阅读说明：本技术 一种氨氯地平阿托伐他汀钙缓释片及其制备方法 (Amlodipine atorvastatin calcium sustained release tablet and preparation method thereof ) 是由 陈岑波 陈盈 潘裕生 愉悦 王海翔 于 2020-04-07 设计创作，主要内容包括：本发明提供了一种氨氯地平阿托伐他汀钙缓释片及其制备方法,氨氯地平阿托伐他汀钙缓释片,其组成包括常释部分药物和缓释部分药物,常释部分药物由原料药、填充剂、崩解剂、粘合剂、润滑剂组成；缓释部分药物由原料药、填充剂、崩解剂、助流剂、粘合剂、润滑剂组成。本发明可同时治疗高血压和高血脂疾病,常释部分药物在体内迅速释放,奏效快；缓释部分药物缓慢释放,持续维持平稳的有效血药浓度的效果。(The invention provides an amlodipine atorvastatin calcium sustained release tablet and a preparation method thereof, the amlodipine atorvastatin calcium sustained release tablet comprises a normally released part medicament and a sustained release part medicament, wherein the normally released part medicament comprises raw material medicaments, a filling agent, a disintegrating agent, an adhesive and a lubricating agent; the slow-release part of the medicine consists of raw material medicines, a filling agent, a disintegrating agent, a glidant, an adhesive and a lubricant. The invention can treat hypertension and hyperlipemia at the same time, and the normally released part of the medicine is released quickly in vivo, so the effect is fast; the sustained-release part of the drug is slowly released, and the effect of stable effective blood concentration is continuously maintained.)

1. The amlodipine atorvastatin calcium sustained release tablet is characterized in that: the sustained-release tablet comprises a normally-released part medicament and a sustained-release part medicament, wherein the normally-released part medicament consists of raw material medicaments, a filling agent, a disintegrating agent, an adhesive and a lubricating agent; the slow release part of the medicine consists of bulk drugs, a filling agent, a disintegrating agent, a glidant, an adhesive and a lubricant; the content of atorvastatin calcium in the normally released part of the medicine is 10-20 parts by mass, and the content of amlodipine is 5 parts by mass; the content of atorvastatin calcium in the sustained-release part of the medicine is 10-20 parts, and the content of amlodipine is 5 parts; the amlodipine atorvastatin calcium sustained release tablet is a double-layer tablet prepared by twice pressing.

2. The amlodipine atorvastatin calcium sustained release tablet according to claim 1, wherein: the contents of the components of the normally-released part of the medicine are as follows:

3. the amlodipine atorvastatin calcium sustained release tablet according to claim 2, wherein: the filler comprises 60 parts by mass of microcrystalline cellulose 101 and 37.15 parts by mass of 200-mesh lactose; the disintegrating agent is croscarmellose sodium, the adhesive is hydroxypropyl methylcellulose, and the lubricant is magnesium stearate.

4. The amlodipine atorvastatin calcium sustained release tablet according to claim 2, wherein: the content of each component of the slow-release part of the medicine is as follows:

5. the amlodipine atorvastatin calcium sustained release tablet according to claim 4, wherein: the filling agent is microcrystalline cellulose PH102, the adhesive is hydroxypropyl methyl cellulose, the glidant is silicon dioxide, and the lubricant is magnesium stearate.

6. The preparation method of the amlodipine atorvastatin calcium sustained release tablet of claim 4, characterized by comprising the following steps:

(1) sieving the raw materials and the auxiliary materials with a 80-mesh sieve respectively for later use;

(2) preparation process of normally-released partial medicine

Uniformly mixing atorvastatin calcium, amlodipine, a filling agent and a disintegrating agent, adding a purified water solution of an adhesive to prepare a soft material, and sieving with a 18-mesh sieve for granulation; drying at 80 deg.C, sieving with 18 mesh sieve, adding lubricant, and mixing to obtain normal-release part;

(3) process for preparing slow-releasing medicine

Uniformly mixing the atorvastatin calcium, the amlodipine, the filler, the flow aid and the adhesive according to the formula amount, adding the mixed powder into a dry granulating machine for granulation, and screening granules between 18 meshes and 80 meshes to perform the next process; granulating the granules larger than 18 meshes by using a 18-mesh screen of a swing type granulator, granulating all the materials smaller than 80 meshes again, sieving the obtained granules by using a 18-mesh screen of the swing type granulator, and granulating the granules larger than 18 meshes by using a 18-mesh screen of the swing type granulator; mixing the dry-method granulated and granulated material with lubricant to prepare slow-release part of the medicine for standby;

(4) tabletting the prepared normal-release part medicine and the prepared slow-release part medicine in a double-layer tabletting machine;

(5) film coating process

Slowly adding the film coating premix into a 95% ethanol solution under the condition of stirring to prepare a suspension with the mass percentage of 10%; coating with a coating pan, and increasing weight by 1.0% to obtain the final product.

7. The method of claim 6, wherein: in the normal-release part of the medicine, the filler comprises 60 parts of microcrystalline cellulose 101 and 37.15 parts of 200-mesh lactose; the disintegrating agent is croscarmellose sodium, the adhesive is hydroxypropyl methylcellulose, and the lubricating agent is magnesium stearate;

in the slow-release part of the medicine, the filler is microcrystalline cellulose PH102, the adhesive is hydroxypropyl methyl cellulose, the glidant is silicon dioxide, and the lubricant is magnesium stearate.

Technical Field

The invention relates to the technical field of pharmacy, in particular to a medicament capable of treating hypertension and hyperlipidemia simultaneously, namely amlodipine atorvastatin calcium sustained-release tablets.

Background

Cardiovascular disease is one of the most common and serious diseases that endanger human health, especially the middle-aged and the elderly, and high blood pressure and dyslipidemia are important risk factors for atherosclerosis, coronary heart disease, and other cardiovascular and cerebrovascular diseases. Survey shows that hyperlipidemia of middle-aged and elderly people in China accounts for over 50 percent, and the total incidence rate of population is 7-8 percent. Of the hyperlipidemic patients, more than 80% fail to control blood lipids to the nationally recommended level, of which only less than half are receiving treatment with lipid lowering drugs. It is reported that 55% of patients with hypertension have hyperlipidemia, and 43% of patients with hyperlipidemia have hypertension. Therefore, the medicine for treating hypertension and hyperlipidemia simultaneously is developed, and has high social and economic significance.

The amlodipine Atorvastatin Calcium sustained release tablet contains two drug components with the leading market sales at present, namely amlodipine (Valsartan) for treating hypertension, congestive heart failure and post-myocardial infarction and Atorvastatin Calcium (Atorvastatin Calcium) for reducing blood fat. The chemical names of the L-valine are respectively N-valeryl-N- [ [2' - (1H-tetrazole-5-yl) biphenyl-4-yl ] methyl ] -L-valine and 7- [2- (4-fluorophenyl) -3-phenyl-4- (anilino formyl) -5- (-2 propyl) pyrrole-1-yl ] -3, 5-dihydroxy calcium heptoate. The chemical structural formula is as follows:

amlodipine is an angiotensin II receptor antagonist antihypertensive drug, and the drug has the effects of blocking the type I (AT1) receptor of angiotensin II, increasing the blood plasma level of angiotensin II, stimulating the unblocked AT2 receptor and simultaneously countering the AT1 receptor, thereby achieving the effects of dilating blood vessels and reducing blood pressure. Amlodipine is a drug used in the united states for the treatment of hypertension, congestive heart failure, post-myocardial infarction. The levamlodipine developed and produced by Ciba-Jiaji of Switzerland acquired the related patent rights in the United states and Europe respectively in 1995 and 1996, and was first marketed in Germany in 7 months in 1996, and thereafter was marketed in Europe, the United states and Japan in succession. Ciba-Geigy incorporated Nowa with Shande Shi in 1996. Amlodipine has the characteristics of lasting and stable blood pressure reducing effect and small toxic and side effect.

Atorvastatin calcium tablets are used for treating hypercholesterolemia patients with primary hypercholesterolemia. Including patients with familial hypercholesterolemia (hetero type) or combined hyperlipidemia (type IIa and IIb corresponding to Fredrickson's classification), use of the product can treat elevated Total Cholesterol (TC), elevated low density lipoprotein cholesterol (LDL-C), elevated apolipoprotein B (apo B) and elevated Triglycerides (TG) if the therapeutic effects of diet therapy and other non-drug therapies are not satisfactory. In homozygous familial hypercholesterolemia, atorvastatin can be used in combination with other lipid lowering therapies (such as LDL plasma dialysis) or alone (when no other treatment is available) to lower TC and LDL-C. Coronary heart disease or coronary heart disease (such as diabetes, symptomatic atherosclerosis disease, etc.) with hypercholesterolemia or mixed dyslipidemia, and the product is suitable for: reducing the risk of non-fatal myocardial infarction, reducing the risk of fatal and non-fatal stroke, reducing the risk of revascularization, reducing the risk of hospitalization due to congestive heart failure, and reducing the risk of angina pectoris. Lipitor (the english trade name is Lipitor, the common name is atorvastatin calcium tablets) is a lipid-lowering drug developed by the company pfeiri. Lipitor has real world use experience of nearly 20 years, is being used in 137 countries, and has efficacy and safety proven in over 400 clinical trials and 2.3 billion patients' annual clinical drug use experience. The consistency of a plurality of evidence-based evidences and clinical practices proves that the Lipitor 10-80mg can effectively reduce low-density lipoprotein cholesterol (LDL-C), and for patients with coronary heart disease, ischemic stroke, diabetes, hypertension and other cardiovascular diseases at high risk, the Lipitor is proved to reduce main cardiovascular disease events and has good safety.

The two medicines are used together, so that a good synergistic effect can be generated, the medicine taking of patients suffering from hypertension and hyperlipidemia is facilitated, and the medicine taking compliance of the patients can be improved. The amlodipine atorvastatin calcium sustained release tablet simultaneously contains two active components, has beautiful appearance, is convenient to take and is easy to master the dosage.

Disclosure of Invention

The invention can treat hypertension and hyperlipemia at the same time, and the normally released part of the medicine is released quickly in vivo, so the effect is fast; the sustained-release part of the drug is slowly released, and the effect of stable effective blood concentration is continuously maintained.

In order to solve the problems in the prior art, the invention adopts the following scheme to solve, and the amlodipine atorvastatin calcium sustained-release tablet comprises a normally-released part medicament and a sustained-released part medicament, and comprises the following components in percentage by weight:

the normal-release part of the medicine components and the content

The content of each component of the slow-release part of the medicine is as follows:

further, as a preferred scheme of the invention, the components and contents are as follows:

the normal-release part of the medicine components and the content

Sustained release of partial drug components and contents

The invention also discloses a preparation method of the amlodipine atorvastatin calcium sustained release tablet, which comprises the following steps:

(1) sieving the raw materials and the auxiliary materials with a 80-mesh sieve respectively for later use;

(2) preparation process of normally-released partial medicine

Uniformly mixing atorvastatin calcium, amlodipine, a filling agent and a disintegrating agent, adding a purified water solution of an adhesive to prepare a soft material, and sieving with a 18-mesh sieve for granulation; drying at 80 deg.C, sieving with 18 mesh sieve, adding lubricant, and mixing to obtain normal-release part;

(3) process for preparing slow-releasing medicine

Uniformly mixing the atorvastatin calcium, the amlodipine, the filler, the flow aid and the adhesive according to the formula amount, adding the mixed powder into a dry granulating machine for granulation, and screening granules between 18 meshes and 80 meshes to perform the next process; granulating the granules larger than 18 meshes by using a 18-mesh screen of a swing type granulator, granulating all the materials smaller than 80 meshes again, sieving the obtained granules by using a 18-mesh screen of the swing type granulator, and granulating the granules larger than 18 meshes by using a 18-mesh screen of the swing type granulator; mixing the dry-method granulated and granulated material with lubricant to prepare slow-release part of the medicine for standby;

(4) tabletting the prepared normal-release part medicine and the prepared slow-release part medicine in a double-layer tabletting machine;

(5) film coating process

Slowly adding the film coating premix into a 95% ethanol solution under the condition of stirring to prepare a suspension with the mass percentage of 10%; coating with a coating pan, and increasing weight by 1.0% to obtain the final product.

The atorvastatin calcium and amlodipine are combined for use, so that a good synergistic effect can be generated, the medicine taking of patients suffering from hypertension and hyperlipidemia is facilitated, and the medicine taking compliance of the patients can be improved. The dissolution curve of the multi-batch sustained release tablets prepared by the preparation method has no obvious change under high humidity condition, and the dissolution release is uniform, which shows that the dissolution stability of the sample is good, and the dosage is easy to master; the components in the medicine are stable under high temperature and high humidity (60 + -2 deg.C, RH75 + -5%).

Detailed Description