CN1969849A - Stable pharmaceutical composition containing pitavastatin calcium and preparation process thereof - Google Patents
Stable pharmaceutical composition containing pitavastatin calcium and preparation process thereof Download PDFInfo
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Abstract
The invention discloses a drug composition and making method of stable calcium Bimvastatin, which comprises the following parts: 0.01-10% calcium Bimvastatin, 10- 93% filler, 1-30% disintegration agent, 0.01-5% lubricant and 0.1-80% alkali findings.
Description
Technical field:
The present invention relates to pharmaceutical composition, provide pharmaceutical composition of a kind of HMG-CoA of making reductase inhibitor Pitavastatin calcium stable and preparation method thereof specifically.
Background technology:
The HMG-CoA reductase inhibitor is the class medicine in the treatment hyperlipidemia, and existing various preparations are sold on market.Wherein Pitavastatin Calcium (as figure below) is the former medicine that grinds of Japanese Kowa company Ltd, is used for the treatment of hypercholesterolemia.In its molecular structure, contain 3, the organic group of 5-dihydroxy-6-heptenoic acid.The satisfied surely requirement pharmaceutically because its preparation differs aspect storage stability need possess the pharmaceutical composition that superior storage stability is arranged.
Past, existing people proposed HMG-CoA reductase inhibitor fluvastatin sodium and a kind of alkaline stable, make capsule or tablet (US 5356896) by wet granule compression tablet technology or freeze-drying, prepared granule is faint yellow, and Film coated tablets of making or capsular disintegration time are 10 ~ 30 minutes; Enteric coatel tablets or capsular disintegration time are generally 30 ~ 60 minutes; Film coated tablets or capsular dissolution reached 75% (USP oar method) at 30 minutes; Film coated tablets or capsule are stored under moistureproof lucifuge condition and were reached 99% in 18 months.
The somebody cooperates the active component of HMG-CoA reductase inhibitor with (US 6911472) with pharmaceutical adjunct, prepare with wet granulation technology, the reuse amino sugar is regulated pH to 7.0 ~ 8.7, makes tablet, and this tablet can be preserved January or longer under the normal humidity condition.
Because contain 3 in the HMG-CoA reductase inhibitor, the structure of 5-dihydroxy-6-heptenoic acid has unstability, easily is hydrolyzed and oxidation, needs some specific process to be made into preparation.It is 8 or higher preparation that Japan Patent 5-246844 (examine open) proposes they and a kind of alkaline medium such as sodium carbonate or calcium carbonate are mixed with pH; And Japan Patent 2-6406 (examine open) to propose they and alkaline reagent magnesium oxide or sodium hydroxide pH be 9 or the higher preparation of pH; Proposition is that 7 to 8 alkaline reagent reaches stable with pH in Japan Patent 5-354654 (examine open).In these patents, all be with wet granulation technology tabletting or coating.
In these all researchs, adopted wet granulation technology to carry out tabletting or filled capsules bar none.Because the limitation of wet granulation technology, Zhi Bei pharmaceutical composition still can not reach stable effect pharmaceutically fully like this.In this case, the present inventor has carried out long-term deep research to the pharmaceutical composition and the production technology of Pitavastatin Calcium, the result is by adding acceptable alkaline medium on the pharmacology in preparation, adopt the dry granulation tablet forming technique that does not contain adhesive simultaneously, found to have the pharmaceutical composition of excellent stability, thereby finished the present invention at aspects such as shelf life stabilities.
The invention provides stabilizing pharmaceutical composition that contains Pitavastatin Calcium and preparation method thereof.
Summary of the invention:
The purpose of this invention is to provide a kind of stabilizing pharmaceutical composition that contains Pitavastatin Calcium and preparation method thereof, in preparation process, do not contain any adhesive, when adopting the dry granulation tablet forming technique, add basic auxiliary and make this pharmaceutical composition reach steady statue.The pharmaceutical composition that solves the wet granulation acquisition exists adhesive and baking temperature to the influential technical problem of principal agent stability.
As the present inventor,, various researchs have been carried out in order to obtain the stable pharmaceutical composition that contains Pitavastatin Calcium.The result is surprised to find that acceptable alkaline medium on the suitable pharmacology of in preparation process adding, adopt the dry granulation tabletting that does not contain any adhesive simultaneously, can make the stable stabilizing pharmaceutical composition that contains Pitavastatin Calcium, thereby finish the present invention.The described adhesive that do not contain, be meant the adhesive that does not contain pharmaceutically, comprise wetting agent, adhesive such as starch, dextrin, gelatin, sodium carboxymethyl cellulose, ethyl cellulose, methylcellulose, hypromellose, polyvinylpyrrolidone, wetting agent such as water and Different concentrations of alcohol solution.
HMG-CoA reductase inhibitor Pitavastatin Calcium as active component of the present invention is known, perhaps can be prepared by known method.
This pharmaceutical composition adsorbed have low amounts of water in minor amount of water or this pharmaceutical composition in, can make pharmaceutical composition form " little-pH " of band alkalescence around particulate as the acceptable basic auxiliary of the pharmacology of component of the present invention.
The compressing dry granulation technology comprises direct powder compression and dry granulation tabletting.Direct powder compression is meant the powder of medicine with after suitable adjuvant mixes, without granulation and the method for direct compression; The dry granulation tabletting is meant and will be after medicine and the auxiliary materials and mixing be pressed into sheet with suitable equipment, and then is broken into the granule of suitable size, or directly medicine and adjuvant mixed the dried granule that is squeezed into, and adds the method for tabletting behind the mixing such as lubricant again.Compare with wet granule compression tablet technology, it has following characteristics: 1, do not add adhesive in the prescription, avoided the influence of adhesive such as moisture and organic solvent to principal agent; 2, avoid moist granule when drying temperature to the influence of principal agent; 3, get rid of the interference of adhesive and temperature, help 3,5-is dihydric stable; 4, simplified granulation, drying (lyophilizing) operation, technology is simple, helps automatic continuous production, shortens working hours, and saves cost; 5, do not contain adhesive in the prescription, directly reduce production costs.
Technical scheme of the present invention is: by in these pharmaceutical compositions of prepared of method pelletizing press sheet or filled capsules the time, pharmaceutical composition of the present invention is made up of Pitavastatin Calcium, filler, disintegrating agent, lubricant and basic auxiliary.
Wherein the Pitavastatin Calcium weight percentage is: 0.01～10%.
Filler includes but not limited to lactose, mannitol, Icing Sugar, starch, microcrystalline Cellulose, sorbitol, calcium sulfate, calcium hydrogen phosphate etc., can singly use, and also can share.The percentage by weight of consumption is generally 10～93%, and preferable amount is 15～80%.
Disintegrating agent comprises starch, carboxymethyl starch sodium, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose (calcium) etc., and they can singly be used, and also can share.The percentage by weight of consumption is generally 1-30%, preferable amount 2～25%.
Lubricant comprises Pulvis Talci, magnesium stearate and micropowder silica gel etc., and they can singly be used, and also can share, and the percentage by weight of consumption is generally 0.01～5%, preferred 0.1～3%.
The basic auxiliary that adds is calcium phosphate, potassium phosphate, calcium hydrogen phosphate, sodium silicate, potassium silicate, magnesium silicate, the sodium salt of calcium chloride, ethylenediaminetetraacetic acid, iron salt and calcium salt, calcium citrate, calcium succinate and various amino acid whose sodium salt and calcium salt etc.The percentage by weight of consumption is generally 0.1～80%, preferable amount 5～70%.
If needs are arranged, can also in pharmaceutical composition of the present invention, add some suitable composition pharmaceutically, as correctives, coloring agent etc.
When adopting dry granulation, can adopt direct powder compression or filled capsules or dry granulation tabletting, preferred dry granulation tabletting or filled capsules.
By in the technology of method pelletizing press sheet or filled capsules, can make this pharmaceutical composition be formulated into various forms of solid preparations, as tablet, capsule, granule, chewable tablet etc.Preferential Film coated tablets or coated tablet, the more preferably Film coated tablets of adopting.
Preferred solid preparation Film coated tablets in the pharmaceutical composition of the present invention can adopt buried tube type spray coating pot, air suspension fluidized bed and high-efficiency coating machine to carry out film coating, preferred high-efficiency coating machine bag Film coated tablets.
Thin film coating material (solution) comprises polymer film-forming material, plasticizer and solvent and in order to prevent from the unilateral thin film to produce the defoamer of bubble.Deng.Polymer film-forming material can be selected hypromellose, hydroxypropyl cellulose, polyvinylpyrrolidone and (stomach dissolution type) polyacrylic resin class etc. for use, preferred hydroxypropyl cellulose aqueous dispersion.Plasticizer comprises glycerol, Polyethylene Glycol etc.; Solvent is only selected purified water for use.If necessary, can also in coating material, add coloring agent, screening agent etc.
Solvent in coating material adopts the purpose of purified water to be, guarantees organic solvent to 3, and 5-dihydroxy-6-heptenoic acid does not constitute destruction, and having workshop simultaneously need not be explosion-proof, production safety, and handled easily, advantage such as reduce cost.
Such method makes in this preparation of drug combination process, avoided of the influence of factors such as high temperature, humidity and organic solvent to HMG-CoA reductase inhibitor Pitavastatin Calcium, improved pharmaceutically necessary general aspects, as stability, disintegration time, dissolution and related substance etc., reduced the technological operation step simultaneously, simplified apparatus reduces production costs, and helps the big continuously production of industry.
The present invention will be described in detail below by the embodiment that provides, but the present invention is not limited to these embodiment.Used adjuvant is pharmaceutical grade among the embodiment.
The specific embodiment:
Embodiment one
Set of dispense is than one
Pitavastatin Calcium 1mg
Lactose 15mg
Microcrystalline Cellulose 10mg
Calcium phosphate 50mg
Carboxymethyl starch sodium 5mg
Magnesium stearate 1mg
Add up to 82mg
Wet granulation technology: by prescription with lactose, microcrystalline Cellulose, calcium phosphate and carboxymethyl starch sodium mix homogeneously, again the Pitavastatin Calcium of recipe quantity and mixed powder by the equivalent abundant mix homogeneously of dilution method that progressively increases; It is an amount of to add 5% concentration hypromellose solution, stirs and makes wet granular; Wet grain is placed in 50 ℃ the aeration-drying baking oven after the drying, takes out, add magnesium stearate, mix homogeneously (doing pellet moisture 0.73%).The directly suitable tablet of tablet forming on tablet machine.
The dry method direct compression technology that does not contain adhesive: by writing out a prescription with lactose, microcrystalline Cellulose, calcium phosphate, carboxymethyl starch sodium and magnesium stearate mix homogeneously, again the Pitavastatin Calcium of 1mg and mixed powder by equivalent progressively increase (dry powder moisture 0.51%), the i.e. directly suitable tablet of tablet forming on tablet machine behind the abundant mix homogeneously of dilution method.
Result: check that with the HPLC method in the Chinese Pharmacopoeia version appendix in 2000 lactone content of two kinds of method for makings and disintegration time mensuration method check disintegration time respectively:
| Condition (label) | Wet granule compression tablet technology | The dry method direct compression technology that does not contain adhesive | ||
| Lactone (%) | Disintegration time (branch) | Lactone (%) | Disintegration time (branch) | |
| Room temperature 0 day | 0.099 | 5 | 0 | 1 |
| 40 ℃ of temperature, humidity 75%, 5 day | 0.124 | 4 | 0 | 1 |
| 40 ℃ of temperature, humidity 75%, 14 day | 0.197 | 5 | 0.125 | 1 |
Embodiment two
Earlier with following set of dispense than in two the adjuvant mix homogeneously, must mixed powder; Again the Pitavastatin Calcium of 1mg and mixed powder by the equivalent abundant mix homogeneously of dilution method that progressively increases, or, promptly get the Pitavastatin Calcium mixed powder by the high-speed stirring mixer mix homogeneously.
Again mixed powder is inserted dry press, be pressed into the thin slice of suitable hardness; Then thin slice is passed through oscillating granulator, pulverize and make granule; Add lubricant simultaneously,, promptly get the medicament composition granule of Pitavastatin Calcium with the abundant mixing of high efficient mixed machine.
Then medicament composition granule is passed through the tablet machine tabletting, i.e. the directly suitable tablet of tablet forming on tablet machine.
At last Opadry is made film coating liquid aqueous dispersion, plain sheet is wrapped film-coat, promptly get the Pitavastatin Calcium Film coated tablets, weightening finish about 3% by high-efficiency coating machine.
Set of dispense is than two:
Pitavastatin Calcium 1mg
Lactose 15mg
Microcrystalline Cellulose 10mg
Calcium phosphate 50mg
Carboxymethyl starch sodium 5mg
Magnesium stearate 2mg
Opadry 3mg
Add up to 86mg
Result: coated tablet is placed 40 ℃ of temperature, carry out accelerated tests under humidity 75% condition, result such as following table:
| The investigation time | Content (%) | Dissolution (%) | Related substance (%) | Disintegration time (branch) | Uniformity of dosage units |
| 0 day | 100.0 | 98.02 | 0.66 | 3 | Qualified |
| 1 month | 102.26 | 102.1 | 0.79 | 3 | Qualified |
| 2 months | 102.08 | 95.09 | 0.76 | 4 | Qualified |
| 3 months | 102.82 | 93.80 | 1.05 | 4 | Qualified |
| 6 months | 97.40 | 92.66 | 1.63 | 4 | Qualified |
The detection of more than investigating the experimental design and the project of investigation all requires to carry out according to Chinese Pharmacopoeia version in 2000.
Embodiment three
The preparation of Pitavastatin Calcium Film coated tablets: after lactose, microcrystalline Cellulose and calcium hydrogen phosphate being mixed than three ratios in set of dispense, adopt the equivalent dilution method mix homogeneously that progressively increases, mixed powder is inserted in the dry press, laminate in the ratio of Pitavastatin Calcium; And then thin slice is put into oscillating granulator be ground into granule, adding lubricant simultaneously, mix homogeneously in mixer promptly gets the medicament composition granule of Pitavastatin Calcium.
Then medicament composition granule is passed through the tablet machine tabletting, i.e. the directly suitable tablet of tablet forming on tablet machine.
At last Opadry is made film coating liquid aqueous dispersion, plain sheet is wrapped film-coat, promptly get the Pitavastatin Calcium Film coated tablets, weightening finish about 3% by high-efficiency coating machine.
The preparation of Pitavastatin capsule: after lactose, microcrystalline Cellulose and calcium hydrogen phosphate being mixed than three ratios in set of dispense, adopt the equivalent dilution method mix homogeneously that progressively increases, mixed powder is inserted in the dry press, laminate in the ratio of Pitavastatin Calcium; And then thin slice is put into oscillating granulator be ground into granule, adding lubricant simultaneously, mix homogeneously in mixer promptly gets the medicament composition granule of Pitavastatin Calcium.Then with medicament composition granule by capsule filling machine, go in the suitable gelatine capsule particles filled, promptly get the Pitavastatin calcium capsule.
Set of dispense is than three:
Pitavastatin Calcium 1mg
Lactose 18mg
Microcrystalline Cellulose 30mg
Calcium hydrogen phosphate 60mg
Low-substituted hydroxypropyl cellulose 10mg
Magnesium stearate 1mg
Opadry 3mg
Add up to 123mg
This diaphragm is accelerated tests (40 ℃ of temperature, humidity 75%) three months, content 99.65%, and dissolution 93.27%, related substance 0.85%, disintegration time 5 minutes, uniformity of dosage units is qualified.
This capsule is accelerated tests (40 ℃ of temperature, humidity 75%) three months, content 98.41%, and dissolution 97.13%, related substance 1.02%, 6 minutes disintegrations, uniformity of dosage units is qualified.
Embodiment four
After microcrystalline Cellulose, calcium sulfate, carboxymethyl starch sodium and sodium ethylene diamine tetracetate being mixed than four ratios in set of dispense, adopt the equivalent dilution method mix homogeneously that progressively increases, mixed powder is inserted in the dry press, laminate in the ratio of Pitavastatin Calcium; And then thin slice is put into oscillating granulator be ground into granule, adding low-substituted hydroxypropyl cellulose and magnesium stearate lubricant and Pulvis Talci simultaneously, mix homogeneously in mixer promptly gets the medicament composition granule of Pitavastatin Calcium.
Then medicament composition granule is passed through the tablet machine tabletting, i.e. the directly suitable tablet of tablet forming on tablet machine.
At last Opadry is made film coating liquid aqueous dispersion, plain sheet is wrapped film-coat, promptly get the Pitavastatin Calcium Film coated tablets, weightening finish about 3% by high-efficiency coating machine.
Set of dispense is than four:
Pitavastatin Calcium 1mg
Microcrystalline Cellulose 18mg
Calcium sulfate 20mg
Carboxymethyl starch sodium 8mg
Low-substituted hydroxypropyl cellulose 6mg
Sodium ethylene diamine tetracetate 15mg
Magnesium stearate 1mg
Pulvis Talci 1mg
Opadry 3mg
Add up to 73mg
Said preparation is accelerated tests (40 ℃ of temperature, humidity 75%) three months, content 98.92%, and dissolution 94.33%, related substance 0.76%, disintegration time 4 minutes, uniformity of dosage units is qualified.
Embodiment five
Pitavastatin Calcium calcium diaphragm must prepare: after microcrystalline Cellulose, calcium phosphate and crospolyvinylpyrrolidone being mixed than five ratios in set of dispense, adopt the equivalent dilution method mix homogeneously that progressively increases in the ratio of Pitavastatin Calcium, add the lubricant micropowder silica gel again, mix homogeneously in mixer promptly gets the medicament composition granule of Pitavastatin Calcium.
Then medicament composition granule is passed through the tablet machine tabletting, i.e. the directly suitable tablet of tablet forming on tablet machine.
At last Opadry is made film coating liquid aqueous dispersion, plain sheet is wrapped film-coat, promptly get the Pitavastatin Calcium Film coated tablets, weightening finish about 3% by high-efficiency coating machine.
The Pitavastatin Calcium capsule must prepare: after microcrystalline Cellulose, calcium phosphate and crospolyvinylpyrrolidone being mixed than five ratios in set of dispense, adopt the equivalent dilution method mix homogeneously that progressively increases in the ratio of Pitavastatin Calcium, add the lubricant micropowder silica gel again, mix homogeneously in mixer promptly gets the medicament composition granule of Pitavastatin Calcium.
Then with medicament composition granule by capsule filling machine, go in the suitable gelatine capsule particles filled, promptly get the Pitavastatin calcium capsule.
Set of dispense is than five:
Pitavastatin Calcium 1mg
Microcrystalline Cellulose 10mg
Calcium phosphate 50mg
Crospolyvinylpyrrolidone 3mg
Micropowder silica gel 1mg
Opadry 2mg
Add up to 67mg
This Film coated tablets is accelerated tests (40 ℃ of temperature, humidity 75%) three months, content 99.32%, and dissolution 92.31%, related substance 0.82%, disintegration time 2 minutes, uniformity of dosage units is qualified.
This capsule is accelerated tests (40 ℃ of temperature, humidity 75%) three months, content 97.88%, and dissolution 93.57%, related substance 1.11%, disintegration time 6 minutes, uniformity of dosage units is qualified.
Embodiment six:
After microcrystalline Cellulose, calcium phosphate and crospolyvinylpyrrolidone being mixed than six ratios in set of dispense, adopt the equivalent dilution method mix homogeneously that progressively increases in the ratio of Pitavastatin Calcium, add the lubricant micropowder silica gel again, mix homogeneously in mixer promptly gets the medicament composition granule of Pitavastatin Calcium.
Then medicament composition granule is passed through the tablet machine tabletting, i.e. the directly suitable tablet of tablet forming on tablet machine.
At last Opadry is made film coating liquid aqueous dispersion, plain sheet is wrapped film-coat, promptly get the Pitavastatin Calcium Film coated tablets, weightening finish about 3% by high-efficiency coating machine.
Set of dispense is than six:
Pitavastatin Calcium 1mg
Microcrystalline Cellulose 60mg
Lactose 50mg
Calcium hydrogen phosphate 60mg
Calcium phosphate 40mg
Low-substituted hydroxypropyl cellulose 15mg
Carboxymethyl starch sodium 10mg
Magnesium stearate 2mg
Micropowder silica gel 2mg
Opadry 6mg
Add up to 246mg
Said preparation is accelerated tests (40 ℃ of temperature, humidity 75%) three months, content 99.32%, and dissolution 92.31%, related substance 0.82%, disintegration time 2 minutes, uniformity of dosage units is qualified.
Comparative example one:
With the dry tablet forming technique of wet granulation:
Than seven with pregelatinized Starch, lactose, microcrystalline Cellulose and carboxymethyl starch sodium mix homogeneously, the Pitavastatin Calcium of proportional quantity handle and mixed powder are by the equivalent abundant mix homogeneously of dilution method that progressively increases again by set of dispense; The hypromellose alcoholic solution of adding 5% stirs and makes wet granular; Wet grain is placed in 50 ℃ the aeration-drying baking oven after the drying, takes out, add magnesium stearate, mix homogeneously promptly gets the drug particles of Pitavastatin Calcium.
Then medicament composition granule is passed through the tablet machine tabletting, i.e. the directly suitable tablet of tablet forming on tablet machine.
At last Opadry is made film coating liquid aqueous dispersion, plain sheet is wrapped film-coat, promptly get the Pitavastatin Calcium Film coated tablets, weightening finish about 3% by high-efficiency coating machine.
Set of dispense is than seven:
Pitavastatin Calcium 1mg
Pregelatinized Starch 18mg
Lactose 34mg
Microcrystalline Cellulose 20
Carboxymethyl starch sodium 5mg
5% hypromellose alcoholic solution is an amount of
Magnesium stearate 2mg
Opadry 3mg
Add up to 83mg
Result: carry out 24 months long-time stability investigation according to version Chinese Pharmacopoeia in 2000.
The results are shown in following table.
| The investigation time | Assay (%) | Disintegration (branch) | Relevant goods and materials (%) | Dissolution (%) | Uniformity of dosage units |
| 0 day | 98.98 | 3 | 1.31 | 96.21 | Qualified |
| 24 months | 98.05 | 3 | 5.44 | 96.05 | Qualified |
The result shows, Pitavastatin Calcium Film coated tablets with the wet granulation technology preparation, long-term placement through 24 months, though indexs such as assay, disintegration, dissolution and uniformity of dosage units all meet the pharmacopeia requirement, but severe overweight in the inspection of key project related substance illustrates that such technology preparation can not reach requirement pharmaceutically.
Utilizability on the industry:
Pharmaceutical composition of the present invention is by do not contain any binder in preparation process, when adopting the dry granulation tablet forming technique, adding basic auxiliary makes this pharmaceutical composition reach the composition of stable state, has good bin stability, even pharmaceutically desired long-time stability also can reach, and demonstrate good pharmacy characteristic, disintegration time shortens, stripping is accelerated, fast intestinal absorption and security can be used as pharmaceutical preparation and performs well in medical usage.
Claims (16)
1, a kind of stable pharmaceutical composition that contains Pitavastatin Calcium, comprise principal agent Pitavastatin Calcium and pharmaceutic adjuvant, described pharmaceutic adjuvant comprises filler, disintegrating agent, lubricant, it is characterized in that pharmaceutic adjuvant also includes basic auxiliary, and pharmaceutic adjuvant does not contain adhesive.
2, pharmaceutical composition according to claim 1, it is characterized in that the described adhesive that do not contain, be meant the adhesive that does not contain pharmaceutically, comprise wetting agent, adhesive such as starch, dextrin, gelatin, sodium carboxymethyl cellulose, ethyl cellulose, methylcellulose, hypromellose, polyvinylpyrrolidone, wetting agent such as water and Different concentrations of alcohol solution.
3, pharmaceutical composition according to claim 1, the weight proportion that it is characterized in that described each component of pharmaceutical composition is: Pitavastatin Calcium 0.01～10%, filler 10～93%, disintegrating agent 1～30%, lubricant 0.01～5%, basic auxiliary 0.1～80%.
4, pharmaceutical composition according to claim 3 is characterized in that described filler is selected from one or more in lactose, mannitol, Icing Sugar, starch, microcrystalline Cellulose, sorbitol, calcium sulfate and the calcium hydrogen phosphate.
5, pharmaceutical composition according to claim 4 is characterized in that filler loading is 15%～80%.
6, pharmaceutical composition according to claim 3 is characterized in that described disintegrating agent is selected from one or more in starch, carboxymethyl starch sodium, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, the cross-linked carboxymethyl cellulose calcium.
7, pharmaceutical composition according to claim 6, the consumption that it is characterized in that disintegrating agent is 2～25%.
8, pharmaceutical composition according to claim 3 is characterized in that described lubricant is selected from one or more in Pulvis Talci, magnesium stearate and the micropowder silica gel.
9, pharmaceutical composition according to claim 8 is characterized in that lubricant quantity is 0.1～3%.
10, according to claim 1 or 3 described pharmaceutical compositions, it is characterized in that described basic auxiliary is selected from the sodium salt of calcium phosphate, potassium phosphate, calcium hydrogen phosphate, sodium silicate, potassium silicate, magnesium silicate, calcium chloride, ethylenediaminetetraacetic acid, iron salt and calcium salt, calcium citrate, calcium succinate and various amino acid whose sodium salt and calcium salt one or more.
11, pharmaceutical composition according to claim 10 is characterized in that the basic auxiliary consumption is 5～70%.
12, the described preparation of drug combination method of claim 1, it is characterized in that pharmaceutic adjuvant does not contain adhesive, adopt a kind of in direct powder compression, dry granulation tabletting or the filled capsules, direct powder compression is meant the powder of principal agent with after pharmaceutic adjuvant mixes, without granulation and the method for direct compression; The dry granulation tabletting is meant and will be pressed into sheet behind principal agent and the pharmaceutic adjuvant mixing, and then the granule that is broken into, or directly principal agent and pharmaceutic adjuvant are mixed the dried granule that is squeezed into, add tabletting behind the lubricant mixing again, filled capsules is meant goes into capsule with the particle packing behind powder formulated in the direct powder compression or the dry granulation.
13, pharmaceutical composition according to claim 1, the dosage form that it is characterized in that this pharmaceutical composition is an oral solid formulation.
14, pharmaceutical composition according to claim 13 is characterized in that described oral solid formulation is a tablet.
15, pharmaceutical composition according to claim 13 is characterized in that described oral solid formulation is a capsule.
16, pharmaceutical composition according to claim 14 is characterized in that described tablet is Film coated tablets or coated tablet.
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| CN101890013A (en) * | 2010-07-27 | 2010-11-24 | 北京华禧联合科技发展有限公司 | Pitavastatin calcium composition stabilized by using alkaline reagent and preparation method thereof |
| CN102688206A (en) * | 2012-05-29 | 2012-09-26 | 石药集团中奇制药技术（石家庄）有限公司 | Pitavastatin calcium tablet and preparation method thereof |
| CN103961354A (en) * | 2013-02-05 | 2014-08-06 | 深圳信立泰药业股份有限公司 | Stable rosuvastatin calcium pharmaceutical composition and preparation method thereof |
| CN104644586A (en) * | 2015-03-20 | 2015-05-27 | 王雪雁 | Medicinal composition for treating cardiovascular disease |
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| CN105343008A (en) * | 2015-12-15 | 2016-02-24 | 青岛华之草医药科技有限公司 | Pitavastatin calcium composition |
| CN105982874A (en) * | 2015-10-19 | 2016-10-05 | 迪沙药业集团有限公司 | Pitavastatin calcium composition |
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| CN107854443A (en) * | 2017-11-28 | 2018-03-30 | 徐州生物工程职业技术学院 | A kind of Pitavastatin calcium dispersible tablet and preparation method thereof |
| CN108158990A (en) * | 2018-03-07 | 2018-06-15 | 孙奉生 | The production technology of Pitavastatin Ca oral liquid |
| TWI636783B (en) * | 2012-04-18 | 2018-10-01 | 友霖生技醫藥股份有限公司 | Stable formulations of pitavastatin |
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- 2005-11-24 CN CN 200510110676 patent/CN1969849A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101890013A (en) * | 2010-07-27 | 2010-11-24 | 北京华禧联合科技发展有限公司 | Pitavastatin calcium composition stabilized by using alkaline reagent and preparation method thereof |
| TWI636783B (en) * | 2012-04-18 | 2018-10-01 | 友霖生技醫藥股份有限公司 | Stable formulations of pitavastatin |
| CN102688206A (en) * | 2012-05-29 | 2012-09-26 | 石药集团中奇制药技术（石家庄）有限公司 | Pitavastatin calcium tablet and preparation method thereof |
| CN102688206B (en) * | 2012-05-29 | 2014-08-20 | 石药集团中奇制药技术（石家庄）有限公司 | Pitavastatin calcium tablet and preparation method thereof |
| EP3269362A1 (en) * | 2012-08-08 | 2018-01-17 | KOWA Co., Ltd. | Pharmaceutical composition comprising pitavastatine |
| EP2883547A4 (en) * | 2012-08-08 | 2016-02-10 | Kowa Co | Medicine |
| EP3124017A1 (en) * | 2012-08-08 | 2017-02-01 | Kowa Company, Ltd. | Pharmaceutical composition comprising pitavastatine |
| CN103961354A (en) * | 2013-02-05 | 2014-08-06 | 深圳信立泰药业股份有限公司 | Stable rosuvastatin calcium pharmaceutical composition and preparation method thereof |
| CN104644586A (en) * | 2015-03-20 | 2015-05-27 | 王雪雁 | Medicinal composition for treating cardiovascular disease |
| CN104644587A (en) * | 2015-03-20 | 2015-05-27 | 王雪雁 | Preparation method of medicine composition for treating cardiovascular disease |
| CN105982874A (en) * | 2015-10-19 | 2016-10-05 | 迪沙药业集团有限公司 | Pitavastatin calcium composition |
| CN105343008A (en) * | 2015-12-15 | 2016-02-24 | 青岛华之草医药科技有限公司 | Pitavastatin calcium composition |
| CN107126423A (en) * | 2017-05-02 | 2017-09-05 | 华润双鹤药业股份有限公司 | Pitavastatin Calcium tablet pharmaceutical composition and its dry type or wet type preparation method |
| CN107126423B (en) * | 2017-05-02 | 2020-05-15 | 华润双鹤药业股份有限公司 | Pitavastatin calcium tablet pharmaceutical composition and dry or wet preparation method thereof |
| CN107854443A (en) * | 2017-11-28 | 2018-03-30 | 徐州生物工程职业技术学院 | A kind of Pitavastatin calcium dispersible tablet and preparation method thereof |
| CN110063944A (en) * | 2018-01-24 | 2019-07-30 | 北京红太阳药业有限公司 | A kind of Levamlodipine besylate atorvastatin and preparation method thereof |
| CN110063944B (en) * | 2018-01-24 | 2021-07-16 | 北京红太阳药业有限公司 | Levamlodipine besylate atorvastatin calcium tablet and preparation method thereof |
| CN108158990A (en) * | 2018-03-07 | 2018-06-15 | 孙奉生 | The production technology of Pitavastatin Ca oral liquid |
| CN112999178A (en) * | 2021-03-01 | 2021-06-22 | 乐普制药科技有限公司 | Ezetimibe pitavastatin calcium compound double-layer tablet |
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