9561188B2 (en) | 2006-04-03 | 2017-02-07 | Intellipharmaceutics Corporation | Controlled release delivery device comprising an organosol coat |
US10960077B2 (en) | 2006-05-12 | 2021-03-30 | Intellipharmaceutics Corp. | Abuse and alcohol resistant drug composition |
DE602007009377D1 (en) | 2006-05-30 | 2010-11-04 | Intarcia Therapeutics Inc | SECONDARY FLOW MODULATOR WITH AN INTERNAL CHANNEL FOR AN OSMOTIC OUTPUT SYSTEM |
US20100297226A1 (en) * | 2006-06-01 | 2010-11-25 | Dexcel Pharma Technologies Ltd. | Multiple unit pharmaceutical formulation |
US20070281017A1 (en) * | 2006-06-06 | 2007-12-06 | Endo Pharmaceuticals Inc., A Delaware Corporation | Sustained release oxycodone composition with acrylic polymer and metal hydroxide |
TW200808695A (en) * | 2006-06-08 | 2008-02-16 | Amgen Inc | Benzamide derivatives and uses related thereto |
AU2007259143A1 (en) * | 2006-06-08 | 2007-12-21 | Amgen Inc. | Benzamide derivatives and uses related thereto |
AU2006344611A1 (en) * | 2006-06-16 | 2007-12-21 | Gumlink A/S | Chewing gum comprising a hydrophobic enzyme formulation |
TWI418561B (en) | 2006-06-22 | 2013-12-11 | Anadys Pharmaceuticals Inc | Prodrugs of 5-amino-3-(3'-deoxy-β-d-ribofuranosyl)-thiazolo[4,5-d]pyrimidin-2,7-dione |
US20080026061A1 (en) * | 2006-06-22 | 2008-01-31 | Reichwein John F | Crystalline N-(4-chloro-3-methyl-5-isoxazolyl)-2-[2-methyl-4.5-(methylenedioxy)phenylacetyl]-thiophene-3-sulfonamide |
MX2008016519A (en) | 2006-06-22 | 2009-01-30 | Anadys Pharmaceuticals Inc | Pyrro[1,2-b]pyridazinone compounds. |
GB0613333D0 (en) * | 2006-07-05 | 2006-08-16 | Controlled Therapeutics Sct | Hydrophilic polyurethane compositions |
GB0613638D0 (en) | 2006-07-08 | 2006-08-16 | Controlled Therapeutics Sct | Polyurethane elastomers |
WO2008008373A2 (en) | 2006-07-11 | 2008-01-17 | Arubor Corp | Rhinosinusitis prevention and therapy with proinflammatory cytokine inhibitors |
US7528115B2 (en) | 2006-07-18 | 2009-05-05 | Anadys Pharmaceuticals, Inc. | Carbonate and carbamate prodrugs of thiazolo[4,5-d]pyrimidines |
CL2007002218A1 (en) | 2006-08-03 | 2008-03-14 | Celgene Corp Soc Organizada Ba | USE OF 3- (4-AMINO-1-OXO-1,3-DIHIDRO-ISOINDOL-2-IL) -PIPERIDINE 2,6-DIONA FOR THE PREPARATION OF A USEFUL MEDICINAL PRODUCT FOR THE TREATMENT OF LAYER CELL LYMPHOMA. |
US20080045603A1 (en) * | 2006-08-04 | 2008-02-21 | John Devane | Methods for treating at least one condition having MT1 receptor, 5HT2B receptor, and L-type calcium channel activity |
KR101200728B1 (en) | 2006-08-09 | 2012-11-13 | 인타르시아 세라퓨틱스 인코포레이티드 | Osmotic delivery system and piston assemblies |
US8063225B2 (en) | 2006-08-14 | 2011-11-22 | Chembridge Corporation | Tricyclic compound derivatives useful in the treatment of neoplastic diseases, inflammatory disorders and immunomodulatory disorders |
EP2051696A2 (en) * | 2006-08-18 | 2009-04-29 | Morton Grove Pharmaceuticals, Inc. | Stable liquid levetiracetam compositions and methods |
US9114133B2 (en) | 2006-08-25 | 2015-08-25 | U.S. Dept. Of Veterans Affairs | Method of improving diastolic dysfunction |
US8877780B2 (en) | 2006-08-30 | 2014-11-04 | Celgene Corporation | 5-substituted isoindoline compounds |
US20080057122A1 (en) * | 2006-08-31 | 2008-03-06 | Aaipharma Inc. | Acetaminophen pharmaceutical compositions |
US8128460B2 (en) * | 2006-09-14 | 2012-03-06 | The Material Works, Ltd. | Method of producing rust inhibitive sheet metal through scale removal with a slurry blasting descaling cell |
US8601530B2 (en) * | 2006-09-19 | 2013-12-03 | The Invention Science Fund I, Llc | Evaluation systems and methods for coordinating software agents |
AU2007297597B2 (en) | 2006-09-21 | 2013-02-21 | Kyorin Pharmaceuticals Co., Ltd. | Serine hydrolase inhibitors |
US8779154B2 (en) | 2006-09-26 | 2014-07-15 | Qinglin Che | Fused ring compounds for inflammation and immune-related uses |
DK2428513T3 (en) | 2006-09-26 | 2017-08-21 | Celgene Corp | 5-substituted quinazolinone derivatives as anti-cancer agents |
PL2124556T3 (en) | 2006-10-09 | 2015-02-27 | Charleston Laboratories Inc | Pharmaceutical compositions |
EP1914234A1 (en) * | 2006-10-16 | 2008-04-23 | GPC Biotech Inc. | Pyrido[2,3-d]pyrimidines and their use as kinase inhibitors |
GB0620685D0 (en) | 2006-10-18 | 2006-11-29 | Controlled Therapeutics Sct | Bioresorbable polymers |
US20110046164A1 (en) | 2006-10-19 | 2011-02-24 | Genzyme Corporation | Purine Derivatives for Treatment of Cystic Diseases |
JP2010507585A (en) | 2006-10-19 | 2010-03-11 | オースペックス・ファーマシューティカルズ・インコーポレイテッド | Substituted indole |
US7731604B2 (en) * | 2006-10-31 | 2010-06-08 | Taylor Made Golf Company, Inc. | Golf club iron head |
WO2008057604A2 (en) * | 2006-11-08 | 2008-05-15 | The Regents Of The University Of California | Small molecule therapeutics, syntheses of analogues and derivatives and methods of use |
US20080207641A1 (en) | 2006-11-13 | 2008-08-28 | Synta Pharmaceuticals Corp. | Cyclohexenyl-aryl compounds for inflammation and immune-related uses |
US20080260655A1 (en) | 2006-11-14 | 2008-10-23 | Dov Tamarkin | Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses |
US9040816B2 (en) | 2006-12-08 | 2015-05-26 | Nanocopoeia, Inc. | Methods and apparatus for forming photovoltaic cells using electrospray |
WO2008079371A1 (en) * | 2006-12-22 | 2008-07-03 | Encysive Pharmaceuticals, Inc. | Modulators of c3a receptor and methods of use thereof |
AU2007343726A1 (en) * | 2006-12-26 | 2008-07-24 | Amgen Inc. | N-cyclohexyl benzamides and benzeneacetamides as inhibitors of 11-beta-hydroxysteroid dehydrogenases |
ES2353448T3 (en) | 2007-01-16 | 2011-03-02 | Purdue Pharma L.P. | HETEROCYCLIC-SUBSTITUTED PIPERIDINS AS LIGANDOS OF ORL-1. |
JP5322951B2 (en) | 2007-02-09 | 2013-10-23 | リガンド・ファーマシューティカルズ・インコーポレイテッド | Novel antagonist of glucagon receptor |
AR065431A1 (en) | 2007-02-21 | 2009-06-10 | Sepracor Inc | SOLID FORMS THAT INCLUDE (-) -O-DEMETILVENLAFAXIN AND USES OF THE SAME. |
PL2144604T3 (en) * | 2007-02-28 | 2012-02-29 | Conatus Pharmaceuticals Inc | Methods for the treatment of chronic viral hepatitis C using RO 113-0830 |
WO2008106167A1 (en) * | 2007-02-28 | 2008-09-04 | Conatus Pharmaceuticals, Inc. | Combination therapy comprising matrix metalloproteinase inhibitors and caspase inhibitors for the treatment of liver diseases |
EP3103790B1 (en) | 2007-03-15 | 2018-05-09 | Auspex Pharmaceuticals, Inc. | Substituted phenethylamine with serotoninergic and/or norepinephrinergic activity |
WO2008118712A1 (en) * | 2007-03-22 | 2008-10-02 | Alkermes, Inc. | Coacervation process |
CA2683415C (en) | 2007-04-04 | 2020-12-08 | Sigmoid Pharma Limited | An oral pharmaceutical composition |
AU2008244523B2 (en) | 2007-04-23 | 2012-02-16 | Intarcia Therapeutics, Inc. | Suspension formulations of insulinotropic peptides and uses thereof |
EP2586428B1 (en) | 2007-04-26 | 2023-11-08 | Sublimity Therapeutics Limited | Manufacture of multiple minicapsules |
AU2008246202B2 (en) | 2007-04-27 | 2011-12-01 | Purdue Pharma L.P. | Therapeutic agents useful for treating pain |
JP5462784B2 (en) | 2007-04-27 | 2014-04-02 | パーデュー、ファーマ、リミテッド、パートナーシップ | TRPV1 antagonists and uses thereof |
US7892776B2 (en) | 2007-05-04 | 2011-02-22 | The Regents Of The University Of California | Screening assay to identify modulators of protein kinase A |
EP2019101A1 (en) * | 2007-07-26 | 2009-01-28 | GPC Biotech AG | Pyrazol[3,4-d]pyrimidin-4-one useful as Kinase Inhibitor |
KR101581289B1 (en) | 2007-05-31 | 2015-12-31 | 세프라코 아이엔시. | Phenyl substituted cycloalkylamines as monoamine reuptake inhibitors |
AU2008287542C1 (en) | 2007-06-01 | 2015-01-22 | The Trustees Of Princeton University | Treatment of viral infections by modulation of host cell metabolic pathways |
US8415294B2 (en) * | 2007-06-05 | 2013-04-09 | Arizona Board Of Regents | Cyclodepsipeptides with antineoplastic activity and methods of using to inhibit cancer and microbial growth |
IL183818A0 (en) * | 2007-06-10 | 2007-10-31 | Shimon Harpaz | Uniformly abrasive confectionery product and process therefor |
US20080317865A1 (en) * | 2007-06-20 | 2008-12-25 | Alkermes, Inc. | Quench liquids and washing systems for production of microparticles |
AU2008275752A1 (en) * | 2007-07-06 | 2009-01-15 | Nuon Therapeutics, Inc. | Treatment of neuropathic pain |
CN101801188A (en) * | 2007-07-12 | 2010-08-11 | 特拉加拉医药品公司 | Methods and compositions for the treatment of cancer, tumors, and tumor-related disorders |
WO2009012263A2 (en) * | 2007-07-18 | 2009-01-22 | The Trustees Of Columbia University In The City Of New York | Tissue-specific micrornas and compositions and uses thereof |
CA2695143A1 (en) | 2007-08-01 | 2009-02-05 | Synta Pharmaceuticals Corp. | Heterocycle-aryl compounds for inflammation and immune-related uses |
US8349841B2 (en) | 2007-08-01 | 2013-01-08 | Synta Pharmaceuticals Corp. | Vinyl-aryl derivatives for inflammation and immune-related uses |
US20090036414A1 (en) * | 2007-08-02 | 2009-02-05 | Mutual Pharmaceutical Company, Inc. | Mesalamine Formulations |
WO2009020590A1 (en) * | 2007-08-07 | 2009-02-12 | Celgene Corporation | Methods for treating lymphomas in certain patient populations and screening patients for said therapy |
US8636982B2 (en) | 2007-08-07 | 2014-01-28 | Foamix Ltd. | Wax foamable vehicle and pharmaceutical compositions thereof |
JP5572549B2 (en) | 2007-08-13 | 2014-08-13 | リガンド・ファーマシューティカルズ・インコーポレイテッド | Novel activator of glucokinase |
US20090062242A1 (en) * | 2007-08-28 | 2009-03-05 | Agi Therapeutics Plc | Methods and compositions for treating gastrointestinal conditions |
TWI448289B (en) | 2007-08-31 | 2014-08-11 | Purdue Pharma Lp | Substituted-quinoxaline-type piperidine compounds and the uses thereof |
AU2008299903B2 (en) * | 2007-09-11 | 2013-08-29 | Kyorin Pharmaceutical Co., Ltd | Cyanoaminoquinolones and tetrazoloaminoquinolones as GSK-3 inhibitors |
CN101855229A (en) | 2007-09-12 | 2010-10-06 | 埃迪威克斯生物科学公司 | Spirocyclic aminoquinolones as GSK-3 inhibitors |
CN104211684A (en) | 2007-09-26 | 2014-12-17 | 细胞基因公司 | 6-, 7-, or 8-Substituted Quinazolinone Derivatives and Compositions Comprising and Methods of Using the Same |
US20090211576A1 (en) * | 2007-10-02 | 2009-08-27 | Timo Lehtonen | Safety and abuse deterrent improved device |
US20090264421A1 (en) * | 2007-10-05 | 2009-10-22 | Bible Keith C | Methods and Compositions for Treating Cancer |
WO2009052454A2 (en) | 2007-10-19 | 2009-04-23 | University Of California | Compositions and methods for ameliorating cns inflammation, psychosis, delirium, ptsd or ptss |
WO2009069006A2 (en) | 2007-11-30 | 2009-06-04 | Foamix Ltd. | Foam containing benzoyl peroxide |
WO2009072007A2 (en) | 2007-12-07 | 2009-06-11 | Foamix Ltd. | Carriers, formulations, methods for formulating unstable active agents for external application and uses thereof |
WO2010041141A2 (en) | 2008-10-07 | 2010-04-15 | Foamix Ltd. | Oil-based foamable carriers and formulations |
US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
NZ586094A (en) | 2008-01-08 | 2012-06-29 | Purdue Pharma Lp | Proline analogs as ligands for cannabinoid receptors for the treatment of pain |
EP2240022B1 (en) | 2008-01-09 | 2016-12-28 | Charleston Laboratories, Inc. | Bilayered tablets comprising oxycodone and promethazine |
EP2242476A2 (en) | 2008-01-14 | 2010-10-27 | Foamix Ltd. | Poloxamer foamable pharmaceutical compositions with active agents and/or therapeutic cells and uses |
EP2240155B1 (en) | 2008-02-13 | 2012-06-06 | Intarcia Therapeutics, Inc | Devices, formulations, and methods for delivery of multiple beneficial agents |
US8729070B2 (en) | 2008-02-20 | 2014-05-20 | Targia Pharmaceuticals | CNS pharmaceutical compositions and methods of use |
WO2009105256A2 (en) * | 2008-02-20 | 2009-08-27 | Celgene Corporation | Method of treating cancer by administering an immunomodulatory compound in combination with a cd40 antibody or cd40 ligand |
WO2009104080A2 (en) | 2008-02-20 | 2009-08-27 | Targia Pharmaceuticals | Cns pharmaceutical compositions and methods of use |
WO2009111611A2 (en) * | 2008-03-05 | 2009-09-11 | Proteotech Inc. | Compounds, compositions and methods for the treatment of islet amyloid polypeptide (iapp) accumulation in diabetes |
US8658163B2 (en) | 2008-03-13 | 2014-02-25 | Curemark Llc | Compositions and use thereof for treating symptoms of preeclampsia |
MX2010010172A (en) | 2008-03-17 | 2010-11-25 | Ambit Biosciences Corp | Quinazoline derivatives as raf kinase modulators and methods of use thereof. |
WO2009117097A1 (en) | 2008-03-19 | 2009-09-24 | Chembridge Corporation | Novel tyrosine kinase inhibitors |
US9249147B2 (en) | 2008-03-19 | 2016-02-02 | Chembridge Corporation | Tyrosine kinase inhibitors |
US20110118243A1 (en) * | 2008-03-20 | 2011-05-19 | Lynn Chambers | Anti-inflammatory drug delivery system |
EP2687213B1 (en) | 2008-03-27 | 2019-01-23 | Celgene Corporation | Solid forms comprising (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, compositions thereof, and uses thereof |
KR20140142323A (en) | 2008-03-27 | 2014-12-11 | 셀진 코포레이션 | Solid forms comprising (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, compositions thereof, and uses thereof |
US8138169B2 (en) | 2008-04-11 | 2012-03-20 | Comgenrx, Inc. | Combination therapy for bipolar disorder |
US8084025B2 (en) | 2008-04-18 | 2011-12-27 | Curemark Llc | Method for the treatment of the symptoms of drug and alcohol addiction |
EP2112150B1 (en) | 2008-04-22 | 2013-10-16 | Forma Therapeutics, Inc. | Improved raf inhibitors |
EP2112152A1 (en) | 2008-04-22 | 2009-10-28 | GPC Biotech AG | Dihydropteridinones as Plk Inhibitors |
WO2009139880A1 (en) * | 2008-05-13 | 2009-11-19 | Celgene Corporation | Thioxoisoindoline compounds and compositions and methods of using the same |
NZ589469A (en) * | 2008-05-20 | 2012-08-31 | Cerenis Therapeutics Holding S A | Niacin and NSAID combination for reducing niacin-induced flushing |
US20090311335A1 (en) * | 2008-06-12 | 2009-12-17 | Scott Jenkins | Combination of a triptan and an nsaid |
US11016104B2 (en) | 2008-07-01 | 2021-05-25 | Curemark, Llc | Methods and compositions for the treatment of symptoms of neurological and mental health disorders |
AU2009277172B2 (en) | 2008-07-02 | 2014-05-29 | Idenix Pharmaceuticals, Inc. | Compounds and pharmaceutical compositions for the treatment of viral infections |
UA99540C2 (en) | 2008-07-21 | 2012-08-27 | Пердью Фарма Л.П. | Substituted-quinoxaline-type bridged-piperidine compounds and the uses thereof |
ME01665B (en) | 2008-07-30 | 2014-09-20 | Purdue Pharma Lp | Buprenorphine analogs |
KR101599089B1 (en) | 2008-08-13 | 2016-03-02 | 메타베이시스 테라퓨틱스, 인크. | Glucagon antagonists |
EP2348863A4 (en) | 2008-09-04 | 2012-03-07 | Anacor Pharmaceuticals Inc | Boron-containing small molecules |
WO2010039237A1 (en) * | 2008-10-01 | 2010-04-08 | Synta Pharmaceuticals Corp. | Compounds for inflammation and immune-related uses |
WO2010042834A1 (en) | 2008-10-09 | 2010-04-15 | Anadys Pharmaceuticals, Inc. | A method of inhibiting hepatitis c virus by combination of a 5,6-dihydro-1h-pyridin-2-one and one or more additional antiviral compounds |
US8759362B2 (en) * | 2008-10-24 | 2014-06-24 | Purdue Pharma L.P. | Bicycloheteroaryl compounds and their use as TRPV1 ligands |
US8703962B2 (en) * | 2008-10-24 | 2014-04-22 | Purdue Pharma L.P. | Monocyclic compounds and their use as TRPV1 ligands |
US8546388B2 (en) * | 2008-10-24 | 2013-10-01 | Purdue Pharma L.P. | Heterocyclic TRPV1 receptor ligands |
MX2011004470A (en) | 2008-10-29 | 2011-05-31 | Celgene Corp | Isoindoline compounds for use in the treatment of cancer. |
CN102317261B (en) | 2008-12-16 | 2015-11-25 | 桑诺维恩药品公司 | Triple reuptake inhibitor and application method thereof |
AU2009330192A1 (en) | 2008-12-22 | 2011-07-14 | Sloan-Kettering Institute For Cancer Research | Methods for treating or preventing cancer and neurodegenerative diseases |
CA2747811A1 (en) | 2008-12-22 | 2010-07-01 | Sloan-Kettering Institute For Cancer Research | Coumarin-based compounds |
US8536114B2 (en) | 2008-12-31 | 2013-09-17 | Scynexis, Inc. | Macrocycles |
CA2747703C (en) | 2009-01-06 | 2021-06-15 | Curemark Llc | Compositions and methods for the treatment or the prevention of infections by e. coli |
AU2010203709B2 (en) | 2009-01-06 | 2014-05-22 | Galenagen, Llc | Compositions and methods for the treatment or prevention of Staphylococcus Aureus infections and for the Eradication or reduction of Staphylococcus Aureus on surfaces |
US9504274B2 (en) * | 2009-01-27 | 2016-11-29 | Frito-Lay North America, Inc. | Methods of flavor encapsulation and matrix-assisted concentration of aqueous foods and products produced therefrom |
US20100189845A1 (en) * | 2009-01-27 | 2010-07-29 | Frito-Lay North America Inc. | Flavor Encapsulation and Method Thereof |
WO2010088450A2 (en) | 2009-01-30 | 2010-08-05 | Celladon Corporation | Methods for treating diseases associated with the modulation of serca |
CN102340992B (en) | 2009-02-09 | 2014-11-05 | 桑诺维恩药品公司 | Pyrrolidine triple reuptake inhibitors |
CA2750123A1 (en) | 2009-02-10 | 2010-08-19 | Celgene Corporation | Methods of using and compositions comprising pde4 modulators for treatment, prevention and management of tuberculosis |
US8568793B2 (en) | 2009-02-11 | 2013-10-29 | Hope Medical Enterprises, Inc. | Sodium nitrite-containing pharmaceutical compositions |
SG173639A1 (en) | 2009-02-11 | 2011-09-29 | Sunovion Pharmaceuticals Inc | Histamine h3 inverse agonists and antagonists and methods of use thereof |
US20120053159A1 (en) | 2009-02-11 | 2012-03-01 | Muller George W | Isotopologues of lenalidomide |
KR20170053733A (en) * | 2009-02-24 | 2017-05-16 | 리터 파마슈티컬즈 인코오포레이티드 | Prebiotic formulations and methods of use |
MY159327A (en) * | 2009-02-27 | 2016-12-25 | Ambit Biosciences Corp | Jak kinase modulating quinazoline derivatives and methods of use thereof |
US8193372B2 (en) | 2009-03-04 | 2012-06-05 | Idenix Pharmaceuticals, Inc. | Phosphothiophene and phosphothiazole HCV polymerase inhibitors |
JP2012520314A (en) | 2009-03-11 | 2012-09-06 | アムビト ビオスシエンセス コルポラチオン | Combination of indazolylaminopyrrolotriazine and taxane for cancer treatment |
BRPI1008974A2 (en) * | 2009-03-11 | 2017-06-06 | Kyorin Seiyaku Kk | compound, pharmaceutical composition, and method for treating, preventing or ameliorating a gsk-3 mediated disease |
NZ595372A (en) | 2009-03-27 | 2013-11-29 | Vetdc Inc | Pyrimidinyl and 1,3,5-triazinyl benzimidazole sulfonamides and their use in cancer therapy |
WO2010110686A1 (en) | 2009-03-27 | 2010-09-30 | Pathway Therapeutics Limited | Pyrimidinyl and 1,3,5 triazinyl benzimidazoles and their use in cancer therapy |
US9056050B2 (en) | 2009-04-13 | 2015-06-16 | Curemark Llc | Enzyme delivery systems and methods of preparation and use |
US9901551B2 (en) | 2009-04-20 | 2018-02-27 | Ambra Bioscience Llc | Chemosensory receptor ligand-based therapies |
US8828953B2 (en) * | 2009-04-20 | 2014-09-09 | NaZura BioHealth, Inc. | Chemosensory receptor ligand-based therapies |
CA2758976C (en) | 2009-04-20 | 2015-02-03 | Alain Baron | Chemosensory receptor ligand-based therapies |
DK2421829T3 (en) | 2009-04-22 | 2016-01-04 | Axikin Pharmaceuticals Inc | 2,5-disubstituted aryl sulfonamide CCR3 antagonists |
PE20150925A1 (en) | 2009-04-22 | 2015-06-14 | Axikin Pharmaceuticals Inc | CCR3 ANTAGONISTS OF ARYLSULFONAMIDE 2,5-DISUSTITUID |
PE20150759A1 (en) | 2009-04-22 | 2015-05-15 | Axikin Pharmaceuticals Inc | CCR3 ARYLSULFONAMIDE ANTAGONISTS |
US20120087872A1 (en) | 2009-04-28 | 2012-04-12 | Foamix Ltd. | Foamable Vehicles and Pharmaceutical Compositions Comprising Aprotic Polar Solvents and Uses Thereof |
US20100292281A1 (en) * | 2009-05-15 | 2010-11-18 | The University Of Kentucky Research Foundation | Treatment of mci and alzheimer's disease |
US9968574B2 (en) * | 2009-05-15 | 2018-05-15 | The University Of Kentucky Research Foundation | Treatment of MCI and Alzheimer's disease |
US9278070B2 (en) | 2009-05-18 | 2016-03-08 | Sigmoid Pharma Limited | Composition comprising oil drops |
JP5645816B2 (en) | 2009-05-25 | 2014-12-24 | 国立大学法人東京工業大学 | Pharmaceutical composition comprising core factor related to proliferation and differentiation of central nerve cell |
CA2764808A1 (en) | 2009-06-10 | 2010-12-16 | Sunovion Pharmaceuticals Inc. | Histamine h3 inverse agonists and antagonists and methods of use thereof |
US9050276B2 (en) | 2009-06-16 | 2015-06-09 | The Trustees Of Columbia University In The City Of New York | Autism-associated biomarkers and uses thereof |
WO2011003870A2 (en) | 2009-07-06 | 2011-01-13 | Creabilis S.A. | Mini-pegylated corticosteroids, compositions including same, and methods of making and using same |
EP2451802A1 (en) | 2009-07-07 | 2012-05-16 | Pathway Therapeutics, Inc. | Pyrimidinyl and 1,3,5-triazinyl benzimidazoles and their use in cancer therapy |
JP5905387B2 (en) | 2009-07-08 | 2016-04-20 | ホープ メディカル エンタープライゼズ,インコーポレイテッド ディービーエー ホープ ファーマシュティカルズHope Medical Enterprises,Inc.Dba Hope Pharmaceuticals | Pharmaceutical composition containing sodium thiosulfate |
WO2011006012A1 (en) | 2009-07-08 | 2011-01-13 | Charleston Laboratories Inc. | Pharmaceutical compositions |
US20110021591A1 (en) * | 2009-07-21 | 2011-01-27 | Gordon Douglas J | Phenylbutazone carrier formulation showing increased bioactivity in animals |
EP2467144A1 (en) | 2009-07-24 | 2012-06-27 | ViroLogik GmbH | Combination of proteasome inhibitors and anti-hepatitis medication for treating hepatitis |
WO2011013008A2 (en) | 2009-07-29 | 2011-02-03 | Foamix Ltd. | Non surface active agent non polymeric agent hydro-alcoholic foamable compositions, breakable foams and their uses |
WO2011013009A2 (en) | 2009-07-29 | 2011-02-03 | Foamix Ltd. | Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses |
US8404728B2 (en) | 2009-07-30 | 2013-03-26 | Mayo Foundation For Medical Education And Research | Small-molecule botulinum toxin inhibitors |
WO2011014775A1 (en) | 2009-07-31 | 2011-02-03 | The Brigham And Women's Hospital, Inc. | Modulation of sgk1 expression in th17 cells to modulate th17-mediated immune responses |
WO2011017389A1 (en) | 2009-08-05 | 2011-02-10 | Idenix Pharmaceuticals, Inc. | Macrocyclic serine protease inhibitors useful against viral infections, particularly hcv |
GB2485327A (en) | 2009-08-12 | 2012-05-09 | Sigmoid Pharma Ltd | Immunomodulatory compositions comprising a polymer matrix and an oil phase |
MX2012001974A (en) | 2009-08-19 | 2012-04-11 | Ambit Biosciences Corp | Biaryl compounds and methods of use thereof. |
NZ599215A (en) | 2009-09-04 | 2014-11-28 | United Paragon Associates Inc | Compounds for treating disorders or diseases associated with neurokinin 2 receptor activity |
US20120172350A1 (en) | 2009-09-11 | 2012-07-05 | Sunovion Pharmaceuticals Inc. | Histamine h3 inverse agonists and antagonists and methods of use thereof |
SI2462246T1 (en) | 2009-09-28 | 2018-01-31 | Intarcia Therapeutics, Inc. | Rapid establishment and/or termination of substantial steady-state drug delivery |
AU2010300641B2 (en) | 2009-09-30 | 2016-03-17 | Acura Pharmaceuticals, Inc. | Methods and compositions for deterring abuse |
US9849142B2 (en) | 2009-10-02 | 2017-12-26 | Foamix Pharmaceuticals Ltd. | Methods for accelerated return of skin integrity and for the treatment of impetigo |
MX359879B (en) | 2009-10-02 | 2018-10-12 | Foamix Pharmaceuticals Ltd | Topical tetracycline compositions. |
US20110136751A1 (en) | 2009-10-06 | 2011-06-09 | Green Molecular | Use of Polyphenols in the Treatment of Cancer |
WO2011046609A2 (en) * | 2009-10-15 | 2011-04-21 | Appleton Papers Inc. | Encapsulation |
MX2012004577A (en) | 2009-10-19 | 2012-06-13 | Synta Pharmaceuticals Corp | Combination cancer therapy with hsp90 inhibitory compounds. |
US8470817B2 (en) * | 2009-10-26 | 2013-06-25 | Sunesis Pharmaceuticals, Inc. | Compounds and methods for treatment of cancer |
EP2325185A1 (en) | 2009-10-28 | 2011-05-25 | GPC Biotech AG | Plk inhibitor |
WO2011056764A1 (en) | 2009-11-05 | 2011-05-12 | Ambit Biosciences Corp. | Isotopically enriched or fluorinated imidazo[2,1-b][1,3]benzothiazoles |
WO2011063076A1 (en) | 2009-11-19 | 2011-05-26 | Itherx Pharmaceuticals, Inc. | Methods of treating hepatitis c virus with oxoacetamide compounds |
CN102781443A (en) | 2009-11-19 | 2012-11-14 | 细胞基因公司 | Apremilast For The Treatment Of Sarcoidosis |
US20110123672A1 (en) * | 2009-11-23 | 2011-05-26 | Xiaohu Xia | Gum bases, chewing gums based thereupon, and methods for making the same |
WO2011064769A1 (en) | 2009-11-24 | 2011-06-03 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Methods and pharmaceutical compositions for the treatment of hot flashes |
WO2011069002A1 (en) | 2009-12-02 | 2011-06-09 | Alquest Therapeutics, Inc. | Organoselenium compounds and uses thereof |
SG181466A1 (en) | 2009-12-04 | 2012-07-30 | Sunovion Pharmaceuticals Inc | Formulations, salts and polymorphs of transnorsertraline and uses thereof |
CN102762575B (en) | 2009-12-04 | 2015-04-15 | 桑诺维恩药品公司 | Multicyclic compounds and methods of use thereof |
CN102869367A (en) | 2009-12-09 | 2013-01-09 | 西尼克斯公司 | Novel cyclic peptides |
SG181797A1 (en) | 2009-12-18 | 2012-07-30 | Idenix Pharmaceuticals Inc | 5,5-fused arylene or heteroarylene hepatitis c virus inhibitors |
WO2011079091A1 (en) | 2009-12-22 | 2011-06-30 | Celgene Corporation | (methylsulfonyl) ethyl benzene isoindoline derivatives and their therapeutical uses |
US20110238036A1 (en) * | 2009-12-23 | 2011-09-29 | Psivida Us, Inc. | Sustained release delivery devices |
WO2011079313A1 (en) * | 2009-12-23 | 2011-06-30 | Map Pharmaceuticals, Inc. | Novel ergoline analogs |
US20120010131A1 (en) | 2009-12-30 | 2012-01-12 | Scynexis, Inc. | Novel cyclosporin analogues |
ES2699692T3 (en) | 2010-01-04 | 2019-02-12 | Mapi Pharma Ltd | Deposit system comprising glatiramer acetate |
USRE49251E1 (en) | 2010-01-04 | 2022-10-18 | Mapi Pharma Ltd. | Depot systems comprising glatiramer or pharmacologically acceptable salt thereof |
EP2851070A1 (en) | 2010-01-05 | 2015-03-25 | Celgene Corporation | A combination of lenalidomide and artesunate/artemisone for treating cancer |
WO2011089166A1 (en) | 2010-01-19 | 2011-07-28 | Virologik Gmbh | Semicarbazone proteasome inhibitors for treating hiv and hepatitis infection |
WO2011094890A1 (en) | 2010-02-02 | 2011-08-11 | Argusina Inc. | Phenylalanine derivatives and their use as non-peptide glp-1 receptor modulators |
US8409628B2 (en) * | 2010-02-04 | 2013-04-02 | Penguin IP Holdings, Inc. | Methods and compositions for oxygenation of skin to treat skin disorders |
WO2011097525A1 (en) | 2010-02-05 | 2011-08-11 | Tragara Pharmaceuticals, Inc. | Solid state forms of macrocyclic kinase inhibitors |
MX337169B (en) | 2010-02-11 | 2016-02-16 | Celgene Corp | Arylmethoxy isoindoline derivatives and compositions comprising and methods of using the same. |
EP2542542B1 (en) | 2010-03-02 | 2015-04-22 | Axikin Pharmaceuticals, Inc. | Isotopically enriched arylsulfonamide ccr3 antagonists |
WO2011112689A2 (en) | 2010-03-11 | 2011-09-15 | Ambit Biosciences Corp. | Saltz of an indazolylpyrrolotriazine |
MX2012010367A (en) | 2010-03-12 | 2012-11-23 | Celgene Corp | Methods for the treatment of non-hodgkin's lymphomas using lenalidomide, and gene and protein biomarkers as a predictor. |
US20110223297A1 (en) * | 2010-03-12 | 2011-09-15 | Pepsico., Inc. | Anti-Caking Agent for Flavored Products |
JP5818873B2 (en) | 2010-03-17 | 2015-11-18 | アクシキン ファーマシューティカルズ インコーポレーテッド | Arylsulfonamide CCR3 antagonist |
MX341050B (en) | 2010-04-07 | 2016-08-05 | Celgene Corp * | Methods for treating respiratory viral infection. |
EP2556082B1 (en) | 2010-04-08 | 2017-02-22 | Emory University | Substituted androst-4-ene diones |
US9205086B2 (en) | 2010-04-19 | 2015-12-08 | Synta Pharmaceuticals Corp. | Cancer therapy using a combination of a Hsp90 inhibitory compounds and a EGFR inhibitor |
US20130156755A1 (en) | 2010-04-19 | 2013-06-20 | Synta Pharmaceuticals Corp. | Cancer therapy using a combination of a hsp90 inhibitory compounds and a vegf inhibitor |
WO2011137249A1 (en) | 2010-04-28 | 2011-11-03 | Ritter Pharmaceuticals, Inc. | Prebiotic formulations and methods of use |
WO2011140360A1 (en) | 2010-05-05 | 2011-11-10 | The Trustees Of Columbia University In The City Of New York | Radiolabeled compounds and uses thereof |
AU2011255438A1 (en) | 2010-05-20 | 2013-01-10 | Synta Pharmaceuticals Corp. | Method of treating lung adenocarcinoma with Hsp90 inhibitory compounds |
US20120064175A1 (en) | 2010-05-20 | 2012-03-15 | Synta Pharmaceuticals Corp. | HSP90 Inhibitors for Treating Non-Small Cell Lung Cancer in Wild-Type EGFR and/or KRAS Patients |
WO2011149824A1 (en) | 2010-05-24 | 2011-12-01 | Synta Pharmaceuticals Corp. | Cancer therapy using a combination of a hsp90 inhibitory compound and a topoisomerase ii inhibitor |
AU2011258217B2 (en) | 2010-05-26 | 2016-12-15 | Sunovion Pharmaceuticals Inc. | Heteroaryl compounds and methods of use thereof |
WO2011150198A1 (en) | 2010-05-27 | 2011-12-01 | Ambit Biosciences Corporation | Azolyl urea compounds and methods of use thereof |
WO2011150201A2 (en) | 2010-05-27 | 2011-12-01 | Ambit Biosciences Corporation | Azolyl amide compounds and methods of use thereof |
CN102918031A (en) | 2010-05-28 | 2013-02-06 | 通用电气健康护理有限公司 | Radiolabeled compounds and methods thereof |
MX2012013879A (en) | 2010-06-01 | 2013-04-03 | Biotheryx Inc | Hydroxypyridone derivatives, pharmaceutical compositions thereof, and their therapeutic use for treating proliferative diseases. |
CN103153309A (en) | 2010-06-01 | 2013-06-12 | 拜欧赛里克斯公司 | Methods of treating hematologic malignancies using 6-cyclohexyl-1-hydroxy-4-methyl-2(1h)-pyridone |
AU2011265047B2 (en) | 2010-06-07 | 2014-10-23 | Novomedix, Llc | Furanyl compounds and the use thereof |
US20140200270A1 (en) | 2013-01-11 | 2014-07-17 | Summa Health System | Vitamins c and k for treating polycystic diseases |
CA2805745C (en) | 2010-07-19 | 2019-01-15 | Summa Health System | Vitamin c and chromium-free vitamin k, and compositions thereof for treating an nfkb-mediated condition or disease |
JP5820476B2 (en) | 2010-08-24 | 2015-11-24 | アルギアックス ファルマコウティカルス ゲーエムベーハーALGIAX Pharmaceuticals GmbH | New use of leflunomide and malononitrile trilamide |
CN103298805A (en) | 2010-09-01 | 2013-09-11 | 埃姆比特生物科学公司 | Quinazoline compounds and methods of use thereof |
WO2012030913A1 (en) | 2010-09-01 | 2012-03-08 | Ambit Biosciences Corporation | An optically active pyrazolylaminoquinazoline, and pharmaceutical compositions and methods of use thereof |
US20130317045A1 (en) | 2010-09-01 | 2013-11-28 | Ambit Biosciences Corporation | Thienopyridine and thienopyrimidine compounds and methods of use thereof |
US20130225614A1 (en) | 2010-09-01 | 2013-08-29 | Ambit Biosciences Corporation | 4-azolylaminoquinazoline derivatives and methods of use thereof |
EP2611809A1 (en) | 2010-09-01 | 2013-07-10 | Ambit Biosciences Corporation | Azolopyridine and azolopyrimidine compounds and methods of use thereof |
JP5872558B2 (en) | 2010-09-01 | 2016-03-01 | アムビト ビオスシエンセス コルポラチオン | Pyrazolylaminoquinazoline hydrobromide |
WO2012030944A2 (en) | 2010-09-01 | 2012-03-08 | Ambit Biosciences Corporation | Quinoline and isoquinoline compounds and methods of use thereof |
EP2611502A1 (en) | 2010-09-01 | 2013-07-10 | Ambit Biosciences Corporation | Adenosine a3 receptor modulating compounds and methods of use thereof |
WO2012030912A1 (en) | 2010-09-01 | 2012-03-08 | Ambit Biosciences Corporation | 7-cyclylquinazoline derivatives and methods of use thereof |
US20130225615A1 (en) | 2010-09-01 | 2013-08-29 | Ambit Biosciences Corporation | 2-cycloquinazoline derivatives and methods of use thereof |
WO2012037155A2 (en) | 2010-09-13 | 2012-03-22 | Gtx, Inc. | Tyrosine kinase inhibitors |
WO2012044641A1 (en) | 2010-09-29 | 2012-04-05 | Pathway Therapeutics Inc. | 1,3,5-triazinyl benzimidazole sulfonamides and their use in cancer therapy |
AU2011313906B2 (en) | 2010-10-11 | 2015-08-13 | Axikin Pharmaceuticals, Inc. | Salts of arylsulfonamide CCR3 antagonists |
CN103391784A (en) | 2010-10-15 | 2013-11-13 | 纽约市哥伦比亚大学理事会 | Obesity-related genes and their proteins and uses thereof |
LT2629776T (en) | 2010-10-18 | 2017-11-10 | Cerenis Therapeutics Holding Sa | Compounds, compositions and methods useful for cholesterol mobilisation |
US9486463B2 (en) | 2010-10-19 | 2016-11-08 | Ambra Bioscience Llc | Chemosensory receptor ligand-based therapies |
US9149959B2 (en) | 2010-10-22 | 2015-10-06 | Monosol Rx, Llc | Manufacturing of small film strips |
PT2632451T (en) | 2010-10-29 | 2017-12-14 | Algiax Pharmaceuticals Gmbh | Use of malononitrilamides in neuropathic pain |
WO2012064808A1 (en) | 2010-11-09 | 2012-05-18 | Synta Pharmaceuticals Corp | Tetrazolyl - tetrahydropyridine compounds for inflammation and immune - related uses |
CA2817577A1 (en) | 2010-11-10 | 2012-05-18 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
GB201020032D0 (en) | 2010-11-25 | 2011-01-12 | Sigmoid Pharma Ltd | Composition |
WO2012078649A1 (en) | 2010-12-06 | 2012-06-14 | Follica, Inc. | Methods for treating baldness and promoting hair growth |
WO2012078492A1 (en) | 2010-12-06 | 2012-06-14 | Celgene Corporation | A combination therapy with lenalidomide and a cdk inhibitor for treating multiple myeloma |
WO2012078757A2 (en) | 2010-12-08 | 2012-06-14 | Synta Pharmaceuticals Corp. | Combination breast cancer therapy with hsp90 inhibitory compounds |
WO2012080050A1 (en) | 2010-12-14 | 2012-06-21 | F. Hoffmann-La Roche Ag | Solid forms of a phenoxybenzenesulfonyl compound |
US9532977B2 (en) | 2010-12-16 | 2017-01-03 | Celgene Corporation | Controlled release oral dosage forms of poorly soluble drugs and uses thereof |
ES2753198T5 (en) | 2010-12-16 | 2023-05-31 | Amgen Europe Gmbh | Oral pharmaceutical forms of controlled release of poorly soluble drugs and their uses |
AU2011346749A1 (en) | 2010-12-22 | 2013-05-02 | Purdue Pharma L.P. | Phosphorus-substituted quinoxaline-type piperidine compounds and uses thereof |
KR20140035331A (en) | 2011-01-07 | 2014-03-21 | 엘셀릭스 테라퓨틱스 인코포레이티드 | Chemosensory receptor ligand-based therapies |
US8809349B2 (en) | 2011-01-10 | 2014-08-19 | Infinity Pharmaceuticals, Inc. | Processes for preparing isoquinolinones and solid forms of isoquinolinones |
EP2663549B1 (en) | 2011-01-10 | 2018-03-14 | Celgene Corporation | Phenethylsulfone isoindoline derivatives as inhibitors of pde 4 and/or cytokines |
US9757355B2 (en) | 2011-01-10 | 2017-09-12 | Celgene Corporation | Oral dosage forms of cyclopropanecarboxylic acid {2-[(1S)-1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide |
US8765760B2 (en) | 2011-01-11 | 2014-07-01 | Sunovion Pharmaceuticals, Inc. | [1,2,4] triazol [1,5-a] pyrazines useful as inhibitors of phosphodiesterases |
US20130331357A1 (en) | 2011-01-11 | 2013-12-12 | Synta Pharmaceuticals Corp. | Combination therapy of hsp90 inhibitory compounds with proteasome inhibitors |
US9045417B2 (en) | 2011-01-14 | 2015-06-02 | Celgene Corporation | Isotopologues of isoindole derivatives |
EP2665477B1 (en) | 2011-01-20 | 2015-09-09 | Bionevia Pharmaceuticals Inc. | Modified release compositions of epalrestat or a derivative thereof and methods for using the same |
WO2012106299A1 (en) | 2011-01-31 | 2012-08-09 | Celgene Corporation | Pharmaceutical compositions of cytidine analogs and methods of use thereof |
EP2670426B1 (en) | 2011-01-31 | 2017-05-10 | The General Hospital Corporation | Multimodal trail molecules and uses in cellular therapies |
WO2012109398A1 (en) | 2011-02-10 | 2012-08-16 | Idenix Pharmaceuticals, Inc. | Macrocyclic serine protease inhibitors, pharmaceutical compositions thereof, and their use for treating hcv infections |
MX350838B (en) | 2011-02-11 | 2017-09-18 | Grain Proc Corporation * | Salt composition. |
US8287903B2 (en) * | 2011-02-15 | 2012-10-16 | Tris Pharma Inc | Orally effective methylphenidate extended release powder and aqueous suspension product |
US20120208755A1 (en) | 2011-02-16 | 2012-08-16 | Intarcia Therapeutics, Inc. | Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers |
WO2012116061A1 (en) | 2011-02-23 | 2012-08-30 | Synta Pharmaceuticals Corp. | Combination therapy of hsp90 inhibitory compounds with radiotherapy |
AU2012243289A1 (en) | 2011-02-24 | 2013-08-29 | Synta Pharmaceuticals Corp. | Prostate cancer therapy with Hsp90 inhibitory compounds |
US9795792B2 (en) | 2011-02-25 | 2017-10-24 | Medtronic, Inc. | Emergency mode switching for non-pacing modes |
WO2012116247A1 (en) | 2011-02-25 | 2012-08-30 | Synta Pharmaceuticals Corp. | Hsp90 inhibitory compounds in treating jak/stat signaling-mediated cancers |
EP2683376B1 (en) | 2011-03-07 | 2018-11-28 | Celgene Corporation | Methods for treating diseases using isoindoline compounds |
EP2683384B1 (en) | 2011-03-11 | 2015-12-09 | Celgene Corporation | Methods of treating cancer using 3-(5-amino-2-methyl-4-oxo-4h-quinazolin-3-yl)-piperidine-2,6-dione |
SG192946A1 (en) | 2011-03-11 | 2013-09-30 | Celgene Corp | Solid forms of 3-(5-amino-2methyl-4-oxo-4h-quinazolin-3-yl)-piperidine-2,6-dione, and their pharmaceutical compositions and uses |
WO2012123353A1 (en) | 2011-03-17 | 2012-09-20 | Algiax Pharmaceuticals Gmbh | Novel use of benzofuranylsulfonates |
US20140038967A1 (en) | 2011-03-17 | 2014-02-06 | Algiax Pharmaceuticals Gmbh | Novel use for imidazotriazinones |
WO2012129237A2 (en) | 2011-03-20 | 2012-09-27 | Trustees Of Boston University | Therapeutic agent for emphysema and copd |
WO2012135160A1 (en) | 2011-03-28 | 2012-10-04 | Pathway Therapeutics Inc. | (alpha- substituted aralkylamino and heteroarylalkylamino) pyrimidinyl and 1,3,5 -triazinyl benzimidazoles, pharmaceutical compositions containing them, and these compounds for use in treating proliferative diseases |
WO2012135299A1 (en) | 2011-03-28 | 2012-10-04 | Deuteria Pharmaceuticals Inc | 2',6'-dioxo-3'-deutero-piperdin-3-yl-isoindoline compounds |
EP2691389A1 (en) | 2011-03-28 | 2014-02-05 | MEI Pharma, Inc. | (alpha-substituted cycloalkylamino and heterocyclylamino) pyrimidinyl and 1,3,5-triazinyl benzimidazoles, pharmaceutical compositions thereof, and their use in treating proliferative diseases |
EP2691388A1 (en) | 2011-03-28 | 2014-02-05 | MEI Pharma, Inc. | (fused ring arylamino and heterocyclylamino) pyrimidynyl and 1,3,5-triazinyl benzimidazoles, pharmaceutical compositions thereof, and their use in treating proliferative diseases |
US20120252721A1 (en) | 2011-03-31 | 2012-10-04 | Idenix Pharmaceuticals, Inc. | Methods for treating drug-resistant hepatitis c virus infection with a 5,5-fused arylene or heteroarylene hepatitis c virus inhibitor |
WO2012154321A1 (en) | 2011-03-31 | 2012-11-15 | Idenix Pharmaceuticals, Inc. | Compounds and pharmaceutical compositions for the treatment of viral infections |
WO2012158271A1 (en) | 2011-04-06 | 2012-11-22 | Anadys Pharmaceuticals, Inc. | Bridged polycyclic compounds as antiviral agents |
EP2699317B1 (en) | 2011-04-21 | 2016-08-10 | Mapi Pharma Limited | Random pentapolymer for treatment of autoimmune diseases |
JP5976100B2 (en) | 2011-04-21 | 2016-08-23 | キュアマーク リミテッド ライアビリティ カンパニー | Compounds for the treatment of neuropsychiatric disorders |
CN103635188B (en) | 2011-04-28 | 2017-03-22 | 细胞基因公司 | Methods and compositions using PDE4 inhibitors for the treatment and management of autoimmune and inflammatory diseases |
ES2656944T3 (en) | 2011-04-29 | 2018-03-01 | Intercontinental Great Brands Llc | Encapsulated acid, method of preparation thereof, and chewing gum comprising it |
WO2012149299A2 (en) | 2011-04-29 | 2012-11-01 | Celgene Corporaiton | Methods for the treatment of cancer and inflammatory diseases using cereblon as a predictor |
US9604978B2 (en) | 2011-05-03 | 2017-03-28 | Synta Pharmaceuticals Corp. | Compounds for inflammation and immune-related uses |
US9480696B2 (en) | 2011-05-04 | 2016-11-01 | Trustees Of Boston University | Proton-motive force stimulation to potentiate aminoglycoside antibiotics against persistent bacteria |
EP2714038A1 (en) | 2011-05-24 | 2014-04-09 | Synta Pharmaceuticals Corp. | Combination therapy of hsp90 inhibitory compounds with mtor/pi3k inhibitors |
CN103827100B (en) | 2011-06-07 | 2015-08-12 | 安那迪斯药品股份有限公司 | For reducing [1,2,4] thiadiazine 1,1-dioxide compound of serum uric acid |
RU2011122942A (en) | 2011-06-08 | 2012-12-20 | Общество С Ограниченной Ответственностью "Асинэкс Медхим" | NEW KINAZ INHIBITORS |
US20140221427A1 (en) | 2011-06-22 | 2014-08-07 | Celgene Corporation | Isotopologues of pomalidomide |
PT2723732T (en) | 2011-06-22 | 2017-02-17 | Purdue Pharma Lp | Trpv1 antagonists including dihydroxy substituent and uses thereof |
CN103827113A (en) | 2011-06-23 | 2014-05-28 | Map药物公司 | Novel fluoroergoline analogs |
US9119793B1 (en) | 2011-06-28 | 2015-09-01 | Medicis Pharmaceutical Corporation | Gastroretentive dosage forms for doxycycline |
WO2013003697A1 (en) | 2011-06-30 | 2013-01-03 | Trustees Of Boston University | Method for controlling tumor growth, angiogenesis and metastasis using immunoglobulin containing and proline rich receptor-1 (igpr-1) |
AU2012280931A1 (en) | 2011-07-07 | 2014-02-27 | Synta Pharmaceuticals Corp. | Treating cancer with HSP90 inhibitory compounds |
AU2012284088B2 (en) | 2011-07-19 | 2015-10-08 | Infinity Pharmaceuticals Inc. | Heterocyclic compounds and uses thereof |
AR088218A1 (en) | 2011-07-19 | 2014-05-21 | Infinity Pharmaceuticals Inc | USEFUL HETEROCICLICAL COMPOUNDS AS PI3K INHIBITORS |
GB201112987D0 (en) | 2011-07-28 | 2011-09-14 | Ge Healthcare Ltd | Novel compound |
US9394293B2 (en) | 2011-08-10 | 2016-07-19 | Purdue Pharma L.P. | TRPV1 antagonists including dihydroxy substituent and uses thereof |
WO2013022872A1 (en) | 2011-08-10 | 2013-02-14 | Celgene Corporation | Gene methylation biomarkers and methods of use thereof |
CN103930126A (en) | 2011-08-12 | 2014-07-16 | Bsrc亚历山大.弗莱明 | TNF superfamily trimerization inhibitors |
US10806711B2 (en) | 2011-08-12 | 2020-10-20 | University Of Cincinnati | Method of treating acute decompensated heart failure with probenecid |
CA2844809A1 (en) | 2011-08-19 | 2013-02-28 | Synta Pharmaceuticals Corp. | Combination cancer therapy of hsp90 inhibitor with antimetabolite |
EP2959899B1 (en) | 2011-08-23 | 2017-02-22 | Cornerstone Therapeutics Inc. | Use of zileuton for the treatment of nasal polyps in cystic fibrosis patients |
EP2751093A1 (en) | 2011-08-29 | 2014-07-09 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
TW201329096A (en) | 2011-09-12 | 2013-07-16 | Idenix Pharmaceuticals Inc | Substituted carbonyloxymethylphosphoramidate compounds and pharmaceutical compositions for the treatment of viral infections |
JP2014526474A (en) | 2011-09-12 | 2014-10-06 | アイディニックス ファーマシューティカルズ インコーポレイテッド | Compounds and pharmaceutical compositions for the treatment of viral infections |
JP2014526558A (en) | 2011-09-23 | 2014-10-06 | セルジーン コーポレイション | Romidepsin and 5-azacytidine for use in the treatment of lymphoma |
US20130244950A1 (en) | 2011-09-26 | 2013-09-19 | Celgene Corporation | Combination therapy for chemoresistant cancers |
WO2013049332A1 (en) | 2011-09-29 | 2013-04-04 | Infinity Pharmaceuticals, Inc. | Inhibitors of monoacylglycerol lipase and methods of their use |
WO2013052776A1 (en) | 2011-10-07 | 2013-04-11 | Cedars-Sinai Medical Center | Compositions and methods for tumor imaging and targeting by a class of organic heptamethine cyanine dyes that possess dual nuclear and near-infrared properties |
US20140271657A1 (en) | 2011-10-12 | 2014-09-18 | Children's Medical Center Corporation | Combinatorial compositions and methods of treating hemoglobinopathies |
WO2013056070A2 (en) | 2011-10-14 | 2013-04-18 | Ambit Biosciences Corporation | Heterocyclic compounds and methods of use thereof |
EP2768838A1 (en) | 2011-10-14 | 2014-08-27 | IDENIX Pharmaceuticals, Inc. | Substituted 3',5'-cyclic phosphates of purine nucleotide compounds and pharmaceutical compositions for the treatment of viral infections |
TWI558401B (en) | 2011-11-01 | 2016-11-21 | 西建公司 | Methods for treating cancers using oral formulations of cytidine analogs |
US9439899B2 (en) | 2011-11-02 | 2016-09-13 | Synta Pharmaceuticals Corp. | Cancer therapy using a combination of HSP90 inhibitors with topoisomerase I inhibitors |
CA2853806C (en) | 2011-11-02 | 2020-07-14 | Synta Pharmaceuticals Corp. | Combination therapy of hsp90 inhibitors with platinum-containing agents |
WO2013071049A1 (en) | 2011-11-10 | 2013-05-16 | Trustees Of Boston College | Gramicidin a mutants that function as antibiotics with improved solubility and reduced toxicity |
EP2780010A1 (en) | 2011-11-14 | 2014-09-24 | Synta Pharmaceuticals Corp. | Combination therapy of hsp90 inhibitors with braf inhibitors |
EP2797912B1 (en) | 2011-12-01 | 2016-05-25 | Purdue Pharma L.P. | Azetidine-substituted quinoxaline-type piperidine compounds and uses thereof |
US20130143867A1 (en) | 2011-12-02 | 2013-06-06 | Sychroneuron Inc. | Acamprosate formulations, methods of using the same, and combinations comprising the same |
WO2013085902A1 (en) | 2011-12-05 | 2013-06-13 | The University Of Texas M.D. | Combination therapy methods for treating an inflammatory breast cancer |
JP5946921B2 (en) | 2011-12-08 | 2016-07-06 | パーデュー、ファーマ、リミテッド、パートナーシップ | Quaternized buprenorphine analogues |
CA2859173A1 (en) | 2011-12-19 | 2013-06-27 | Map Pharmaceuticals, Inc. | Novel iso-ergoline derivatives |
WO2013095708A1 (en) | 2011-12-21 | 2013-06-27 | Map Pharmaceuticals, Inc. | Novel neuromodulatory compounds |
DK2800578T3 (en) | 2012-01-05 | 2019-03-25 | Boston Medical Ct Corp | SLIT-ROBO SIGNAL FOR DIAGNOSIS AND TREATMENT OF Kidney Diseases |
JP6175074B2 (en) | 2012-01-06 | 2017-08-02 | エルセリクス セラピューティクス インコーポレイテッド | Compositions and methods for treating metabolic disorders |
KR20190120430A (en) | 2012-01-06 | 2019-10-23 | 엘셀릭스 테라퓨틱스 인코포레이티드 | Biguanide compositions and methods of treating metabolic disorders |
US10189825B2 (en) | 2012-02-08 | 2019-01-29 | Sunovion Pharmaceuticals Inc. | Heteroaryl compounds and methods of use thereof |
ES2671608T3 (en) | 2012-02-21 | 2018-06-07 | Celgene Corporation | Solid forms of 3- (4-nitro-1-oxoisoindolin-2-yl) piperidine-2,6-dione |
WO2013130600A1 (en) | 2012-02-29 | 2013-09-06 | Ambit Biosciences Corporation | Solid forms comprising optically active pyrazolylaminoquinazoline, compositions thereof, and uses therewith |
WO2013133708A1 (en) | 2012-03-07 | 2013-09-12 | Stichting Vu-Vumc | Compositions and methods for diagnosing and treating intellectual disability syndrome, autism and autism related disorders |
CN104302640A (en) | 2012-03-16 | 2015-01-21 | 埃克希金医药品有限公司 | 3,5-diaminopyrazole kinase inhibitors |
ES2779698T3 (en) | 2012-03-19 | 2020-08-18 | Brigham & Womens Hospital Inc | Growth differentiation factor 11 (GDF) for the treatment of age-related cardiovascular conditions |
US10039777B2 (en) | 2012-03-20 | 2018-08-07 | Neuro-Lm Sas | Methods and pharmaceutical compositions of the treatment of autistic syndrome disorders |
WO2013148864A1 (en) | 2012-03-27 | 2013-10-03 | Andrei Gudkov | Curaxins for use in treating breast cancer and method for identifying patients likely to respond |
AU2013239663A1 (en) | 2012-03-28 | 2014-10-09 | Synta Pharmaceuticals Corp. | Triazole derivatives as HSP90 inhibitors |
CA2868323A1 (en) | 2012-04-04 | 2013-10-10 | Synta Pharmaceuticals Corp. | Novel triazole compounds that modulate hsp90 activity |
PT2833905T (en) | 2012-04-04 | 2018-08-06 | Halozyme Inc | Combination therapy with hyaluronidase and a tumor-targeted taxane |
US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
WO2013156232A1 (en) | 2012-04-16 | 2013-10-24 | Algiax Pharmaceuticals Gmbh | Use of benzofuranylsulfonates in neuropathic pain |
WO2013156231A1 (en) | 2012-04-16 | 2013-10-24 | Algiax Pharmaceuticals Gmbh | Use of imidazotriazinones in neuropathic pain |
CA3120681A1 (en) | 2012-04-17 | 2013-10-24 | Purdue Pharma L.P. | Systems and methods for treating an opioid-induced adverse pharmacodynamic response |
WO2013158928A2 (en) | 2012-04-18 | 2013-10-24 | Elcelyx Therapeutics, Inc. | Chemosensory receptor ligand-based therapies |
WO2013163758A1 (en) | 2012-05-01 | 2013-11-07 | Boyd Shelley Romayne | Methods for treating and diagnosing blinding eye diseases |
JP2015516439A (en) | 2012-05-10 | 2015-06-11 | シンタ ファーマシューティカルズ コーポレーション | Treating cancer with Hsp90-inhibiting compounds |
EP2858976B1 (en) | 2012-05-11 | 2018-03-14 | Purdue Pharma LP | Benzomorphan compounds as opioid receptors modulators |
WO2013177195A1 (en) | 2012-05-22 | 2013-11-28 | Idenix Pharmaceuticals, Inc. | 3',5'-cyclic phosphate prodrugs for hcv infection |
EP2852604B1 (en) | 2012-05-22 | 2017-04-12 | Idenix Pharmaceuticals LLC | 3',5'-cyclic phosphoramidate prodrugs for hcv infection |
NZ702744A (en) | 2012-05-22 | 2016-12-23 | Idenix Pharmaceuticals Llc | D-amino acid compounds for liver disease |
US10350278B2 (en) | 2012-05-30 | 2019-07-16 | Curemark, Llc | Methods of treating Celiac disease |
EP2861562B1 (en) | 2012-06-14 | 2018-05-09 | Mayo Foundation For Medical Education And Research | Pyrazole derivatives as inhibitors of stat3 |
JP6427097B2 (en) | 2012-06-15 | 2018-11-21 | ザ ブリガム アンド ウィメンズ ホスピタル インコーポレイテッドThe Brigham and Women’s Hospital, Inc. | Compositions for treating cancer and methods for producing said compositions |
US9012640B2 (en) | 2012-06-22 | 2015-04-21 | Map Pharmaceuticals, Inc. | Cabergoline derivatives |
ES2699810T3 (en) | 2012-06-29 | 2019-02-12 | Celgene Corp | Methods to determine the efficacy of drugs using cereblon-associated proteins |
GB201212010D0 (en) | 2012-07-05 | 2012-08-22 | Sigmoid Pharma Ltd | Formulations |
JP2015522080A (en) | 2012-07-11 | 2015-08-03 | エルセリクス セラピューティクス インコーポレイテッド | Compositions for reducing cardiovascular metabolic risk comprising statins, biguanides, and additional agents |
US9085561B2 (en) | 2012-07-30 | 2015-07-21 | Purdue Pharma L.P. | Cyclic urea- or lactam-substituted quinoxaline-type piperidines as ORL-1 modulators |
WO2014022332A1 (en) | 2012-07-31 | 2014-02-06 | The Brigham And Women's Hospital, Inc. | Modulation of the immune response |
CN108938642A (en) | 2012-08-09 | 2018-12-07 | 细胞基因公司 | Immune related and inflammatory disease treatment |
SG10201701057SA (en) | 2012-08-09 | 2017-03-30 | Celgene Corp | Methods of treating cancer using 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione |
CN104703978B (en) | 2012-08-09 | 2018-05-11 | 细胞基因公司 | Salt and solid form of compound and combinations thereof and application method |
US9587281B2 (en) | 2012-08-14 | 2017-03-07 | Celgene Corporation | Cereblon isoforms and their use as biomarkers for therapeutic treatment |
EP2884961B1 (en) | 2012-08-15 | 2019-03-06 | Tris Pharma Inc. | Methylphenidate extended release chewable tablet |
US10624859B2 (en) | 2012-08-20 | 2020-04-21 | Rhodes Technologies | Systems and methods for increasing stability of dronabinol compositions |
US9315514B2 (en) | 2012-08-27 | 2016-04-19 | Rhodes Technologies | 1,3-dioxanomorphides and 1,3-dioxanocodides |
US9605074B2 (en) | 2012-08-30 | 2017-03-28 | The General Hospital Corporation | Multifunctional nanobodies for treating cancer |
WO2014036528A2 (en) | 2012-08-31 | 2014-03-06 | Ixchel Pharma, Llc | Agents useful for treating obesity, diabetes and related disorders |
AU2013312420A1 (en) | 2012-09-07 | 2015-02-26 | Axikin Pharmaceuticals, Inc. | Isotopically enriched arylsulfonamide CCR3 antagonists |
BR112015005243A2 (en) | 2012-09-10 | 2017-07-04 | Celgene Corp | Methods For Treating Locally Advanced Breast Cancer |
WO2014055647A1 (en) | 2012-10-03 | 2014-04-10 | Mei Pharma, Inc. | (sulfinyl and sulfonyl benzimidazolyl) pyrimidines and triazines, pharmaceutical compositions thereof, and their use for treating proliferative diseases |
EA030189B8 (en) | 2012-10-08 | 2018-10-31 | Иденикс Фармасьютикалз Ллс | 2'-chloro nucleoside analogs for hcv infection |
EP2906241B1 (en) | 2012-10-12 | 2020-01-08 | The Brigham and Women's Hospital, Inc. | Enhancement of the immune response |
WO2014062856A1 (en) | 2012-10-16 | 2014-04-24 | Halozyme, Inc. | Hypoxia and hyaluronan and markers thereof for diagnosis and monitoring of diseases and conditions and related methods |
US20140112886A1 (en) | 2012-10-19 | 2014-04-24 | Idenix Pharmaceuticals, Inc. | Dinucleotide compounds for hcv infection |
US10723754B2 (en) | 2012-10-22 | 2020-07-28 | Idenix Pharmaceuticals Llc | 2′,4′-bridged nucleosides for HCV infection |
PT2914296T (en) | 2012-11-01 | 2018-10-30 | Infinity Pharmaceuticals Inc | Treatment of cancers using pi3 kinase isoform modulators |
CA2890177A1 (en) | 2012-11-08 | 2014-05-15 | Summa Health System | Vitamin c, vitamin k, a polyphenol, and combinations thereof for wound healing |
JP6400592B2 (en) | 2012-11-09 | 2018-10-03 | パーデュー、ファーマ、リミテッド、パートナーシップ | Benzomorphan analogs and uses thereof |
JP2015536991A (en) | 2012-11-09 | 2015-12-24 | セルジーン コーポレイション | How to treat bone loss |
EP2938624A1 (en) | 2012-11-14 | 2015-11-04 | IDENIX Pharmaceuticals, Inc. | D-alanine ester of sp-nucleoside analog |
WO2014078427A1 (en) | 2012-11-14 | 2014-05-22 | Idenix Pharmaceuticals, Inc. | D-alanine ester of rp-nucleoside analog |
CA2889906A1 (en) | 2012-11-29 | 2014-06-05 | Sunovion Pharmaceuticals Inc. | Triazolo-pyrazine derivatives useful in the treatment of disorders of the central nervous system |
RU2673818C2 (en) | 2012-11-30 | 2018-11-30 | Экьюра Фармасьютикалз, Инк. | Self-regulated release of active pharmaceutical ingredient |
ES2689921T3 (en) | 2012-11-30 | 2018-11-16 | Novomedix, Llc | Substituted biarylsulfonamides and their uses |
WO2014087226A1 (en) | 2012-12-07 | 2014-06-12 | Purdue Pharma L.P. | Buprenorphine analogs as opiod receptor modulators |
ES2621305T3 (en) | 2012-12-14 | 2017-07-03 | Purdue Pharma Lp | Spirocyclic morphinans and their use |
TW201434836A (en) | 2012-12-14 | 2014-09-16 | Purdue Pharma Lp | Nitrogen containing morphinan derivatives and the use thereof |
US8980906B2 (en) | 2012-12-14 | 2015-03-17 | Purdue Pharma L.P. | Pyridonemorphinan analogs and biological activity on opioid receptors |
WO2014099941A1 (en) | 2012-12-19 | 2014-06-26 | Idenix Pharmaceuticals, Inc. | 4'-fluoro nucleosides for the treatment of hcv |
SG11201504931SA (en) | 2012-12-21 | 2015-07-30 | Map Pharmaceuticals Inc | Novel methysergide derivatives |
WO2014102588A2 (en) | 2012-12-27 | 2014-07-03 | Purdue Pharma L.P. | Indole and indoline-type piperidine compounds and uses thereof |
WO2014102589A1 (en) | 2012-12-27 | 2014-07-03 | Purdue Pharma L.P. | Quinazolin-4(3h)-one-type piperidine compounds and uses thereof |
WO2014102590A1 (en) | 2012-12-27 | 2014-07-03 | Purdue Pharma L.P. | Substituted piperidin-4-amino-type compounds and uses thereof |
WO2014102592A2 (en) | 2012-12-27 | 2014-07-03 | Purdue Pharma L.P. | Oxime/substituted quinoxaline-type piperidine compounds and uses thereof |
US9090618B2 (en) | 2012-12-27 | 2015-07-28 | Purdue Pharma L.P. | Substituted benzimidazole-type piperidine compounds and uses thereof |
JP6159417B2 (en) | 2012-12-28 | 2017-07-05 | パーデュー、ファーマ、リミテッド、パートナーシップ | Substituted morphinans and uses thereof |
JP6159416B2 (en) | 2012-12-28 | 2017-07-05 | パーデュー、ファーマ、リミテッド、パートナーシップ | 7,8-cyclic morphinan analogs |
CA2896871A1 (en) | 2012-12-31 | 2014-07-03 | Kerry L. Spear | Heterocyclic compounds and methods of use thereof |
SG11201505240QA (en) | 2013-01-05 | 2015-08-28 | Elcelyx Therapeutics Inc | Delayed-release composition comprising biguanide |
US9617607B2 (en) | 2013-01-08 | 2017-04-11 | Enzo Biochem, Inc. | Diagnosis and treatment of viral diseases |
WO2014110127A1 (en) | 2013-01-08 | 2014-07-17 | Enzo Biochem, Inc. | Diagnosis and treatment of viral diseases |
US8999393B1 (en) | 2013-01-09 | 2015-04-07 | Edgemont Pharmaceuticals Llc | Sustained release formulations of lorazepam |
CA2935495C (en) | 2013-01-14 | 2021-04-20 | Deuterx, Llc | 3-(5-substituted-4-oxoquinazolin-3(4h)-yl)-3-deutero-piperidine-2,6-dione derivatives |
WO2014116573A1 (en) | 2013-01-22 | 2014-07-31 | Celgene Corporation | Processes for the preparation of isotopologues of 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione and pharmaceutically acceptable salts thereof |
CN104955483A (en) | 2013-01-30 | 2015-09-30 | 法莫斯医疗公司 | Treatments for depression and other diseases with a low dose agent |
EP2951160B1 (en) | 2013-01-31 | 2019-04-24 | Purdue Pharma LP | Benzomorphan analogs and the use thereof |
US20150366890A1 (en) | 2013-02-25 | 2015-12-24 | Trustees Of Boston University | Compositions and methods for treating fungal infections |
US9309275B2 (en) | 2013-03-04 | 2016-04-12 | Idenix Pharmaceuticals Llc | 3′-deoxy nucleosides for the treatment of HCV |
US9339541B2 (en) | 2013-03-04 | 2016-05-17 | Merck Sharp & Dohme Corp. | Thiophosphate nucleosides for the treatment of HCV |
AU2014244053B2 (en) | 2013-03-13 | 2018-08-30 | University Of Cincinnati | Treatment of a diastolic cardiac dysfunction with a TRPV2 receptor agonist |
US9872854B2 (en) | 2013-03-14 | 2018-01-23 | Celgene Corporation | Methods for the treatment of psoriatic arthritis using apremilast |
WO2014143643A1 (en) | 2013-03-15 | 2014-09-18 | The Regents Of The University Of California, A California Corporation | Acyclic nucleoside phosphonate diesters |
US10842802B2 (en) | 2013-03-15 | 2020-11-24 | Medicis Pharmaceutical Corporation | Controlled release pharmaceutical dosage forms |
US8969358B2 (en) | 2013-03-15 | 2015-03-03 | Purdue Pharma L.P. | Buprenorphine analogs |
NZ629037A (en) | 2013-03-15 | 2017-04-28 | Infinity Pharmaceuticals Inc | Salts and solid forms of isoquinolinones and composition comprising and methods of using the same |
US9187515B2 (en) | 2013-04-01 | 2015-11-17 | Idenix Pharmaceuticals Llc | 2′,4′-fluoro nucleosides for the treatment of HCV |
AU2014248263A1 (en) | 2013-04-02 | 2015-10-15 | Celgene Corporation | Methods and compositions using 4-amino-2-(2,6-dioxo-piperidine-3-yl)-isoindoline-1,3-dione for treatment and management of central nervous system cancers |
JP2016518357A (en) | 2013-04-08 | 2016-06-23 | プレジデント アンド フェローズ オブ ハーバード カレッジ | Methods and compositions for rejuvenating skeletal muscle stem cells |
DK3003309T3 (en) | 2013-05-30 | 2020-12-14 | Infinity Pharmaceuticals Inc | Treatment of cancer with PI3 kinase isoform modulators |
WO2014197744A1 (en) | 2013-06-05 | 2014-12-11 | Synchroneuron, Inc. | Acamprosate formulations, methods of using the same, and combinations comprising the same |
US10005779B2 (en) | 2013-06-05 | 2018-06-26 | Idenix Pharmaceuticals Llc | 1′,4′-thio nucleosides for the treatment of HCV |
WO2014197835A2 (en) | 2013-06-06 | 2014-12-11 | The General Hospital Corporation | Methods and compositions for the treatment of cancer |
EP3881859B1 (en) | 2013-06-11 | 2024-03-06 | President and Fellows of Harvard College | Compositions for increasing neurogenesis and angiogenesis |
MX2015017123A (en) | 2013-06-14 | 2016-08-03 | Invictus Oncology Pvt Ltd | Lipid-based platinum compounds and nanoparticles. |
EP2815749A1 (en) | 2013-06-20 | 2014-12-24 | IP Gesellschaft für Management mbH | Solid form of 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione having specified X-ray diffraction pattern |
WO2014203140A1 (en) | 2013-06-22 | 2014-12-24 | Wockhardt Limited | Solid oral pharmaceutical compositions comprising fixed dose combination of acetaminophen, dicyclomine and dextropropoxyphene or salts thereof |
ES2703623T3 (en) | 2013-06-28 | 2019-03-11 | Purdue Pharma Lp | Opioid antagonists for use in the treatment of arrhythmia induced by opioid analgesics |
WO2015017713A1 (en) | 2013-08-01 | 2015-02-05 | Idenix Pharmaceuticals, Inc. | D-amino acid phosphoramidate pronucleotides of halogeno pyrimidine compounds for liver disease |
CA2924141C (en) | 2013-08-22 | 2022-06-07 | The General Hospital Corporation | 5-amino 4-cyano substituted oxazole and thiazole derivatives as inhibitors of human 12/15-lipoxygenase |
CA2922361C (en) | 2013-08-29 | 2022-07-12 | Trustees Of Boston University | Intermediate metabolism products to potentiate aminoglycoside antibiotics in bacterial infections |
CN105683182A (en) | 2013-08-30 | 2016-06-15 | 埃姆比特生物科学公司 | Biaryl acetamide compounds and methods of use thereof |
NZ631142A (en) | 2013-09-18 | 2016-03-31 | Axikin Pharmaceuticals Inc | Pharmaceutically acceptable salts of 3,5-diaminopyrazole kinase inhibitors |
US20160229866A1 (en) | 2013-09-20 | 2016-08-11 | Idenix Pharmaceuticals Inc. | Hepatitis c virus inhibitors |
US20160213659A1 (en) | 2013-09-24 | 2016-07-28 | George Sylvestre | Treatment of burn pain by trpv1 modulators |
WO2015051336A1 (en) | 2013-10-03 | 2015-04-09 | David Wise | Compositions and methods for treating pelvic pain and other conditions |
PE20160685A1 (en) | 2013-10-04 | 2016-07-23 | Infinity Pharmaceuticals Inc | HETEROCYCLIC COMPOUNDS AND USES OF THEM |
US9751888B2 (en) | 2013-10-04 | 2017-09-05 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
CA2928779A1 (en) | 2013-10-21 | 2015-04-30 | The General Hospital Corporation | Methods relating to circulating tumor cell clusters and the treatment of cancer |
US20160244452A1 (en) | 2013-10-21 | 2016-08-25 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
WO2015061683A1 (en) | 2013-10-25 | 2015-04-30 | Idenix Pharmaceuticals, Inc. | D-amino acid phosphoramidate and d-alanine thiophosphoramidate pronucleotides of nucleoside compounds useful for the treatment of hcv |
WO2015065876A1 (en) | 2013-10-29 | 2015-05-07 | Thomas Jefferson University | Methods of prevention or treatment for pathologic thrombosis or inflammation |
WO2015066370A1 (en) | 2013-11-01 | 2015-05-07 | Idenix Pharmaceuticals, Inc. | D-alanine phosphoramidate pronucleotides of 2'-methyl 2'-fluoro guanosine nucleoside compounds for the treatment of hcv |
GB201319792D0 (en) | 2013-11-08 | 2013-12-25 | Sigmoid Pharma Ltd | Formulations |
PL3068414T3 (en) | 2013-11-11 | 2021-08-30 | Naturex Inc. | Compositions and methods useful in treatment of lower urinary tract symptoms, benign prostatic hyperplasia, erectile dysfunction |
EP3074039A4 (en) | 2013-11-26 | 2017-10-11 | The Brigham and Women's Hospital, Inc. | Compositions and methods for modulating an immune response |
EP3074399A1 (en) | 2013-11-27 | 2016-10-05 | Idenix Pharmaceuticals LLC | 2'-dichloro and 2'-fluoro-2'-chloro nucleoside analogues for hcv infection |
KR20160099090A (en) | 2013-11-27 | 2016-08-19 | 아이데닉스 파마슈티칼스 엘엘씨 | Nucleotides for the treatment of liver cancer |
DK3079712T3 (en) | 2013-12-11 | 2022-04-25 | Massachusetts Gen Hospital | USE OF MÜLLER INHIBITANT SUBSTANCE (MIS) PROTEINS FOR CONTRACEPTION AND OVARIAN RESERVE PRESERVATION |
WO2015095419A1 (en) | 2013-12-18 | 2015-06-25 | Idenix Pharmaceuticals, Inc. | 4'-or nucleosides for the treatment of hcv |
JP6599334B2 (en) | 2013-12-20 | 2019-10-30 | ザ ジェネラル ホスピタル コーポレイション | Methods and assays for circulating tumor cells in the blood |
US9682123B2 (en) | 2013-12-20 | 2017-06-20 | The Trustees Of Columbia University In The City Of New York | Methods of treating metabolic disease |
US9988392B2 (en) | 2013-12-26 | 2018-06-05 | Purdue Pharma L.P. | 7-beta-alkyl analogs of orvinols |
WO2015097545A1 (en) | 2013-12-26 | 2015-07-02 | Purdue Pharma L.P. | Opioid receptor modulating oxabicyclo[2.2.2]octane morphinans |
US9994571B2 (en) | 2013-12-26 | 2018-06-12 | Purdue Pharma L.P. | 10-substituted morphinan hydantoins |
US9340542B2 (en) | 2013-12-26 | 2016-05-17 | Purdue Pharma L.P. | Propellane-based compounds and the use thereof |
US10550088B2 (en) | 2013-12-27 | 2020-02-04 | Purdue Pharma L.P. | 6-substituted and 7-substituted morphinan analogs and the use thereof |
EP3089978B1 (en) | 2013-12-30 | 2018-08-29 | Purdue Pharma L.P. | Pyridone-sulfone morphinan analogs as opioid receptor ligands |
WO2015109037A1 (en) | 2014-01-15 | 2015-07-23 | Deuterx, Llc | Methods of treating neurological, metabolic, and other disorders using enantiopure deuterium-enriched pioglitazone |
EP3096749B1 (en) | 2014-01-24 | 2019-05-15 | Celgene Corporation | Methods for the treatment of obesity using apremilast |
EP3114122A1 (en) | 2014-03-05 | 2017-01-11 | Idenix Pharmaceuticals LLC | Solid forms of a flaviviridae virus inhibitor compound and salts thereof |
WO2015138420A1 (en) | 2014-03-10 | 2015-09-17 | Kadmon Corporation, Llc | Treatment of brain and central nervous system tumors |
EP3119744B1 (en) | 2014-03-18 | 2019-03-06 | Algiax Pharmaceuticals GmbH | 2-cyano-3-cyclopropyl-3-hydroxy-n-aryl-thioacrylamide derivatives |
SG10201808053XA (en) | 2014-03-19 | 2018-10-30 | Infinity Pharmaceuticals Inc | Heterocyclic compounds for use in the treatment of pi3k-gamma mediated disorders |
US10202398B2 (en) | 2014-03-20 | 2019-02-12 | Capella Therapeutics, Inc. | Benzimidazole derivatives as ERBB tyrosine kinase inhibitors for the treatment of cancer |
CA2943220C (en) | 2014-03-20 | 2024-01-16 | Capella Therapeutics, Inc. | Benzimidazole derivatives as erbb tyrosine kinase inhibitors for the treatment of cancer |
US11369588B2 (en) | 2014-03-20 | 2022-06-28 | The Trustees Of Princeton University | NADPH production by the 10-formyl-THF pathway, and its use in the diagnosis and treatment of disease |
US20170107300A1 (en) | 2014-03-21 | 2017-04-20 | The Brigham And Women's Hospital, Inc. | Methods and compositions for treatment of immune-related diseases or disorders and/or therapy monitoring |
EP3122337A4 (en) | 2014-03-26 | 2017-11-08 | Sun Pharma Advanced Research Company Ltd | Abuse deterrent immediate release coated reservoir solid dosage form |
AU2015241198A1 (en) | 2014-04-03 | 2016-11-17 | Invictus Oncology Pvt. Ltd. | Supramolecular combinatorial therapeutics |
WO2015153841A1 (en) | 2014-04-04 | 2015-10-08 | Ritter Pharmaceuticals, Inc. | Methods and compositions for microbiome alteration |
US10106549B2 (en) | 2014-04-09 | 2018-10-23 | Siteone Therapeutics, Inc. | 10′,11′-modified saxitoxins useful for the treatment of pain |
WO2015161137A1 (en) | 2014-04-16 | 2015-10-22 | Idenix Pharmaceuticals, Inc. | 3'-substituted methyl or alkynyl nucleosides for the treatment of hcv |
WO2015164364A2 (en) | 2014-04-25 | 2015-10-29 | The Brigham And Women's Hospital, Inc. | Methods to manipulate alpha-fetoprotein (afp) |
AU2015249666A1 (en) | 2014-04-25 | 2016-11-17 | The Brigham And Women's Hospital, Inc. | Compositions and methods for treating subjects with immune-mediated diseases |
WO2015168079A1 (en) | 2014-04-29 | 2015-11-05 | Infinity Pharmaceuticals, Inc. | Pyrimidine or pyridine derivatives useful as pi3k inhibitors |
AU2015259471A1 (en) | 2014-05-12 | 2016-11-24 | Conatus Pharmaceuticals, Inc. | Treatment of the complications of chronic liver disease with caspase inhibitors |
US9480676B2 (en) | 2014-05-15 | 2016-11-01 | Celgene Corporation | Use of PDE4 inhibitors and combinations thereof for the treatment of cystic fibrosis |
EP3142663A1 (en) | 2014-05-16 | 2017-03-22 | Celgene Corporation | Compositions and methods for the treatment of atherosclerotic cardiovascular diseases with pde4 modulators |
WO2015179366A1 (en) | 2014-05-19 | 2015-11-26 | Northeastern University | Serotonin receptor-targeting compounds and methods |
EP3145500A1 (en) | 2014-05-23 | 2017-03-29 | Sigmoid Pharma Limited | Celecoxib formulations useful for treating colorectal cancer |
JP2017516779A (en) | 2014-05-28 | 2017-06-22 | アイデニクス・ファーマシューティカルズ・エルエルシー | Nucleoside derivatives for cancer treatment |
WO2015187541A1 (en) | 2014-06-02 | 2015-12-10 | Children's Medical Center Corporation | Methods and compositions for immunomodulation |
JP2017519000A (en) | 2014-06-12 | 2017-07-13 | リガンド・ファーマシューティカルズ・インコーポレイテッド | Glucagon antagonist |
US20150359810A1 (en) | 2014-06-17 | 2015-12-17 | Celgene Corporation | Methods for treating epstein-barr virus (ebv) associated cancers using oral formulations of 5-azacytidine |
US9527815B2 (en) | 2014-06-18 | 2016-12-27 | Biotheryx, Inc. | Hydroxypyridone derivatives, pharmaceutical compositions thereof, and their therapeutic use for treating inflammatory, neurodegenerative, or immune-mediated diseases |
SI3157916T1 (en) | 2014-06-19 | 2019-05-31 | Ariad Pharmaceuticals, Inc. | Heteroaryl compounds for kinase inhibition |
EP3157520B1 (en) | 2014-06-23 | 2019-09-04 | Celgene Corporation | Apremilast for the treatment of a liver disease or a liver function abnormality |
ES2843973T3 (en) | 2014-06-27 | 2021-07-21 | Celgene Corp | Compositions and methods to induce conformational changes in cereblon and other E3 ubiquitin ligases |
US9499514B2 (en) | 2014-07-11 | 2016-11-22 | Celgene Corporation | Antiproliferative compounds and methods of use thereof |
CN106794233B (en) | 2014-08-01 | 2021-11-12 | 布里格姆及妇女医院股份有限公司 | Compositions and methods relating to treatment of pulmonary hypertension |
WO2016025686A1 (en) | 2014-08-15 | 2016-02-18 | Celgene Corporation | Dosage titration of apremilast for the treatment of diseases ameliorated by pde4 inhibition |
PL3182996T3 (en) | 2014-08-22 | 2023-04-17 | Celgene Corporation | Methods of treating multiple myeloma with immunomodulatory compounds in combination with antibodies |
EP3186281B1 (en) | 2014-08-28 | 2019-04-10 | Halozyme, Inc. | Combination therapy with a hyaluronan-degrading enzyme and an immune checkpoint inhibitor |
CA2959386A1 (en) | 2014-08-29 | 2016-03-03 | Lee Adam Wheeler | Methods and compositions for the treatment of cancer |
SG10201902137PA (en) | 2014-09-12 | 2019-04-29 | Tobira Therapeutics Inc | Cenicriviroc combination therapy for the treatment of fibrosis |
KR102589658B1 (en) | 2014-09-15 | 2023-10-13 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | Nucleotide analogs |
EP3194446B1 (en) | 2014-09-18 | 2022-10-26 | Cedars-Sinai Medical Center | Compositions and methods for treating fibrosis |
US9889085B1 (en) | 2014-09-30 | 2018-02-13 | Intarcia Therapeutics, Inc. | Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c |
US9708348B2 (en) | 2014-10-03 | 2017-07-18 | Infinity Pharmaceuticals, Inc. | Trisubstituted bicyclic heterocyclic compounds with kinase activities and uses thereof |
NZ730563A (en) | 2014-10-14 | 2019-05-31 | Halozyme Inc | Compositions of adenosine deaminase-2 (ada2), variants thereof and methods of using same |
US10183056B2 (en) | 2014-10-16 | 2019-01-22 | Cleveland Biolabs, Inc. | Methods and compositions for the treatment of radiation-related disorders |
TN2017000157A1 (en) | 2014-10-21 | 2018-10-19 | Ariad Pharma Inc | Crystalline forms of 5-chloro-n4-[-2-(dimethylphosphoryl) phenyl]-n2-{2-methoxy-4-[4-(4-methylpiperazin-1-yl) piperidin-1-yl] pyrimidine-2,4-diamine |
US20170354639A1 (en) | 2014-10-24 | 2017-12-14 | Biogen Ma Inc. | Diterpenoid derivatives and methods of use thereof |
CA2936741C (en) | 2014-10-31 | 2018-11-06 | Purdue Pharma | Methods and compositions particularly for treatment of attention deficit disorder |
KR20170102223A (en) | 2014-11-07 | 2017-09-08 | 시그모이드 파마 리미티드 | Compositions comprising cyclosporin |
TW201702218A (en) | 2014-12-12 | 2017-01-16 | 美國杰克森實驗室 | Compositions and methods relating to the treatment of cancer, autoimmune disease, and neurodegenerative disease |
JP6707088B2 (en) | 2014-12-16 | 2020-06-10 | セルジーン コーポレイション | Solid form comprising (1E,4E)-2-amino-N,N-dipropyl-8-(4-(pyrrolidine-1-carbonyl)phenyl)-3H-benzo[b]azepine-4-carboxamide, composition thereof , And their use |
MY191736A (en) | 2014-12-23 | 2022-07-13 | Axikin Pharmaceuticals Inc | 3,5-diaminopyrazole kinase inhibitors |
US9676793B2 (en) | 2014-12-23 | 2017-06-13 | Hoffmann-Laroche Inc. | Co-crystals of 5-amino-2-oxothiazolo[4,5-d]pyrimidin-3(2H)-yl-5-hydroxymethyl tetrahydrofuran-3-yl acetate and methods for preparing and using the same |
CA2973978A1 (en) | 2015-01-14 | 2016-07-21 | The Brigham And Women's Hospital, Inc. | Treatment of cancer with anti-lap monoclonal antibodies |
BR112017015510A2 (en) | 2015-01-20 | 2018-01-30 | Xoc Pharmaceuticals Inc | compound of formula (i), method of treatment and / or prevention, d2 receptor agonizing method in one individual, d3 receptor antagonizing method in one individual, 5-ht1d receptor agonizing method in one individual, 5-ht1a receptor agonization in one individual, selective 5-ht1d receptor agonizing method instead of 5-ht1b receptor in one individual, 5-ht2c re-receptor selective agonizing method instead of 5-ht2a or 5 receptor -ht2b in one individual, method of 5-ht2c receptor agonization in one individual, method of providing functional antagonist activity at 5-ht2b receptor or 5-ht7 receptor, and, method of providing functional antagonist activity at adrenergic receptors in one individual |
US9657020B2 (en) | 2015-01-20 | 2017-05-23 | Xoc Pharmaceuticals, Inc. | Ergoline compounds and uses thereof |
CA2976072A1 (en) | 2015-02-09 | 2016-08-18 | Synta Pharmaceuticals Corp. | Combination therapy of hsp90 inhibitors and pd-1 inhibitors for treating cancer |
NZ735736A (en) | 2015-03-10 | 2019-02-22 | Rhodes Tech | Acetate salt of buprenorphine and methods for preparing buprenorphine |
TW201642857A (en) | 2015-04-06 | 2016-12-16 | 西建公司 | Treatment of hepatocellular carcinoma using combination therapy |
EP3285795B1 (en) | 2015-04-22 | 2022-11-16 | Cedars-Sinai Medical Center | Enterically delivered bitter oligopeptides for the treatment for type 2 diabetes and obesity |
US20170042806A1 (en) | 2015-04-29 | 2017-02-16 | Dexcel Pharma Technologies Ltd. | Orally disintegrating compositions |
WO2016189055A1 (en) | 2015-05-27 | 2016-12-01 | Idenix Pharmaceuticals Llc | Nucleotides for the treatment of cancer |
WO2016196664A1 (en) | 2015-06-01 | 2016-12-08 | Cedars-Sinai Medical Center | Methods and use of compounds that bind to rela of nf-kb |
KR20240042548A (en) | 2015-06-03 | 2024-04-02 | 인타르시아 세라퓨틱스 인코포레이티드 | Implant placement and removal systems |
WO2016202721A1 (en) | 2015-06-16 | 2016-12-22 | F. Hoffmann-La Roche Ag | Salts of (s)-4-[(r)-6-(2-chloro-4-fluoro-phenyl)-5-methoxycarbonyl-2-thiazol-2-yl-3,6- dihydro-pyrimidin-4-ylmethyl]-morpholine-3-carboxylic acid, salt former and methods for preparing and using the same |
KR20180015260A (en) | 2015-06-23 | 2018-02-12 | 뉴로크린 바이오사이언시즈 인코퍼레이티드 | VMAT2 inhibitors for the treatment of neurological diseases or disorders |
SI3313818T1 (en) | 2015-06-26 | 2024-03-29 | Celgene Corporation | Methods for the treatment of kaposi's sarcoma or kshv-induced lymphoma using immunomodulatory compounds, and uses of biomarkers |
EP3316888A1 (en) | 2015-07-02 | 2018-05-09 | Celgene Corporation | Combination therapy for treatment of hematological cancers and solid tumors |
RU2018107227A (en) | 2015-07-28 | 2019-08-28 | Виоме Терапьютикс Лимитед | THERAPEUTIC AND PREVENTIVE ANTIBACTERIAL MEANS |
DK3277842T5 (en) | 2015-08-17 | 2020-08-31 | Kura Oncology Inc | PROCEDURES FOR TREATING CANCER PATIENTS WITH FARNESYL TRANSFERASE INHIBITORS |
CA2994729A1 (en) | 2015-08-27 | 2017-03-02 | President And Fellows Of Harvard College | Compositions and methods for treatment of pain |
WO2017040607A1 (en) | 2015-08-31 | 2017-03-09 | Acura Pharmaceuticals, Inc. | Methods and compositions for self-regulated release of active pharmaceutical ingredient |
US11590228B1 (en) | 2015-09-08 | 2023-02-28 | Tris Pharma, Inc | Extended release amphetamine compositions |
EP3347486A4 (en) | 2015-09-09 | 2019-06-19 | The Trustees of Columbia University in the City of New York | Reduction of er-mam-localized app-c99 and methods of treating alzheimer's disease |
EP3355909B1 (en) | 2015-09-28 | 2023-06-07 | Children's Hospital Los Angeles | Methods for treating diseases mediated by erbb4-positive pro-inflammatory macrophages |
JP2018534270A (en) | 2015-09-30 | 2018-11-22 | サイトワン セラピューティクス, インコーポレイテッド | 11,13-modified saxitoxin for the treatment of pain |
KR20180051651A (en) | 2015-10-01 | 2018-05-16 | 히트 바이오로직스, 인코퍼레이티드 | Compositions and methods for adjacent I and II extracellular domains as heterologous chimeric proteins |
US20190255107A1 (en) | 2015-10-09 | 2019-08-22 | The Brigham And Women's Hospital, Inc. | Modulation of novel immune checkpoint targets |
WO2017064657A1 (en) | 2015-10-16 | 2017-04-20 | Invictus Oncology Pvt. Ltd. | Fluorescent anticancer platinum drugs |
CN115322188A (en) | 2015-10-30 | 2022-11-11 | 纽罗克里生物科学有限公司 | VALBENAZINE salts and polymorphs thereof |
WO2017079566A1 (en) | 2015-11-05 | 2017-05-11 | Conatus Pharmaceuticals, Inc. | Caspase inhibitors for use in the treatment of liver cancer |
EP3371311B1 (en) | 2015-11-06 | 2021-07-21 | Orionis Biosciences BV | Bi-functional chimeric proteins and uses thereof |
WO2017083348A1 (en) | 2015-11-11 | 2017-05-18 | Celgene Corporation | Controlled release oral dosage forms of poorly soluble drugs and uses thereof |
US10112924B2 (en) | 2015-12-02 | 2018-10-30 | Astraea Therapeutics, Inc. | Piperdinyl nociceptin receptor compounds |
HUE059065T2 (en) | 2015-12-23 | 2022-10-28 | Neurocrine Biosciences Inc | Synthetic method for preparation of (s)-(2r,3r,11br)-3-isobutyl-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1h-pyrido[2,1,-a]lsoquinolin-2-yl 2-amino-3-methylbutanoate di(4-methylbenzenesulfonate) |
WO2017117118A1 (en) | 2015-12-28 | 2017-07-06 | Celgene Corporation | Compositions and methods for inducing conformational changes in cereblon and other e3 ubiquitin ligases |
CN108697663A (en) | 2015-12-31 | 2018-10-23 | 科内图斯医药公司 | The method that caspase inhibitors are used in liver disease |
KR20180095094A (en) | 2016-01-08 | 2018-08-24 | 셀진 코포레이션 | The use of biomarkers as predictors of clinical susceptibility to treatment methods and therapies for cancer |
AR107320A1 (en) | 2016-01-08 | 2018-04-18 | Celgene Corp | SOLID FORMS OF 2- (4-CHLOROPHENYL) -N - ((2- (2,6-DIOXOPIPERIDIN-3-IL) -1-OXOINDOLIN-5-IL) METHYL) -2,2-DIFLUOROACETAMIDE AND ITS PHARMACEUTICAL COMPOSITIONS AND APPLICATIONS |
WO2017120422A1 (en) | 2016-01-08 | 2017-07-13 | Celgene Corporation | Antiproliferative compounds, and their pharmaceutical compositions and uses |
JP7166923B2 (en) | 2016-02-05 | 2022-11-08 | オリオニス バイオサイエンシズ ビーブイ | Targeted therapeutic agents and their uses |
EP3423041A4 (en) | 2016-03-04 | 2019-09-11 | Charleston Laboratories, Inc. | Pharmaceutical compositions |
JP2019507762A (en) | 2016-03-07 | 2019-03-22 | ブイアイビー ブイゼットダブリュー | CD20 binding single domain antibody |
WO2017161116A1 (en) | 2016-03-17 | 2017-09-21 | Infinity Pharmaceuticals, Inc. | Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as pi3k kinase inhibitors |
EP3442940A1 (en) | 2016-04-11 | 2019-02-20 | Clexio Biosciences Ltd. | Deuterated ketamine derivatives |
WO2017180794A1 (en) | 2016-04-13 | 2017-10-19 | Skyline Antiinfectives, Inc. | Deuterated o-sulfated beta-lactam hydroxamic acids and deuterated n-sulfated beta-lactams |
US20190119758A1 (en) | 2016-04-22 | 2019-04-25 | Kura Oncology, Inc. | Methods of selecting cancer patients for treatment with farnesyltransferase inhibitors |
ES2912921T3 (en) | 2016-04-29 | 2022-05-30 | Fgh Biotech Inc | Disubstituted pyrazole compounds for the treatment of diseases |
JP2019514960A (en) | 2016-05-04 | 2019-06-06 | パーデュー ファーマ エルピー | Oxazoline pseudodimer, pharmaceutical composition and use thereof |
EP3452023A1 (en) | 2016-05-05 | 2019-03-13 | Aquestive Therapeutics, Inc. | Enhanced delivery epinephrine compositions |
US11273131B2 (en) | 2016-05-05 | 2022-03-15 | Aquestive Therapeutics, Inc. | Pharmaceutical compositions with enhanced permeation |
CN109563141A (en) | 2016-05-13 | 2019-04-02 | 奥里尼斯生物科学公司 | To the therapeutic targeting of cellular structures |
US11236141B2 (en) | 2016-05-13 | 2022-02-01 | Orionis Biosciences BV | Targeted mutant interferon-beta and uses thereof |
TWI753910B (en) | 2016-05-16 | 2022-02-01 | 美商拜歐斯瑞克斯公司 | Pyridinethiones, pharmaceutical compositions thereof, and their therapeutic use for treating a proliferative, inflammatory, neurodegenerative, or immune-mediated disease |
MA53353A (en) | 2016-05-16 | 2021-06-09 | Intarcia Therapeutics Inc | GLUCAGON RECEPTOR SELECTIVE POLYPEPTIDES AND METHODS FOR THEIR USE |
USD860451S1 (en) | 2016-06-02 | 2019-09-17 | Intarcia Therapeutics, Inc. | Implant removal tool |
USD840030S1 (en) | 2016-06-02 | 2019-02-05 | Intarcia Therapeutics, Inc. | Implant placement guide |
WO2017214269A1 (en) | 2016-06-08 | 2017-12-14 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
US10076494B2 (en) | 2016-06-16 | 2018-09-18 | Dexcel Pharma Technologies Ltd. | Stable orally disintegrating pharmaceutical compositions |
FI3484475T3 (en) | 2016-07-18 | 2023-12-12 | Pharmena S A | 1-methylnicotinamide for the treatment of cardiovascular disease |
JOP20190008A1 (en) | 2016-07-26 | 2019-01-24 | Purdue Pharma Lp | Treatment and prevention of sleep disorders |
EA201990399A1 (en) | 2016-07-29 | 2019-07-31 | Суновион Фармасьютикалз, Инк. | COMPOUNDS, COMPOSITIONS AND THEIR APPLICATION |
CN116283877A (en) | 2016-07-29 | 2023-06-23 | 赛诺维信制药公司 | Compounds, compositions and uses thereof |
EP3510027B1 (en) | 2016-09-07 | 2022-11-02 | FGH BioTech, Inc. | Di-substituted pyrazole compounds for the treatment of diseases |
US10398641B2 (en) | 2016-09-08 | 2019-09-03 | Foamix Pharmaceuticals Ltd. | Compositions and methods for treating rosacea and acne |
JP2019529419A (en) | 2016-09-19 | 2019-10-17 | エムイーアイ ファーマ,インク. | Combination therapy |
WO2018067991A1 (en) | 2016-10-07 | 2018-04-12 | The Brigham And Women's Hospital, Inc. | Modulation of novel immune checkpoint targets |
US10918628B2 (en) | 2016-10-11 | 2021-02-16 | Deutsches Zentrum Für Neurodegenerative Erkrankungen E. V. (Dzne) | Treatment of synucleinopathies |
US11154591B2 (en) | 2016-10-14 | 2021-10-26 | The Trustees Of Columbia University In The City Of New York | Methods of treating alcohol abuse disorder |
WO2018075993A1 (en) | 2016-10-21 | 2018-04-26 | Da Zen Theranostics, Inc | Compounds and methods to sensitize cancer cells to tyrosine kinase inhibitors |
ES2917000T3 (en) | 2016-10-24 | 2022-07-06 | Orionis Biosciences BV | Target mutant interferon-gamma and uses thereof |
US11124839B2 (en) | 2016-11-03 | 2021-09-21 | Kura Oncology, Inc. | Methods of treating cancer patients with farnesyltransferase inhibitors |
US10106521B2 (en) | 2016-11-09 | 2018-10-23 | Phloronol, Inc. | Eckol derivatives, methods of synthesis and uses thereof |
CN116987014A (en) | 2016-11-09 | 2023-11-03 | 诺沃梅迪科斯有限公司 | Nitrite salts of 1, 1-metformin, pharmaceutical compositions and methods of use |
US10799503B2 (en) | 2016-12-01 | 2020-10-13 | Ignyta, Inc. | Methods for the treatment of cancer |
TW202345829A (en) | 2016-12-02 | 2023-12-01 | 美商紐羅克里生物科學有限公司 | Use of valbenazine for treating schizophrenia or schizoaffective disorder |
EP3565580B1 (en) | 2017-01-03 | 2024-03-06 | i2o Therapeutics, Inc. | Continuous administration of exenatide and co-adminstration of acetaminophen, ethinylestradiol or levonorgestrel |
WO2018140671A1 (en) | 2017-01-27 | 2018-08-02 | Celgene Corporation | 3-(1-oxo-4-((4-((3-oxomorpholino) methyl)benzyl)oxy)isoindolin-2-yl)piperidine-2,6-dione and isotopologues thereof |
JP7199361B2 (en) | 2017-01-27 | 2023-01-05 | ニューロクライン バイオサイエンシーズ,インコーポレイテッド | Methods for administering certain VMAT2 inhibitors |
NZ753781A (en) | 2017-02-06 | 2022-10-28 | Spero Therapeutics Inc | Tebipenem pivoxil crystalline forms, compositions including the same, methods of manufacture, and methods of use |
WO2018141964A1 (en) | 2017-02-06 | 2018-08-09 | Orionis Biosciences Nv | Targeted chimeric proteins and uses thereof |
WO2018144999A1 (en) | 2017-02-06 | 2018-08-09 | Orionis Biosciences, Inc. | Targeted engineered interferon and uses thereof |
EP3580230A1 (en) | 2017-02-07 | 2019-12-18 | VIB vzw | Immune-cell targeted bispecific chimeric proteins and uses thereof |
US11129807B2 (en) | 2017-02-16 | 2021-09-28 | Sunovion Pharmaceuticals Inc. | Methods of treating schizophrenia |
US10137121B2 (en) | 2017-02-21 | 2018-11-27 | Kura Oncology, Inc. | Methods of treating cancer with farnesyltransferase inhibitors |
EP3432883B1 (en) | 2017-02-21 | 2021-07-28 | Kura Oncology, Inc. | Methods of treating cancer with farnesyltransferase inhibitors |
AU2018224852A1 (en) | 2017-02-27 | 2019-07-11 | Shattuck Labs, Inc. | VSIG8-based chimeric proteins |
WO2018164996A1 (en) | 2017-03-06 | 2018-09-13 | Neurocrine Biosciences, Inc. | Dosing regimen for valbenazine |
WO2018165142A1 (en) | 2017-03-07 | 2018-09-13 | Celgene Corporation | Solid forms of 3-(5-amino-2-methyl-4-oxo-4h-quinazolin-3-yl)-piperidine-2,6-dione, and their pharmaceutical compositions and uses |
US11555031B2 (en) | 2017-03-20 | 2023-01-17 | The Broad Institute, Inc. | Compounds and methods for regulating insulin secretion |
WO2018178973A1 (en) | 2017-03-26 | 2018-10-04 | Mapi Pharma Ltd. | Glatiramer depot systems for treating progressive forms of multiple sclerosis |
WO2018183782A1 (en) | 2017-03-29 | 2018-10-04 | Siteone Therapeutics, Inc. | 11,13-modified saxitoxins for the treatment of pain |
AU2018243463C1 (en) | 2017-03-29 | 2022-12-01 | Siteone Therapeutics, Inc. | 11,13-modified saxitoxins for the treatment of pain |
US10695309B2 (en) | 2017-03-31 | 2020-06-30 | Western New England University | Sustained-release liothyronine formulations, method of preparation and method of use thereof |
US20200179352A1 (en) | 2017-04-26 | 2020-06-11 | Neurocrine Biosciences, Inc. | Use of valbenazine for treating levodopa-induced dyskinesia |
JOP20190219A1 (en) | 2017-05-09 | 2019-09-22 | Cardix Therapeutics LLC | Pharmaceutical compositions and methods of treating cardiovascular diseases |
US10085999B1 (en) | 2017-05-10 | 2018-10-02 | Arixa Pharmaceuticals, Inc. | Beta-lactamase inhibitors and uses thereof |
MA49140A (en) | 2017-05-19 | 2020-03-25 | Nflection Therapeutics Inc | MERGED HETEROAROMATIC-ANILINE COMPOUNDS FOR THE TREATMENT OF DERMAL DISORDERS |
JP7212956B2 (en) | 2017-05-19 | 2023-01-26 | エヌフレクション セラピューティクス インコーポレイテッド | Pyrrolopyridine-aniline compounds for the treatment of skin disorders |
EP3630079A4 (en) | 2017-05-31 | 2021-02-24 | The Children's Medical Center Corporation | TARGETING LYSINE DEMETHYLASES (KDMs) AS A THERAPEUTIC STRATEGY FOR DIFFUSE LARGE B-CELL LYMPHOMA |
WO2018223065A1 (en) | 2017-06-01 | 2018-12-06 | Xoc Pharmaceuticals, Inc. | Ergoline derivatives for use in medicine |
WO2019005874A1 (en) | 2017-06-26 | 2019-01-03 | The Trustees Of Columbia University In The City Of New York | Cholinergic agonism for the treatment of pancreatic cancer |
US11168326B2 (en) | 2017-07-11 | 2021-11-09 | Actym Therapeutics, Inc. | Engineered immunostimulatory bacterial strains and uses thereof |
EA202090414A1 (en) | 2017-08-02 | 2020-05-28 | Суновион Фармасьютикалз Инк. | COMPOUNDS AND THEIR APPLICATION |
BR112020002591A2 (en) | 2017-08-07 | 2020-07-28 | Kura Oncology, Inc. | method for treating cancer |
US10806730B2 (en) | 2017-08-07 | 2020-10-20 | Kura Oncology, Inc. | Methods of treating cancer with farnesyltransferase inhibitors |
CN111372567B (en) | 2017-09-21 | 2024-03-15 | 纽罗克里生物科学有限公司 | High dose valphenazine formulations and compositions, methods and kits relating thereto |
US11590081B1 (en) | 2017-09-24 | 2023-02-28 | Tris Pharma, Inc | Extended release amphetamine tablets |
US10993941B2 (en) | 2017-10-10 | 2021-05-04 | Neurocrine Biosciences, Inc. | Methods for the administration of certain VMAT2 inhibitors |
SG11202003194YA (en) | 2017-10-10 | 2020-05-28 | Neurocrine Biosciences Inc | Methods for the administration of certain vmat2 inhibitors |
WO2019097080A1 (en) | 2017-11-20 | 2019-05-23 | Kiakos Konstantinos | 3,5-diarylidenyl-n-substituted-piperid-4-one-derived inhibitors of stat3 pathway acitivty and uses therof |
WO2019113269A1 (en) | 2017-12-08 | 2019-06-13 | Kura Oncology, Inc. | Methods of treating cancer patients with farnesyltransferase inhibitors |
CA3088630A1 (en) | 2017-12-15 | 2019-06-20 | Solarea Bio, Inc. | Microbial compositions and methods for treating type 2 diabetes, obesity, and metabolic syndrome |
CA3085593A1 (en) | 2017-12-18 | 2019-06-27 | Sterngreene, Inc. | Pyrimidine compounds useful as tyrosine kinase inhibitors |
TW201929847A (en) | 2018-01-10 | 2019-08-01 | 美商克拉治療有限責任公司 | Pharmaceutical compositions comprising dicarboxylic acids and their therapeutic applications |
US11701334B2 (en) | 2018-01-10 | 2023-07-18 | Cura Therapeutics, Llc | Pharmaceutical compositions comprising phenylsulfonamides, and their therapeutic applications |
EP3743049A1 (en) | 2018-01-24 | 2020-12-02 | Purdue Pharma LP | Sleep disorder treatment and prevention |
MX2020008208A (en) | 2018-02-05 | 2020-11-09 | Orionis Biosciences Inc | Fibroblast binding agents and use thereof. |
WO2019156565A1 (en) | 2018-02-12 | 2019-08-15 | Fast Forward Pharmaceuticals B.V. | Improved antagonistic anti-human cd40 monoclonal antibodies |
US20210008030A1 (en) | 2018-02-16 | 2021-01-14 | Sunovion Pharmaceuticals Inc. | Methods of treating social function disorders |
BR112020016256A2 (en) | 2018-02-21 | 2020-12-15 | AI Therapeutics, Inc. | COMBINATION THERAPY WITH APILIMOD AND GLUTEN-MATERIAL AGENTS |
EP3768299A1 (en) | 2018-03-22 | 2021-01-27 | The Children's Medical Center Corporation | Methods and compositions relating to lung repair |
US20190351031A1 (en) | 2018-05-16 | 2019-11-21 | Halozyme, Inc. | Methods of selecting subjects for combination cancer therapy with a polymer-conjugated soluble ph20 |
CN108836948B (en) * | 2018-06-11 | 2024-04-12 | 宁波西敦医药包衣科技有限公司 | Product capable of realizing controllable release of nutrients by coating technology |
CN112638387A (en) | 2018-06-14 | 2021-04-09 | 纽罗克里生物科学有限公司 | VMAT2 inhibitor compounds, compositions, and methods related thereto |
WO2020006341A1 (en) | 2018-06-29 | 2020-01-02 | Conatus Pharmaceuticals, Inc. | (s)-3-(2-(4-(benzyl)-3-oxopiperazin-1-yl)acetamido)-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid derivatives and related compounds as caspase inhibitors for treating cardiovascular diseases |
AU2019301699B2 (en) | 2018-07-11 | 2023-11-02 | Actym Therapeutics, Inc. | Engineered immunostimulatory bacterial strains and uses thereof |
EP3836926A4 (en) | 2018-08-15 | 2022-05-04 | Neurocrine Biosciences, Inc. | Methods for the administration of certain vmat2 inhibitors |
EP3844276A2 (en) | 2018-08-28 | 2021-07-07 | Actym Therapeutics, Inc. | Engineered immunostimulatory bacterial strains and uses thereof |
WO2020047319A1 (en) | 2018-08-29 | 2020-03-05 | Shattuck Labs, Inc. | Combination therapies comprising sirp alpha-based chimeric proteins |
CA3111795A1 (en) | 2018-09-05 | 2020-03-12 | Solarea Bio, Inc. | Methods and compositions for treating musculoskeletal diseases |
WO2020072835A1 (en) | 2018-10-03 | 2020-04-09 | Siteone Therapeutics, Inc. | 11,13-modified saxitoxins for the treatment of pain |
EP3873469A2 (en) | 2018-11-01 | 2021-09-08 | Kura Oncology, Inc. | Methods of treating cancer with farnesyltransferase inhibitors |
WO2020102454A1 (en) | 2018-11-13 | 2020-05-22 | Regents Of The University Of Minnesota | Cd40 targeted peptides and uses thereof |
US10722473B2 (en) | 2018-11-19 | 2020-07-28 | Purdue Pharma L.P. | Methods and compositions particularly for treatment of attention deficit disorder |
JP2022513089A (en) | 2018-11-20 | 2022-02-07 | エヌフレクション セラピューティクス インコーポレイテッド | Arylaniline and heteroarylaniline compounds for the treatment of skin cancer |
WO2020106308A1 (en) | 2018-11-20 | 2020-05-28 | Nflection Therapeutics, Inc. | Naphthyridinone-aniline compounds for treatment of dermal disorders |
CN113645964A (en) | 2018-11-20 | 2021-11-12 | 恩福莱克逊治疗有限公司 | Arylaniline and heteroarylaniline compounds for use in fetal marker therapy |
US11572344B2 (en) | 2018-11-20 | 2023-02-07 | Nflection Therapeutics, Inc. | Cyanoaryl-aniline compounds for treatment of dermal disorders |
EP3898609A1 (en) | 2018-12-19 | 2021-10-27 | Shy Therapeutics LLC | Compounds that interact with the ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease |
EP3897638A1 (en) | 2018-12-21 | 2021-10-27 | Kura Oncology, Inc. | Therapies for squamous cell carcinomas |
WO2020132700A1 (en) | 2018-12-21 | 2020-06-25 | Fgh Biotech Inc. | Methods of using inhibitors of srebp in combination with niclosamide and analogs thereof |
US11447468B2 (en) | 2019-02-06 | 2022-09-20 | Dice Alpha, Inc. | IL-17 ligands and uses thereof |
CA3176660A1 (en) | 2019-02-27 | 2020-09-03 | Actym Therapeutics, Inc. | Immunostimulatory bacteria engineered to colonize tumors, tumor-resident immune cells, and the tumor microenvironment |
US20220142983A1 (en) | 2019-03-01 | 2022-05-12 | Kura Oncology, Inc. | Methods of treating cancer with farnesyltransferase inhibitors |
WO2020181165A1 (en) | 2019-03-07 | 2020-09-10 | Conatus Pharmaceuticals Inc. | Caspase inhibitors and methods of use thereof |
AU2020236225A1 (en) | 2019-03-14 | 2021-09-16 | Sunovion Pharmaceuticals Inc. | Salts of a isochromanyl compound and crystalline forms, processes for preparing, therapeutic uses, and pharmaceutical compositions thereof |
TW202108170A (en) | 2019-03-15 | 2021-03-01 | 美商庫拉腫瘤技術股份有限公司 | Methods of treating cancer patients with farnesyltransferase inhibitors |
WO2020193431A1 (en) | 2019-03-22 | 2020-10-01 | Deutsches Krebsforschungszentrum | Novel inhibitors of histone deacetylase 10 |
EP3712127A1 (en) | 2019-03-22 | 2020-09-23 | Deutsches Krebsforschungszentrum | Novel inhibitors of histone deacetylase 10 |
JP2022527495A (en) | 2019-03-29 | 2022-06-02 | クラ オンコロジー, インコーポレイテッド | Treatment of squamous cell carcinoma with farnesyltransferase inhibitor |
TW202102218A (en) | 2019-04-01 | 2021-01-16 | 美商庫拉腫瘤技術股份有限公司 | Methods of treating cancer with farnesyltransferase inhibitors |
US20220257767A1 (en) | 2019-04-03 | 2022-08-18 | President And Fellows Of Harvard College | Ionic liquids for drug delivery |
WO2020223583A1 (en) | 2019-05-02 | 2020-11-05 | Kura Oncology, Inc. | Methods of treating acute myeloid leukemia with farnesyltransferase inhibitors |
WO2020227437A1 (en) * | 2019-05-06 | 2020-11-12 | Axial Biotherapeutics, Inc. | Sustained release solid dosage forms for modulating the colonic microbiome |
JP6890865B1 (en) | 2019-06-03 | 2021-06-18 | 株式会社大分大学先端医学研究所 | Cyclic amide compounds for the treatment of rabies and methods thereof |
EP3986163A2 (en) | 2019-06-19 | 2022-04-27 | Solarea Bio, Inc. | Microbial compositions and methods for producing upgraded probiotic assemblages |
CA3146157A1 (en) | 2019-07-11 | 2021-01-14 | Cura Therapeutics, Llc | Sulfone compounds and pharmaceutical compositions thereof, and their therapeutic applications for the treatment of neurodegenerative diseases |
EP3996813A1 (en) | 2019-07-11 | 2022-05-18 | Cura Therapeutics, LLC | Phenyl compounds and pharmaceutical compositions thereof, and their therapeutic applications |
US11098002B2 (en) | 2019-07-26 | 2021-08-24 | Espervita Therapeutics, Inc. | Functionalized long-chain hydrocarbon mono- and di-carboxylic acids and their use for the prevention or treatment of disease |
US11654124B2 (en) | 2019-07-29 | 2023-05-23 | Amneal Pharmaceuticals Llc | Stabilized formulations of 4-amino-3-substituted butanoic acid derivatives |
US10792262B1 (en) | 2019-07-29 | 2020-10-06 | Saol International Limited | Stabilized formulations of 4-amino-3-substituted butanoic acid derivatives |
US10940141B1 (en) | 2019-08-23 | 2021-03-09 | Neurocrine Biosciences, Inc. | Methods for the administration of certain VMAT2 inhibitors |
WO2021038296A2 (en) | 2019-08-27 | 2021-03-04 | Tonix Pharma Holdings Limited | Modified tff2 polypeptides |
WO2021055376A1 (en) | 2019-09-16 | 2021-03-25 | Dice Alpha, Inc. | Il-17a modulators and uses thereof |
EP4034236A1 (en) | 2019-09-26 | 2022-08-03 | Abionyx Pharma SA | Compounds useful for treating liver diseases |
WO2021067335A1 (en) | 2019-10-01 | 2021-04-08 | Molecular Skin Therapeutics, Inc. | Benzoxazinone compounds as klk5/7 dual inhibitors |
BR112022009139A2 (en) | 2019-11-12 | 2022-09-06 | Actym Therapeutics Inc | IMMUNOSTIMULATING BACTERIA DISPENSING PLATFORMS AND THEIR USE FOR DISPENSING THERAPEUTIC PRODUCTS |
JP2023503899A (en) | 2019-11-22 | 2023-02-01 | プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ | Ionic liquids for drug delivery |
EP4069245A1 (en) | 2019-12-02 | 2022-10-12 | Celgene Corporation | Therapy for the treatment of cancer |
US20230093147A1 (en) | 2020-03-09 | 2023-03-23 | President And Fellows Of Harvard College | Methods and compositions relating to improved combination therapies |
CN115996751A (en) | 2020-04-28 | 2023-04-21 | 哈佛大学校长及研究员协会 | Methods and compositions relating to ionic liquid adjuvants |
WO2021226033A1 (en) | 2020-05-07 | 2021-11-11 | President And Fellows Of Harvard College | Hyaluronic acid drug conjugates |
WO2021242970A1 (en) | 2020-05-29 | 2021-12-02 | Boulder Bioscience Llc | Methods for improved endovascular thrombectomy using 3,3'-diindolylmethane |
EP4157923A2 (en) | 2020-05-29 | 2023-04-05 | President And Fellows Of Harvard College | Living cells engineered with polyphenol-functionalized biologically active nanocomplexes |
EP4168414A1 (en) | 2020-06-18 | 2023-04-26 | Shy Therapeutics LLC | Substituted thienopyrimidines that interact with the ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease |
WO2021262579A1 (en) | 2020-06-23 | 2021-12-30 | President And Fellows Of Harvard College | Compositions and methods relating to combinatorial hyaluronic acid conjugates |
US11319313B2 (en) | 2020-06-30 | 2022-05-03 | Poxel Sa | Crystalline forms of deuterium-enriched pioglitazone |
CA3184852A1 (en) | 2020-07-10 | 2022-01-13 | Lida Katsimpardi | Use of gdf11 to diagnose and treat anxiety and depression |
CA3191433A1 (en) | 2020-08-12 | 2022-02-17 | Actym Therapeutics, Inc. | Immunostimulatory bacteria-based vaccines, therapeutics, and rna delivery platforms |
IL300626A (en) | 2020-08-14 | 2023-04-01 | Siteone Therapeutics Inc | Non-hydrated ketone inhibitors of nav1.7 for the treatment of pain |
US11541009B2 (en) | 2020-09-10 | 2023-01-03 | Curemark, Llc | Methods of prophylaxis of coronavirus infection and treatment of coronaviruses |
US11071739B1 (en) | 2020-09-29 | 2021-07-27 | Genus Lifesciences Inc. | Oral liquid compositions including chlorpromazine |
TW202233173A (en) | 2020-10-30 | 2022-09-01 | 愛爾蘭商Ds生物製藥有限公司 | Pharmaceutical compositions comprising 15-hetre and methods of use thereof |
WO2022155410A1 (en) | 2021-01-15 | 2022-07-21 | President And Fellows Of Harvard College | Methods and compositions relating to anti-mfsd2a antibodies |
WO2022161355A1 (en) | 2021-01-26 | 2022-08-04 | Cytocares (Shanghai) Inc. | Chimeric antigen receptor (car) constructs and nk cells expressing car constructs |
EP4284377A1 (en) | 2021-01-27 | 2023-12-06 | Shy Therapeutics LLC | Methods for the treatment of fibrotic disease |
WO2022165000A1 (en) | 2021-01-27 | 2022-08-04 | Shy Therapeutics, Llc | Methods for the treatment of fibrotic disease |
WO2022187573A1 (en) | 2021-03-05 | 2022-09-09 | President And Fellows Of Harvard College | Methods and compositions relating to cell membrane hybridization and camouflaging |
WO2022189010A1 (en) | 2021-03-07 | 2022-09-15 | Givaudan Sa | Methods and compositions for treating and preventing urinary tract infections |
WO2022189856A1 (en) | 2021-03-08 | 2022-09-15 | Abionyx Pharma Sa | Compounds useful for treating liver diseases |
AU2022232625A1 (en) | 2021-03-10 | 2023-09-28 | Dice Molecules Sv, Inc. | Alpha v beta 6 and alpha v beta 1 integrin inhibitors and uses thereof |
CA3211496A1 (en) | 2021-03-19 | 2022-09-22 | Tiba Biotech Llc | Artificial alphavirus-derived rna replicon expression systems |
EP4326721A1 (en) | 2021-04-22 | 2024-02-28 | Protego Biopharma, Inc. | Spirocyclic imidazolidinones and imidazolidinediones for treatment of light chain amyloidosis |
EP4347568A1 (en) | 2021-05-27 | 2024-04-10 | Protego Biopharma, Inc. | Heteroaryl diamide ire1/xbp1s activators |
WO2022265880A1 (en) | 2021-06-16 | 2022-12-22 | President And Fellows Of Harvard College | Improved methods and compositions for drug delivery relating to ionic liquids |
WO2022271537A1 (en) | 2021-06-25 | 2022-12-29 | President And Fellows Of Harvard College | Compositions and methods relating to injectable microemulsions |
WO2023015240A1 (en) | 2021-08-05 | 2023-02-09 | Bristol-Myers Squibb Company | Tricyclic fused pyrimidine compounds for use as her2 inhibitors |
WO2023034506A1 (en) | 2021-09-01 | 2023-03-09 | Flagship Pioneering Innovations Vi, Llc | Methods and compositions for inducing fetal hemoglobin |
WO2023034507A1 (en) | 2021-09-01 | 2023-03-09 | Flagship Pioneering Innovations Vi, Llc | In vivo and ex vivo methods of modulating t cell exhaustion/de-exhaustion |
US20230083717A1 (en) | 2021-09-01 | 2023-03-16 | Flagship Pioneering Innovations Vi, Llc | Methods and compositions for promoting adipocyte beiging |
WO2023034504A1 (en) | 2021-09-01 | 2023-03-09 | Flagship Pioneering Innovations Vi, Llc | Methods and compositions for inducing fetal hemoglobin, modulating erythroid cell lineages, and perturbing megakaryocyte lineages |
WO2023039164A2 (en) | 2021-09-09 | 2023-03-16 | Flagship Pioneering Innovations Vi, Llc | Methods and compositions for modulating goblet cells and for muco-obstructive diseases |
US20230077584A1 (en) | 2021-09-09 | 2023-03-16 | Flagship Pioneering Innovations Vi, Llc | Methods and compositions for modulating enteroendocrine cells |
WO2023043827A2 (en) | 2021-09-14 | 2023-03-23 | Flagship Pioneering Innovations Vi, Llc | Methods and compositions for perturbing monocyte and neutrophil lineages |
WO2023055457A1 (en) | 2021-09-29 | 2023-04-06 | Amneal Pharmaceuticals Llc | Baclofen-containing granule formulations and reduced patient exposure to metabolite variations |
CA3233824A1 (en) | 2021-10-08 | 2023-04-13 | Samir Mitragotri | Ionic liquids for drug delivery |
EP4162933A1 (en) | 2021-10-08 | 2023-04-12 | Algiax Pharmaceuticals GmbH | Compound for treating non-alcoholic fatty liver disease and related diseases |
WO2023092150A1 (en) | 2021-11-22 | 2023-05-25 | Solarea Bio, Inc. | Methods and compositions for treating musculoskeletal diseases, treating inflammation, and managing symptoms of menopause |
CA3234276A1 (en) | 2021-11-30 | 2023-06-08 | Kura Oncology, Inc. | Macrocyclic compounds having farnesyltransferase inhibitory activity |
US20230190834A1 (en) | 2021-12-21 | 2023-06-22 | Solarea Bio, Inc. | Immunomodulatory compositions comprising microbial entities |
WO2023129577A1 (en) | 2022-01-03 | 2023-07-06 | Lilac Therapeutics, Inc. | Cyclic thiol prodrugs |
US20230303580A1 (en) | 2022-03-28 | 2023-09-28 | Isosterix, Inc. | Inhibitors of the myst family of lysine acetyl transferases |
US20230348909A1 (en) | 2022-03-30 | 2023-11-02 | Biomarin Pharmaceutical Inc. | Dystrophin exon skipping oligonucleotides |
GB2619907A (en) | 2022-04-01 | 2023-12-27 | Kanna Health Ltd | Novel crystalline salt forms of mesembrine |
WO2023201282A1 (en) | 2022-04-14 | 2023-10-19 | Bristol-Myers Squibb Company | Novel gspt1 compounds and methods of use of the novel compounds |
WO2023201348A1 (en) | 2022-04-15 | 2023-10-19 | Celgene Corporation | Methods for predicting responsiveness of lymphoma to drug and methods for treating lymphoma |
WO2023211990A1 (en) | 2022-04-25 | 2023-11-02 | Siteone Therapeutics, Inc. | Bicyclic heterocyclic amide inhibitors of na v1.8 for the treatment of pain |
US20230416741A1 (en) | 2022-05-05 | 2023-12-28 | Biomarin Pharmaceutical Inc. | Method of treating duchenne muscular dystrophy |
WO2023230524A1 (en) | 2022-05-25 | 2023-11-30 | Flagship Pioneering Innovations Vi, Llc | Compositions of secretory and/or catalytic cells and methods using the same |
WO2024054832A1 (en) | 2022-09-09 | 2024-03-14 | Innovo Therapeutics, Inc. | CK1α AND DUAL CK1α / GSPT1 DEGRADING COMPOUNDS |
WO2024073473A1 (en) | 2022-09-30 | 2024-04-04 | Boulder Bioscience Llc | Compositions comprising 3,3'-diindolylmethane for treating non-hemorrhagic closed head injury |
Family Cites Families (109)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA873815A (en) * | 1971-06-22 | G. Mason Stanley | Encapsulated hydrophilic compositions and methods of making them | |
CA494130A (en) * | 1953-06-30 | Western Electric Company, Incorporated | Power and impedance monitor | |
NL6603111A (en) * | 1956-11-24 | 1966-09-20 | ||
US2928770A (en) * | 1958-11-28 | 1960-03-15 | Frank M Bardani | Sustained action pill |
US3115441A (en) * | 1962-06-06 | 1963-12-24 | Victor M Hermelin | Timed release pharmaceutical preparations and method of making the same |
US3432593A (en) * | 1963-09-18 | 1969-03-11 | Key Pharm Inc | Delayed and sustained release type pharmaceutical preparation |
US3341416A (en) * | 1963-12-11 | 1967-09-12 | Ncr Co | Encapsulation of aspirin in ethylcellulose and its product |
GB1056259A (en) * | 1964-11-30 | 1967-01-25 | Lyons & Co Ltd J | Flavour powders |
US3594326A (en) * | 1964-12-03 | 1971-07-20 | Ncr Co | Method of making microscopic capsules |
US3460972A (en) * | 1965-09-29 | 1969-08-12 | Battelle Development Corp | Liquid encapsulation |
US3488418A (en) * | 1965-11-18 | 1970-01-06 | Sterling Drug Inc | Sustained relief analgesic composition |
GB1205769A (en) * | 1966-07-26 | 1970-09-16 | Nat Patent Dev Corp | Polymer compositions containing flavouring or fragrance agents |
AT270071B (en) * | 1966-08-12 | 1969-04-10 | Roehm & Haas Gmbh | Coating varnish for dosage forms |
US3657144A (en) * | 1967-06-05 | 1972-04-18 | Ncr Co | Encapsulation process |
US3594470A (en) * | 1968-02-19 | 1971-07-20 | Abbott Lab | Chewable tablets including coated particles of pseudoephedrine-weak cation exchange resin |
US3732172A (en) * | 1968-02-28 | 1973-05-08 | Ncr Co | Process for making minute capsules and prefabricated system useful therein |
US3576759A (en) * | 1968-04-12 | 1971-04-27 | Ncr Co | Process for en masse production of spherules by desiccation |
JPS5212150B1 (en) * | 1968-06-04 | 1977-04-05 | ||
US3639306A (en) * | 1968-08-08 | 1972-02-01 | Amicon Corp | Encapsulating particles and process for making same |
US3539465A (en) * | 1968-10-08 | 1970-11-10 | Ncr Co | Encapsulation of hydrophilic liquid-in-oil emulsions |
US3634586A (en) * | 1968-12-04 | 1972-01-11 | Bristol Myers Co | Stable aqueous suspensions of ampicillin |
BE744162A (en) * | 1969-01-16 | 1970-06-15 | Fuji Photo Film Co Ltd | ENCAPSULATION PROCESS |
US3567650A (en) * | 1969-02-14 | 1971-03-02 | Ncr Co | Method of making microscopic capsules |
US3642978A (en) * | 1969-03-05 | 1972-02-15 | Mochida Pharm Co Ltd | Process for producing stable cytochrome c preparation |
US3887699A (en) * | 1969-03-24 | 1975-06-03 | Seymour Yolles | Biodegradable polymeric article for dispensing drugs |
GB1287431A (en) * | 1969-04-16 | 1972-08-31 | Aspro Nicholas Ltd | Improvements in pharmaceutical formulations |
US3703576A (en) * | 1969-08-08 | 1972-11-21 | Fuji Photo Film Co Ltd | Method of producing micro-capsules enclosing acetylsalicylic acid therein |
US3629392A (en) * | 1969-08-15 | 1971-12-21 | Gilbert S Banker | Entrapment compositions and processes |
US3780195A (en) * | 1969-10-22 | 1973-12-18 | Balchem Corp | Encapsulation process |
CA923384A (en) * | 1970-02-03 | 1973-03-27 | Abe Jinnosuke | Process for preparing a micro capsule |
DE2010115A1 (en) * | 1970-03-04 | 1971-09-16 | Farbenfabriken Bayer Ag, 5090 Leverkusen | Process for the production of micro-granules |
DE2010416B2 (en) * | 1970-03-05 | 1979-03-29 | Hoechst Ag, 6000 Frankfurt | Orally applicable dosage form with sustained release effect |
US3959457A (en) * | 1970-06-05 | 1976-05-25 | Temple University | Microparticulate material and method of making such material |
DE2031871C3 (en) * | 1970-06-27 | 1974-06-27 | Roehm Gmbh, 6100 Darmstadt | Coating compound for dosage forms |
GB1359643A (en) * | 1970-09-28 | 1974-07-10 | Controlled Medications | Controlled release medicament |
US3725556A (en) * | 1970-11-12 | 1973-04-03 | D Hanssen | Method of manufacturing rapidly disintegrating pharmaceutical tablets |
US3821422A (en) * | 1971-03-04 | 1974-06-28 | Merck & Co Inc | Devil's food cake and other alkaline bakery goods |
JPS5214234B2 (en) * | 1971-07-30 | 1977-04-20 | ||
US3909444A (en) * | 1971-08-05 | 1975-09-30 | Ncr Co | Microcapsule |
JPS528795B2 (en) * | 1971-12-30 | 1977-03-11 | ||
JPS523342B2 (en) * | 1972-01-26 | 1977-01-27 | ||
US4016254A (en) * | 1972-05-19 | 1977-04-05 | Beecham Group Limited | Pharmaceutical formulations |
GB1403584A (en) * | 1972-05-19 | 1975-08-28 | Beecham Group Ltd | Control medicaments |
JPS5438164B2 (en) * | 1972-05-29 | 1979-11-19 | ||
BE791458A (en) * | 1972-07-31 | 1973-05-16 | Merck & Co Inc | MICROENCAPSULE PRODUCT |
DE2237503A1 (en) * | 1972-07-31 | 1974-10-03 | Basf Ag | METHOD OF MANUFACTURING MICROCAPSULES |
JPS4962623A (en) * | 1972-10-18 | 1974-06-18 | ||
JPS4993522A (en) * | 1973-01-12 | 1974-09-05 | ||
US3954959A (en) * | 1973-03-28 | 1976-05-04 | A/S Alfred Benzon | Oral drug preparations |
GB1413186A (en) * | 1973-06-27 | 1975-11-12 | Toyo Jozo Kk | Process for encapsulation of medicaments |
FR2236483B1 (en) * | 1973-07-12 | 1976-11-12 | Choay Sa | |
DE2336218C3 (en) * | 1973-07-17 | 1985-11-14 | Byk Gulden Lomberg Chemische Fabrik Gmbh, 7750 Konstanz | Oral dosage form |
JPS5094112A (en) * | 1973-12-06 | 1975-07-26 | ||
US3962468A (en) * | 1974-03-07 | 1976-06-08 | General Foods Corporation | Spray-dried L-aspartic acid derivatives |
US4118336A (en) * | 1974-03-25 | 1978-10-03 | Toyo Jozo Company, Ltd. | Novel cellulose microcapsules and preparation thereof |
DE2452975C2 (en) * | 1974-11-08 | 1982-09-16 | Dr. C. Otto & Comp. Gmbh, 4630 Bochum | Charging trolleys for coking ovens |
US3996355A (en) * | 1975-01-02 | 1976-12-07 | American Home Products Corporation | Permanent suspension pharmaceutical dosage form |
US4123381A (en) * | 1975-02-20 | 1978-10-31 | Toyo Jozo Company, Ltd. | Process for producing cellulose microcapsules, and resulting cellulose microcapsules |
US4011312A (en) * | 1975-06-25 | 1977-03-08 | American Home Products Corporation | Prolonged release drug form for the treatment of bovine mastitis |
JPS523653A (en) * | 1975-06-27 | 1977-01-12 | Fuji Photo Film Co Ltd | Process for producing fine polymer particles |
US4324683A (en) * | 1975-08-20 | 1982-04-13 | Damon Corporation | Encapsulation of labile biological material |
JPS5840529B2 (en) * | 1975-09-29 | 1983-09-06 | 明治製菓株式会社 | Keikouyou Seizaino Seiho |
PT66201B (en) * | 1976-02-23 | 1978-11-07 | Corvi Mora E | METHOD AND COMPOSITION FOR THE THERAPEUTICS OF BRAIN CIRCULATORY DISEASES |
CH627449A5 (en) * | 1977-03-25 | 1982-01-15 | Hoffmann La Roche | METHOD FOR PRODUCING MICROCRYSTALLINE VITAMIN A-ACETATE, AND DRY, FREE-FLOWING PREPAIRS IN WHICH VITAMIN A-ACETATE IS IN A MICROCRYSTALLINE FORM. |
DE2856901D2 (en) * | 1977-06-07 | 1980-11-13 | Garching Instrumente | Form of implant medicament and preparation process |
NZ189022A (en) * | 1977-12-08 | 1981-11-19 | Beecham Group Ltd | Pharmaceutically acceptable particles of clavulanates dispersed in a polymeric binder |
AT355053B (en) * | 1978-03-03 | 1980-02-11 | Koreska Gmbh W | MICROCAPSULES FOR RECORDING MATERIALS AND METHOD FOR THE PRODUCTION THEREOF |
DE2809659A1 (en) * | 1978-03-07 | 1979-09-13 | Kores Holding Zug Ag | Microcapsules for colour reaction recording material - have walls of alkyl-cellulose and contain aq. acidic metal chloride soln. as Lewis acid |
US4182778A (en) * | 1978-05-17 | 1980-01-08 | General Foods Corporation | Encapsulation of vitamin and mineral nutrients |
US4230687A (en) * | 1978-05-30 | 1980-10-28 | Griffith Laboratories U.S.A., Inc. | Encapsulation of active agents as microdispersions in homogeneous natural polymeric matrices |
US4489055A (en) * | 1978-07-19 | 1984-12-18 | N.V. Sopar S.A. | Process for preparing biodegradable submicroscopic particles containing a biologically active substance and their use |
JPS5524938A (en) * | 1978-08-10 | 1980-02-22 | Nippon Kokan Kk <Nkk> | Manufacture of galvanized cold rolled steel plate excellent in deep drawability |
US4205060A (en) * | 1978-12-20 | 1980-05-27 | Pennwalt Corporation | Microcapsules containing medicament-polymer salt having a water-insoluble polymer sheath, their production and their use |
US4368197A (en) * | 1979-02-21 | 1983-01-11 | Research Corporation | Zinc aminophylline and its use in the treatment of bronchospasms |
US4201822A (en) * | 1979-06-13 | 1980-05-06 | The United States Of America As Represented By The Secretary Of The Army | Novel fabric containing microcapsules of chemical decontaminants encapsulated within semipermeable polymers |
US4293539A (en) * | 1979-09-12 | 1981-10-06 | Eli Lilly And Company | Controlled release formulations and method of treatment |
JPS5569509A (en) * | 1979-11-30 | 1980-05-26 | Mcleod Patrick | Biologically decomposable particle |
US4280995A (en) * | 1979-12-31 | 1981-07-28 | Pharmaceutical Associates, Inc. | Oral suspension of phenytoin |
JPS56152739A (en) * | 1980-04-25 | 1981-11-26 | Tanabe Seiyaku Co Ltd | Production of microcapsule |
US4384975A (en) * | 1980-06-13 | 1983-05-24 | Sandoz, Inc. | Process for preparation of microspheres |
US4361580A (en) * | 1980-06-20 | 1982-11-30 | The Upjohn Manufacturing Company | Aluminum ibuprofen pharmaceutical suspensions |
FR2485370A1 (en) * | 1980-06-30 | 1981-12-31 | Commissariat Energie Atomique | INERTE SUPPORT IN RETICULATED COPOLYMER, METHOD FOR PREPARING THE SAME AND USE THEREOF FOR PRODUCING DELAYED MEDICAMENTS |
US4321253A (en) * | 1980-08-22 | 1982-03-23 | Beatty Morgan L | Suspension of microencapsulated bacampicillin acid addition salt for oral, especially pediatric, administration |
US4389330A (en) * | 1980-10-06 | 1983-06-21 | Stolle Research And Development Corporation | Microencapsulation process |
JPS58401A (en) * | 1981-06-26 | 1983-01-05 | Yokohama Rubber Co Ltd:The | Filled tire |
WO1983000284A1 (en) * | 1981-07-15 | 1983-02-03 | Key Pharma | Sustained release theophylline |
US4587118A (en) * | 1981-07-15 | 1986-05-06 | Key Pharmaceuticals, Inc. | Dry sustained release theophylline oral formulation |
US4452821A (en) * | 1981-12-18 | 1984-06-05 | Gerhard Gergely | Confectionery product, particularly chewing gum, and process for its manufacture |
DE3218150C2 (en) * | 1982-05-14 | 1986-09-25 | Akzo Gmbh, 5600 Wuppertal | Active substance-containing body for long-term release and process for its production |
US4994260A (en) * | 1982-05-28 | 1991-02-19 | Astra Lakemedel Aktiebolag | Pharmaceutical mixture |
US4415547A (en) * | 1982-06-14 | 1983-11-15 | Sterling Drug Inc. | Sustained-release pharmaceutical tablet and process for preparation thereof |
US4530840A (en) * | 1982-07-29 | 1985-07-23 | The Stolle Research And Development Corporation | Injectable, long-acting microparticle formulation for the delivery of anti-inflammatory agents |
US4789516A (en) * | 1983-04-15 | 1988-12-06 | Damon Biotech, Inc | Production of sustained released system |
US4690682A (en) * | 1983-04-15 | 1987-09-01 | Damon Biotech, Inc. | Sustained release |
US4497832A (en) * | 1983-04-18 | 1985-02-05 | Warner-Lambert Company | Chewing gum composition having enhanced flavor-sweetness |
DE3314003A1 (en) * | 1983-04-18 | 1984-10-18 | Boehringer Ingelheim KG, 6507 Ingelheim | DIVISIBLE TABLET WITH DELAYED ACTIVE SUBSTANCE RELEASE AND METHOD FOR THE PRODUCTION THEREOF |
US4590825A (en) | 1983-05-06 | 1986-05-27 | John Vaughn | High torque fastener and driving tool |
GB2141023B (en) * | 1983-06-06 | 1986-09-03 | Robins Co Inc A H | Delayed release formulations |
US4632822A (en) * | 1983-07-20 | 1986-12-30 | Warner-Lambert Company | Magnesium trisilicate suitable for preparation of medicament adsorbates of antiasmatics |
US4647450A (en) * | 1983-07-20 | 1987-03-03 | Warner-Lambert Company | Chewing gum compositions containing magnesium trisilicate absorbates |
US4647459A (en) * | 1983-07-20 | 1987-03-03 | Warner-Lambert Company | Confectionery compositions containing magnesium trisilicate adsorbates |
US4749575A (en) * | 1983-10-03 | 1988-06-07 | Bio-Dar Ltd. | Microencapsulated medicament in sweet matrix |
SE8404808L (en) * | 1983-10-03 | 1985-04-04 | Avner Rotman | MICROCAPCLE PLATE MEDICINE IN SOT MATRIX |
US4818542A (en) * | 1983-11-14 | 1989-04-04 | The University Of Kentucky Research Foundation | Porous microspheres for drug delivery and methods for making same |
JPS6110A (en) * | 1984-06-08 | 1986-01-06 | Sekisui Chem Co Ltd | Preparation of poultice |
US4678516A (en) * | 1984-10-09 | 1987-07-07 | The Dow Chemical Company | Sustained release dosage form based on highly plasticized cellulose ether gels |
IE58110B1 (en) * | 1984-10-30 | 1993-07-14 | Elan Corp Plc | Controlled release powder and process for its preparation |
US4690825A (en) * | 1985-10-04 | 1987-09-01 | Advanced Polymer Systems, Inc. | Method for delivering an active ingredient by controlled time release utilizing a novel delivery vehicle which can be prepared by a process utilizing the active ingredient as a porogen |
US4800087A (en) * | 1986-11-24 | 1989-01-24 | Mehta Atul M | Taste-masked pharmaceutical compositions |
-
1984
- 1984-10-30 IE IE278884A patent/IE58110B1/en not_active IP Right Cessation
-
1985
- 1985-10-24 CH CH4590/85A patent/CH669728A5/fr not_active IP Right Cessation
- 1985-10-29 CA CA000494130A patent/CA1268051A/en not_active Expired - Lifetime
- 1985-10-29 DK DK198504955A patent/DK175329B1/en not_active IP Right Cessation
- 1985-10-29 GB GB08526591A patent/GB2166651B/en not_active Expired
- 1985-10-29 IT IT67913/85A patent/IT1185831B/en active
- 1985-10-29 BE BE0/215789A patent/BE903541Q/en not_active IP Right Cessation
- 1985-10-29 AU AU49161/85A patent/AU579415B2/en not_active Ceased
- 1985-10-29 ZA ZA858300A patent/ZA858300B/en unknown
- 1985-10-29 NL NL8502951A patent/NL193582C/en not_active IP Right Cessation
- 1985-10-29 BE BE0/215788A patent/BE903540A/en not_active IP Right Cessation
- 1985-10-29 SE SE8505099A patent/SE8505099L/en not_active Application Discontinuation
- 1985-10-29 FR FR858516065A patent/FR2572282B1/en not_active Expired
- 1985-10-29 JP JP60242585A patent/JP2820239B2/en not_active Expired - Lifetime
- 1985-10-29 DE DE3538429A patent/DE3538429C2/en not_active Expired - Lifetime
-
1988
- 1988-03-17 US US07/169,447 patent/US4952402A/en not_active Expired - Lifetime
- 1988-03-17 US US07/171,131 patent/US4940588A/en not_active Expired - Lifetime
-
1990
- 1990-07-09 US US07/537,065 patent/US5354556A/en not_active Expired - Lifetime
-
1991
- 1991-06-06 HK HK440/91A patent/HK44091A/en not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
NL8502951A (en) | 1986-05-16 |
NL193582B (en) | 1999-11-01 |
CH669728A5 (en) | 1989-04-14 |
BE903540A (en) | 1986-02-17 |
ZA858300B (en) | 1986-07-30 |
GB2166651B (en) | 1988-11-16 |
DK495585D0 (en) | 1985-10-29 |
JPS61109711A (en) | 1986-05-28 |
GB8526591D0 (en) | 1985-12-04 |
DK495585A (en) | 1986-05-01 |
FR2572282A1 (en) | 1986-05-02 |
AU579415B2 (en) | 1988-11-24 |
DE3538429A1 (en) | 1986-04-30 |
DK175329B1 (en) | 2004-08-23 |
NL193582C (en) | 2000-03-02 |
SE8505099D0 (en) | 1985-10-29 |
BE903541Q (en) | 1986-02-17 |
HK44091A (en) | 1991-06-14 |
IT1185831B (en) | 1987-11-18 |
IE58110B1 (en) | 1993-07-14 |
US4952402A (en) | 1990-08-28 |
FR2572282B1 (en) | 1989-03-31 |
DE3538429C2 (en) | 1996-10-24 |
IT8567913A0 (en) | 1985-10-29 |
US5354556A (en) | 1994-10-11 |
JP2820239B2 (en) | 1998-11-05 |
AU4916185A (en) | 1986-05-08 |
SE8505099L (en) | 1986-05-01 |
US4940588A (en) | 1990-07-10 |
GB2166651A (en) | 1986-05-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA1268051A (en) | Controlled release powder and process for its preparation | |
EP0670716B1 (en) | Tastemasked pharmaceutical materials | |
EP0459695B1 (en) | Taste masking and sustained release coatings for pharmaceuticals | |
EP0411952B1 (en) | Rotogranulations and taste masking coatings for preparation of chewable pharmaceutical tablets | |
DE60036874T2 (en) | PELLET FORMULATION WITH CONTROLLED RELEASE | |
US5156842A (en) | Liquid suspension for oral administration | |
EP0717986B1 (en) | Rotor granulation and coating of acetaminophen, pseudoephedrine, chlorpheniramine, and, optionally, dextromethorphan | |
DE69919713T2 (en) | PHARMACEUTICAL PREPARATION WITH DELAYED ACTIVE INFUSION OF PHENYTOIN SODIUM | |
CA2169376C (en) | Procedure for encapsulating nsaids | |
EP0682945B1 (en) | Oral sustained release preparation | |
CA2172807C (en) | Tastemasked liquid pharmaceutical delivery system | |
AU743154B2 (en) | A pharmaceutical composition having two coating layers | |
EP0851758A1 (en) | Pharmaceutical formulation | |
EP0421582A1 (en) | Chewable spray dried spheroidal microcapsules and polymer coated microcapsules and method for preparing same | |
IE902829A1 (en) | Microencapsulated taste-masked water-insoluble nsaid drug¹materials | |
EP0935460B1 (en) | Taste masked pharmaceutical compositions | |
AU2002242084B2 (en) | Methods and compositions for reducing the taste of pharmaceutically active agents | |
CA2008005A1 (en) | Microencapsulated taste-masked water-insoluble nsaid drug materials |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MKEX | Expiry |