CN103340852A - Pharmaceutical composition containing ezetimibe and atorvastatin - Google Patents
Pharmaceutical composition containing ezetimibe and atorvastatin Download PDFInfo
- Publication number
- CN103340852A CN103340852A CN2013102708710A CN201310270871A CN103340852A CN 103340852 A CN103340852 A CN 103340852A CN 2013102708710 A CN2013102708710 A CN 2013102708710A CN 201310270871 A CN201310270871 A CN 201310270871A CN 103340852 A CN103340852 A CN 103340852A
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- CN
- China
- Prior art keywords
- atorvastatin
- pharmaceutical composition
- described pharmaceutical
- mixture
- ezetimibe
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Links
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 title abstract 2
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 title abstract 2
- 229960005370 atorvastatin Drugs 0.000 title abstract 2
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 title abstract 2
- 229960000815 ezetimibe Drugs 0.000 title abstract 2
- 239000008194 pharmaceutical composition Substances 0.000 title abstract 2
- 238000002360 preparation method Methods 0.000 abstract 3
- 208000024172 Cardiovascular disease Diseases 0.000 abstract 1
- 239000008186 active pharmaceutical agent Substances 0.000 abstract 1
- 208000026106 cerebrovascular disease Diseases 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 230000002526 effect on cardiovascular system Effects 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a novel pharmaceutical composition and a preparation method thereof. According to the preparation method, ezetimibe and atorvastatin are adopted as the active pharmaceutical ingredients, and some auxiliary materials of certain types and proportion are added to prepare and develop an oral preparation through the technological means provided by the invention. The composition is used for treating and/or preventing cardiovascular and cerebrovascular diseases, and belongs to the technical field of medicines.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition that contains according to Ezetimibe and atorvastatin chemical compound, belong to medical technical field.
Background technology
Be a kind of oral, potent fat-reducing medicament according to Ezetimibe, its mechanism of action different with other fat-reducing medicament (as: Statins, cholic acid chelating agent (resinae), fibric acid derivant and vegetalitas sterin carboxylates).This product is attached to the intestinal villi brush border, suppresses the absorption of cholesterol, thereby reduces the transhipment of cholesterol in the liver in the small intestinal, thereby makes the removing that liver cholesterol reserves reduce increases cholesterol in the blood.This product does not increase bile secretion (as cholic acid chelating agent), does not suppress synthetic (as the Statins) of cholesterol in liver yet.
The atorvastatin chemical compound is by suppressing the HMG-CoA reductase in the liver, thereby suppresses the biosynthesis of cholesterol, plays and reduces CHO, TG, LP(a), the effect of LDL-C, the effect of the HDL-C that raises in addition simultaneously.The atorvastatin medicine can not only be regulated total plasma cholesterol and low density lipoprotein, LDL (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol levels, simultaneously can also improve endothelial function, improve and prevent or reverse atherosclerotic plaque, stabilize plaque, regulate inner skin cell function, can obviously reduce plasma C-reactive protein, reduce the inflammatory cell in the atheromatous plaque, reduce the quantity of macrophage, reaction diminishes inflammation.
This product selectivity does not influence small intestinal to the absorption of triglyceride, fatty acid, bile acid, progesterone, ethinylestradiol and vitamin A, D when suppressing cholesterol absorption.This product and HMG-CoA reductase inhibitor are united to use and are treated mutually specific energy separately with any medicine and effectively improve TC in the serum, LDL-C, ApoB, TG and HDL-C level.
Compare with placebo, this product suppresses small intestinal to 54% of cholesterol absorption.Statins reduces liver synthesis cholesterol.Statins reduces liver synthesis cholesterol.Two kinds of drug combinations are the cholesterol reducing level further, is better than the independent application of two kinds of medicines.
Summary of the invention
Two kinds of active component have the different mechanism of action, make the adaptability that compound preparation more can increase the patient, provide better choice for clinical medicine, so exploitation compound preparation good market prospect.
But unexpectedly, when exploitation during compound preparation, it is more unstable that preparation becomes, atorvastatin especially, and related substance increases very fast.The stability that increases atorvastatin shows you easily sees, needs to add alkaline matter, and as sodium bicarbonate, calcium carbonate etc. try in test to strengthen the consumption of alkaline matter, yet stability are still relatively poor, and the result can not accept.
Surprisingly, when removing active component according to Ezetimibe in the prescription, prescription still becomes stable, and in put procedure, the impurity of atorvastatin changes little.So it is unstable that prescription becomes, be owing to added according to Ezetimibe, further test, when mixing, place two kinds of principal agents, find that atorvastatin is especially unstable.Surprisingly, when taking the preparation means, when two kinds of active component were isolated, two kinds of compositions were comparatively stable.
The present invention is according to the pharmaceutical composition of Ezetimibe and atorvastatin, it is characterized in that, two kinds of active component do not contact mutually in this mixture, and this mixture can be made tablet or capsule, the especially suitable bilayer tablet of making.
And atorvastatin comprises atorvastatin or its hydrate, Atorvastatin calcium or its hydrate, atorvastatin zinc or its hydrate, atorvastatin magnesium or its hydrate, and the unit formulation content of described atorvastatin chemical compound is 10mg～80mg.Described unit formulation input amount according to Ezetimibe is 5mg～20mg.
Pharmaceutical composition of the present invention, it provides good stable.This mixture was placed for 4 weeks under 60 ℃ of conditions, and the content of atorvastatin reduces to be no more than 2.0%, and its stability meets the requirements.
The specific embodiment
Comparative example's 1 tablet
| The supplementary material kind | Inventory (gram) |
| According to Ezetimibe | 10 |
| Atorvastatin calcium | 10 |
| Lactose monohydrate | 55 |
| Microcrystalline Cellulose | 30 |
| Polyvidone | 4 |
| Sodium bicarbonate | 10 |
| Sodium carboxymethyl cellulose | 8 |
| Sodium lauryl sulphate | 2 |
| Magnesium stearate | 1 |
Preparation technology: polyvidone is dissolved in makes binding agent in the suitable quantity of water, standby.Two kinds of principal agents were pulverized 80 mesh sieves respectively, and were standby.With principal agent and adjuvant mix homogeneously, add binding agent, to granulate, drying adds magnesium stearate, mixing, tabletting.
Embodiment 2 bilayer tablets
| The supplementary material kind | Inventory (gram) |
| According to Ezetimibe | 10 |
| Lactose monohydrate | 55 |
| Microcrystalline Cellulose | 30 |
| Polyvidone | 4 |
| Sodium carboxymethyl cellulose | 8 |
| Sodium lauryl sulphate | 2 |
| Magnesium stearate | 1 |
| Atorvastatin calcium | 10 |
| Lactose monohydrate | 55 |
| Microcrystalline Cellulose | 20 |
| Polyvidone | 4 |
| Sodium bicarbonate | 10 |
| Sodium carboxymethyl cellulose | 2 |
| Magnesium stearate | 0 |
Preparation technology: polyvidone is dissolved in makes binding agent in the suitable quantity of water, standby.Two kinds of principal agents were pulverized 80 mesh sieves respectively, and were standby.Two kinds of principal agents and adjuvant are granulated separately, and be pressed into double-layer tablet.
Place 60 ℃ of environment to preserve for 4 weeks respectively above-mentioned two kinds of finished products, measure the content of atorvastatin, as follows:
| Time | The comparative example 1 | Embodiment 1 |
| Initial value | 99.62 | 99.58 |
| 2 weeks | 97.26 | 99.66 |
| 4 weeks | 95.33 | 99.49 |
By experimental result as can be known, by formulation method two kinds of compositions are isolated, can effectively improve the stability of goods.
Claims (9)
1. contain the pharmaceutical composition according to Ezetimibe and atorvastatin, it is characterized in that, two kinds of active component are present in the single solid dosage forms with the entity that separates.
2. the described pharmaceutical composition of claim 1 is characterized in that, this mixture is tablet.
3. the described pharmaceutical composition of claim 1 is characterized in that, this mixture is capsule.
4. the described pharmaceutical composition of claim 1 is characterized in that, atorvastatin comprises atorvastatin or its hydrate, Atorvastatin calcium or its hydrate, atorvastatin zinc or its hydrate, atorvastatin magnesium or its hydrate.
5. the described pharmaceutical composition of claim 1 is characterized in that, described unit formulation input amount according to Ezetimibe is 5mg～20mg.
6. the described pharmaceutical composition of claim 1 is characterized in that, the unit formulation content of described atorvastatin chemical compound is 10mg～800mg.
7. claim 2 or 3 described pharmaceutical compositions is characterized in that, this mixture was placed for 4 weeks under 60 ℃ of conditions, and the content of atorvastatin reduces to be no more than 2.0%.
8. the described pharmaceutical composition of claim 2 is characterized in that, this mixture is bilayer tablet.
9. the described pharmaceutical composition of claim 2 is characterized in that, this mixture is the clad sheet agent, and the internal layer small pieces are coated tablet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013102708710A CN103340852A (en) | 2013-07-01 | 2013-07-01 | Pharmaceutical composition containing ezetimibe and atorvastatin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013102708710A CN103340852A (en) | 2013-07-01 | 2013-07-01 | Pharmaceutical composition containing ezetimibe and atorvastatin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103340852A true CN103340852A (en) | 2013-10-09 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2013102708710A Pending CN103340852A (en) | 2013-07-01 | 2013-07-01 | Pharmaceutical composition containing ezetimibe and atorvastatin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103340852A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103585157A (en) * | 2013-11-13 | 2014-02-19 | 武汉武药科技有限公司 | Double-layer tablet containing ezetimibe and rosuvastatin and preparation method thereof |
| CN103784436A (en) * | 2014-02-27 | 2014-05-14 | 安徽联创药物化学有限公司 | Lipid-lowering compound preparation and preparation method thereof |
| CN105832723A (en) * | 2016-04-15 | 2016-08-10 | 浙江巨泰药业有限公司 | Ezetimibe and atorvastatin calcium tablet and preparation method thereof |
| CN113908130A (en) * | 2021-09-22 | 2022-01-11 | 山东省药学科学院 | A chip for treating hypercholesterolemia |
| TWI760067B (en) * | 2020-08-13 | 2022-04-01 | 友霖生技醫藥股份有限公司 | Solid oral pharmaceutical composition |
| CN114945356A (en) * | 2020-01-14 | 2022-08-26 | 日东制药股份有限公司 | Tablet comprising atorvastatin and tolbutamide |
| US11833133B2 (en) | 2020-08-13 | 2023-12-05 | Orient Pharma Co., Ltd. | Solid oral pharmaceutical composition |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011002422A2 (en) * | 2009-07-02 | 2011-01-06 | Bilgic Mahmut | Solubility enhancing pharmaceutical formulation |
| CN101961492A (en) * | 2009-07-23 | 2011-02-02 | 邬林祥 | Ezetimibe compound preparation for treating dyslipidemia |
| CN102300561A (en) * | 2008-12-01 | 2011-12-28 | 力奇制药公司 | Pharmaceutical Composition Comprising Ezetimibe And Simvastatin |
| CN102357096A (en) * | 2011-09-09 | 2012-02-22 | 北京阜康仁生物制药科技有限公司 | Statins zinc salt-containing blood fat-reducing composite |
-
2013
- 2013-07-01 CN CN2013102708710A patent/CN103340852A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102300561A (en) * | 2008-12-01 | 2011-12-28 | 力奇制药公司 | Pharmaceutical Composition Comprising Ezetimibe And Simvastatin |
| WO2011002422A2 (en) * | 2009-07-02 | 2011-01-06 | Bilgic Mahmut | Solubility enhancing pharmaceutical formulation |
| CN101961492A (en) * | 2009-07-23 | 2011-02-02 | 邬林祥 | Ezetimibe compound preparation for treating dyslipidemia |
| CN102357096A (en) * | 2011-09-09 | 2012-02-22 | 北京阜康仁生物制药科技有限公司 | Statins zinc salt-containing blood fat-reducing composite |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103585157A (en) * | 2013-11-13 | 2014-02-19 | 武汉武药科技有限公司 | Double-layer tablet containing ezetimibe and rosuvastatin and preparation method thereof |
| CN103585157B (en) * | 2013-11-13 | 2016-02-03 | 武汉武药科技有限公司 | A kind of double-layer tablet containing Ezetimibe and Rosuvastatin and preparation method thereof |
| CN103784436A (en) * | 2014-02-27 | 2014-05-14 | 安徽联创药物化学有限公司 | Lipid-lowering compound preparation and preparation method thereof |
| CN103784436B (en) * | 2014-02-27 | 2016-06-01 | 安徽联创生物医药股份有限公司 | A kind of blood fat-decreasing compound preparation and its preparation method |
| CN105832723A (en) * | 2016-04-15 | 2016-08-10 | 浙江巨泰药业有限公司 | Ezetimibe and atorvastatin calcium tablet and preparation method thereof |
| CN105832723B (en) * | 2016-04-15 | 2018-06-15 | 浙江巨泰药业有限公司 | A kind of Ezetimibe atorvastatin and preparation method thereof |
| CN114945356A (en) * | 2020-01-14 | 2022-08-26 | 日东制药股份有限公司 | Tablet comprising atorvastatin and tolbutamide |
| TWI760067B (en) * | 2020-08-13 | 2022-04-01 | 友霖生技醫藥股份有限公司 | Solid oral pharmaceutical composition |
| US11833133B2 (en) | 2020-08-13 | 2023-12-05 | Orient Pharma Co., Ltd. | Solid oral pharmaceutical composition |
| CN113908130A (en) * | 2021-09-22 | 2022-01-11 | 山东省药学科学院 | A chip for treating hypercholesterolemia |
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| C06 | Publication | ||
| PB01 | Publication | ||
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| WD01 | Invention patent application deemed withdrawn after publication | ||
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Application publication date: 20131009 |