CN101224205B - Composition of atorvastatin and levorotatory amlodipine and preparing method thereof - Google Patents

Composition of atorvastatin and levorotatory amlodipine and preparing method thereof Download PDF

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CN101224205B
CN101224205B CN2007100076674A CN200710007667A CN101224205B CN 101224205 B CN101224205 B CN 101224205B CN 2007100076674 A CN2007100076674 A CN 2007100076674A CN 200710007667 A CN200710007667 A CN 200710007667A CN 101224205 B CN101224205 B CN 101224205B
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amount
consumption
atorvastatin calcium
maleic acid
levamlodipine
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CN101224205A (en
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王金戌
白敏�
杨汉煜
陈素锐
申东民
陈玉洁
刘海丽
杜旭召
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Shijiazhuang Pharmaceutical Group Ouyi Pharma Co Ltd
CSPC Zhongqi Pharmaceutical Technology Shijiazhuang Co Ltd
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CSPC Zhongqi Pharmaceutical Technology Shijiazhuang Co Ltd
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Abstract

The invention relates to a combination of atorvastatin and levamlodipine, mainly consists of levamlodipine or officinal salt thereof, atorvastatin or officinal salt thereof, alkali metal salt, and cyclodextrin and derivatives thereof and guarantees the stability and the bioavailability of atorvastatin and levamlodipine.

Description

The composition and method of making the same of a kind of atorvastatin and Levamlodipine
Technical field
The present invention relates to the compositions of a kind of atorvastatin (atorvastatin) or its officinal salt and Levamlodipine or its officinal salt, and this preparation of drug combination method.
Technical background
Hypertension, hyperlipidemia are two important risk factor that cause diseases such as atherosclerosis, angina pectoris, the myocardium ridge are dead, cerebral infarction, renal damage.So, pay close attention to hypertension, hyperlipidemia, actively control having very important significance of cardiovascular and cerebrovascular disease.
Hypertension and hyperlipidemia not only all are to cause arteriosclerotic risk factor, and relation is also very close between the two.The both more easily betides bodily form overweight people; Have a liking for high fat, high salt, high-carbonhydrate diet, or hobby tobacco and wine person; It is irregular to live, and pressure is big, the psychentonia person; Hypertension or hyperlipidemia family disease history person are arranged.Also have a large amount of research datas to show, many hypertensive patients are with lipid metabolic disorder, and the content of blood cholesterol and triglyceride significantly increases than the normal person.On the other hand, the also normal complicated hypertension of many hyperlipemias, both are cause effect relation, but what is still not fully aware of at present for why being fruit.
The CN98808460.0 of company of Pfizer application on August 11st, 1998 discloses the use of uniting of amlodipine and atorvastatin, is used for the treatment of angina pectoris, atherosclerosis, hypertension and hyperlipemia.My company finds after further research, atorvastatin (atorvastatin) and Levamlodipine are united use and can be worked in coordination with and be used for the treatment of hypertension and hyperlipidemia, and applied for CN200510065440.6 on April 8th, 2005, on April 30th, 2005, the CN200510012488.0 of Ouyi Pharmaceutical Industry Co., Ltd., Shijiazhuang Pharmaceutical Group's application confirmed that the use effect of uniting of atorvastatin and Levamlodipine is better than atorvastatin and racemic amlodipine.
Simultaneously, the CN98808460.0 of Pfizer application discloses the oral administration form of suspension, tablet, pill, capsule, powder, adjuvant is conventional excipient, disintegrating agent, binding agent, wherein excipient is the tablet of sodium citrate, calcium carbonate and calcium phosphate, disintegrating agent is a starch, preferred potato starch or tapioca and certain composition silicate, and binding agent such as polyvinylpyrrolidone, sucrose, gelatin and arabic gum.
And I CN200510065440.6 of company's application has only mentioned use tablet form of medication in description, does not provide clear and definite composition.
CN200510012488.0 has mentioned atorvastatin and Levamlodipine in an embodiment and has share and make tablet, and this tablet is with beta-schardinger dextrin-Levamlodipine to be carried out enclose, only improves the dissolution of Levamlodipine.
Find through retrieval analysis prior art, the easy moisture absorption of amorphous atorvastatin, with become unstable after oxygen contacts, the crystallization atorvastatin is all extremely sensitive for the environment and the light of heat, moist, low pH value, therefore, need provide a kind of and can guarantee various forms of atorvastatins or the stability of its officinal salt in the compound recipe coupling of preparation treatment hypertension and hyperlipidemia, guarantee not influence the dosage form that maybe can increase the dissolution of two kinds of active ingredients simultaneously again.
Summary of the invention
In order to overcome the shortcoming of above dosage form, the invention provides the compositions of a kind of atorvastatin or its officinal salt and Levamlodipine or its officinal salt.
The compositions of a kind of atorvastatin and Levamlodipine is made up of following ingredients and weight percentage thereof:
Form weight percentage (%)
Levamlodipine or its officinal salt 0.1～10
Atorvastatin or its officinal salt 1～30
Alkaline metal salt 1～35
Cyclodextrin and derivant 1～60 thereof
Filler 5～80
Other adjuvants 0.1～20
The present invention further is made up of following ingredients and weight percentage thereof:
Form weight percentage (%)
Levamlodipine or its officinal salt 0.1～10
Atorvastatin or its officinal salt 3～30
Alkaline metal salt 3～10
Cyclodextrin and derivant 5～30 thereof
Filler 10～50
Other adjuvants 0.5～10
Wherein the Levamlodipine officinal salt is selected from pharmaceutically acceptable salts such as maleate, benzene sulfonate, hydrochlorate, formates, acetate, hydrobromate, aspartic acid, mesylate, sulphuric acid or tartaric acid.The Levamlodipine officinal salt is preferably maleic acid, benzenesulfonic acid.
Atorvastatin or its officinal salt can be amorphous, crystallization or above both mixture, and officinal salt is half calcium salt.
Alkaline metal oxide or its salt are selected from sodium salt, potassium salt, calcium salt, magnesium salt, more particularly be selected from sodium carbonate, sodium bicarbonate, sodium hydroxide, sodium silicate, sodium phosphate, sodium dihydrogen phosphate, sodium hydrogen phosphate, sodium silicate, calcium oxide, calcium carbonate, magnesium carbonate, magnesium bicarbonate, sodium citrate or magnesium citrate, or above two or more mixture.
Cyclodextrin comprises alpha-cyclodextrin, beta-schardinger dextrin-or gamma-cyclodextrin.
Cyclodextrin derivative comprises: hydroxyethyl-, HP-, dihydroxypropyl-beta-schardinger dextrin-, methyl-beta-schardinger dextrin-, glucose ring dextrin, maltose cyclodextrin, maltotriose cyclodextrin, methylol cyclodextrin or sulfoalkyl cyclodextrin, or above two or more mixture.
Filler is selected from microcrystalline Cellulose, lactose, sucrose, starch, xylitol, glucose or mannitol, or above two or more mixture.
Other adjuvants are selected from disintegrating agent, lubricant or binding agent, or above two or more mixture.
Disintegrating agent is selected from microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose or carboxymethyl starch sodium, or above two or more mixture.
Lubricant is selected from magnesium stearate, Pulvis Talci, or above two kinds of mixture.
Binding agent is selected from water, ethanol, starch slurry, polyvidone or various cellulose, or above two or more mixture.
The compositions of a kind of atorvastatin and Levamlodipine can be oral administered dosage forms such as tablet, capsule, granule, can add an amount of sweeting agent, correctives in addition during the preparation granule.
The preparation method of a kind of atorvastatin and levo-amlodipine:
(1) various supplementary material pulverize separately is crossed 100 mesh sieves;
(2) will in add each supplementary material by the equivalent method mix homogeneously that progressively increases, it is an amount of to add binding agent, granulate, oven dry, granulate is sneaked into and is added adjuvant, tabletting, coating.
The capsular preparation method of a kind of atorvastatin and Levamlodipine:
(1) various supplementary material pulverize separately is crossed 100 mesh sieves;
(2) will in add each supplementary material by the equivalent method mix homogeneously that progressively increases, it is an amount of to add binding agent, granulate, oven dry, granulate is sneaked into and is added adjuvant, filled capsules.
The preparation method of a kind of atorvastatin and Levamlodipine granule:
(1) various supplementary material pulverize separately is crossed 100 mesh sieves;
(2) will in add each supplementary material by the equivalent method mix homogeneously that progressively increases, it is an amount of to add binding agent, granulate, oven dry, granulate is sneaked into and is added adjuvant, packing.
Detection method (is example with the tablet):
1, dissolution
Getting this product, is solvent according to dissolution method (two appendix XC second methods of Chinese Pharmacopoeia version in 2005) with the phosphate buffer, and rotating speed is that per minute 75 changes, operation in accordance with the law.In the time of 30 minutes, get solution 5ml, filter, get subsequent filtrate as need testing solution; Measure according to the method under the assay item, calculate the stripping quantity of every middle Levamlodipine and Atorvastatin calcium respectively, limit is 75% of labelled amount, should be up to specification.
2, related substance
Get fine powder under the assay item, precision takes by weighing in right amount, adds mobile phase and is diluted to scale, shakes up, in contrast solution.Precision is measured contrast solution and is injected chromatograph of liquid, regulate detection sensitivity, make Atorvastatin calcium main constituent peak height be about 20%～25% of full scale, precision is measured above-mentioned two kinds of solution injection chromatograph of liquid again, the record chromatogram is to 2 times of Atorvastatin calcium peak retention time, and each impurity peak area sum must not be greater than 2 times of contrast solution Atorvastatin calcium peak area.
3, assay
Get 10 of this product, the accurate title, decided porphyrize, precision takes by weighing in right amount, adds mobile phase and is diluted to scale, shakes up, filter, get subsequent filtrate 20 μ l and inject chromatograph of liquid, the record chromatogram calculates the content of Levamlodipine and Atorvastatin calcium in the test sample respectively with peak area by external standard method.
The inventor is through to the retrieval of prior art, and by a large amount of experiment sievings, determines at last to unite and use alkaline metal salt and cyclodextrin, can better keep the stability and the bioavailability of compound recipe of the present invention.
Being example to calcium carbonate, cyclodextrin in the alkalinous metal, carry out preliminary prescription screening (concrete prescription sees Table 1), and compare to 5 with the embodiment 1 of CN200510012488.0, wherein the cyclodextrin ratios of embodiment 1,2,3 is identical, choose embodiment 1 as a comparison case 1, embodiment 4 and 5 difference are 2,3 (concrete prescription sees Table 2) as a comparison case, and its stripping, content, related substance are detected, and assay sees Table 3.
Table 1-1 prescription screening table of the present invention (weight: g)
Table 1-2 prescription screening table of the present invention (weight: g)
Figure G07107667420070202D000062
Annotate: supplementary material is per 1000 preparation unit's consumptions in the form.
Table 3 experimental result
Figure G07107667420070202D000081
Testing result shows, in 3～10% scopes, beta-schardinger dextrin-is in 5～30% scope at the percentage by weight of alkali metal salt, and the stability and the dissolution of Atorvastatin calcium and Levamlodipine compositions are best; At the percentage by weight of alkali metal salt in 1～35% scope, beta-schardinger dextrin-is in 1～60% scope, the stability of Atorvastatin calcium and Levamlodipine compositions and dissolution still can, stability, the dissolution of said composition is defective in all the other scopes.
The invention has the advantages that: unite and use alkali metal salt and beta-schardinger dextrin-use in conjunction, cooperate suitable adjuvant, the every index and the dissolution of the stability of Atorvastatin calcium and Levamlodipine compositions are good.
The specific embodiment
Further specify the present invention with hereinafter embodiment, described embodiment should not be construed as limiting the invention.
Embodiment 1: Atorvastatin calcium and maleic acid levo amido chloro diping sheet
Prescription:
Title consumption (g) percentage by weight (%)
Maleic acid levo amido chloro diping 2.5 1.7
(being equivalent to Levamlodipine)
Atorvastatin calcium 10 6.7
Calcium carbonate 1.5 1
Low-substituted hydroxypropyl cellulose 42 28
Cross-linking sodium carboxymethyl cellulose 96
Beta-schardinger dextrin-15 10
Amylum pregelatinisatum 65 43.3
Magnesium stearate 1.5 1
The polyvidone alcoholic solution is an amount of
Gross weight 150g
The Opadry coating powder is an amount of
Concrete preparation method is as follows: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, maleic acid levo amido chloro diping, calcium carbonate, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, beta-schardinger dextrin-, amylum pregelatinisatum mix homogeneously of recipe quantity, add the binding agent polyvidone alcoholic solution that has prepared and make soft material in right amount, granulate, dry, dried granule granulate, calculating adds tabletting behind adjuvant magnesium stearate consumption and the abundant mix homogeneously of dried granule, adopts conventional coating method to carry out coating, coated tablet.
Embodiment 2: Atorvastatin calcium and maleic acid levo amido chloro diping sheet
Prescription:
Title consumption (g) percentage by weight (%)
Maleic acid levo amido chloro diping 2.5 1.3
(being equivalent to Levamlodipine)
Atorvastatin calcium 20 11.1
Calcium carbonate 5.4 3
Microcrystalline Cellulose 102.4 56.9
Polyvinylpolypyrrolidone 85
Beta-schardinger dextrin-36 20
Hydroxypropyl emthylcellulose alcoholic solution an amount of 2.3
Magnesium stearate 1.5 1
Gross weight 180
The Opadry coating powder is an amount of
Concrete preparation method is as follows: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, maleic acid levo amido chloro diping, calcium carbonate, microcrystalline Cellulose, polyvinylpolypyrrolidone, beta-schardinger dextrin-mix homogeneously of recipe quantity, add the binding agent hydroxypropyl emthylcellulose alcoholic solution that has prepared and make soft material in right amount, granulate, dry, dried granule granulate, calculating adds tabletting behind adjuvant magnesium stearate consumption and the abundant mix homogeneously of dried granule, adopts conventional coating method to carry out coating, coated tablet.
Embodiment 3: atorvastatin and Levamlodipine beaylate tablets
Prescription:
Title consumption (g) percentage by weight (%)
Levamlodipine besylate
(being equivalent to Levamlodipine) 2.5 1.0
Atorvastatin calcium 40 16.7
Calcium carbonate 12 5
Microcrystalline Cellulose 50 20.8
Polyvinylpolypyrrolidone 12 5
Methyl-beta-schardinger dextrin-24 10
Lactose 92 38.3
The hydroxypropyl emthylcellulose alcoholic solution is an amount of
Magnesium stearate 1.5 0.6
Gross weight 240
The Opadry coating powder is an amount of
Concrete preparation method is as follows: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, Levamlodipine besylate, calcium carbonate, microcrystalline Cellulose, polyvinylpolypyrrolidone, methyl-beta-schardinger dextrin-, lactose mix homogeneously of recipe quantity, add the binding agent hydroxypropyl emthylcellulose alcoholic solution that has prepared and make soft material in right amount, granulate, dry, dried granule granulate, calculating adds tabletting behind adjuvant magnesium stearate consumption and the abundant mix homogeneously of dried granule, adopts conventional coating method to carry out coating, coated tablet.
Embodiment 4: atorvastatin and maleic acid levo amido chloro diping sheet
Prescription:
Title consumption (g) percentage by weight (%)
Maleic acid levo amido chloro diping 5 3.3
(being equivalent to Levamlodipine)
Atorvastatin calcium 10 6.7
Sodium bicarbonate 15 10
Low-substituted hydroxypropyl cellulose 42 28
Polyvinylpolypyrrolidone 7.5 5
Beta-schardinger dextrin-7.5 5
Lactose 63 42
The polyvidone alcoholic solution is an amount of
Magnesium stearate 1.5 1
Gross weight 150
The Opadry coating powder is an amount of
Concrete preparation method is as follows: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, maleic acid levo amido chloro diping, sodium bicarbonate, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, beta-schardinger dextrin-, lactose mix homogeneously of recipe quantity, add the binding agent polyvidone alcoholic solution that has prepared and make soft material in right amount, granulate, dry, dried granule granulate, calculating adds tabletting behind adjuvant magnesium stearate consumption and the abundant mix homogeneously of dried granule, adopts conventional coating method to carry out coating, coated tablet.
Embodiment 5: Atorvastatin calcium and maleic acid levo amido chloro diping sheet
Prescription:
Title consumption (g) percentage by weight (%)
Maleic acid levo amido chloro diping 5 2.8
(being equivalent to Levamlodipine)
Atorvastatin calcium 20 11.1
Calcium oxide 36 20
Cross-linking sodium carboxymethyl cellulose 10.8 6
Beta-schardinger dextrin-54 30
Lactose 48.5 26.9
The polyvidone alcoholic solution is an amount of
Pulvis Talci 1.5 0.8
Gross weight 180
The Opadry coating powder is an amount of
Concrete preparation method is as follows: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, maleic acid levo amido chloro diping, calcium oxide, cross-linking sodium carboxymethyl cellulose, beta-schardinger dextrin-, lactose mix homogeneously of recipe quantity, add the binding agent polyvidone alcoholic solution that has prepared and make soft material in right amount, granulate, dry, dried granule granulate, calculating adds tabletting behind adjuvant amount of talc and the abundant mix homogeneously of dried granule, adopts conventional coating method to carry out coating, coated tablet.
Embodiment 6: Atorvastatin calcium and maleic acid levo amido chloro diping sheet
Prescription:
Title consumption (g) percentage by weight (%)
Maleic acid levo amido chloro diping 5 2.1
(being equivalent to Levamlodipine)
Atorvastatin calcium 40 16.7
Sodium bicarbonate 48 20
Microcrystalline Cellulose 45 18.8
Cross-linking sodium carboxymethyl cellulose 14.4 6
HP-12 5
Mannitol 68 28.3
The polyvidone alcoholic solution is an amount of
Pulvis Talci 1.5 0.6
Gross weight 240
The Opadry coating powder is an amount of
Concrete preparation method is as follows: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, maleic acid levo amido chloro diping, sodium bicarbonate, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, HP-, mannitol mix homogeneously of recipe quantity, add the binding agent polyvidone alcoholic solution that has prepared and make soft material in right amount, granulate, dry, dried granule granulate, calculating adds tabletting behind adjuvant amount of talc and the abundant mix homogeneously of dried granule, adopts conventional coating method to carry out coating, coated tablet
Embodiment 7: Atorvastatin calcium and Levamlodipine beaylate tablets
Prescription:
Title consumption (g) percentage by weight (%)
Levamlodipine besylate 5 1.4
(being equivalent to Levamlodipine)
Atorvastatin calcium 80 22.2
Calcium carbonate 126 35
Amylum pregelatinisatum 42 11.7
Polyvinylpolypyrrolidone 9 0.3
HP-3.6 1
Lactose 65 18.1
Starch slurry is an amount of
Magnesium stearate 1.5 0.4
Gross weight 360
The Opadry coating powder is an amount of
Concrete preparation method is as follows: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, Levamlodipine besylate, calcium carbonate, amylum pregelatinisatum, polyvinylpolypyrrolidone, HP-, lactose mix homogeneously of recipe quantity, add the adhesive starch slurry solution that has prepared and make soft material in right amount, granulate, dry, dried granule granulate, calculating adds tabletting behind adjuvant magnesium stearate consumption and the abundant mix homogeneously of dried granule, adopts conventional coating method to carry out coating, coated tablet
Embodiment 8: Atorvastatin calcium and maleic acid levo amido chloro diping granule
Prescription:
Title consumption (g) percentage by weight (%)
Maleic acid levo amido chloro diping 10 6.7
(being equivalent to Levamlodipine)
Atorvastatin calcium 10 6.7
Calcium lactate 7.5 5
Microcrystalline Cellulose 20 13.3
Polyvinylpolypyrrolidone 7.5 5
HP-60 40
Icing Sugar 30 20
Aspartame 0.75 0.5
Pulvis Talci 1.5 1
The polyvidone alcoholic solution is an amount of
Gross weight 150
Concrete preparation method is as follows: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, maleic acid levo amido chloro diping, calcium lactate, microcrystalline Cellulose, polyvinylpolypyrrolidone, HP-, Icing Sugar, aspartame mix homogeneously of recipe quantity, add the binding agent polyvidone alcoholic solution that has prepared and make soft material in right amount, granulate, dry, dried granule granulate, calculating is carried out packing after adding adjuvant amount of talc and the abundant mix homogeneously of dried granule, gets granule.
Embodiment 9: Atorvastatin calcium and Levamlodipine beaylate tablets
Prescription:
Title consumption (g) percentage by weight (%)
Levamlodipine besylate 10 5.6
(being equivalent to Levamlodipine)
Atorvastatin calcium 20 11.1
Sodium phosphate 95
Microcrystalline Cellulose 38 21.1
Polyvinylpolypyrrolidone 7 3.9
Hydroxyethyl-90 50
The hydroxypropyl emthylcellulose alcoholic solution is an amount of
Magnesium stearate 1.5 0.8
Gross weight 180
The Opadry coating powder is an amount of
Concrete preparation method is as follows: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, Levamlodipine besylate, sodium phosphate, microcrystalline Cellulose, polyvinylpolypyrrolidone, hydroxyethyl-mix homogeneously of recipe quantity, add the binding agent hydroxypropyl emthylcellulose alcoholic solution that has prepared and make soft material in right amount, granulate, dry, dried granule granulate, calculating adds tabletting behind adjuvant magnesium stearate consumption and the abundant mix homogeneously of dried granule, adopts conventional coating method to carry out coating, coated tablet.
Embodiment 10: Atorvastatin calcium and maleic acid levo amido chloro diping sheet
Prescription:
Title consumption (g) percentage by weight (%)
Maleic acid levo amido chloro diping 10 4.2
(being equivalent to Levamlodipine)
Atorvastatin calcium 40 16.7
Sodium silicate 12 5
Cross-linking sodium carboxymethyl cellulose 12 5
Beta-schardinger dextrin-144 60
Lactose 15 6.25
Magnesium stearate 1.5 0.6
Alcoholic solution is an amount of
Gross weight 240
The Opadry coating powder is an amount of
Concrete preparation method is as follows: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, maleic acid levo amido chloro diping, sodium silicate, cross-linking sodium carboxymethyl cellulose, beta-schardinger dextrin-, lactose mix homogeneously of recipe quantity, add alcoholic solution and make soft material in right amount, granulate, dry, dried granule granulate, calculating adds tabletting behind adjuvant magnesium stearate consumption and the abundant mix homogeneously of dried granule, adopts conventional coating method to carry out coating, coated tablet.
Embodiment 11: atorvastatin and Levamlodipine besylate capsule
Prescription:
Title consumption (g) percentage by weight (%)
Levamlodipine besylate 10 2.8
(being equivalent to Levamlodipine)
Atorvastatin calcium 80 22.2
Sodium bicarbonate 36 10
Microcrystalline Cellulose 65 18.1
Cross-linking sodium carboxymethyl cellulose 18 5
HP-18 5
Lactose 120 33.3
Starch slurry is an amount of
Pulvis Talci 3.6 1
Gross weight 360
Concrete preparation method is as follows: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, Levamlodipine besylate, sodium bicarbonate, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, HP-, lactose mix homogeneously of recipe quantity, add an amount of starch slurry system soft material, granulate, dry, dried granule granulate, calculating adds behind adjuvant amount of talc and the abundant mix homogeneously of dried granule encapsulated, capsule.

Claims (11)

  1. One kind by Atorvastatin calcium and maleic acid levo amido chloro diping as the tablet of active component, it is characterized in that: form by following ingredients and consumption thereof:
    Title consumption g
    Maleic acid levo amido chloro diping 2.5
    Atorvastatin calcium 10
    Calcium carbonate 1.5
    Low-substituted hydroxypropyl cellulose 42
    Cross-linking sodium carboxymethyl cellulose 9
    Beta-schardinger dextrin-15
    Amylum pregelatinisatum 65
    Magnesium stearate 1.5
    The polyvidone alcoholic solution is an amount of
    Gross weight 150g
    The Opadry coating powder is an amount of
    Wherein, the consumption of maleic acid levo amido chloro diping adopts the mode of the amount that is converted to Levamlodipine to represent,
    Described as follows as the preparation method of the tablet of active component by Atorvastatin calcium and maleic acid levo amido chloro diping: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, maleic acid levo amido chloro diping, calcium carbonate, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, beta-schardinger dextrin-, amylum pregelatinisatum mix homogeneously of recipe quantity, add the binding agent polyvidone alcoholic solution that has prepared and make soft material in right amount, granulate, dry, dried granule granulate, calculating adds tabletting behind adjuvant magnesium stearate consumption and the abundant mix homogeneously of dried granule, adopts conventional coating method to carry out coating, coated tablet.
  2. One kind by Atorvastatin calcium and maleic acid levo amido chloro diping as the tablet of active component, it is characterized in that: form by following ingredients and consumption thereof:
    Title consumption g
    Maleic acid levo amido chloro diping 2.5
    Atorvastatin calcium 20
    Calcium carbonate 5.4
    Microcrystalline Cellulose 102.4
    Polyvinylpolypyrrolidone 8
    Beta-schardinger dextrin-36
    The hydroxypropyl emthylcellulose alcoholic solution is an amount of
    Magnesium stearate 1.5
    Gross weight 180
    The Opadry coating powder is an amount of
    Wherein, the consumption of maleic acid levo amido chloro diping adopts the mode of the amount that is converted to Levamlodipine to represent,
    Described as follows as the preparation method of the tablet of active component by Atorvastatin calcium and maleic acid levo amido chloro diping: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, maleic acid levo amido chloro diping, calcium carbonate, microcrystalline Cellulose, polyvinylpolypyrrolidone, beta-schardinger dextrin-mix homogeneously of recipe quantity, add the binding agent hydroxypropyl emthylcellulose alcoholic solution that has prepared and make soft material in right amount, granulate, dry, dried granule granulate, calculating adds tabletting behind adjuvant magnesium stearate consumption and the abundant mix homogeneously of dried granule, adopts conventional coating method to carry out coating, coated tablet.
  3. One kind by Atorvastatin calcium and Levamlodipine besylate as the tablet of active component, it is characterized in that: form by following ingredients and consumption thereof:
    Title consumption g
    Levamlodipine besylate 2.5
    Atorvastatin calcium 40
    Calcium carbonate 12
    Microcrystalline Cellulose 50
    Polyvinylpolypyrrolidone 12
    Methyl-beta-schardinger dextrin-24
    Lactose 92
    The hydroxypropyl emthylcellulose alcoholic solution is an amount of
    Magnesium stearate 1.5
    Gross weight 240
    The Opadry coating powder is an amount of
    Wherein, the consumption of Levamlodipine besylate adopts the mode of the amount that is converted to Levamlodipine to represent,
    Described as follows as the preparation method of the tablet of active component by Atorvastatin calcium and Levamlodipine besylate: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, Levamlodipine besylate, calcium carbonate, microcrystalline Cellulose, polyvinylpolypyrrolidone, methyl-beta-schardinger dextrin-, lactose mix homogeneously of recipe quantity, add the binding agent hydroxypropyl emthylcellulose alcoholic solution that has prepared and make soft material in right amount, granulate, dry, dried granule granulate, calculating adds tabletting behind adjuvant magnesium stearate consumption and the abundant mix homogeneously of dried granule, adopts conventional coating method to carry out coating, coated tablet.
  4. One kind by Atorvastatin calcium and maleic acid levo amido chloro diping as the tablet of active component, it is characterized in that: form by following ingredients and consumption thereof:
    Title consumption g
    Maleic acid levo amido chloro diping 5
    Atorvastatin calcium 10
    Sodium bicarbonate 15
    Low-substituted hydroxypropyl cellulose 42
    Polyvinylpolypyrrolidone 7.5
    Beta-schardinger dextrin-7.5
    Lactose 63
    The polyvidone alcoholic solution is an amount of
    Magnesium stearate 1.5
    Gross weight 150
    The Opadry coating powder is an amount of
    Wherein, the consumption of maleic acid levo amido chloro diping adopts the mode of the amount that is converted to Levamlodipine to represent,
    Described as follows as the preparation method of the tablet of active component by Atorvastatin calcium and maleic acid levo amido chloro diping: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, maleic acid levo amido chloro diping, sodium bicarbonate, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, beta-schardinger dextrin-, lactose mix homogeneously of recipe quantity, add the binding agent polyvidone alcoholic solution that has prepared and make soft material in right amount, granulate, dry, dried granule granulate, calculating adds tabletting behind adjuvant magnesium stearate consumption and the abundant mix homogeneously of dried granule, adopts conventional coating method to carry out coating, coated tablet.
  5. One kind by Atorvastatin calcium and maleic acid levo amido chloro diping as the tablet of active component, it is characterized in that: form by following ingredients and consumption thereof:
    Title consumption g
    Maleic acid levo amido chloro diping 5
    Atorvastatin calcium 20
    Calcium oxide 36
    Cross-linking sodium carboxymethyl cellulose 10.8
    Beta-schardinger dextrin-54
    Lactose 48.5
    The polyvidone alcoholic solution is an amount of
    Pulvis Talci 1.5
    Gross weight 180
    The Opadry coating powder is an amount of
    Wherein, the consumption of maleic acid levo amido chloro diping adopts the mode of the amount that is converted to Levamlodipine to represent,
    Described as follows as the preparation method of the tablet of active component by Atorvastatin calcium and maleic acid levo amido chloro diping: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, maleic acid levo amido chloro diping, calcium oxide, cross-linking sodium carboxymethyl cellulose, beta-schardinger dextrin-, lactose mix homogeneously of recipe quantity, add the binding agent polyvidone alcoholic solution that has prepared and make soft material in right amount, granulate, dry, dried granule granulate, calculating adds tabletting behind adjuvant amount of talc and the abundant mix homogeneously of dried granule, adopts conventional coating method to carry out coating, coated tablet.
  6. One kind by Atorvastatin calcium and maleic acid levo amido chloro diping as the tablet of active component, it is characterized in that: form by following ingredients and consumption thereof:
    Title consumption g
    Maleic acid levo amido chloro diping 5
    Atorvastatin calcium 40
    Sodium bicarbonate 48
    Microcrystalline Cellulose 45
    Cross-linking sodium carboxymethyl cellulose 14.4
    HP-12
    Mannitol 68
    The polyvidone alcoholic solution is an amount of
    Pulvis Talci 1.5
    Gross weight 240
    The Opadry coating powder is an amount of
    Wherein, the consumption of maleic acid levo amido chloro diping adopts the mode of the amount that is converted to Levamlodipine to represent,
    Described as follows as the preparation method of the tablet of active component by Atorvastatin calcium and maleic acid levo amido chloro diping: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, maleic acid levo amido chloro diping, sodium bicarbonate, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, HP-, mannitol mix homogeneously of recipe quantity, add the binding agent polyvidone alcoholic solution that has prepared and make soft material in right amount, granulate, dry, dried granule granulate, calculating adds tabletting behind adjuvant amount of talc and the abundant mix homogeneously of dried granule, adopts conventional coating method to carry out coating, coated tablet.
  7. 7. one kind by Atorvastatin calcium and the Levamlodipine besylate tablet as active component,
    It is characterized in that: form by following ingredients and consumption thereof:
    Title consumption g
    Levamlodipine besylate 5
    Atorvastatin calcium 80
    Calcium carbonate 126
    Amylum pregelatinisatum 42
    Polyvinylpolypyrrolidone 9
    HP-3.6
    Lactose 65
    Starch slurry is an amount of
    Magnesium stearate 1.5
    Gross weight 360
    The Opadry coating powder is an amount of
    Wherein, the consumption of Levamlodipine besylate adopts the mode of the amount that is converted to Levamlodipine to represent,
    Described as follows as the preparation method of the tablet of active component by Atorvastatin calcium and Levamlodipine besylate: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, Levamlodipine besylate, calcium carbonate, amylum pregelatinisatum, polyvinylpolypyrrolidone, HP-, lactose mix homogeneously of recipe quantity, add the adhesive starch slurry solution that has prepared and make soft material in right amount, granulate, dry, dried granule granulate, calculating adds tabletting behind adjuvant magnesium stearate consumption and the abundant mix homogeneously of dried granule, adopts conventional coating method to carry out coating, coated tablet.
  8. One kind by Atorvastatin calcium and maleic acid levo amido chloro diping as the granule of active component, it is characterized in that: form by following ingredients and consumption thereof:
    Title consumption g
    Maleic acid levo amido chloro diping 10
    Atorvastatin calcium 10
    Calcium lactate 7.5
    Microcrystalline Cellulose 20
    Polyvinylpolypyrrolidone 7.5
    HP-60
    Icing Sugar 30
    Aspartame 0.75
    Pulvis Talci 1.5
    The polyvidone alcoholic solution is an amount of
    Gross weight 150
    Wherein, the consumption of maleic acid levo amido chloro diping adopts the mode of the amount that is converted to Levamlodipine to represent,
    Described as follows as the preparation method of the granule of active component by Atorvastatin calcium and maleic acid levo amido chloro diping: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, maleic acid levo amido chloro diping, calcium lactate, microcrystalline Cellulose, polyvinylpolypyrrolidone, HP-, Icing Sugar, aspartame mix homogeneously of recipe quantity, add the binding agent polyvidone alcoholic solution that has prepared and make soft material in right amount, granulate, dry, dried granule granulate, calculating is carried out packing after adding adjuvant amount of talc and the abundant mix homogeneously of dried granule, gets granule.
  9. One kind by Atorvastatin calcium and Levamlodipine besylate as the tablet of active component, it is characterized in that: form by following ingredients and consumption thereof:
    Title consumption g
    Levamlodipine besylate 10
    Atorvastatin calcium 20
    Sodium phosphate 9
    Microcrystalline Cellulose 38
    Polyvinylpolypyrrolidone 7
    Hydroxyethyl-90
    The hydroxypropyl emthylcellulose alcoholic solution is an amount of
    Magnesium stearate 1.5
    Gross weight 180
    The Opadry coating powder is an amount of
    Wherein, the consumption of Levamlodipine besylate adopts the mode of the amount that is converted to Levamlodipine to represent,
    Described as follows as the preparation method of the tablet of active component by Atorvastatin calcium and Levamlodipine besylate: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, Levamlodipine besylate, sodium phosphate, microcrystalline Cellulose, polyvinylpolypyrrolidone, hydroxyethyl-mix homogeneously of recipe quantity, add the binding agent hydroxypropyl emthylcellulose alcoholic solution that has prepared and make soft material in right amount, granulate, dry, dried granule granulate, calculating adds tabletting behind adjuvant magnesium stearate consumption and the abundant mix homogeneously of dried granule, adopts conventional coating method to carry out coating, coated tablet.
  10. One kind by Atorvastatin calcium and maleic acid levo amido chloro diping as the tablet of active component, it is characterized in that: form by following ingredients and consumption thereof:
    Title consumption g
    Maleic acid levo amido chloro diping 10
    Atorvastatin calcium 40
    Sodium silicate 12
    Cross-linking sodium carboxymethyl cellulose 12
    Beta-schardinger dextrin-144
    Lactose 15
    Magnesium stearate 1.5
    Alcoholic solution is an amount of
    Gross weight 240
    The Opadry coating powder is an amount of
    Wherein, the consumption of maleic acid levo amido chloro diping adopts the mode of the amount that is converted to Levamlodipine to represent,
    Described as follows as the preparation method of the tablet of active component by Atorvastatin calcium and maleic acid levo amido chloro diping: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, maleic acid levo amido chloro diping, sodium silicate, cross-linking sodium carboxymethyl cellulose, beta-schardinger dextrin-, lactose mix homogeneously of recipe quantity, add alcoholic solution and make soft material in right amount, granulate, dry, dried granule granulate, calculating adds tabletting behind adjuvant magnesium stearate consumption and the abundant mix homogeneously of dried granule, adopts conventional coating method to carry out coating, coated tablet.
  11. 11. one kind by Atorvastatin calcium and Levamlodipine besylate as the capsule of active component, it is characterized in that: form by following ingredients and consumption thereof:
    Title consumption g
    Levamlodipine besylate 10
    Atorvastatin calcium 80
    Sodium bicarbonate 36
    Microcrystalline Cellulose 65
    Cross-linking sodium carboxymethyl cellulose 18
    HP-18
    Lactose 120
    Starch slurry is an amount of
    Pulvis Talci 3.6
    Gross weight 360
    Wherein, the consumption of Levamlodipine besylate adopts the mode of the amount that is converted to Levamlodipine to represent,
    Described as follows as the capsular preparation method of active component by Atorvastatin calcium and Levamlodipine besylate: with the supplementary material pulverize separately, it is standby to cross 100 mesh sieves; After taking by weighing the Atorvastatin calcium, Levamlodipine besylate, sodium bicarbonate, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, HP-, lactose mix homogeneously of recipe quantity, add an amount of starch slurry system soft material, granulate, dry, dried granule granulate, calculating adds behind adjuvant amount of talc and the abundant mix homogeneously of dried granule encapsulated, capsule.
CN2007100076674A 2007-01-20 2007-01-20 Composition of atorvastatin and levorotatory amlodipine and preparing method thereof Active CN101224205B (en)

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Publication number Priority date Publication date Assignee Title
CN102028662B (en) * 2009-09-30 2011-10-19 江西施美制药有限公司 Levamlodipine besylate tablet, preparation process thereof and control method for relevant materials
CN102274224A (en) * 2011-06-30 2011-12-14 北京嘉林药业股份有限公司 oral solid composition of atorvastatin and amlodipine and preparation method thereof
CN102846608A (en) * 2012-09-13 2013-01-02 北京万全阳光医学技术有限公司 Pharmaceutical composition containing amlodipine and atorvastatin calcium, and preparation method thereof
JP2020019731A (en) * 2018-07-31 2020-02-06 日本食品化工株式会社 Bitter taste inhibitor of amlodipine besilate

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1642526A (en) * 2002-02-14 2005-07-20 兰贝克赛实验室有限公司 Formulations of atorvastatin stabilized with alkali metal additions
CN1843357A (en) * 2005-04-08 2006-10-11 石药集团中奇制药技术（石家庄）有限公司 Pharmaceutical compositions of levoamlodipine and atorvastatin
CN1857726A (en) * 2005-04-30 2006-11-08 石家庄制药集团欧意药业有限公司 Medicine composition for treating hypertension complicated with hyperlipemia and cardiac and cerebral vascular diseases

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1642526A (en) * 2002-02-14 2005-07-20 兰贝克赛实验室有限公司 Formulations of atorvastatin stabilized with alkali metal additions
CN1843357A (en) * 2005-04-08 2006-10-11 石药集团中奇制药技术（石家庄）有限公司 Pharmaceutical compositions of levoamlodipine and atorvastatin
CN1857726A (en) * 2005-04-30 2006-11-08 石家庄制药集团欧意药业有限公司 Medicine composition for treating hypertension complicated with hyperlipemia and cardiac and cerebral vascular diseases

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