CN101695575A - Pharmaceutical composition containing statin-type lipid-lowering medicaments, phenformin-type hypoglycemic medicaments and nicotinic acid - Google Patents
Pharmaceutical composition containing statin-type lipid-lowering medicaments, phenformin-type hypoglycemic medicaments and nicotinic acid Download PDFInfo
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Abstract
The invention relates to a pharmaceutical composition containing statin-type lipid-lowering medicaments, phenformin-type hypoglycemic medicaments, nicotinic acid and a pharmaceutical carrier and belonging to the pharmaceutical field. The invention also relates to the application of the composition in the preparation of medicaments for preventing or treating diabetes and hyperlipidemia complications.
Description
Technical field
The present invention relates to contain pharmaceutical composition of stanin fat-reducing medicament, biguanide antidiabetic medicament, nicotinic acid and pharmaceutically suitable carrier and this pharmaceutical composition is used for preventing or treating the medicine of diabetes and hyperlipidemia complications in preparation purposes.The invention belongs to pharmaceutical field.
Background technology
Diabetes are metabolic diseases of a kind of multi-pathogenesis, are characterized in chronic hyperglycemia, follow because of insulin secretion and/or effect the defective sugar, fat and the protein metabolism disorder that cause.Point out in the report on October 12nd, 2004 " Chinese residents nutrition and Health Situation " that Ministry of Public Health, the Department of Science and Technology and State Statistics Bureau announce: China 18 years old and above resident's diabetes prevalence are 2.6%, and the impaired fasting glucose (IFG) rate is 1.9%.Estimate the existing number of patients more than 2,000 ten thousand of national diabetes, other has nearly 2,000 ten thousand people's impaired fasting glucose (IFG).The city prevalence is apparently higher than the rural area.Compare with diabetes sampling survey data in 1996, the big city more than 20 years old diabetes prevalence by 4.6% rise to 6.4%, small and medium-sized cities rise to 3.9% by 3.4%.Diabetes are still serious public health problem of China.
Hyperlipidemia is meant cholesterol in the blood plasma, triglyceride, phospholipid and the lipid compositions such as fat acid of fatization a kind of disease disease of increasing not.Hyperlipemia is that cholesterol, triglyceride and the low-density lipoprotein white level in the blood plasma that is caused by a variety of causes raises and a kind of disease of a kind of whole body matter Developmental and Metabolic Disorder that high density lipoprotein is low excessively.
The biguanides antidiabetic drug, mainly acting on islets of langerhans organizes outward, increase the zymolysis of intramuscular glucose, increase the utilization of surrounding tissue to glucose, suppress the absorption of glucose, suppress glyconeogenesis in the liver, increase Insulin receptor INSR number in the target cell and, thereby reach hypoglycemic purpose the affinity of eyelash island element.Biguanide antidiabetic medicament comprises phenformin (Phenformin), metformin (Metformin), buformin (Bufonamin).
Statins (HMG-CoA reductase inhibitor) is if drug main generates the effect of performance accent fat by suppressing cholesterol.Statins is applicable to that mainly it is main patient that blood TC and LDL-C increase.The stanin fat-reducing medicament of extensive use comprises lovastatin (lovatatin), simvastatin (simvastatin), pravastatin (pravastatin), mevastatin (mevastatin), fluvastatin (fluvastatin), atorvastatin (atovastatin), cerivastatin (cerivastatin), Rosuvastatin (rosuvastatin) or Pitavastatin (Pitavastatin) clinically.
Nicotinic acid is also referred to as vitamin B3, or vitamin PP.It is one of 13 kinds of vitamin of needed by human, is a kind of water soluble vitamins, belongs to vitamin B complex.Nicotinic acid is converted into nicotiamide in human body, nicotiamide is nadide and coenzyme II ingredient, participates in the body lipid metabolism, the process that the oxidizing process of Tissue respiration and saccharide anaerobic are decomposed.
Summary of the invention
Purpose of the present invention provides a kind of pharmaceutical composition, and this pharmaceutical composition contains a kind of, nicotinic acid and the pharmaceutically suitable carrier in a kind of, the biguanide antidiabetic medicament in the stanin fat-reducing medicament.
For realizing purpose of the present invention, the present invention by the following technical solutions:
A kind of pharmaceutical composition contains a kind of, nicotinic acid and pharmaceutically suitable carrier in a kind of, the biguanide antidiabetic medicament in the stanin fat-reducing medicament.
In pharmaceutical composition provided by the invention, except that stanin fat-reducing medicament chemical compound itself, can also be selected from the active metabolite or the salt of stanin fat-reducing medicament.Stanin fat-reducing medicament comprises lovastatin (lovatatin), simvastatin (simvastatin), pravastatin (pravastatin), mevastatin (mevastatin), fluvastatin (fluvastatin), atorvastatin (atovastatin), Rosuvastatin (rosuvastatin) and Pitavastatin (Pitavastatin).Wherein, lovastatin content is 5mg-80mg, and simvastatin content is 5mg-80mg, pravastatin content is 5mg-40mg, and fluvastatin content is 10mg-40mg, and atorvastatin content is 5mg-80mg, Rosuvastatin content is 10mg-40mg, and Pitavastatin content is 1mg-10mg.
In pharmaceutical composition provided by the invention, except that biguanide antidiabetic medicament chemical compound itself, can also be selected from the active metabolite or the salt of biguanide antidiabetic medicament chemical compound.Biguanide antidiabetic medicament comprises phenformin (Phenformin), metformin (Metformin), buformin (Bufonamin).Wherein, phenformin content is 25mg-200mg, and metformin content is 250mg-1500mg.
In pharmaceutical composition provided by the invention, the content of nicotinic acid is 25mg-1000mg.
In the pharmaceutical composition provided by the invention, stanin fat-reducing medicament is a lovastatin, and content is 5mg-80mg; Biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; The content of nicotinic acid is 25mg-1000mg.
In the pharmaceutical composition provided by the invention, stanin fat-reducing medicament is a lovastatin, and content is 5mg-80mg; Biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; The content of nicotinic acid is 25mg-1000mg.
In the pharmaceutical composition provided by the invention, stanin fat-reducing medicament is a simvastatin, and content is 5mg-80mg; Biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; The content of nicotinic acid is 25mg-1000mg.
In the pharmaceutical composition provided by the invention, stanin fat-reducing medicament is a simvastatin, and content is 5mg-80mg; Biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; The content of nicotinic acid is 25mg-1000mg.
In the pharmaceutical composition provided by the invention, stanin fat-reducing medicament is a pravastatin, and content is 5mg-40mg; Biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; The content of nicotinic acid is 25mg-1000mg.
In the pharmaceutical composition provided by the invention, stanin fat-reducing medicament is a pravastatin, and content is 5mg-40mg; Biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; The content of nicotinic acid is 25mg-1000mg.
In the pharmaceutical composition provided by the invention, stanin fat-reducing medicament is a fluvastatin, and content is 10mg-40mg; Biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; The content of nicotinic acid is 25mg-1000mg.
In the pharmaceutical composition provided by the invention, stanin fat-reducing medicament is a fluvastatin, and content is 10mg-40mg; Biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; The content of nicotinic acid is 25mg-1000mg.
In the pharmaceutical composition provided by the invention, stanin fat-reducing medicament is an atorvastatin, and content is 5mg-80mg; Biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; The content of nicotinic acid is 25mg-1000mg.
In the pharmaceutical composition provided by the invention, stanin fat-reducing medicament is an atorvastatin, and content is 5mg-80mg; Biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; The content of nicotinic acid is 25mg-1000mg.
In the pharmaceutical composition provided by the invention, stanin fat-reducing medicament is a Rosuvastatin, and content is 10mg-40mg; Biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; The content of nicotinic acid is 25mg-1000mg.
In the pharmaceutical composition provided by the invention, stanin fat-reducing medicament is a Rosuvastatin, and content is 10mg-40mg; Biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; The content of nicotinic acid is 25mg-1000mg.
In the pharmaceutical composition provided by the invention, stanin fat-reducing medicament is a Pitavastatin, and content is 1mg-10mg; Biguanide antidiabetic medicament is a phenformin, and content is 25mg-200mg; The content of nicotinic acid is 25mg-1000mg.
In the pharmaceutical composition provided by the invention, stanin fat-reducing medicament is a Pitavastatin, and content is 1mg-10mg; Biguanide antidiabetic medicament is a metformin, and content is 250mg-1500mg; The content of nicotinic acid is 25mg-1000mg.
Term " medicinal content " is meant that the clinician grants content of medicines according to the diseased individuals degree that is in a bad way to diseased individuals in order to reach effective control or treatment disease purpose.Be to be understood that the medicinal content of medicine provided by the invention is not limitation of the present invention, but to of the present invention preferred, generally, in this content was scope, this medicine can produce effective therapeutic effect to diseased individuals.Diseased individuals is meant the self-existent life entity of suffering from disease, and in the present invention, life entity refers to the mankind especially.Should be appreciated that in the prior art, human pharmaceutical use content or medicinal content range can with mammal, as rat, mice etc., converting is fit to medicinal content or the content range that corresponding animal is suitable for to draw.
According to the present invention, active component in the pharmaceutical composition is the solvent in the compositions, one of them active component comes from a kind of in the stanin fat-reducing medicament, and active component comes a kind of in biguanide antidiabetic medicament, and an active component is from nicotinic acid; The dosage form of this pharmaceutical composition includes but not limited to conventional tablet, bilayer tablet, multilayer tablet, slow releasing tablet, the single chamber controlled release tablet, two chambers controlled release tablet, the pore type controlled release tablet, sublingual lozenge, oral cavity quick disintegrating slice, dispersible tablet, enteric coatel tablets, granule, pill, enteric coated capsule, delayed-release tablet, regularly/the position releasing piece, conventional capsule, slow releasing capsule, controlled release capsule, the capsule that contains micropill or small pieces, the pH dependent form capsule that contains micropill or small pieces, oral liquid, membrane or patch, what should particularly point out is to contain stanin fat-reducing medicament, the pharmaceutical composition of biguanide antidiabetic medicament and nicotinic acid is made tablet or capsule.
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into common oral preparation, comprise conventional tablet, conventional capsule, granule etc., described pharmaceutically suitable carrier includes excipient and the accessory drugs that helps reactive compound is mixed with pharmaceutical formulation when making tablet, compositions as one or more materials of starch, microcrystalline Cellulose, inorganic salts, sucrose, dextrin, lactose, sodium chloride, citric acid and sodium sulfite etc. belongs to this area general knowledge.
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into slow releasing preparation, comprise excipient and adjuvant etc.Described excipient and adjuvant have comprised that the adjuvant of slow releasing function is that the solubility/insoluble salt of hydroxypropyl methylcellulose and/or ethyl cellulose and/or polyacrylic resin class and/or polycarboxy ethene and/or alginic acid and/or ethyl cellulose and/or other play the adjuvant of slow releasing function, the hypromellose employing includes the extensive stock of hydroxypropyl methylcellulose (HPMC) such as U.S. many elegant (Methocel) of all size, ethyl cellulose adopts the extensive stock that includes ethyl cellulose (EC), and polyacrylic resin adopts and includes polyacrylic resin II, the acrylic resin of III class or analog such as all size (Eudragit).
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into controlled release preparation, comprise that active medicine has reached the adjuvant of controlled release effect.The above-mentioned adjuvant that plays the controlled release effect is polyoxyethylene and/or hypromellose and/or ethyl cellulose and/or sodium chloride and/or lactose and/or mannitol and/or fructose and/or glucose and/or sucrose or low-substituted hydroxypropyl cellulose and/or cross-linking sodium carboxymethyl cellulose and/or crospolyvinylpyrrolidone and/or cellulose acetate.Above-mentioned adjuvant is pharmaceutical carrier, expanding material, permeation-promoter, solubilizing agent, binding agent, wetting agent, lubricant, coloring agent, porogen, membrane material, antiplastering aid, plasticizer, lucifuge agent, solvent.Pharmaceutical carrier, expanding material can adopt polyoxyethylene, hypromellose, ethyl cellulose, hydroxypropyl cellulose, methylcellulose, Glyceryl Behenate class etc.; Permeation-promoter can adopt sodium chloride, lactose, mannitol etc.; Solubilizing agent can be adopted sodium lauryl sulphate or poloxamer etc.; Binding agent can adopt polyvinylpyrrolidone, hypromellose, chitosan, sodium alginate, methylcellulose, ethyl cellulose, starch slurry, arabic gum, gelatin, sucrose, polyvinyl alcohol etc.; Wetting agent can adopt the ethanol-water solution of dehydrated alcohol, water, various concentration; Lubricant can adopt stearic acid, magnesium stearate, Pulvis Talci, starch, paraffin etc.; Coloring agent can adopt natural pigment such as carmine, amaranth, lemon yellow, bright orchid, indigo, brownish red ferrum oxide and synthetic dyestuff or the like; Porogen can adopt sucrose, mannitol, Polyethylene Glycol, titanium dioxide, Pulvis Talci, silicon dioxide etc.; Membrane material can adopt cellulose acetate, ethyl cellulose, hydroxypropyl emthylcellulose acetic acid succinate, beautiful jade Cellulose Acetate Phthalate, poly-phthalic acid vinyl acetate cellulose, hydroxypropyl cellulose, hydroxyethyl-cellulose etc.; Solvent can adopt acetone, dehydrated alcohol, ethanol, water etc.
Also contain the pharmaceutics acceptable carrier in the said composition, can be made into sublingual lozenge, oral cavity quick disintegrating slice or dispersible tablet etc.; Comprise excipient and adjuvant etc.Described excipient and adjuvant have mannitol, sorbitol, maltose alcohol, low substituted hydroxy-propyl methylcellulose, microcrystalline Cellulose, carboxymethyl starch sodium, cross-linked carboxymethyl cellulose sodium, crospolyvinylpyrrolidone, processing agar, cyclodextrin, glycyrrhizic acid, stevioside, citric acid, Oleum menthae, eucalyptus oil, Oleum Caryophylli, Fructus Citri Limoniae oil, citrus seed oil and some other correctives that wraps up with microcapsule etc.
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition; can be made into enteric coatel tablets or enteric coated capsule etc.; comprise excipient and adjuvant etc.; described excipient and adjuvant have starch; microcrystalline Cellulose; inorganic salts; hydroxypropyl emthylcellulose; ethyl cellulose; the polyacrylic resin class; polycarboxy ethene; the solubility of alginic acid/insoluble salt; octadecanol; stearic acid; sodium chloride; cysteine; the compositions of one or more materials of citric acid and sodium sulfite etc.; enteric-coating material comprises: Lac; the cellulose acetate phthalate ester; crylic acid resin (as Eudragit L and S type etc.); the polyvinyl acetate phthalic acid ester; phthalic acid hypromellose ester; succinic acid acetic acid hydroxypropyl methylcellulose, and plasticizer is (as diethyl phthalate; Polyethylene Glycol; propylene glycol; glycerol triacetate; dimethyl phthalate; dibutyl sebacate; triethyl citrate; tributyl citrate; CitroflexA-2; the acetylated monoglycerides of Oleum Ricini and percentage etc.) with porogen various medicaments adjuvants such as (as PEG6000).
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition; can be made into slow releasing capsule; controlled release capsule; the capsule that contains micropill or small pieces; contain the pH dependent form capsule of micropill or small pieces etc.; comprise excipient and adjuvant; described excipient and adjuvant have starch; microcrystalline Cellulose; inorganic salts; hydroxypropyl emthylcellulose; ethyl cellulose; the polyacrylic resin class; polycarboxy ethene; the solubility of alginic acid/insoluble salt; octadecanol; stearic acid; sodium chloride; cysteine; the compositions of one or more materials of citric acid and sodium sulfite etc., coating material comprises: Lac; the cellulose acetate phthalate ester; ethyl cellulose; hydroxypropyl emthylcellulose; hydroxypropyl cellulose; crylic acid resin (as Eudragit L and S type etc.); the polyvinyl acetate phthalic acid ester; phthalic acid hypromellose ester; succinic acid acetic acid hydroxypropyl methylcellulose; the polyvinyl acetate phthalic acid ester; and plasticizer is (as diethyl phthalate; Polyethylene Glycol; propylene glycol; glycerol triacetate; dimethyl phthalate; dibutyl sebacate; triethyl citrate; tributyl citrate; CitroflexA-2; the acetylated monoglycerides of Oleum Ricini and percentage etc.) with porogen various medicaments adjuvants such as (as PEG6000).
Also contain the pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into dosage forms such as granule, oral liquid, membrane, patch.Described pharmaceutically acceptable carrier includes excipient and the adjuvant that helps reactive compound is mixed with pharmaceutical formulation when making the patch membrane; as polyvinyl alcohol, Triafol T, ethylene-vinyl acetate copolymer, polyvinylpyrrolidone, polyacrylamide, polybutene class pressure sensitive adhesive, crylic acid resin pressure sensitive adhesive, silicone pressure sensitive adhesive etc.; and back lining materials such as polrvinyl chloride, polyethylene, aluminium foil, polypropylene, polyester, the compositions of one or more materials of protecting film such as polyethylene, polystyrene, polypropylene etc.
Preparation of the present invention can use or use in turn with any order simultaneously, and is best to use simultaneously.Comprise in the above-mentioned use simultaneously that best uses with fixed combination with fixed combination and on-fixed combination.
Preparation of the present invention can be taken once or twice every day, perhaps with slow release or controlled release mode every day or a few days takes once every other day or at interval.Take once wherein preferred every day.
Described pharmaceutical composition can flexible using with " Combined drug box " form.Above-mentioned " Combined drug box " is a kind of case type container, the drug regimen of built-in multiple content form, and take description." Combined drug box " more is applicable to personalized medicine.
Pharmaceutical composition provided by the invention can be applied to prevention or treatment diabetes and hyperlipidemia complications disease.
The medicine that pharmaceutical composition provided by the invention is made has the effect of obvious treatment diabetes and hyperlipidemia complications disease, therefore is that anti-diabetic preferably merges high blood cholesterol drug.
In clinical practice or the scientific research document of having delivered, we do not find that as yet stanin fat-reducing medicament, biguanide antidiabetic medicament and nicotinic acid unites the treatment that is used for diabetes and hyperlipidemia complications.In experiment, we find, the medicine that the compositions of stanin fat-reducing medicament provided by the invention, biguanide antidiabetic medicament and nicotinic acid is made has excellent curative to prevention or treatment diabetes and hyperlipidemia complications.
The present invention will be further described below in conjunction with the specific embodiment, is not limitation of the invention, all any this areas of carrying out according to content of the present invention be equal to replacement, all belong to protection scope of the present invention.
The specific embodiment
The consumption of the preparation process of following pharmaceutical preparation embodiment and used material of preparation or the used material of preparation is not limited to character express; all formulation methods that contains pharmaceutical composition provided by the invention; all belong to protection scope of the present invention; but concrete experimental technique reference drug preparation quick-reference book is as " pharmaceutical necessities is used and preparation ", " pharmaceutics ", " Biopharmaceutics and Pharmacokinetics " etc.
Embodiment 1～5: the preparation of the lovastatin/biguanides of different content proportioning/nicotinic acid tablet (1000 amounts)
Preparation technology:
(1) lovastatin, biguanides and the nicotinic acid that takes by weighing recipe quantity is crossed behind 100 mesh sieves standby by equivalent incremental method mix homogeneously;
(2) other adjuvants are crossed behind 100 mesh sieves standby respectively;
(3) press after the pregelatinized Starch, microcrystalline Cellulose, carboxymethylstach sodium mixing of recipe quantity again and mixed crude drug equivalent incremental method mix homogeneously;
(4) add binding agent and make soft material in right amount, 24 mesh sieves are granulated, 20 mesh sieve granulate, 40～45 ℃ of dryings;
(5) dried granule adds an amount of magnesium stearate mixing, tabletting behind the assay.
Embodiment 6～11: the preparation of Statins/metformin hydrochloride/nicotinic acid tablet (1000 amounts)
Preparation technology:
(1) Statins, metformin hydrochloride and the nicotinic acid that takes by weighing recipe quantity is crossed behind 100 mesh sieves standby by equivalent incremental method mix homogeneously;
(2) other adjuvants are crossed behind 100 mesh sieves standby respectively;
(3) press after the pregelatinized Starch, microcrystalline Cellulose, carboxymethylstach sodium mixing of recipe quantity again and mixed crude drug equivalent incremental method mix homogeneously;
(4) add binding agent and make soft material in right amount, 24 mesh sieves are granulated, 20 mesh sieve granulate, 40～45 ℃ of dryings;
(5) dried granule adds an amount of magnesium stearate mixing, tabletting behind the assay.
Embodiment 12～18: the capsular preparation of Statins/phenformin hydrochloride/nicotinic acid (1000 amounts)
Preparation technology:
(1) Statins, phenformin hydrochloride and the nicotinic acid that takes by weighing recipe quantity is crossed behind 100 mesh sieves standby by equivalent incremental method mix homogeneously;
(2) other adjuvants are crossed behind 100 mesh sieves standby respectively;
(3) press behind the pregelatinized Starch of recipe quantity and the carboxymethylstach sodium mixing again and mixed crude drug equivalent incremental method mix homogeneously;
(4) add binding agent and make soft material in right amount, 24 mesh sieves are granulated, 20 mesh sieve granulate, 40～45 ℃ of dryings;
(5) dried granule adds an amount of magnesium stearate mixing, filled capsules behind the assay.
Embodiment 19～25: the particulate preparation of Statins/metformin hydrochloride/nicotinic acid (1000 bags of amounts)
| Simvastatin | ??/ | ??10g | ??/ | ??/ | ??/ | ??/ | ??/ |
| Pravastatin sodium | ??/ | ??/ | ??10g | ??/ | ??/ | ??/ | ??/ |
| Simvastatin | ??/ | ??10g | ??/ | ??/ | ??/ | ??/ | ??/ |
| Fluvastatin sodium | ??/ | ??/ | ??/ | ??20g | ??/ | ??/ | ??/ |
| Atorvastatin calcium | ??/ | ??/ | ??/ | ??/ | ??10g | ??/ | ??/ |
| Rosuvastain calcium | ??/ | ??/ | ??/ | ??/ | ??/ | ??10g | ??/ |
| Pitavastatin Calcium | ??/ | ??/ | ??/ | ??/ | ??/ | ??/ | ??2g |
| Metformin hydrochloride | ??500g | ??500g | ??500g | ??500g | ??500g | ??500g | ??500g |
| Nicotinic acid | ??1000g | ??1000g | ??1000g | ??1000g | ??1000g | ??1000g | ??1000g |
| Lactose | ??80g | ??80g | ??80g | ??80g | ??80g | ??80g | ??80g |
| Pregelatinized Starch | ??100g | ??100g | ??100g | ??100g | ??100g | ??100g | ??100g |
| Carboxymethylstach sodium | ??15g | ??15g | ??15g | ??15g | ??15g | ??15g | ??15g |
| Aspartame | ??5g | ??5g | ??5g | ??5g | ??5g | ??5g | ??5g |
| 5% 30 POVIDONE K 30 BP/USP-30 | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount |
| Magnesium stearate | ??0.5％ | ??0.5％ | ??0.5％ | ??0.5％ | ??0.5％ | ??0.5％ | ??0.5％ |
Preparation technology:
(1) Statins, metformin hydrochloride and the nicotinic acid that takes by weighing recipe quantity is crossed behind 100 mesh sieves standby by equivalent incremental method mix homogeneously;
(2) other adjuvants are crossed behind 100 mesh sieves standby respectively;
(3) press behind lactose, pregelatinized Starch, carboxymethylstach sodium and the aspartame mixing of recipe quantity again and mixed crude drug equivalent incremental method mix homogeneously;
(4) add binding agent and make soft material in right amount, 24 mesh sieves are granulated, 40～45 ℃ of dryings;
(5) 20 mesh sieve granulate remove fine powder with 80 mesh sieves sieve then;
(6) dried granule adds an amount of magnesium stearate mixing, packs behind the assay.
Embodiment 26～32: the particulate preparation of Statins/metformin hydrochloride/nicotinic acid (1000 bags of amounts)
| Atorvastatin calcium | ??/ | ??/ | ??/ | ??/ | ??10g | ??/ | ??/ |
| Rosuvastain calcium | ??/ | ??/ | ??/ | ??/ | ??/ | ??10g | ??/ |
| Pitavastatin Calcium | ??/ | ??/ | ??/ | ??/ | ??/ | ??/ | ??2g |
| Metformin hydrochloride | ??500g | ??500g | ??500g | ??500g | ??500g | ??500g | ??500g |
| Nicotinic acid | ??2000g | ??2000g | ??2000g | ??2000g | ??2000g | ??2000g | ??2000g |
| Lactose | ??80g | ??80g | ??80g | ??80g | ??80g | ??80g | ??80g |
| Pregelatinized Starch | ??100g | ??100g | ??100g | ??100g | ??100g | ??100g | ??100g |
| Carboxymethylstach sodium | ??15g | ??15g | ??15g | ??15g | ??15g | ??15g | ??15g |
| Aspartame | ??5g | ??5g | ??5g | ??5g | ??5g | ??5g | ??5g |
| 5% 30 POVIDONE K 30 BP/USP-30 | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount |
| Magnesium stearate | ??0.5％ | ??0.5％ | ??0.5％ | ??0.5％ | ??0.5％ | ??0.5％ | ??0.5％ |
Preparation technology:
(1) Statins, metformin hydrochloride and the nicotinic acid that takes by weighing recipe quantity is crossed behind 100 mesh sieves standby by equivalent incremental method mix homogeneously;
(2) other adjuvants are crossed behind 100 mesh sieves standby respectively;
(3) press behind lactose, pregelatinized Starch, carboxymethylstach sodium and the aspartame mixing of recipe quantity again and mixed crude drug equivalent incremental method mix homogeneously;
(4) add binding agent and make soft material in right amount, 24 mesh sieves are granulated, 40～45 ℃ of dryings;
(5) 20 mesh sieve granulate remove fine powder with 80 mesh sieves sieve then;
(6) dried granule adds an amount of magnesium stearate mixing, packs behind the assay.
Embodiment 33～39: the particulate preparation of Statins/phenformin hydrochloride/nicotinic acid (1000 bags of amounts)
| Phenformin hydrochloride | ??50g | ??50g | ??50g | ??50g | ??50g | ??50g | ??50g |
| Nicotinic acid | ??1000g | ??1000g | ??1000g | ??1000g | ??1000g | ??1000g | ??1000g |
| Lactose | ??80g | ??80g | ??80g | ??80g | ??80g | ??80g | ??80g |
| Pregelatinized Starch | ??100g | ??100g | ??100g | ??100g | ??100g | ??100g | ??100g |
| Carboxymethylstach sodium | ??15g | ??15g | ??15g | ??15g | ??15g | ??15g | ??15g |
| Aspartame | ??5g | ??5g | ??5g | ??5g | ??5g | ??5g | ??5g |
| 5% 30 POVIDONE K 30 BP/USP-30 | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount |
| Magnesium stearate | ??0.5％ | ??0.5％ | ??0.5％ | ??0.5％ | ??0.5％ | ??0.5％ | ??0.5％ |
Preparation technology:
(1) Statins, phenformin hydrochloride and the nicotinic acid that takes by weighing recipe quantity is crossed behind 100 mesh sieves standby by equivalent incremental method mix homogeneously;
(2) other adjuvants are crossed behind 100 mesh sieves standby respectively;
(3) press behind lactose, pregelatinized Starch, carboxymethylstach sodium and the aspartame mixing of recipe quantity again and mixed crude drug equivalent incremental method mix homogeneously;
(4) add binding agent and make soft material in right amount, 24 mesh sieves are granulated, 40～45 ℃ of dryings;
(5) 20 mesh sieve granulate remove fine powder with 80 mesh sieves sieve then;
(6) dried granule adds an amount of magnesium stearate mixing, packs behind the assay.
Embodiment 40～42: the preparation of Statins/metformin hydrochloride/niacin slow-release tablet (1000 amounts)
| Magnesium stearate | ??1％ | ??1％ | ??1％ |
Preparation technology:
(1) Statins, metformin hydrochloride and the nicotinic acid that takes by weighing recipe quantity is crossed behind 100 mesh sieves standby by equivalent incremental method mix homogeneously;
(2) other adjuvants are crossed behind 100 mesh sieves standby respectively;
(3) press behind HPMC K15M, pregelatinized Starch, lactose and the carboxymethylstach sodium mixing of recipe quantity again and mixed crude drug equivalent incremental method mix homogeneously;
(4) add binding agent 5% 30 POVIDONE K 30 BP/USP-30 (the appearance agent is a dehydrated alcohol) and make soft material in right amount, 24 mesh sieves are granulated, 40～45 ℃ of dryings;
(5) dried granule adds an amount of magnesium stearate mixing, tabletting behind the assay.
Embodiment 43～45: the preparation of Statins/phenformin hydrochloride/niacin slow-release tablet (1000 amounts)
Preparation technology:
(1) Statins, phenformin hydrochloride and the nicotinic acid that takes by weighing recipe quantity is crossed behind 100 mesh sieves standby by equivalent incremental method mix homogeneously;
(2) other adjuvants are crossed behind 100 mesh sieves standby respectively;
(3) press behind HPMC K15M, pregelatinized Starch, lactose and the carboxymethylstach sodium mixing of recipe quantity again and mixed crude drug equivalent incremental method mix homogeneously;
(4) add binding agent 5% 30 POVIDONE K 30 BP/USP-30 (the appearance agent is a dehydrated alcohol) and make soft material in right amount, 24 mesh sieves are granulated, 20 mesh sieve granulate, 40～45 ℃ of dryings;
(5) dried granule adds an amount of magnesium stearate mixing, tabletting behind the assay.
Embodiment 46: the collaborative effect to hyperlipidemia, blood glucose in diabetic rats and blood fat of lovastatin+metformin hydrochloride+nicotinic acid
90 of healthy Wistar rats, male and female half and half, average weight (194.5 ± 20.3) g.The vena orbitalis posterior clump was adopted hematometry fasting glucose and blood fat after adaptability raised for 1 week, and randomly drawed 10 as the normal control group, the feed conventional feed.After water 12h is can't help in all the other rat fasting, all by 0.3g/kg intraperitoneal injection alloxan normal saline solution 1 time, the high lipid food of feeding simultaneously.Behind the 7d, the tail vein is got the hematometry fasting glucose, choose 76 of the rat of fasting glucose between 11.1～16.8mmol/L as diabetes model, and the vena orbitalis posterior clump is adopted hematometry T-CHOL (TG), triglyceride (TC), high density lipoprotein (HDL-C), low density lipoprotein, LDL (LDL-C) after continuing feed high lipid food 30d.Therefrom choose 57 dyslipidemia persons as the diabetes and hyperlipidemia complications animal pattern, and randomly draw 50 and be divided into 5 groups at random, promptly model control group is 10, the high lipid food of feeding; 10 of metformin hydrochloride groups, the feed high lipid food, metformin hydrochloride 50mg/kg irritates stomach, 1 time/day; 10 of lovastatin groups, the feed high lipid food, lovastatin 1mg/kg irritates stomach, 1 time/day; 10 of lovastatins+nicotinic acid group, the feed high lipid food, lovastatin 1mg/kg+ nicotinic acid 100mg/kg solution is irritated stomach, 1 time/day; Lovastatin+metformin hydrochloride+nicotinic acid group, 10, the feed high lipid food, lovastatin 1mg/kg+ metformin hydrochloride 50mg/kg+ nicotinic acid 100mg/kg irritates stomach, 1 time/day.Each organizes the administration cycle is 60d, and after administration the 20th, 40 and during 60d the vena orbitalis posterior clump adopt hematometry fasting glucose and blood fat.
The statistical method data are used with data
Expression is relatively adopted variance analysis between each group, and P＜0.05 is for significant difference occurring.
Experimental result shows, administration the 60th day, and normal control group fasting glucose, blood fat value do not have significant change; Still there were significant differences than normal matched group for model control group fasting glucose, blood fat; Metformin hydrochloride group and lovastatin+nicotinic acid group fasting blood sugar obviously reduces (P＜0.01 or P＜0.05), with model control group significant difference is arranged relatively, and the metformin hydrochloride group is than lovastatin+nicotinic acid group difference more remarkable (P＜0.05); Lovastatin group and lovastatin+nicotinic acid group fasting plasma lipid obviously reduces, and with model control group significant difference (P＜0.01) is arranged relatively, and lovastatin+nicotinic acid group is than lovastatin group difference more remarkable (P＜0.05); Metformin hydrochloride+glibenclamide+nicotinic acid group blood sugar lowering and blood fat are than other each administration group more remarkable (P＜0.05).
Claims (8)
1. pharmaceutical composition, contain:
1) a kind of in the stanin fat-reducing medicament;
2) a kind of in the biguanide antidiabetic medicament;
3) nicotinic acid;
4) pharmaceutically suitable carrier.
2. according to the compositions described in the claim 1, it is characterized in that: described stanin fat-reducing medicament comprises lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, Rosuvastatin and Pitavastatin.
3. according to the compositions described in the claim 2, it is characterized in that: the content of described lovastatin is that 5mg-80mg, simvastatin are that 5mg-80mg, pravastatin are that 5mg-40mg, fluvastatin are that 10mg-40mg, atorvastatin are that 5mg-80mg, Rosuvastatin are that 10mg-40mg, Pitavastatin are 1mg-10mg.
4. according to the compositions described in the claim 1, it is characterized in that: described biguanide antidiabetic medicament comprises metformin and phenformin.
5. according to the compositions described in the claim 4, it is characterized in that: the content of described metformin is that 250mg-1500mg and phenformin are 25mg-200mg.
6. according to the compositions described in the claim 1, it is characterized in that: the content of described nicotinic acid is 25mg-1000mg.
7. the pharmacy dosage form of any one described compositions of claim 1 to 6 comprises conventional tablet, slow releasing tablet, controlled release tablet, granule, conventional capsule, slow releasing capsule, controlled release capsule.
8. any one described compositions is used for preventing or treating the purposes of the medicine of diabetes and hyperlipidemia complications in the claim 1 to 6 in preparation.
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