CN101606935A - A kind of solid composite medicament that contains clopidogrel - Google Patents
A kind of solid composite medicament that contains clopidogrel Download PDFInfo
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- CN101606935A CN101606935A CNA2008101150918A CN200810115091A CN101606935A CN 101606935 A CN101606935 A CN 101606935A CN A2008101150918 A CNA2008101150918 A CN A2008101150918A CN 200810115091 A CN200810115091 A CN 200810115091A CN 101606935 A CN101606935 A CN 101606935A
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- pharmaceutical composition
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- clopidogrel
- solid composite
- composite medicament
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Abstract
The invention discloses a kind of solid composite medicament that contains clopidogrel, added castor oil hydrogenated as lubricant in this solid composite medicament, effectively increased the stability and the safety of solid composite medicament.
Description
Technical field
The present invention relates to a kind of solid composite medicament that contains clopidogrel, especially a kind of solid composite medicament that contains castor oil hydrogenated as lubricant.
Background technology
Clopidogrel is a kind of epigamic anticoagulant, combines with its receptor by the inhibition adenosine phosphate and works.Clopidogrel is a kind of prodrug of non-activity, becomes active metabolite performance drug effect through liver cell pigment P450 metabolic conversion.Patent FR2245948 and FR2530247 disclose clopidogrel and have had significant antiplatelet aggregation and antithrombotic effect.Clopidogrel reaches the curative effect of prevention of stroke and heart attack by suppressing the chance that platelet aggregation has reduced obstruction of artery.And can effectively treat atherosis with prevention of arterial.Clopidogrel is usually with its sulphate form administration.
But clopidogrel is had an effect between the magnesium stearate lubricant that can and use always and is degraded into clopidogrel acid the metal ion instability.
Disclose use zinc stearate place of magnesium stearate magnesium among the EP1310245, but this kind method still can be introduced metal ion, long-term placement still can cause related substance to increase.
Disclose use glycerol Palmic acid stearate and micropowder silica gel place of magnesium stearate magnesium among the CN1935119, effectively increased the stability of solid preparation, but can make particulate mobile decline, the tabletting process has been caused difficulty.
WO2005/070464 discloses by use hydrogenated vegetable oil and carboxymethyl starch sodium and has share as lubricant, and adopts direct compression to reach the increase stability of formulation.
The applicant is by a large amount of tests, and surprised discovery uses castor oil hydrogenated as lubricant separately, also can reach identical effect.And adopt this method, and can prepare with the method for wet granulation, also can make sample that good stable is arranged.
Summary of the invention
The invention provides a kind of solid composite medicament that contains clopidogrel, said composition uses castor oil hydrogenated as lubricant, adopts wet granulation technology, can not only effectively improve stability of formulation, and preparation method is simple, is suitable for large-scale production.
This solid composite medicament provided by the invention does not contain metal ion in the lubricant of employing.
This solid composite medicament provided by the invention adopts castor oil hydrogenated as lubricant, and the percentage by weight in solid composite medicament is 0.5～3%.
This solid composite medicament that contains provided by the invention, the shared percentage by weight of clopidogrel is 10～70%.
This solid composite medicament provided by the invention adopts Clopidogrel Hydrogensulfate.
This solid composite medicament provided by the invention also contains filler, disintegrating agent, binding agent, chelating agent and coating material.
This solid composite medicament provided by the invention, filler are one or more the mixture in lactose, microcrystalline Cellulose, pre-paying starch, starch, the mannitol.
This solid composite medicament provided by the invention, disintegrating agent are one or more the mixture in low-substituted hydroxypropyl cellulose, sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, the swollen speed.
This solid composite medicament provided by the invention, chelating agent are a kind of among EDTA-2Na, the EDTA-Ca-Na.
This solid composite medicament provided by the invention, can adopt into following method or similar approach preparation:
Raw material pulverizing is crossed 120 orders, and other adjuvants are crossed 80 orders, and castor oil hydrogenated is crossed 60 orders, and is standby; Add supplementary material in taking by weighing by recipe quantity, mixing as wetting agent system soft material, is crossed 18 mesh sieve system granules with purified water; 50 ℃ of forced air dryings to weightless less than 3.5% (90 ℃, 5min); Dried granule is crossed 24 order granulate, adds castor oil hydrogenated and adds adjuvant, mix homogeneously with other; Measure granule content, determine that sheet is heavy; No. 10 scrobicula stampings; 12% Opadry II 85G68918 coating solution coating, weightening finish 3%; Check, packing.
The specific embodiment
The present invention is described in further detail below in conjunction with embodiment, but be not limited to following embodiment.Wherein " % " is meant " percentage by weight ".
Embodiment 1
Preparation method: Clopidogrel Hydrogensulfate was pulverized 120 orders, and other adjuvants are crossed 80 orders, and castor oil hydrogenated is crossed 60 orders, and is standby; Take by weighing Clopidogrel Hydrogensulfate, lactose, microcrystalline Cellulose, L-HPC (interior) by recipe quantity, mixing as wetting agent system soft material, is crossed 18 mesh sieve system granules with purified water; 50 ℃ of forced air dryings to weightless less than 3.5% (90 ℃, 5min); Dried granule is crossed 24 order granulate, adds castor oil hydrogenated and L-HPC (outward), mix homogeneously; Measure granule content, determine that sheet is heavy; No. 10 scrobicula stampings; 12% Opadry II 85G68918 coating solution coating, weightening finish 3%; Check, packing.
Embodiment 2
Preparation method: Clopidogrel Hydrogensulfate was pulverized 120 orders, and other adjuvants are crossed 80 orders, and castor oil hydrogenated is crossed 60 orders, and is standby; Take by weighing Clopidogrel Hydrogensulfate, pre-paying starch, microcrystalline Cellulose, sodium carboxymethyl cellulose, EDTA-2Na mixing by recipe quantity, as wetting agent system soft material, cross 18 mesh sieve system granules with purified water; 50 ℃ of forced air dryings to weightless less than 3.5% (90 ℃, 5min); Dried granule is crossed 24 order granulate, adds castor oil hydrogenated, mix homogeneously; Measure granule content, determine that sheet is heavy; No. 10 scrobicula stampings; 12% Opadry II85G68918 coating solution coating, weightening finish 3%; Check, packing.
Embodiment 3
Preparation method: Clopidogrel Hydrogensulfate was pulverized 120 orders, and other adjuvants are crossed 80 orders, and castor oil hydrogenated is crossed 60 orders, and is standby; Take by weighing Clopidogrel Hydrogensulfate, mannitol, microcrystalline Cellulose, polyvinylpolypyrrolidone mixing by recipe quantity, as wetting agent system soft material, cross 18 mesh sieve system granules with purified water; 50 ℃ of forced air dryings to weightless less than 3.5% (90 ℃, 5min); Dried granule is crossed 24 order granulate, adds castor oil hydrogenated, mix homogeneously; Measure granule content, determine that sheet is heavy; No. 10 scrobicula stampings; 12% Opadry II85G68918 coating solution coating, weightening finish 3%; Check, packing.
Place after 24 months under the embodiment 1-3 room temperature, its every index sees the following form:
0 day and the sample comparison in 24 months of table 1 embodiment 1-3
Claims (8)
1. a solid composite medicament that contains clopidogrel is characterized in that comprising the lubricant that does not contain metal ion.
2. pharmaceutical composition according to claim 1 is characterized in that described lubricant is a castor oil hydrogenated.
3. pharmaceutical composition according to claim 1 is characterized in that the percentage by weight that described castor oil hydrogenated accounts for compositions is 0.5～3%.
4. pharmaceutical composition according to claim 1 is characterized in that described clopidogrel is a Clopidogrel Hydrogensulfate.
5. pharmaceutical composition according to claim 1 is characterized in that also containing filler, disintegrating agent, binding agent, chelating agent and coating material.
6. pharmaceutical composition according to claim 5 is characterized in that described filler is one or more the mixture in lactose, microcrystalline Cellulose, pre-paying starch, starch, the mannitol.
7. pharmaceutical composition according to claim 5 is characterized in that described disintegrating agent is one or more the mixture in low-substituted hydroxypropyl cellulose, sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, the swollen speed.
8. pharmaceutical composition according to claim 5 is characterized in that described chelating agent is a kind of among EDTA-2Na, the EDTA-Ca-Na.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008101150918A CN101606935A (en) | 2008-06-16 | 2008-06-16 | A kind of solid composite medicament that contains clopidogrel |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008101150918A CN101606935A (en) | 2008-06-16 | 2008-06-16 | A kind of solid composite medicament that contains clopidogrel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101606935A true CN101606935A (en) | 2009-12-23 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2008101150918A Pending CN101606935A (en) | 2008-06-16 | 2008-06-16 | A kind of solid composite medicament that contains clopidogrel |
Country Status (1)
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| CN (1) | CN101606935A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101851247A (en) * | 2010-06-04 | 2010-10-06 | 浙江华海药业股份有限公司 | Composition containing clopidogrel bisulfate crystal particles |
| CN110339178A (en) * | 2019-06-28 | 2019-10-18 | 广州白云山天心制药股份有限公司 | A kind of preparation method of clopidogrel bisulfate solid preparation |
-
2008
- 2008-06-16 CN CNA2008101150918A patent/CN101606935A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101851247A (en) * | 2010-06-04 | 2010-10-06 | 浙江华海药业股份有限公司 | Composition containing clopidogrel bisulfate crystal particles |
| CN101851247B (en) * | 2010-06-04 | 2013-05-29 | 浙江华海药业股份有限公司 | Composition containing clopidogrel bisulfate crystal particles |
| CN110339178A (en) * | 2019-06-28 | 2019-10-18 | 广州白云山天心制药股份有限公司 | A kind of preparation method of clopidogrel bisulfate solid preparation |
| CN110339178B (en) * | 2019-06-28 | 2021-07-02 | 广州白云山天心制药股份有限公司 | Preparation method of clopidogrel hydrogen sulfate solid preparation |
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| C12 | Rejection of a patent application after its publication | ||
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Application publication date: 20091223 |