CN1507859A - Pravastatin preparation formula - Google Patents
Pravastatin preparation formula Download PDFInfo
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- CN1507859A CN1507859A CNA021512396A CN02151239A CN1507859A CN 1507859 A CN1507859 A CN 1507859A CN A021512396 A CNA021512396 A CN A021512396A CN 02151239 A CN02151239 A CN 02151239A CN 1507859 A CN1507859 A CN 1507859A
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- aminoacid
- pravastatin
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- amino acid
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Abstract
The present relates to a pravastatin preparation formula for curing angiocardiopathy. It is characterized by that said formula contains medicinal active component pravastatin sodium, at the same time contains one or several kinds of amino acids or amino acid salts as stabilizing agent, and the pH value of pravastatin preparation aqueous emulsion is 6.0-8.9.
Description
Technical field:
The present invention relates to a kind of pravastatin pharmaceutical formulation, can be used for treating the cardiovascular disease that causes by hyperlipidemia, belong to the cardiovascular drugs technical field.
Background technology:
Cardiovascular disease has been human main cause of death, and its incidence and mortality all is in first of all diseases.Industrialized country cardiovascular disease occurred and has been very popular in the middle of last century, and the cardiovascular disease death toll has accounted for half of total death toll.From absolute number, China is cardiovascular diseases's big country.And along with the improving constantly of living standards of the people, the change of life style and dietary habit makes the incidence rate of various cardiovascular disease be tending towards rising.The main pathological basis that confirms cardiovascular disease after deliberation is an atherosclerosis, and hyperlipidemia is to cause atherosclerotic primary factor, so lipid lowerers has caused people's attention at the importance aspect the minimizing cardiovascular disease incidence rate.
In the blood lipid-lowering medicine of numerous types, last century early eighties class hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor that grown up, it is statins, because the high efficiency of their cholesterol reducing, suppress synthetic high selectivity of cholesterol and hypotoxicity, become in the cardiovascular drugs development the most actively, development is the field the most rapidly.Wherein pravastatin sodium (pravastatin sodium) is a kind of novel statins antilipemic drugs that developed recently gets up, and is evident in efficacy because its high-efficiency low-toxicity, and advantages such as better tolerance are acknowledged as in such medicine the most rising a kind of.
The structural formula of pravastatin sodium is:
Pravastatin is unstable under sour environment, and degraded forms various analogs easily, thereby influences its therapeutic effect.Therefore design the appropriate formulation prescription, it is significant to strengthen the long-time stability of pravastatin under condition of storage.
The pravastatin pharmaceutical formulation of having reported at present or by adding alkaline inorganic matter, as magnesium oxide, make preparation keep alkaline environment, thereby improve the stability of pravastatin, but said preparation by oral enter the human stomach after, when dissolving, can cause local pH value too high, greater than 9, be generally 10, thereby destroy the natural sour environment of stomach, may influence self body function of human body; Perhaps, make the influence of its acid and alkali environment, thereby improve the stability of pravastatin, but the cyclodextrin material can hinder the release of pravastatin at stomach, and be unfavorable for that it is absorbed by human body by adding cyclodextrin material parcel pravastatin.
Summary of the invention:
The purpose of this invention is to provide a kind of pravastatin pharmaceutical formulation with good stability.
For realizing above purpose, technical scheme of the present invention provides a kind of pravastatin pharmaceutical formulation with good stability, be characterized in being, comprise the active constituents of medicine pravastatin sodium in the pravastatin pharmaceutical formulation, comprise one or more aminoacid or amino acid salts simultaneously as stabilizing agent, the pH value of pravastatin preparation water slurry is 6.0～8.9.
Pravastatin pharmaceutical formulation of the present invention comprises following composition:
(1). active constituents of medicine pravastatin, its percentage by weight can be 1%～60%.
(2). as the aminoacid or the amino acid salts of stabilizing agent, aminoacid is meant that to contain all employed by people, can be the mixture of alanine, arginine, agedoite, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine one of them or they; Amino acid salts can be an aminoacid sodium, potassium amino acid, amino acid calcium, amino-acid zinc, amino acid-magnesium chelate, aminoacid aluminum, the aminoacid ammonium salt, the amino acid salts hydrochlorate, sulforamidate, aminoacid acetate, aminoacid phosphate, aminoacid nitrate, the aminoacid citrate, the aminoacid malate, the aminoacid adipate, the aminoacid fumarate, the aminoacid lactate, the aminoacid maleate, the aminoacid sorbate, the aminoacid succinate, aminoacid winestone hydrochlorate, the mixture of aminoacid pyruvate one of them or they; The percentage by weight of aminoacid or amino acid salts can be 0.1%～90%.
(3). filler can be the mixture of lactose, sucrose, corn starch, mannitol, sorbitol, wooden cellulose, microcrystalline Cellulose, calcium carbonate one of them or they; Its percentage by weight can be 5%～90%.
(4). binding agent, can be the mixture of little product cellulose, polyvinyl alcohol, natural gum, polyvinylpyrrolidone, lactose, sucrose, corn starch, Brazil wax, paraffin, spermaceti, polyethylene, microwax one of them or they, its percentage by weight can be 0.5%～20%.
(5). disintegrating agent, can be that cross-linking sodium carboxymethyl cellulose, starch glycolate are received, the mixture of corn starch, microcrystalline Cellulose, zeopan one of them or they, its percentage by weight can be 0.5%～10%.
(6). lubricant can be the mixture of magnesium stearate, Palmic acid, calcium stearate, zinc stearate, hydrogenated vegetable oil, Talcum, silicon dioxide one of them or they, and its percentage by weight can be 0.5%～2%.
Pravastatin pharmaceutical formulation of the present invention can prepare by the following method:
To be dissolved in the suitable quantity of water as the aminoacid or the amino acid salts of stabilizing agent, regulating pH value is 6.0～8.9, add the pravastatin sodium stirring and dissolving, add binding agent, as polyvinylpyrrolidone, stirring and dissolving, add filler, as lactose, microcrystalline Cellulose, stirring and evenly mixing, make into the wet granular shape, above-mentioned wet granular is crossed 24 mesh sieves, and then 50 ℃ of air-flow oven dryings 3 hours, dry back granule is crossed 30 mesh sieves, add disintegrating agent, receive as starch glycolate, and lubricant, as magnesium stearate, stirring and evenly mixing strikes out tablet then.The stability of pravastatin in described tablet can detect by accelerated stability test.The pravastatin tablet is after storing a period of time under 60 ℃ of conditions or under 40 ℃/75% relative humidity condition, with HPLC methods analyst pravastatin content and purity.
Advantage of the present invention is that pravastatin has good stability in described pharmaceutical formulation, the native compound that is needed by human body as the aminoacid or the amino acid salts of stabilizing agent, safe and reliable, the pH value of preparation water slurry does not influence the human body self body function near neutral.
The specific embodiment:
A kind of embodiment with pravastatin pharmaceutical formulation of good stability that the present invention is proposed describes in further detail below.
Embodiment 1:
According to following formulation pravastatin preparation:
Composition
Percentage by weight (%)
Pravastatin sodium 5
Sodium glutamate 1
Lactose 74
Microcrystalline Cellulose 15
Cross-linking sodium carboxymethyl cellulose 2.5
Polyvinylpyrrolidone 1.5
Magnesium stearate 1
Take by weighing 2 gram sodium glutamate and be dissolved in the suitable quantity of water, regulating pH value is 8.8, adds 10 gram pravastatin sodium stirring and dissolving, add 3 gram polyvinylpyrrolidone stirring and dissolving, add 148 gram lactose, 30 gram microcrystalline Cellulose stirring and evenly mixings make into the wet granular shape, above-mentioned wet granular is crossed 24 mesh sieves, 50 ℃ of air-flow oven dryings 3 hours, dry back granule was crossed 30 mesh sieves then, added 5 gram cross-linking sodium carboxymethyl celluloses and 2 gram magnesium stearate, stirring and evenly mixing strikes out tablet then.
Above-mentioned tablet detects the stability of pravastatin after storing 2 months under the condition of 40 ℃/75% relative humidity, the result is as follows:
Initial
2 months
Pravastatin content (%) 99.95 99.35
Related substance (%) 0.63 1.15
Water slurry pH 8.58 8.52
The result shows that the pravastatin tablet has good stable.
Embodiment 2:
According to following formulation pravastatin preparation:
Composition
Percentage by weight (%)
Pravastatin sodium 5
Lysine hydrochloride 5
Lactose 70
Microcrystalline Cellulose 15
Cross-linking sodium carboxymethyl cellulose 2
Polyvinylpyrrolidone 1.5
Magnesium stearate 1.5
Take by weighing 10 gram lysine hydrochlorides and be dissolved in the suitable quantity of water, regulating pH value is 8.8, adds 10 gram pravastatin sodium stirring and dissolving, add 3 gram polyvinylpyrrolidone stirring and dissolving, add 140 gram lactose, 30 gram microcrystalline Cellulose stirring and evenly mixings make into the wet granular shape, above-mentioned wet granular is crossed 24 mesh sieves, 50 ℃ of air-flow oven dryings 3 hours, dry back granule was crossed 30 mesh sieves then, added 4 gram cross-linking sodium carboxymethyl celluloses and 3 gram magnesium stearate, stirring and evenly mixing strikes out tablet then.
Above-mentioned tablet detects the stability of pravastatin after storing 2 months under the condition of 40 ℃/75% relative humidity, the result is as follows:
Initial
2 months
Pravastatin content (%) 101.8 99.92
Related substance (%) 0.57 1.05
Water slurry pH 8.46 8.42
The result shows that the pravastatin tablet has good stable.
Claims (13)
1. pravastatin pharmaceutical formulation, comprise one or more filleies, one or more binding agents, one or more disintegrating agents, one or more lubricants is characterized in that, also comprise the active constituents of medicine pravastatin sodium in the prescription, comprise one or more aminoacid or amino acid salts simultaneously as stabilizing agent, the pH value of pravastatin preparation water slurry is 6.0～8.9.
2. pravastatin pharmaceutical formulation according to claim 1 is characterized in that, described pravastatin sodium percentage by weight can be 1%～60%.
3. pravastatin pharmaceutical formulation according to claim 1, it is characterized in that, described aminoacid is meant that to contain all employed by people, can be the mixture of alanine, arginine, agedoite, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine one of them or they.
4. pravastatin pharmaceutical formulation according to claim 1, it is characterized in that, described amino acid salts is meant that to contain all employed by people, can be aminoacid sodium, potassium amino acid, amino acid calcium, amino-acid zinc, amino acid-magnesium chelate, aminoacid aluminum, the aminoacid ammonium salt, the amino acid salts hydrochlorate, sulforamidate, aminoacid acetate, aminoacid phosphate, aminoacid nitrate, the aminoacid citrate, the aminoacid malate, the aminoacid adipate, the aminoacid fumarate, the aminoacid lactate, the aminoacid maleate, the aminoacid sorbate, the aminoacid succinate, aminoacid winestone hydrochlorate, the mixture of aminoacid pyruvate one of them or they.
5. pravastatin pharmaceutical formulation according to claim 1 is characterized in that, the percentage by weight of described aminoacid or amino acid salts can be 0.1%～90%.
6. pravastatin pharmaceutical formulation according to claim 1 is characterized in that, described filler can be the mixture of lactose, sucrose, corn starch, mannitol, sorbitol, wooden cellulose, microcrystalline Cellulose, calcium carbonate one of them or they.
7. pravastatin pharmaceutical formulation according to claim 1 is characterized in that, described filler percentage by weight can be 5%～90%.
8. pravastatin pharmaceutical formulation according to claim 1, it is characterized in that described binding agent can be the mixture of microcrystalline Cellulose, polyvinyl alcohol, natural gum, polyvinylpyrrolidone, lactose, sucrose, corn starch, Brazil wax, paraffin, spermaceti, polyethylene, microwax one of them or they.
9. pravastatin pharmaceutical formulation according to claim 1 is characterized in that, described binder wt percentage ratio can be 0.5%～20%.
10. pravastatin pharmaceutical formulation according to claim 1 is characterized in that, described disintegrating agent can be that cross-linking sodium carboxymethyl cellulose, starch glycolate are received, the mixture of corn starch, microcrystalline Cellulose, zeopan one of them or they.
11. pravastatin pharmaceutical formulation according to claim 1 is characterized in that, described disintegrating agent percentage by weight can be 0.5%～10%.
12. pravastatin pharmaceutical formulation according to claim 1 is characterized in that, described lubricant can be the mixture of magnesium stearate, Palmic acid, calcium stearate, zinc stearate, hydrogenated vegetable oil, Talcum, silicon dioxide one of them or they.
13. pravastatin pharmaceutical formulation according to claim 1 is characterized in that, described lubricant percentage by weight can be 0.5%～2%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA021512396A CN1507859A (en) | 2002-12-17 | 2002-12-17 | Pravastatin preparation formula |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA021512396A CN1507859A (en) | 2002-12-17 | 2002-12-17 | Pravastatin preparation formula |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1507859A true CN1507859A (en) | 2004-06-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA021512396A Pending CN1507859A (en) | 2002-12-17 | 2002-12-17 | Pravastatin preparation formula |
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| CN (1) | CN1507859A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014139469A1 (en) * | 2013-03-15 | 2014-09-18 | Wuhan Qr Science And Technology Development Co. | Ornithine- or aspartate-containing compositions and the uses thereof |
| CN105246472A (en) * | 2013-03-15 | 2016-01-13 | 武汉启瑞科技发展有限公司 | Ornithine- or aspartate-containing compositions and the uses thereof |
| CN107913257A (en) * | 2016-10-10 | 2018-04-17 | 北京阜康仁生物制药科技有限公司 | A kind of pharmaceutical composition comprising rosuvastain calcium and preparation method thereof |
-
2002
- 2002-12-17 CN CNA021512396A patent/CN1507859A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014139469A1 (en) * | 2013-03-15 | 2014-09-18 | Wuhan Qr Science And Technology Development Co. | Ornithine- or aspartate-containing compositions and the uses thereof |
| CN105246472A (en) * | 2013-03-15 | 2016-01-13 | 武汉启瑞科技发展有限公司 | Ornithine- or aspartate-containing compositions and the uses thereof |
| CN105246472B (en) * | 2013-03-15 | 2018-10-12 | 武汉朗来科技发展有限公司 | Composition containing ornithine and/or L-aminobutanedioic acid and its application |
| CN107913257A (en) * | 2016-10-10 | 2018-04-17 | 北京阜康仁生物制药科技有限公司 | A kind of pharmaceutical composition comprising rosuvastain calcium and preparation method thereof |
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