CN101590051A - The pharmaceutical composition that contains nicotinic acid, HMG-CoA reductase inhibitor and alpha-glucosidase inhibitor - Google Patents
The pharmaceutical composition that contains nicotinic acid, HMG-CoA reductase inhibitor and alpha-glucosidase inhibitor Download PDFInfo
- Publication number
- CN101590051A CN101590051A CNA2008101139162A CN200810113916A CN101590051A CN 101590051 A CN101590051 A CN 101590051A CN A2008101139162 A CNA2008101139162 A CN A2008101139162A CN 200810113916 A CN200810113916 A CN 200810113916A CN 101590051 A CN101590051 A CN 101590051A
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- CN
- China
- Prior art keywords
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- pharmaceutical composition
- nicotinic acid
- acarbose
- tablet
- Prior art date
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- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 title claims abstract description 213
- 229960003512 nicotinic acid Drugs 0.000 title claims abstract description 116
- 235000001968 nicotinic acid Nutrition 0.000 title claims abstract description 116
- 239000011664 nicotinic acid Substances 0.000 title claims abstract description 116
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 82
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 title claims abstract description 21
- 239000003888 alpha glucosidase inhibitor Substances 0.000 title claims abstract description 21
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 title claims abstract description 20
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 title claims abstract description 20
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 35
- 239000003814 drug Substances 0.000 claims abstract description 31
- 238000002360 preparation method Methods 0.000 claims abstract description 29
- 229940079593 drug Drugs 0.000 claims abstract description 15
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims abstract description 12
- 208000033679 diabetic kidney disease Diseases 0.000 claims abstract description 12
- 230000002265 prevention Effects 0.000 claims abstract description 8
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 claims description 60
- 229960002632 acarbose Drugs 0.000 claims description 48
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 claims description 48
- OJRHUICOVVSGSY-RXMQYKEDSA-N (2s)-2-chloro-3-methylbutan-1-ol Chemical compound CC(C)[C@H](Cl)CO OJRHUICOVVSGSY-RXMQYKEDSA-N 0.000 claims description 31
- FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 claims description 24
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- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 21
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- AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 claims description 15
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- BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 claims description 15
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 14
- 229960004844 lovastatin Drugs 0.000 claims description 14
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 14
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 14
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims description 14
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- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 claims description 12
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- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims description 12
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- FJLGEFLZQAZZCD-MCBHFWOFSA-N (3R,5S)-fluvastatin Chemical compound C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 FJLGEFLZQAZZCD-MCBHFWOFSA-N 0.000 claims 2
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 18
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- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
Abstract
The present invention relates to the pharmaceutical composition of HMG-CoA reductase inhibitor, alpha-glucosidase inhibitor and the pharmaceutics acceptable carrier of a kind of nicotinic acid that contains pharmaceutical dosage, pharmaceutical dosage, and said composition is used for preventing or treating the purposes of diabetes, prevention or treatment diabetic nephropathy drugs in preparation.The medicine that pharmaceutical composition provided by the invention is made be better than single medicine aspect prevention or treatment diabetes, prevention or the treatment diabetic nephropathy, and more convenient patient takes.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition that contains nicotinic acid, HMG-CoA reductase inhibitor, alpha-glucosidase inhibitor and pharmaceutics acceptable carrier, and said composition is used for preventing or treating the purposes of diabetes, prevention or treatment diabetic nephropathy drugs in preparation.The invention belongs to pharmaceutical field.
Background technology
Diabetes (diabetes mellitus, DM) be the metabolism disorder that causes by Different types of etiopathogenises, be characterized in chronic hyperglycemia, with hypoinsulinism and/or effect obstacle, cause carbohydrate, fat, protein metabolism disorder, cause chronic injury, the dysfunction depletion of multiple organ.Development along with diabetes, under influence of various factors such as age, diabetic duration, glycemic control quality, diet control, blood pressure level, smoking and genetic predisposition, diabetics easily forms various vascular complications, comprises trunk complication and microvascular complication.Diabetes trunk complication is higher 2～6 times than the general population as the incidence rate that merges coronary heart disease, and the incidence rate of cerebral infarction and lower extremities than the high 3-4 of general population doubly.Diabetes microvascular complication such as kidney damage and retinopathy are especially apparently higher than the general population.Years of researches and observation show that diabetic vascular complications is one of deadly major cause of morbidity of diabetics.Hyperlipidemia is the main risk factor of type 2 diabetes mellitus trunk complication, Britain's diabetes perspective study (UKPDS) is found, in average 10 years following up a case by regular visits to, the intensive treatment group has reduced by 0.9 percentage point than conventional therapy group glycolated hemoglobin (HbAlc), cause blood capillary terminal point incident 25% (P＜0.01) that descended, but the macroangiopathic incident does not have obvious minimizing, the incidence rate of M (P=0.052) on a declining curve.Can good blood sugar control can reduce microangiopathic complication, but prevent coronary heart disease still uncertain.
(nicotinic acid NA) belongs to vitamin B group to nicotinic acid, is the cofactor in a kind of internal metabolism process.Heavy dose of nicotinic acid can have tangible blood lipid regulation effect.It is generally acknowledged after nicotinic acid is converted into cigarette phthalein amine in vivo and bring into play pharmacological action, the latter is nadide and coenzyme II ingredient, participates in the body lipid metabolism, the process that the oxidizing process of Tissue respiration and sugared anaerobic are decomposed.Nicotinic acid also can reduce the utilization of coenzyme A: by suppressing proteic synthetic the synthetic of cholesterol that influence of extra-low density, heavy dose still can reduce the concentration of serum cholesterol and triglyceride, and the peripheral vasodilation effect is arranged.Internal and external test proof nicotinic acid has the effect of direct inhibition cell steatolysis, causes that blood plasma free fatty acid (FFA) level sharply reduces (＞10 times).FFA is the raw material of the synthetic TG of liver, and FFA reduces, and influence synthetic TG of liver and VLDL, and VLDL is the predecessor of LDL, so nicotinic acid reduction serum TG and VLDL level also cause the reduction of LDL level.
3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor is called for short Statins (statins) medicine, it is the rate-limiting enzyme that acts on liver synthesis cholesterol specifically, can make the synthetic minimizing of cholesterol, low density lipoprotein, LDL (LDL) receptor active strengthens, LDL removes increase in the serum thereby make, the effect that improves HDL-C (HDL-C) simultaneously in addition and reduce triacylglycerol (TC).
The alpha-glucosidase inhibitor full name is an alpha-glucosidase inhibitor; it is the hyperglycemia medicine that a class has unique blood sugar lowering mechanism; it mainly acts on is by delaying intestinal the absorption of glucose to be reached the too high purpose of blood sugar control, and has cardiovascular protective effect.At present alpha-glucosidase inhibitor mainly contains 3 kinds of acarbose (Acarbose), voglibose (Voglibose), miglitol (Miglito 1).
Summary of the invention
The purpose of this invention is to provide a kind of at the pharmaceutical composition that has advantage aspect prevention or treatment diabetes, prevention or the treatment diabetic nephropathy.For realizing above-mentioned purpose of the present invention, the present invention by the following technical solutions:
A kind of pharmaceutical composition is made up of the nicotinic acid of pharmaceutical dosage, the HMG-CoA reductase inhibitor of pharmaceutical dosage, the alpha-glucosidase inhibitor and the pharmaceutics acceptable carrier of pharmaceutical dosage.
In the present invention, the content of nicotinic acid is 25～1000mg, and the content of HMG-CoA reductase inhibitor is 1～80mg, and the content of alpha-glucosidase inhibitor is 10～600mg.
According to the present invention, the HMG-CoA reductase inhibitor comprises simvastatin (Simvastatin), pravastatin (Pravastatin), fluvastatin (Fluvastatin), lovastatin (Lovastatin), atorvastatin (Atovastatin), mevastatin (Mevastatin), rosuvastatin (Rosuvastatin) and Pitavastatin (Pitavastatin) etc.Wherein, lovastatin content is 2mg-80mg, simvastatin content is 2mg-80mg, pravastatin content is 2mg-40mg, and mevastatin content is 2mg-80mg, and fluvastatin content is 10mg-80mg, atorvastatin content is 5mg-80mg, cerivastatin content is 0.1mg-0.3mg, and Rosuvastatin content is 10mg-40mg, and Pitavastatin content is 1mg-10mg.
According to the present invention, alpha-glucosidase inhibitor comprises acarbose, voglibose and miglitol etc.Wherein, acarbose content is that 25mg-600mg, voglibose content are that 0.05mg-0.6mg, miglitol content are 25mg-300mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, simvastatin and acarbose as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of simvastatin is 1mg-15mg, and the content of acarbose is 25mg-100mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, pravastatin sodium and acarbose as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of pravastatin sodium is 2mg-10mg, and the content of acarbose is 25mg-100mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, fluvastatin and acarbose as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of fluvastatin is 2mg-20mg, and the content of acarbose is 25mg-100mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, lovastatin and acarbose as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of lovastatin is 3mg-20mg, and the content of acarbose is 25mg-100mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, Atorvastatin calcium and acarbose as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of Atorvastatin calcium is 2mg-20mg, and the content of acarbose is 25mg-100mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, mevastatin and acarbose as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of mevastatin is 10mg-40mg, and the content of acarbose is 25mg-100mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, rosuvastatin and acarbose as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of rosuvastatin is 1mg-10mg, and the content of acarbose is 25mg-100mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, Pitavastatin and acarbose as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of Pitavastatin is 0.5mg-4mg, and the content of acarbose is 25mg-100mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, simvastatin and voglibose as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of simvastatin is 1mg-15mg, and the content of voglibose is 0.05mg-0.6mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, pravastatin sodium and voglibose as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of pravastatin sodium is 2mg-10mg, and the content of voglibose is 0.05mg-0.6mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, fluvastatin and voglibose as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of fluvastatin is 2mg-20mg, and the content of voglibose is 0.05mg-0.6mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, lovastatin and voglibose as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of lovastatin is 3mg-20mg, and the content of voglibose is 0.05mg-0.6mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, Atorvastatin calcium and voglibose as active component, wherein the content of nicotinic acid is 25mg-1000mg, the content of Atorvastatin calcium is 2mg-20mg, and the content of voglibose is 0.05mg-0.6mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, mevastatin and voglibose as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of mevastatin is 10mg-40mg, and the content of voglibose is 0.05mg-0.6mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, rosuvastatin and voglibose as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of rosuvastatin is 1mg-10mg, and the content of voglibose is 0.05mg-0.6mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, Pitavastatin and voglibose as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of Pitavastatin is 0.5mg-4mg, and the content of voglibose is 0.05mg-0.6mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, pravastatin sodium and miglitol as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of pravastatin sodium is 2mg-10mg, and the content of miglitol is 25mg-300mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, fluvastatin and miglitol as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of fluvastatin is 2mg-20mg, and the content of miglitol is 25mg-300mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, lovastatin and miglitol as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of lovastatin is 3mg-20mg, and the content of miglitol is 25mg-300mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, Atorvastatin calcium and miglitol as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of Atorvastatin calcium is 2mg-20mg, and the content of miglitol is 25mg-300mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, mevastatin and miglitol as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of mevastatin is 10mg-40mg, and the content of miglitol is 25mg-300mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, rosuvastatin and miglitol as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of rosuvastatin is 1mg-10mg, and the content of miglitol is 25mg-300mg.
As a kind of pharmaceutical composition of the present invention, pharmaceutical composition provided by the invention by nicotinic acid, Pitavastatin and miglitol as active component, wherein the content of nicotinic acid is 25mg-1000mg, and the content of Pitavastatin is 0.5mg-4mg, and the content of miglitol is 25mg-300mg.
Term " pharmaceutical dosage " is meant that the clinician grants the dosage of medicine to diseased individuals according to the diseased individuals degree that is in a bad way in order to reach effective treatment, prevent or to delay the purpose of disease.Be to be understood that medicine pharmaceutical dosage provided by the invention is not a limitation of the present invention, but to of the present invention preferred.Generally, in this dosage preferable range, this medicine can produce disease that the patient takes a disease and effectively treats, prevents or delay effect.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 dosage or pharmaceutical dosage scope can with mammal, as rat, mice etc., converting is fit to pharmaceutical dosage or the dosage 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 nicotinic acid, a kind of from HMG-CoA reductase inhibitor or its officinal salt of second active component, and the 3rd active component is from alpha-glucosidase inhibitor.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 nicotinic acid, the pharmaceutical composition of HMG-CoA reductase inhibitor and alpha-glucosidase inhibitor 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 pharmaceutics acceptable carrier includes excipient and the adjuvant that helps reactive compound is mixed with pharmaceutical formulation when making tablet, compositions as one or more materials of starch, sucrose, dextrin, microcrystalline Cellulose, inorganic salts, 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 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.
Chemical compound in the pharmaceutical composition provided by the invention can be granted diseased individuals simultaneously in identical preparation, also grant diseased individuals discriminably in succession.If grant diseased individuals in succession, then the delay of granting of second (or additional) active component should not cause active component to unite the loss of the beneficial effect that brings.If grant diseased individuals simultaneously, the chemical compound in the compositions can mix and be present in the same pharmaceutical dosage forms, also can independently exist respectively with same dosage form.If independently exist respectively with same dosage form, then pharmaceutical composition can flexible existing with " Combined drug box " form." Combined drug box " is a kind of case type container, the drug regimen of built-in one or more dosage forms, and operation instructions.The compound tablet that a kind of and described alpha-glucosidase inhibitor in preferred in the present invention described nicotinic acid, described HMG-CoA reductase inhibitor and the officinal salt thereof is formed.
Chemical compound in the pharmaceutical composition provided by the invention can be granted diseased individuals simultaneously in preparation inequality, also grant diseased individuals discriminably in succession.If grant diseased individuals in succession, then the delay of granting of second (or additional) active component should not cause active component to unite the loss that brings beneficial effect.If grant diseased individuals simultaneously, the chemical compound in the compositions independently exists with different dosage forms, and pharmaceutical composition also can flexible existing with " Combined drug box " form." Combined drug box " is a kind of case type container, the drug regimen of built-in one or more dosage forms, and operation instructions.
The pharmaceutical composition that another object of the present invention provides the alpha-glucosidase inhibitor of a kind of, the pharmaceutical dosage in the HMG-CoA reductase inhibitor of the nicotinic acid that contains pharmaceutical dosage, pharmaceutical dosage or its officinal salt and pharmaceutically suitable carrier is used for preventing or treating the purposes of the medicine of diabetes in preparation.
The pharmaceutical composition that another object of the present invention provides the alpha-glucosidase inhibitor of a kind of, the pharmaceutical dosage in the HMG-CoA reductase inhibitor of the nicotinic acid that contains pharmaceutical dosage, pharmaceutical dosage or its officinal salt and pharmaceutically suitable carrier is used for preventing or treating the purposes of diabetic nephropathy drugs in preparation.
In all purposes provided by the invention, the HMG-CoA reductase inhibitor is selected from a kind of in simvastatin, pravastatin, fluvastatin, lovastatin, atorvastatin, mevastatin, rosuvastatin and the Pitavastatin, preferred atorvastatin, simvastatin.
In all purposes provided by the invention, alpha-glucosidase inhibitor is selected from acarbose, voglibose and miglitol, preferred acarbose.
Advantage of the present invention is:
The invention provides the pharmaceutical composition of HMG-CoA reductase inhibitor, alpha-glucosidase inhibitor and pharmaceutically suitable carrier of the nicotinic acid that contains pharmaceutical dosage, pharmaceutical dosage.The combined effect of nicotinic acid, HMG-CoA reductase inhibitor and alpha-glucosidase inhibitor be not each active substance each self-applying simply add and, but have more significant effect aspect treatment or prevent diabetes and the diabetic complication.That is to say that nicotinic acid, HMG-CoA reductase inhibitor and alpha-glucosidase inhibitor administering drug combinations have been obtained synergy.Pharmaceutical composition provided by the invention has remarkable advantages on the therapeutic effect of blood sugar lowering, and has the beneficial effect of tangible prevent diabetes complication, is treatment or prevent diabetes and diabetes complicated disease drug preferably therefore.
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: preparation compound niacin simvastatin acarbose tablet (1000 amounts)
Prescription: nicotinic acid 500g
Simvastatin 5g
Acarbose 100g
Microcrystalline Cellulose 10g
Carboxymethyl starch sodium 20g
Low-substituted hydroxypropyl cellulose 20g
5% 30 POVIDONE K 30 BP/USP-30 (95% alcoholic solution) is an amount of
Magnesium stearate 1%
Preparation method:
(1) nicotinic acid, simvastatin and the acarbose of getting recipe quantity crossed behind 100 mesh sieves standby by equivalent incremental method mix homogeneously respectively;
(2) other adjuvant is crossed 100 mesh sieves respectively after, in 75 ℃ of dry about 2h;
(3) get microcrystalline Cellulose, carboxymethyl starch sodium, the low-substituted hydroxypropyl cellulose mixing of recipe quantity, then with mixed crude drug by equivalent incremental method mix homogeneously;
(4) add 5% 30 POVIDONE K 30 BP/USP-3095% alcoholic solution and make soft material in right amount, 24 mesh sieves are granulated, 40 ℃ of dryings, and controlling particulate water content is 2-3%, 20 mesh sieve granulate;
(5) with dried granule and magnesium stearate mix homogeneously, tabletting behind the assay, aluminium-plastic bubble plate packing.
Embodiment 2: preparation compound niacin pravastatin sodium acarbose tablet (1000 amounts)
Prescription: nicotinic acid 500g
Pravastatin sodium 5g
Acarbose 100g
Microcrystalline Cellulose 10g
Carboxymethyl starch sodium 20g
Low-substituted hydroxypropyl cellulose 20g
5% 30 POVIDONE K 30 BP/USP-30 (95% alcoholic solution) is an amount of
Magnesium stearate 1%
Preparation method: with embodiment 1.
Embodiment 3: preparation compound niacin Atorvastatin calcium voigelibo sugar-tablet (1000 amounts)
Prescription: nicotinic acid 500g
Atorvastatin calcium 10g
Voglibose 0.2g
Microcrystalline Cellulose 10g
Carboxymethyl starch sodium 20g
Low-substituted hydroxypropyl cellulose 20g
5% 30 POVIDONE K 30 BP/USP-30 (95% alcoholic solution) is an amount of
Magnesium stearate 1%
Preparation method: with embodiment 1.
Embodiment 4: preparation compound niacin fluvastatin acarbose capsule (1000)
Prescription: nicotinic acid 500g
Fluvastatin 10g
Acarbose 100g
Lactose 100～200g
Carboxymethyl starch sodium 15～25g
5% 30 POVIDONE K 30 BP/USP-30 (95% alcoholic solution) is an amount of
Magnesium stearate 1%
Preparation method: supplementary material was pulverized 80 mesh sieves, drying for standby.The nicotinic acid, fluvastatin, acarbose of getting recipe quantity are according to equivalent incremental method mix homogeneously, add 100～200g lactose, 15～25g carboxymethyl starch sodium (the definite consumption of adjuvant is adjusted according to the active medicine consumption), according to equivalent incremental method uniform mixing, make soft material with 10% polyvidone alcoholic solution, 20 mesh sieves are granulated, 60 ℃ of dry about 2h, 20 mesh sieve granulate, controlling particulate water content is 2-3%, with dried granule and recipe quantity magnesium stearate mix homogeneously, semi-finished product detect, and measure content, the Capsules of packing into promptly gets 1000 capsules.Note lucifuge in the preparation process.The qualified back of product inspection aluminium-plastic bubble plate packing keeps in Dark Place.
Embodiment 5: preparation compound niacin lovastatin acarbose capsule (1000)
Prescription: nicotinic acid 500g
Lovastatin 8g
Acarbose 100g
Lactose 100～200g
Carboxymethyl starch sodium 20g
5% 30 POVIDONE K 30 BP/USP-30 (95% alcoholic solution) is an amount of
Magnesium stearate 1%
Preparation method: with embodiment 4.
Embodiment 5: preparation compound niacin mevastatin miglitol granule
Prescription: nicotinic acid 500g
Mevastatin 8g
Miglitol 25g
Lactose 850～950g
Carboxymethyl starch sodium 10～20g
Arabic gum 2g
10% polyvidone aqueous solution is an amount of
Orange flavor 2g
Aspartame 5g
Polyethylene Glycol 1%
Preparation method: supplementary material was pulverized 80 mesh sieves, drying for standby.Get the nicotinic acid of recipe quantity, mevastatin, miglitol is according to equivalent incremental method mix homogeneously, add 850～950g lactose, 10～20g carboxymethyl starch sodium (the definite consumption of adjuvant is adjusted according to the active medicine consumption), according to equivalent incremental method uniform mixing, make soft material with 10% polyvidone alcoholic solution, 18 mesh sieves are granulated, 60 ℃ of dry about 2h, 16 mesh sieve granulate, controlling particulate water content is below 2%, with dried granule and recipe quantity orange flavor, aspartame, the magnesium stearate mix homogeneously, semi-finished product detect, and measure content, and the aluminum bag of packing into promptly gets 1000 bags.Note lucifuge in the preparation process.
Embodiment 6: nicotinic acid Atorvastatin calcium acarbose compositions is to the influence of blood glucose in diabetic rats
90 Wistar male rats give normal diet and feed, and the tail vein is got blood behind the 10d, measures fasting blood sugar.Choose fasting blood sugar less than 88 of the rats of 7.8mmol/L, randomly draw 15 rats as the blank group.All the other rats stop eating behind the 24h, all by 0.3g/kg intraperitoneal injection alloxan normal saline solution 1 time, recover normal feeding, measure fasting blood sugar after continuing to raise 10d, therefrom choose 60 of the diabetes rat of blood glucose value between 11.1～16.8mmol/L, be divided into 4 groups at random, i.e. model group, nicotinic acid+Atorvastatin calcium group, acarbose group and nicotinic acid+Atorvastatin calcium+acarbose group, 15 every group.Blank group, model group rat gavage the physiology saline solution 1 time by 10ml/kg every day; Nicotinic acid+Atorvastatin calcium group rat gavages nicotinic acid 100mg/kg Atorvastatin calcium 10mg/kg1 time every day; Acarbose group rat gavages acarbose 100mg/kg 1 time every day; Nicotinic acid+Atorvastatin calcium+acarbose group gavages nicotinic acid 100mg/kg, Atorvastatin calcium 10mg/kg and acarbose 100mg/kg every day.Broken end was got blood after each organized survival rats administration 15d, measured blood glucose value once more.Blood glucose value adopts the ortho-aminotoluene method of improvement to measure.
Table 1 nicotinic acid Atorvastatin calcium acarbose compositions to the influence of diabetes rat fasting glucose (x ± s, n=10)
| Group | n | Dosage (mg/kg) | Blood glucose value (mmol/L) before the treatment | Treatment back blood glucose value (mmol/L) |
| The blank group | 15 | - | 5.88±1.12 | 5.86±1.07 |
| Model group | 13 | - | 12.55±1.36 ** | 12.61±1.02 ** |
| Nicotinic acid+Atorvastatin calcium group | 14 | 200 | 12.63±1.61 ** | 12.45±1.16 ** |
| The acarbose group | 14 | 100 | 12.74±1.01 ** | 8.56±1.39 ## |
| Nicotinic acid+Atorvastatin calcium+acarbose group | 15 | 200+5+100 | 12.61±1.16 ** | 6.73±1.65 ##▲▲$ |
Annotate: compare * * P＜0.01 with the blank group; Compare ##P＜0.01 with model group; Compare with nicotinic acid+Atorvastatin calcium group, ▲ ▲ P＜0.01; Compare ， $P＜0.05 with the acarbose group
As shown in Table 1, compare, after the modeling of intraperitoneal injection alloxan, respectively organize the rat blood sugar value and all obviously raise (P＜0.01), show diabetes rat modeling success with the blank group.Compare with the model group rat, nicotinic acid+Atorvastatin calcium group rat blood sugar value does not have significant change, and acarbose group, nicotinic acid+Atorvastatin calcium+acarbose group rat blood sugar value then obviously reduce, and significant significant difference (P＜0.01) is arranged.Compare with the acarbose group, nicotinic acid+Atorvastatin calcium+acarbose group blood glucose value further reduces, and has compared significant difference with the acarbose group.The pharmaceutical composition that shows nicotinic acid, Atorvastatin calcium and acarbose composition can be brought into play the drug effect effect of more effectively treating hyperglycemia than single medicine.
Embodiment 7: niacin simvastatin acarbose compositions is to the preventive effect of diabetic nephropathy rat
The rat adaptability was raised 7 days, was divided into normal control group and experimental group at random.With streptozotocin (STZ, U.S. Sigma company product, 0.1mmol/L citrate buffer solution is made into 1% concentration, sterilize through filtering with microporous membrane, by the 60mg/kg lumbar injection) bring out the experimental group rat diabetes, get tail blood after 72 hours and survey blood glucose, the rat of all blood glucose between 11.1～16.8mmol/L enters the diabetes rat group.Diabetes rat is divided into 4 groups at random: model group, nicotinic acid+simvastatin group, acarbose group, nicotinic acid+simvastatin+acarbose group, 15 every group.Press dosage gastric infusion in the table 7 every day.The 12nd week behind the blood sugar increasing, got urine sample with urine analyzer detection microdose urine protein and urine erythrocyte in 24 hours after the last administration, albumin and erythrocytic number of animals appear in the calculating urine.The The above results that records is albuminuria and hematuria number of animals difference to occur between x 2 check comparable group.
Table 2 niacin simvastatin acarbose compositions is to the preventive effect of diabetic nephropathy rat
| Group | n | Dosage (mg/kg) | The albuminuria number of animals appears | The hematuria number of animals appears |
| The blank group | 15 | - | 0/15 | 0/15 |
| Model group | 12 | - | 13/13 ** | 13/13 ** |
| Nicotinic acid+simvastatin group | 13 | 200 | 9/14 # | 8/14 # |
| The acarbose group | 14 | 100 | 5/12 ## | 5/12 ## |
| Nicotinic acid+simvastatin+acarbose group | 15 | 200+5+100 | 3/14 ##▲▲$ | 2/14 ##▲▲$ |
Annotate: compare * * P＜0.01 with the blank group; Compare #P＜0.05, ##P＜0.01 with model group; Compare with nicotinic acid+simvastatin group, ▲ ▲ P＜0.01; Compare ， $P＜0.05 with the acarbose group
Microdose urine protein and urine erythrocyte are that the typical case of diabetic nephropathy characterizes, so when microalbumin and erythrocyte occurring in diabetes rat is urinated, can think that this diabetes rat suffers from diabetic nephropathy.Albuminuria and hematuria all appear in the model group diabetes rat, the rat number that albuminuria and hematuria appear in niacin simvastatin group diabetes rat is respectively 9 and 8, the rat number that albuminuria and hematuria appear in acarbose group diabetes rat is respectively 5 and 5, and appearring in niacin simvastatin acarbose group diabetes rat, the rat number of albuminuria and hematuria significantly is less than model group, the niacin simvastatin group, show that the niacin simvastatin Acarbose medicine composition has the remarkable effect of diabetes and nephropathy preventing, and preventive effect significantly is better than the niacin simvastatin combination or the acarbose list is used.
Embodiment 8: nicotinic acid Atorvastatin calcium acarbose compositions is to the preventive effect of diabetic nephropathy rat
Experimental technique and statistical method are with embodiment 7, and medication and drug dose see Table 3
Table 3 nicotinic acid Atorvastatin calcium acarbose compositions is to the preventive effect of diabetic nephropathy rat
| Group | n | Dosage (mg/kg) | The albuminuria number of animals appears | The hematuria number of animals appears |
| The blank group | 15 | - | 0/15 | 0/15 |
| Model group | 13 | - | 10/12 ** | 10/12 ** |
| Nicotinic acid+Atorvastatin calcium group | 13 | 50 | 7/13 ### | 8/13 ## |
| The acarbose group | 15 | 50 | 5/13 ## | 6/13 ## |
| Nicotinic acid+Atorvastatin calcium+acarbose group | 15 | 50+10+50 | 3/15 ##▲▲$$ | 4/15 ##▲▲$$ |
Annotate: compare * * P＜0.01 with the blank group; Compare ##P＜0.01 with model group; Compare with nicotinic acid+Atorvastatin calcium group, ▲ ▲ P＜0.01; Compare ， $$P＜0.01 with the acarbose group
As can be seen from Table 3, albuminuria and hematuria all appear in the 12nd all model group diabetes rats behind the blood sugar increasing, the rat number that albuminuria and hematuria appear in nicotinic acid Atorvastatin calcium group diabetes rat is respectively 7 and 8, the rat number that albuminuria and hematuria appear in acarbose group diabetes rat is respectively 5 and 6, and appearring in nicotinic acid Atorvastatin calcium acarbose group diabetes rat, the rat number of albuminuria and hematuria is respectively 3 and 4, significantly be less than model group, nicotinic acid Atorvastatin calcium group or acarbose group, show that nicotinic acid+Atorvastatin calcium+Acarbose medicine composition has the remarkable effect of diabetes and nephropathy preventing, and preventive effect significantly is better than the niacin simvastatin combination or the acarbose list is used.
Claims (9)
1. pharmaceutical composition, contain:
1) nicotinic acid of pharmaceutical dosage;
2) the HMG-CoA reductase inhibitor of pharmaceutical dosage;
3) alpha-glucosidase inhibitor of pharmaceutical dosage; And
4) pharmaceutically suitable carrier.
2. the pharmaceutical composition described in claim 1, it is characterized in that: described HMG-CoA reductase inhibitor comprises simvastatin, pravastatin sodium, fluvastatin, lovastatin, Atorvastatin calcium, mevastatin, rosuvastatin and Pitavastatin.
3. the pharmaceutical composition described in the claim 2, it is characterized in that: described simvastatin content is that 1mg-15mg, pravastatin sodium content are that 2mg-10mg, fluvastatin content are that 2mg-20mg, lovastatin content are that 3mg-20mg, atorvastatin calcium content are that 2mg-20mg, mevastatin content are that 10mg-40mg, rosuvastatin content are that 1mg-10mg, Pitavastatin content are 0.5mg-4mg.
4. the pharmaceutical composition described in claim 1, it is characterized in that: described alpha-glucosidase inhibitor comprises acarbose, voglibose and miglitol.
5. the pharmaceutical composition described in claim 4, it is characterized in that: described acarbose content is that 25mg-100mg, voglibose content are that 0.05mg-0.6mg, miglitol content are 25mg-300mg.
6. the pharmaceutical composition described in claim 1, it is characterized in that: described nicotinic acid content is 25mg-1000mg.
7. each described pharmaceutical composition is made conventional tablet in the claim 1 to 6, 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.
8. the purposes of each described pharmaceutical composition in the medicine of preparation prevention or treatment diabetes in the claim 1 to 7.
9. the purposes of each described pharmaceutical composition in preparation prevention or treatment diabetic nephropathy drugs in the claim 1 to 7.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103054888A (en) * | 2012-12-30 | 2013-04-24 | 成都恒瑞制药有限公司 | Solid oral preparation containing acarbose and atorvastatin calcium and preparation method of solid oral preparation |
| CN103110622A (en) * | 2013-02-04 | 2013-05-22 | 成都恒瑞制药有限公司 | Solid oral agent containing voglibose and atorvastatin calcium and preparation method thereof |
| CN112451678A (en) * | 2020-12-04 | 2021-03-09 | 首都医科大学附属北京朝阳医院 | HMG-CoA reductase inhibitor-vitamin D pharmaceutical composition and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1205934C (en) * | 2003-01-20 | 2005-06-15 | 鲁南制药股份有限公司 | Composition for treating hyperlipemia |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103054888A (en) * | 2012-12-30 | 2013-04-24 | 成都恒瑞制药有限公司 | Solid oral preparation containing acarbose and atorvastatin calcium and preparation method of solid oral preparation |
| CN103054888B (en) * | 2012-12-30 | 2015-08-12 | 成都恒瑞制药有限公司 | Solid orally ingestible containing acarbose and Atorvastatin calcium and preparation method thereof |
| CN103110622A (en) * | 2013-02-04 | 2013-05-22 | 成都恒瑞制药有限公司 | Solid oral agent containing voglibose and atorvastatin calcium and preparation method thereof |
| CN112451678A (en) * | 2020-12-04 | 2021-03-09 | 首都医科大学附属北京朝阳医院 | HMG-CoA reductase inhibitor-vitamin D pharmaceutical composition and application thereof |
| CN112451678B (en) * | 2020-12-04 | 2022-08-02 | 首都医科大学附属北京朝阳医院 | HMG-CoA reductase inhibitor-vitamin D pharmaceutical composition and application thereof |
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