WO1998000169A1 - Hydrophobic preparations containing medium chain monoglycerides - Google Patents
Hydrophobic preparations containing medium chain monoglycerides Download PDFInfo
- Publication number
- WO1998000169A1 WO1998000169A1 PCT/GB1997/001775 GB9701775W WO9800169A1 WO 1998000169 A1 WO1998000169 A1 WO 1998000169A1 GB 9701775 W GB9701775 W GB 9701775W WO 9800169 A1 WO9800169 A1 WO 9800169A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- preparation
- hydrophobic preparation
- hydrophobic
- hydrophilic
- oil phase
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/23—Calcitonins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
Definitions
- the present invention relates to preparations of substances in hydrophobic solvents in which they would not normally be soluble and to processes for obtaining these preparations
- the invention relates to preparations of hydrophilic species in mixtures of medium chain monoglyce ⁇ des (MCMs) and diglyce ⁇ des
- the invention in particular applies to hydrophilic macromolecules which would not normally be soluble in oils or other hydrophobic solvents
- the above-described preparations provide simple and efficient methods for solubilising macomolecules such as proteins
- the macromolecule delivery properties of the preparations can be improved by the use of a particular oil phase and, optionally, particular amphiphiles.
- This is particularly advantageous when the macromolecule to be solubilised is a protein, eg a pharmaceutically active protein, since the preparations disclosed herein provide not only enhanced uptake of the therapeutic macromolecule but also good dose repeatability.
- the present invention provides a hydrophobic preparation comprisin :
- hydrophilic species is one that is not normally soluble in the one or more monoglycerides.
- hydrophobic preparation is a preparation in which the hydrophilic species is not present in aqueous phase. Such a hydrophobic preparation is particularly suitable for use in orally delivering a hydrophilic macromolecule such as a protein.
- the prior art does contain a number of examples of the use of medium chain monoglycerides as permeation enhancers in the intestine (Sekine et al, J.Pharmacobiodyn. , 7:856-63 (1984); Higaki et al, J .Pharmacobioayn. , 9:532-9 (1986); Unowsky et al, Chemotherapy, 34:272-6 (1988); Watanabe et al, J.Pharm.Sci. , 77:847-9 (1988); Yeh et al, Pharm.Res. , 11: 1148-54 (1994); Constinides et al, Pharm.Res.
- Preparations in accordance with the invention will generally have no bulk aqueous phase and may have no free water molecules.
- the oil phase i) will comprise a mixture of medium chain mono- and diglycerides.
- medium chain glycerides useful in the present invention have chain lengths of 8 to 10 carbon atoms, for example, they can comprise straight chain saturated fatty acids.
- the oil phase i) may comprise one or more medium chain monoglycerides together with at least one other component such as oleic acid, glycerol mono-oleate or gelucires.
- the essential component will be the medium chain monoglyceride(s).
- the oil component used should be such that the amount of monoglyceride(s) present should be maximised while ensuring that the oil component remains liquid at a temperature of 45°C or lower.
- monoglyceride(s) can make up 40-90% of the total amount of oil present, preferably 60-70% .
- An example of a suitable mixture of glycerides is Akoline MCMTM which contains both medium chain mono- and diglycerides, available from Karlshamns Sweden AB, S/374 82 Karlshamn, Sweden.
- the ratio of amphiphile: macromolecule is in the range 1 : 1 to 20: 1 by weight and more preferably in the range 2: 1 to 8: 1 by weight.
- amphiphiles examples include phospholipids such as phosphatidyl choline, phosphatidic acid, phosphatidyl glycerol, phosphatidyl ethanolamine and lyso- derivatives of these, octyl glucoside and other glycolipids, tocopherol succinate and cholesterol hemisuccinate.
- phospholipids such as phosphatidyl choline, phosphatidic acid, phosphatidyl glycerol, phosphatidyl ethanolamine and lyso- derivatives of these, octyl glucoside and other glycolipids, tocopherol succinate and cholesterol hemisuccinate.
- Other suitable amphiphiles include phosphatidyl serine, sodium docusate and hydroxypropyl cellulose. More than one amphiphile may be used.
- amphiphile used is a bile salt.
- bile salt and bile acid are used interchangeably because whether the salt or its conjugate acid is present will depend on the pH of the surrounding environment.
- Bile salts are naturally occurring surfactants. They are a group of compounds with a common "backbone” structure based on cholanic acid found in all mammals and higher vegetables. Bile salts may be mono-, di- or tri-hydroxylated; they always contain a 3 -hydroxyl group whereas the other hydroxyl groups, most commonly found at C 6 , C 7 or C
- amphiphilic polyhydric sterols bearing carboxyl groups as part of the primary side chain.
- the most common examples of these in mammals result from cholesterol metabolism and are found in the bile and, in derivatised form, throughout the intestine.
- the term may also apply to synthetic analogues of naturally occurring bile salts which display similar biological effects, or to microbially derived molecules such as fusidic acid and its derivatives.
- the bile salt may be either unconjugated or conjugated.
- unconjugated refers to a bile salt in which the primary side chain has a single carboxyl group which is at the terminal position and which is unsubstituted.
- unconjugated bile salts include cholate, ursodeoxycholate, chenodeoxycholate and deoxycholate.
- a conjugated bile salt is one in which the primary side chain has a carboxyl group which is substituted. Often the substituent will be an amino acid derivative which is linked via its nitrogen atom to the carboxyl group of the bile salt.
- conjugated bile salts include taurocholate, glycocholate, taurodeoxycholate and glycodeoxycholate.
- Suitable bile salts include cholate, deoxycholate, chenodeoxycholate and ursodeoxycholate, with ursodeoxycholate being particularly preferred.
- Other bile salts which may be employed include taurocholate, taurodeoxycholate, tauroursodeoxycholate, taurochenodeoxycholate, glycholate, glycodeoxycholate, glycoursodeoxycholate, glycochenodeoxycholate, lithocholate, taurolithocholate and, glycolithocholate.
- hydrophilic species relates to any species which is generally soluble in aqueous solvents but insoluble in hydrophobic solvents.
- the range of hydrophilic species of use in the present invention is diverse but hydrophilic macromolecules represent an example of a species which may be used.
- macromolecules are suitable for use in the present invention.
- the macromolecular compound will be hydrophilic or will at least have hydrophilic regions since there is usually little difficulty in solubilising a hydrophobic macromolecule in oily solutions.
- suitable macromolecules include proteins and glycoproteins, oligo and polynucleic acids, for example DNA, eg plasmid DNA. and RNA, as well as DNA and/or RNA analogues, polysaccharides such as heparin (particularly low molecular weight heparin) and supramolecular assemblies of any of these including, in some cases, whole cells or organelles.
- a small molecule such as a vitamin in association with a macromolecule, particularly a polysaccharide such as a cyclodextrin.
- Small molecules such as vitamin B12 may also be chemically conjugated with macromolecules and may thus be included in the compositions.
- Factor IX tissue plasminogen activator, superoxide dismutase. catalase, peroxidase, ferritin, interferon.
- Factor VIII and fragments thereof all of the above proteins can be from any suitable source).
- Other proteins include soy bean trypsin inhibitor. GLPl . other blood coagulation factors, somatostatin, hirudin, and LHRH and analogues and fragments of all of them.
- Mixtures of one or more of these or other proteins may be solubilised by the invention.
- the process of the present invention is of use in solubilising smaller organic molecules as well as or instead of macromolecules.
- small organic molecules include glucose, carboxyfluorescin and many pharmaceutical agents, for example anti-cancer agents, but, of course, the process could equally be applied to other small organic molecules, for example vitamins or pharmaceutically or biologically active agents.
- compounds such as calcium chloride and sodium phosphate can also be solubilised using this process.
- the present invention would be particularly advantageous for pharmaceutically and biologically active agents since the use of non aqueous solutions may enable the route by which the molecule enters the body to be varied, for example to increase bioavailability.
- Small organic molecules which may be incorporated into macromolecule-containing preparations of the invention include stabilising agents such as polyglycerols, PEGs and glycerol (particularly in the case of insulin or, possibly, other proteins), chelating agents, such as citric acid. EDTA and EGTA, and antioxidants such as ascorbate.
- an inorganic material such as a small inorganic molecule or a colloidal substance, for example a colloidal metal.
- a colloidal metal such as colloidal gold, palladium, platinum or rhodium
- hydrophobic preparations of the invention may also optionally comprise further components.
- antioxidants include antioxidants, metal chelating agents, buffering agents and dispersion agents.
- suitable dispersion agents include surface active agents such as the Tween, Span and Brij classes of agent, as well as polyoxyethylated castor oil derivatives, and other POE-containing surfactants.
- hydrophobic preparations of the present invention can be prepared using a method comprising:
- hydrophobic preparations of the present invention can be prepared by methods disclosed in PCT patent application No. PCT/GB97/00749 which comprise:
- hydrophilic solvent removal step is carried out under conditions which maintain the hydrophobic phase in a solid state.
- the hydrophilic species and the amphiphile are first dissolved in a hydrophilic solvent, eg an aqueous solvent, often water alone, and this solution is then brought into association with the glyceride mixture.
- a hydrophilic solvent eg an aqueous solvent
- the hydrophilic solvent removal step is conveniently achieved by lyophilisation, such that it is carried out at temperatures which will ensure that the glyceride mixture is maintained in the solid state until all the water has been removed.
- the oil may become liquid during lyophilisation, as a result of local rises in temperature in parts of the solid block (usually at the surface and edges) where all the hydrophilic solvent has already been removed.
- the cooling effect deriving from sublimation of hydrophilic solvent no longer exists, and in those areas the oil will melt. This situation will lead to the production of a satisfactory end-product providing that the oil is allowed to drain away from the remainder of the solid block as soon as it appears (if not, then accumulating oil will form a layer which prevents further
- the temperature during lyophilisation can be maintained such that the oil remains solid even after the hydrophilic solvent has been driven off.
- the temperature of the preparation is elevated to produce the single phase preparation. This can often simply be achieved by bringing the lyophilised preparation up to room temperature which in turn will cause the glyceride mixture to return to the liquid state.
- Other methods for removal of hydrophilic solvent may also be employed, eg spray drying.
- hydrophobic preparations of the present invention are extremely versatile and have many applications. They may either be used alone or they may be combined with an aqueous phase to form an emulsion or similar two phase composition which forms a second aspect of the invention.
- a two phase composition comprising a hydrophilic phase and a hydrophobic phase, the hydrophobic phase comprising a hydrophobic preparation of the invention which is obtainable by the methods described above.
- the hydrophobic phase will be dispersed in the hydrophilic phase.
- the hydrophobic preparations of the invention have particular advantages in that the hydrophilic species is readily taken up, eg into the bloodstream following oral administration. They are therefore particularly suitable for the oral delivery of proteins for example.
- the preparations of the invention will also provide advantages for other routes of admimstration, eg topical or vaginal
- the present invention provides a pharmaceutical formulation comprising a hydrophobic preparation of the invention
- Pharmaceutical formulations within the scope of the invention include capsules, tablets and other presentations
- the present invention provides the use of a hydrophobic preparation of the invention in the preparation of a medicament for oral delivery of a hydrophilic species, for instance a hydrophilic macromolecule such as a protein
- the invention can also be used to modify the immune response, whether by stimulation or suppression
- step 9 To each vial in step 9 add 1ml of ako ne/polysorbate 80 mixture from step 10 using a large volume positive displacement dispenser
- step 5 To each vial in step 5 add 1ml of akoline/polysorbate 80 mixture from step 6 using a large volume positive displacement dispenser.
- Example 1 As in Example 1. except that (a) the phospholipid dispersion was omitted (b) the protein-containing lyophilate was not dissolved in oil phase, (c) prior to administration to animals the protein lyophilate was dissolved in 4ml phosphate-buffered saline and (d) the resulting solution was added to 2ml of the oil phase (Akoline MCM/Tween 80) and dispersed by vortexing.
- formulation (1) As for formulation (1) except that 7.3mg of insulin (200iu), 2mg of aprotinin. and 1 ml of Akoline/Tween 80 oil phase employed.
- Example 4 Exactly as in Example 4 except that aprotinin omitted from the preparation.
- the animal model employed for testing oral formulations of calcitonin is the juvenile pig.
- the pig is selected because it has similar weight to man and the strucmre, function and size of the small intestine are similar to the human small intestine.
- the animals were surgically manipulated so that material could be introduced directly into the jejunum via an in-dwelling cannula. This also reduces the uncertainty usually associated with oral administration as to time of arrival of the dose in the intestine, and leads to improvement in the quality of the statistics obtained.
- a fine plastic cannula was surgically inserted into the jejunum of the pig and then brought out under the skin onto the back of the pig so that the test materials can be injected into the jejunum without distressing the animal.
- An indwelling catheter which was also brought out through the back skin was inserted into the aorta via the medium saphenous artery so that repeated blood samples could be obtained.
- a second catheter was also introduced in a carotid artery.
- Pigs were tested while fully conscious in the fasting state and peptide formulations were administered via the oral route after three baseline blood samples were taken.
- a single experiment usually occupied a period of 8 to 9 hours and the surgically-prepared pigs participated in tests up to three times per week over a four week period.
- the pigs were killed and the intestines examined for macroscopic and microscopic changes.
- the dosing solutions were given by instillation via the in- dwelling cannula into the jejunum.
- the cannula was flushed through before dosing with 1ml warm (25-30°C) sterile phosphate-buffered saline, and flushed through after dosing with 5 ml of the same material at the same temperature.
- Calcitonin incorporated in the Hpidic delivery system was given as a dispersion in which 2ml of oil was vortexed in 4ml of warm phosphate buffered saline, and 1.3ml of the resultant dispersion was administered to each animal. Each animal received 5000iu of calcitonin.
- Insulin formulations were also given as dispersions in which 1ml of oil containing 200iu insulin was dispersed in 2ml of warm phosphate saline before all three millilitres were administered i.j. to a single animal. Sample Collection in Animals
- the catheters used for collection of blood were flushed once daily with heparinised saline (500iu/ml). On sampling days a less concentrated heparin solution (50iu/ml) was used in the catheters between sampling.
- the blood samples were handled as follows :-
- the first 2ml was taken into a plastic heparinised container.
- the samples were then stored at +4°C for up to 30 minutes before they were centrifuged in a refrigerated centrifuge at 3000 rpm for 20 minutes.
- the resultant plasma was then divided and transferred into two suitable containers and frozen to -20 °C prior to colorimetric assay of plasma calcium or glucaose concentrations using a Kone autoanalyser. One sample was assayed and the other retained.
- Tables 1 and 2 below present the results of the animal studies in terms of AUC of fall in either calcium or glucose levels, as well as peak fall in calcium or glucose level.
- Table 1 Results For Calcitonin formulations as described in Example 5
Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP10503931A JP2000515130A (en) | 1996-07-02 | 1997-07-02 | Hydrophobic preparations containing medium-chain monoglycerides |
BR9710179A BR9710179A (en) | 1996-07-02 | 1997-07-02 | Hydrophobic preparation preparation in pharmaceutical emulation and use of a hydrophobic preparation |
EP97929411A EP0910411A1 (en) | 1996-07-02 | 1997-07-02 | Hydrophobic preparations containing medium chain monoglycerides |
AU33526/97A AU709013B2 (en) | 1996-07-02 | 1997-07-02 | Hydrophobic preparations containing medium chain monoglycerides |
NZ333115A NZ333115A (en) | 1996-07-02 | 1997-07-02 | Preparation of hydrophillic macromolecules in hydrophobic solvents such as medium chain monoglycerides and diglcerides |
US09/218,289 US6258377B1 (en) | 1996-07-02 | 1998-12-22 | Hydrophobic preparations containing medium chain monoglycerides |
NO986211A NO986211L (en) | 1996-07-02 | 1998-12-30 | Hydrophobic preparations containing medium chain monoglycerides |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9613858.1A GB9613858D0 (en) | 1996-07-02 | 1996-07-02 | Hydrophobic preparations |
GB9613858.1 | 1996-07-02 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/218,289 Continuation US6258377B1 (en) | 1996-07-02 | 1998-12-22 | Hydrophobic preparations containing medium chain monoglycerides |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1998000169A1 true WO1998000169A1 (en) | 1998-01-08 |
Family
ID=10796214
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/GB1997/001775 WO1998000169A1 (en) | 1996-07-02 | 1997-07-02 | Hydrophobic preparations containing medium chain monoglycerides |
Country Status (13)
Country | Link |
---|---|
US (1) | US6258377B1 (en) |
EP (1) | EP0910411A1 (en) |
JP (1) | JP2000515130A (en) |
KR (1) | KR20000022353A (en) |
AU (1) | AU709013B2 (en) |
BR (1) | BR9710179A (en) |
CA (1) | CA2259233A1 (en) |
GB (1) | GB9613858D0 (en) |
ID (1) | ID18568A (en) |
NO (1) | NO986211L (en) |
NZ (1) | NZ333115A (en) |
WO (1) | WO1998000169A1 (en) |
ZA (1) | ZA975856B (en) |
Cited By (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000033866A1 (en) * | 1998-12-04 | 2000-06-15 | Provalis Uk Limited | Pharmaceutical compositions containing insulin |
JP2000191684A (en) * | 1998-11-30 | 2000-07-11 | Mcneil Ppc Inc | Production of dispersable sterol and stanol composition |
KR100508695B1 (en) * | 2001-02-13 | 2005-08-17 | 한국과학기술연구원 | Formulation for oral delivery of insulin and preparation method thereof |
US7153930B1 (en) | 1999-07-30 | 2006-12-26 | James Duncan Morrison | Peptide transport |
US20080119443A1 (en) * | 2006-07-03 | 2008-05-22 | Academia Sinica | Certain lithocholic acid analogues that inhibit sialyltransferase |
US8029823B2 (en) | 1999-06-14 | 2011-10-04 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
WO2012152707A1 (en) * | 2011-05-06 | 2012-11-15 | Vaxcine Ltd | Microemulsions |
WO2012152709A1 (en) * | 2011-05-06 | 2012-11-15 | Vaxcine Ltd | Hydrophobic preparations |
US8314058B2 (en) | 2003-04-15 | 2012-11-20 | Axcess Limited | Uptake of macromolecules |
US8377897B2 (en) | 1998-05-21 | 2013-02-19 | Isis Pharmaceuticals, Inc. | Compositions and methods for non-parenteral delivery of oligonucleotides |
US8691785B2 (en) | 1997-07-01 | 2014-04-08 | Isis Pharmaceuticals, Inc. | Compositions and methods for non-parenteral delivery of oligonucleotides |
US8802087B2 (en) | 2004-03-22 | 2014-08-12 | Abbott Products Gmbh | Pharmaceutical compositions of lipase-containing products, in particular of pancreation |
US8895064B2 (en) | 1999-06-14 | 2014-11-25 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
US9198871B2 (en) | 2005-08-15 | 2015-12-01 | Abbott Products Gmbh | Delayed release pancreatin compositions |
US10004704B2 (en) | 2010-10-29 | 2018-06-26 | Infirst Healthcare Limited | Compositions and methods for treating chronic inflammation and inflammatory diseases |
US10072256B2 (en) | 2006-05-22 | 2018-09-11 | Abbott Products Gmbh | Process for separating and determining the viral load in a pancreatin sample |
US10143671B2 (en) | 2010-10-29 | 2018-12-04 | Infirst Healthcare Limited | Solid solution compositions and use in chronic inflammation |
US10154964B2 (en) | 2011-09-07 | 2018-12-18 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
US10155042B2 (en) | 2010-10-29 | 2018-12-18 | Infirst Healthcare Limited | Compositions and methods for treating chronic inflammation and inflammatory diseases |
US10213381B2 (en) | 2010-10-29 | 2019-02-26 | Infirst Healthcare Limited | Solid solution compositions and use in chronic inflammation |
US10363232B2 (en) | 2010-10-29 | 2019-07-30 | Infirst Healthcare Limited | Compositions and methods for treating severe pain |
US10695431B2 (en) | 2010-10-29 | 2020-06-30 | Infirst Healthcare Limited | Solid solution compositions and use in cardiovascular disease |
US10695432B2 (en) | 2010-10-29 | 2020-06-30 | Infirst Healthcare Limited | Solid solution compositions and use in severe pain |
US10704037B2 (en) | 2005-07-29 | 2020-07-07 | Abbott Products Gmbh | Processes for the manufacture and use of pancreatin |
US11202831B2 (en) | 2010-10-29 | 2021-12-21 | Infirst Healthcare Limited | Solid solution compositions and use in cardiovascular disease |
US11224659B2 (en) | 2010-10-29 | 2022-01-18 | Infirst Healthcare Limited | Solid solution compositions and use in severe pain |
US11266607B2 (en) | 2005-08-15 | 2022-03-08 | AbbVie Pharmaceuticals GmbH | Process for the manufacture and use of pancreatin micropellet cores |
US11730709B2 (en) | 2010-10-29 | 2023-08-22 | Infirst Healthcare Limited | Compositions and methods for treating severe pain |
Families Citing this family (43)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7169889B1 (en) * | 1999-06-19 | 2007-01-30 | Biocon Limited | Insulin prodrugs hydrolyzable in vivo to yield peglylated insulin |
ES2235456T3 (en) * | 1999-10-08 | 2005-07-01 | Coty B.V. | COSMETIC PREPARATION OF ACTIVE SUBSTANCES WITH A PROTECTION FACTOR AGAINST SYNERGICALLY IMPROVED RADICALS. |
EP1346726A4 (en) * | 2000-12-25 | 2004-09-15 | Shiseido Co Ltd | Sympathetic-activating perfume composition |
US7060675B2 (en) * | 2001-02-15 | 2006-06-13 | Nobex Corporation | Methods of treating diabetes mellitus |
CN1160122C (en) | 2001-04-20 | 2004-08-04 | 清华大学 | Method of preparing oil-phase oral insulin preparation |
EP1401477A4 (en) * | 2001-05-25 | 2005-02-02 | Human Genome Sciences | Chemokine beta-1 fusion proteins |
US6828305B2 (en) * | 2001-06-04 | 2004-12-07 | Nobex Corporation | Mixtures of growth hormone drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
US7713932B2 (en) | 2001-06-04 | 2010-05-11 | Biocon Limited | Calcitonin drug-oligomer conjugates, and uses thereof |
US6828297B2 (en) | 2001-06-04 | 2004-12-07 | Nobex Corporation | Mixtures of insulin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
US6713452B2 (en) | 2001-06-04 | 2004-03-30 | Nobex Corporation | Mixtures of calcitonin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
US6835802B2 (en) | 2001-06-04 | 2004-12-28 | Nobex Corporation | Methods of synthesizing substantially monodispersed mixtures of polymers having polyethylene glycol moieties |
US7312192B2 (en) * | 2001-09-07 | 2007-12-25 | Biocon Limited | Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
US7030082B2 (en) * | 2001-09-07 | 2006-04-18 | Nobex Corporation | Pharmaceutical compositions of drug-oligomer conjugates and methods of treating disease therewith |
US6913903B2 (en) * | 2001-09-07 | 2005-07-05 | Nobex Corporation | Methods of synthesizing insulin polypeptide-oligomer conjugates, and proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
US6770625B2 (en) | 2001-09-07 | 2004-08-03 | Nobex Corporation | Pharmaceutical compositions of calcitonin drug-oligomer conjugates and methods of treating diseases therewith |
US7166571B2 (en) * | 2001-09-07 | 2007-01-23 | Biocon Limited | Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
EP2261250B1 (en) | 2001-12-21 | 2015-07-01 | Human Genome Sciences, Inc. | GCSF-Albumin fusion proteins |
US7731947B2 (en) * | 2003-11-17 | 2010-06-08 | Intarcia Therapeutics, Inc. | Composition and dosage form comprising an interferon particle formulation and suspending vehicle |
GB0308732D0 (en) * | 2003-04-15 | 2003-05-21 | Axcess Ltd | Absorption enhancers |
DK2626368T3 (en) | 2004-07-19 | 2017-02-27 | Biocon Ltd | INSULIN OLIGOMS CONJUGATES, FORMULATIONS AND APPLICATIONS THEREOF |
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 |
NZ572003A (en) | 2006-05-30 | 2010-07-30 | Intarcia Therapeutics Inc | Two-piece, internal-channel osmotic delivery system flow modulator with spiral fluid channel |
WO2008021133A2 (en) | 2006-08-09 | 2008-02-21 | Intarcia Therapeutics, Inc. | Osmotic delivery systems and piston assemblies |
NZ580447A (en) | 2007-04-23 | 2011-06-30 | Intarcia Therapeutics Inc | Suspension formulations of insulinotropic peptides and uses thereof |
JP5868594B2 (en) | 2007-10-16 | 2016-02-24 | バイオコン・リミテッドBiocon Limited | Orally administrable solid pharmaceutical composition and process thereof |
US8343140B2 (en) | 2008-02-13 | 2013-01-01 | Intarcia Therapeutics, Inc. | Devices, formulations, and methods for delivery of multiple beneficial agents |
CN102112110A (en) * | 2008-06-06 | 2011-06-29 | 米尔纳医疗股份有限公司 | Novel compositions for the in vivo delivery of RNAi agents |
WO2010113177A2 (en) | 2009-03-31 | 2010-10-07 | Reliance Life Sciences Pvt. Ltd. | Oral insulin delivery systems for controlling diabetes |
NZ624569A (en) | 2009-09-28 | 2016-01-29 | Intarcia Therapeutics Inc | Rapid establishment and/or termination of substantial steady-state drug delivery |
EP2380920A1 (en) * | 2010-04-22 | 2011-10-26 | QGel SA | Hydrogel precursor formulation and production process thereof |
JP6051157B2 (en) * | 2010-07-14 | 2016-12-27 | 中国医学科学院▲薬▼物研究所 | Insulin lipid complex and preparation method and preparation |
US20120208755A1 (en) | 2011-02-16 | 2012-08-16 | Intarcia Therapeutics, Inc. | Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers |
BR112014029188B1 (en) * | 2012-05-31 | 2020-02-11 | Terumo Kabushiki Kaisha | PH SENSITIVE VEHICLE AND METHOD OF PREPARING THE SAME, AND PH SENSITIVE DRUG AND PH SENSITIVE DRUG COMPOSITION CONTAINING THE VEHICLE, AND CULTURE METHOD USING THE SAME |
SG10201704472QA (en) * | 2013-01-14 | 2017-07-28 | Infirst Healthcare Ltd | Solid solution compositions and use in chronic inflammation |
CN104968330A (en) * | 2013-01-14 | 2015-10-07 | 因佛斯特医疗有限公司 | Compositions and methods for treating severe pain |
EP2950821A1 (en) * | 2013-02-04 | 2015-12-09 | InFirst Healthcare Limited | Compositions and methods for treating chronic inflammation and inflammatory diseases |
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 |
MX2017015504A (en) | 2015-06-03 | 2018-05-15 | Intarcia Therapeutics Inc | Implant placement and removal systems. |
SG11201810102SA (en) | 2016-05-16 | 2018-12-28 | Intarcia Therapeutics Inc | Glucagon-receptor selective polypeptides and methods of use thereof |
USD840030S1 (en) | 2016-06-02 | 2019-02-05 | Intarcia Therapeutics, Inc. | Implant placement guide |
USD860451S1 (en) | 2016-06-02 | 2019-09-17 | Intarcia Therapeutics, Inc. | Implant removal tool |
IL307966A (en) | 2017-01-03 | 2023-12-01 | Intarcia Therapeutics Inc | Methods comprising continuous administration of a glp-1 receptor agonist and co-adminstration of a drug |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0260796A1 (en) * | 1986-09-19 | 1988-03-23 | Yamanouchi Pharmaceutical Co. Ltd. | Compositions of neocarzinostatin derivative for oral administration |
WO1993002664A1 (en) * | 1991-07-26 | 1993-02-18 | Smithkline Beecham Corporation | W/o microemulsions |
WO1994008603A1 (en) * | 1992-10-16 | 1994-04-28 | Smithkline Beecham Corporation | Compositions |
WO1994008605A1 (en) * | 1992-10-16 | 1994-04-28 | Smithkline Beecham Corporation | Therapeutic microemulsions |
WO1994012154A1 (en) * | 1992-11-23 | 1994-06-09 | Cortecs Limited | Lipid containing formulation and method for its preparation |
WO1994019003A1 (en) * | 1993-02-17 | 1994-09-01 | Smithkline Beecham Corporation | Microemulsions comprising therapeutic peptides |
WO1995013795A1 (en) * | 1993-11-16 | 1995-05-26 | Cortecs Limited | Hydrophobic preparations |
WO1996017593A1 (en) * | 1994-12-09 | 1996-06-13 | Cortecs Limited | Solubilisation aids for hydrophilic macromolecules |
WO1996017594A1 (en) * | 1994-12-09 | 1996-06-13 | Cortecs Limited | Sequestration agents |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS53107408A (en) * | 1977-02-28 | 1978-09-19 | Yamanouchi Pharmaceut Co Ltd | Micellar preparation for rectal infusion |
DE2964948D1 (en) | 1979-06-11 | 1983-04-07 | Sulzer Ag | Device for supplying the cross warp threads in a weaving machine |
GB9422990D0 (en) | 1994-11-15 | 1995-01-04 | Cortecs Ltd | Immunogenic compositions |
GB9605709D0 (en) | 1996-03-19 | 1996-05-22 | Cortecs Ltd | Method |
-
1996
- 1996-07-02 GB GBGB9613858.1A patent/GB9613858D0/en active Pending
-
1997
- 1997-07-01 ZA ZA975856A patent/ZA975856B/en unknown
- 1997-07-02 EP EP97929411A patent/EP0910411A1/en not_active Withdrawn
- 1997-07-02 WO PCT/GB1997/001775 patent/WO1998000169A1/en not_active Application Discontinuation
- 1997-07-02 ID IDP972303A patent/ID18568A/en unknown
- 1997-07-02 NZ NZ333115A patent/NZ333115A/en unknown
- 1997-07-02 AU AU33526/97A patent/AU709013B2/en not_active Ceased
- 1997-07-02 BR BR9710179A patent/BR9710179A/en not_active Application Discontinuation
- 1997-07-02 CA CA002259233A patent/CA2259233A1/en not_active Abandoned
- 1997-07-02 KR KR1019980710781A patent/KR20000022353A/en not_active Application Discontinuation
- 1997-07-02 JP JP10503931A patent/JP2000515130A/en active Pending
-
1998
- 1998-12-22 US US09/218,289 patent/US6258377B1/en not_active Expired - Fee Related
- 1998-12-30 NO NO986211A patent/NO986211L/en not_active Application Discontinuation
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0260796A1 (en) * | 1986-09-19 | 1988-03-23 | Yamanouchi Pharmaceutical Co. Ltd. | Compositions of neocarzinostatin derivative for oral administration |
WO1993002664A1 (en) * | 1991-07-26 | 1993-02-18 | Smithkline Beecham Corporation | W/o microemulsions |
WO1994008603A1 (en) * | 1992-10-16 | 1994-04-28 | Smithkline Beecham Corporation | Compositions |
WO1994008605A1 (en) * | 1992-10-16 | 1994-04-28 | Smithkline Beecham Corporation | Therapeutic microemulsions |
WO1994012154A1 (en) * | 1992-11-23 | 1994-06-09 | Cortecs Limited | Lipid containing formulation and method for its preparation |
WO1994019003A1 (en) * | 1993-02-17 | 1994-09-01 | Smithkline Beecham Corporation | Microemulsions comprising therapeutic peptides |
WO1995013795A1 (en) * | 1993-11-16 | 1995-05-26 | Cortecs Limited | Hydrophobic preparations |
WO1996017593A1 (en) * | 1994-12-09 | 1996-06-13 | Cortecs Limited | Solubilisation aids for hydrophilic macromolecules |
WO1996017594A1 (en) * | 1994-12-09 | 1996-06-13 | Cortecs Limited | Sequestration agents |
Cited By (62)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8691785B2 (en) | 1997-07-01 | 2014-04-08 | Isis Pharmaceuticals, Inc. | Compositions and methods for non-parenteral delivery of oligonucleotides |
US8377897B2 (en) | 1998-05-21 | 2013-02-19 | Isis Pharmaceuticals, Inc. | Compositions and methods for non-parenteral delivery of oligonucleotides |
JP2000191684A (en) * | 1998-11-30 | 2000-07-11 | Mcneil Ppc Inc | Production of dispersable sterol and stanol composition |
WO2000033866A1 (en) * | 1998-12-04 | 2000-06-15 | Provalis Uk Limited | Pharmaceutical compositions containing insulin |
US9592203B2 (en) | 1999-06-14 | 2017-03-14 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
US9532954B2 (en) | 1999-06-14 | 2017-01-03 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical compositions |
US8293273B2 (en) | 1999-06-14 | 2012-10-23 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
USRE43799E1 (en) | 1999-06-14 | 2012-11-13 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
US10105374B2 (en) | 1999-06-14 | 2018-10-23 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical compositions |
US10064878B2 (en) | 1999-06-14 | 2018-09-04 | Cosmo Technologies Ltd. | Controlled release and taste masking oral pharmaceutical compositions |
US10052286B2 (en) | 1999-06-14 | 2018-08-21 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
US9737489B2 (en) | 1999-06-14 | 2017-08-22 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
US10143698B2 (en) | 1999-06-14 | 2018-12-04 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical compositions |
US8784888B2 (en) | 1999-06-14 | 2014-07-22 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
US8029823B2 (en) | 1999-06-14 | 2011-10-04 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
US8895064B2 (en) | 1999-06-14 | 2014-11-25 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
US9320716B2 (en) | 1999-06-14 | 2016-04-26 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical compositions |
US9192581B2 (en) | 1999-06-14 | 2015-11-24 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
US7153930B1 (en) | 1999-07-30 | 2006-12-26 | James Duncan Morrison | Peptide transport |
KR100508695B1 (en) * | 2001-02-13 | 2005-08-17 | 한국과학기술연구원 | Formulation for oral delivery of insulin and preparation method thereof |
US8314058B2 (en) | 2003-04-15 | 2012-11-20 | Axcess Limited | Uptake of macromolecules |
US8802087B2 (en) | 2004-03-22 | 2014-08-12 | Abbott Products Gmbh | Pharmaceutical compositions of lipase-containing products, in particular of pancreation |
US10704037B2 (en) | 2005-07-29 | 2020-07-07 | Abbott Products Gmbh | Processes for the manufacture and use of pancreatin |
US9198871B2 (en) | 2005-08-15 | 2015-12-01 | Abbott Products Gmbh | Delayed release pancreatin compositions |
US11266607B2 (en) | 2005-08-15 | 2022-03-08 | AbbVie Pharmaceuticals GmbH | Process for the manufacture and use of pancreatin micropellet cores |
US10072256B2 (en) | 2006-05-22 | 2018-09-11 | Abbott Products Gmbh | Process for separating and determining the viral load in a pancreatin sample |
US8940719B2 (en) * | 2006-07-03 | 2015-01-27 | Academia Sinica | Lithocholic acid analogues that inhibit sialyltransferase |
US20080119443A1 (en) * | 2006-07-03 | 2008-05-22 | Academia Sinica | Certain lithocholic acid analogues that inhibit sialyltransferase |
US10154975B2 (en) | 2010-10-29 | 2018-12-18 | Infirst Healthcare Limited | Solid solution compositions and use in chronic inflammation |
US11154500B2 (en) | 2010-10-29 | 2021-10-26 | Infirst Healthcare Limited | Solid solution compositions and use in chronic inflammation |
US11918654B2 (en) | 2010-10-29 | 2024-03-05 | Infirst Healthcare Limited | Solid solution compositions and use in severe pain |
US10004704B2 (en) | 2010-10-29 | 2018-06-26 | Infirst Healthcare Limited | Compositions and methods for treating chronic inflammation and inflammatory diseases |
US10155042B2 (en) | 2010-10-29 | 2018-12-18 | Infirst Healthcare Limited | Compositions and methods for treating chronic inflammation and inflammatory diseases |
US11844773B2 (en) | 2010-10-29 | 2023-12-19 | Infirst Healthcare Limited | Solid solution compositions and use in chronic inflammation |
US10188619B2 (en) | 2010-10-29 | 2019-01-29 | Infirst Healthcare Limited | Solid solution compositions and use in chronic inflammation |
US10213381B2 (en) | 2010-10-29 | 2019-02-26 | Infirst Healthcare Limited | Solid solution compositions and use in chronic inflammation |
US10231943B2 (en) | 2010-10-29 | 2019-03-19 | Infirst Healthcare Limited | Compositions and methods for treating cardiovascular diseases |
US11826428B2 (en) | 2010-10-29 | 2023-11-28 | Infirst Healthcare Limited | Solid solution compositions comprising cannabidiols |
US10363232B2 (en) | 2010-10-29 | 2019-07-30 | Infirst Healthcare Limited | Compositions and methods for treating severe pain |
US10426748B2 (en) | 2010-10-29 | 2019-10-01 | Infirst Healthcare Limited | Compositions and methods for treating chronic inflammation and inflammatory diseases |
US10588878B2 (en) | 2010-10-29 | 2020-03-17 | Infirst Healthcare Limited | Solid solution compositions and use in chronic inflammation |
US10596132B2 (en) | 2010-10-29 | 2020-03-24 | Infirst Healthcare Limited | Solid solution compositions and use in chronic inflammation |
US10653778B2 (en) | 2010-10-29 | 2020-05-19 | Infirst Healthcare Limited | Compositions and methods for treating chronic inflammation and inflammatory diseases |
US11730709B2 (en) | 2010-10-29 | 2023-08-22 | Infirst Healthcare Limited | Compositions and methods for treating severe pain |
US10695431B2 (en) | 2010-10-29 | 2020-06-30 | Infirst Healthcare Limited | Solid solution compositions and use in cardiovascular disease |
US10695432B2 (en) | 2010-10-29 | 2020-06-30 | Infirst Healthcare Limited | Solid solution compositions and use in severe pain |
US11660276B2 (en) | 2010-10-29 | 2023-05-30 | Infirst Healthcare Limited | Compositions and methods for treating chronic inflammation and inflammatory diseases |
US10835490B2 (en) | 2010-10-29 | 2020-11-17 | Infirst Healthcare Limited | Solid solution compositions and use in chronic inflammation |
US10849869B2 (en) | 2010-10-29 | 2020-12-01 | Infirst Healthcare Limited | Compositions and methods for treating chronic inflammation and inflammatory diseases |
US10857114B2 (en) | 2010-10-29 | 2020-12-08 | Infirst Healthcare Limited | Compositions and methods for treating severe pain |
US11000493B2 (en) | 2010-10-29 | 2021-05-11 | Infirst Healthcare Limited | Solid solution compositions and use in chronic inflammation |
US11065218B2 (en) | 2010-10-29 | 2021-07-20 | Infirst Healthcare Limited | Compositions and methods for treating chronic inflammation and inflammatory diseases |
US11103472B2 (en) | 2010-10-29 | 2021-08-31 | Infirst Healthcare Limited | Oral suspensions comprising a non-steroidal anti-inflammatory drug (NSAID) |
US10143671B2 (en) | 2010-10-29 | 2018-12-04 | Infirst Healthcare Limited | Solid solution compositions and use in chronic inflammation |
US11202831B2 (en) | 2010-10-29 | 2021-12-21 | Infirst Healthcare Limited | Solid solution compositions and use in cardiovascular disease |
US11224659B2 (en) | 2010-10-29 | 2022-01-18 | Infirst Healthcare Limited | Solid solution compositions and use in severe pain |
WO2012152707A1 (en) * | 2011-05-06 | 2012-11-15 | Vaxcine Ltd | Microemulsions |
WO2012152709A1 (en) * | 2011-05-06 | 2012-11-15 | Vaxcine Ltd | Hydrophobic preparations |
US10660858B2 (en) | 2011-09-07 | 2020-05-26 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
US10307375B2 (en) | 2011-09-07 | 2019-06-04 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
US10172799B1 (en) | 2011-09-07 | 2019-01-08 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
US10154964B2 (en) | 2011-09-07 | 2018-12-18 | Cosmo Technologies Limited | Controlled release and taste masking oral pharmaceutical composition |
Also Published As
Publication number | Publication date |
---|---|
KR20000022353A (en) | 2000-04-25 |
CA2259233A1 (en) | 1998-01-08 |
AU3352697A (en) | 1998-01-21 |
GB9613858D0 (en) | 1996-09-04 |
BR9710179A (en) | 1999-08-10 |
ID18568A (en) | 1998-04-23 |
NO986211D0 (en) | 1998-12-30 |
ZA975856B (en) | 1999-01-04 |
NO986211L (en) | 1999-03-02 |
EP0910411A1 (en) | 1999-04-28 |
AU709013B2 (en) | 1999-08-19 |
US6258377B1 (en) | 2001-07-10 |
JP2000515130A (en) | 2000-11-14 |
NZ333115A (en) | 2000-06-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU709013B2 (en) | Hydrophobic preparations containing medium chain monoglycerides | |
EP0587659B1 (en) | Pharmaceutical carrier | |
Willimann et al. | Lecithin organogel as matrix for transdermal transport of drugs | |
Treffel et al. | Effect of occlusion on in vitro percutaneous absorption of two compounds with different physicochemical properties | |
Kim et al. | Preparation and evaluation of biphenyl dimethyl dicarboxylate microemulsions for oral delivery | |
Kararli et al. | Oral delivery of a renin inhibitor compound using emulsion formulations | |
WO1998037869A1 (en) | Fat emulsion for oral administration | |
KR20020066776A (en) | Formulation for oral delivery of insulin and preparation method thereof | |
CA2612128C (en) | Methods and formulations for enhancing the absorption and decreasing the absorption variability of orally administered drugs, vitamins and nutrients | |
WO1997030695A1 (en) | Drug delivery compositions suitable for intravenous injection | |
US20040147578A1 (en) | Use of lipoaminoacids as absorption promoters in a pharmaceutical composition | |
PT100400B (en) | MICROEMULATIONS FORMULATIONS CONVERTIVEIS | |
US20020115592A1 (en) | Pharmaceutical compositions containing insulin | |
JP2740465B2 (en) | A novel pharmacological dosage form for transdermal administration | |
Mikov et al. | The influence of 3α, 7α-dihydroxy-12-keto-5β-cholanate on gliclazide pharmacokinetics and glucose levels in a rat model of diabetes | |
EP0746331B1 (en) | Convertible microemulsion formulations | |
Luner et al. | The effects of bile salts and lipids on the physicochemical behavior of gemfibrozil | |
CA2138607A1 (en) | Formulations for orally administered pharmaceutical agents | |
AU764413B2 (en) | A pharmaceutical composition comprising cyclosporin in a lipid carrier | |
WO1996010991A1 (en) | Pharmaceutical composition containing derivatives of sex hormones | |
MXPA99000275A (en) | Hydrophobic preparations containing monoglycerides of average chain | |
WO1999043299A2 (en) | Oral formulation for hydrophilic drugs | |
CN102905693A (en) | Water-soluble pharmaceutical composition comprising at least one therapeutically active substance having hydrophobic properties and at least one compound selected from among sialoglycosphingolipids, glycosphingolipids or a mixture of sialoglycosphingolipids and glycosphingolipids | |
Imai et al. | Mutual effect of egg albumin and fatty acids on bioavailability of dl-α-tocopherol | |
HISAOKA et al. | Studies on liposome-encapsulated carboquone. III. Enhancement of lymphatic transport of carboquone by encapsulation |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 97196069.0 Country of ref document: CN |
|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH HU IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZW AM AZ BY KG KZ MD RU TJ TM |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH KE LS MW SD SZ UG ZW AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 333115 Country of ref document: NZ |
|
WWE | Wipo information: entry into national phase |
Ref document number: 09218289 Country of ref document: US |
|
ENP | Entry into the national phase |
Ref document number: 2259233 Country of ref document: CA Ref document number: 2259233 Country of ref document: CA Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1019980710781 Country of ref document: KR |
|
WWE | Wipo information: entry into national phase |
Ref document number: PA/a/1999/000275 Country of ref document: MX |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1997929411 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 1997929411 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWP | Wipo information: published in national office |
Ref document number: 1019980710781 Country of ref document: KR |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1997929411 Country of ref document: EP |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1019980710781 Country of ref document: KR |