WO2013007092A1

WO2013007092A1 - Medicament for treatment of coronary heart diseases and angina pectoris and preparation method therefor

Info

Publication number: WO2013007092A1
Application number: PCT/CN2011/084983
Authority: WO
Inventors: 胡小虎; 葛小侠
Original assignee: 西安千禾药业有限责任公司
Priority date: 2011-07-13
Filing date: 2011-12-30
Publication date: 2013-01-17
Also published as: CN102872227A; CN102872227B

Abstract

A medicament for treatment of coronary heart diseases and angina pectoris and a preparation method thereof. The medicament comprises the following raw materials of the following weight parts or consists of the following raw materials of the following weight parts: puerariae radix flavones: 4 to 60 parts, hawthorn extract: 1 to 30 parts, gypenosides: 0.4 to 10 parts, soybean oil or salad oil: 5 to 100 parts, beeswax: 0.1 to 3 parts, hydrogenated palm oil: 0.4 to 10 parts, soybean lecithin: 0.2 to 5 parts, dimethicone: 0.01 to 0.5 parts, gelatin: 8 to 150 parts, glycerin: 3 to 80 parts, purified water: 8 to 150 parts, and ethylparaben: 0.01 to 0.8 parts.

Description

Medicine for treating coronary heart disease angina pectoris and preparation method thereof

The invention belongs to the field of traditional Chinese medicine, and particularly relates to a medicine for treating coronary heart disease angina pectoris and preparation method thereof

Coronary heart disease is caused by coronary atherosclerosis coronary vascular stenosis, resulting in myocardial blood supply disorders, due to long myocardial ischemia and hypoxia, it will inevitably lead to cardiomyocyte degeneration, atrophy, myocardial damage, and can lead to heart failure after severe disease progression Wait, directly endangering human life. With the improvement of people's living standards, the incidence and mortality of coronary heart disease in China have also increased year by year, and there is a trend of younger patients. Angina pectoris is the most common symptom of coronary heart disease. Currently, the drugs used to treat coronary heart disease angina pectoris include nitrate preparations, beta blockers, and calcium channel blockers. Although these drugs can alleviate or reduce the onset of angina pectoris, Can not completely solve the problem of coronary artery stenosis and the disease atherosclerosis.

The Chinese patent ZL03134404.6 entitled "A drug for treating coronary heart disease and angina pectoris and a preparation method thereof" discloses a drug for treating coronary heart disease and angina pectoris, and the therapeutic effect of the drug is less breakthrough, and the raw material of Pueraria total The preparation method of flavonoids is complicated and the production cycle is long. Summary of the invention

In order to overcome the shortcomings of the prior art, according to the basic theory of traditional Chinese medicine combined with the progress of modern phytochemistry and pharmacology research of traditional Chinese medicine, the preparation process of total flavonoids of Pueraria lobata was improved, and the preparation parameters of hawthorn extract were adjusted to make the medicine truly The clinical application value can be fully exerted.

Accordingly, the object of the present invention is to provide a medicament for treating coronary heart disease angina pectoris and a preparation method thereof, which are simple in process and low in cost, and the prepared medicament has remarkable curative effect and no toxic side effects.

The object of the present invention is achieved by the following technical solutions:

In one aspect, the invention provides a medicament for treating angina pectoris of coronary heart disease, the medicament comprising the following parts by weight of the raw material or consisting of the following raw materials by weight:

4~60 parts of total flavonoids, 1~30 parts of hawthorn extract, 0.4~10 parts of Gynostemma pentaphyllum, 5~100 parts of soybean oil or salad oil, 0.1~3 parts of beeswax, 0.4~10 parts of hydrogenated palm oil, soybean phospholipid 0.2~5 parts, 0.01~0.5 parts of disilicone oil, 8~150 parts of gelatin, 3~80 parts of glycerin, 8~150 parts of purified water and 0.01~0.8 parts of hydroxyphenylethyl ester;

Wherein, the total flavonoids of pueraria are prepared by the following method: Take Pueraria lobata, crush into coarse powder, infiltrate with ethanol solution with 60%~80% volume by volume for 1 hour, then extract twice by reflux, use 6~10 times of solvent per time, and reflux 1~3 each time. In the hour, the two extracts were combined, filtered, concentrated under reduced pressure to a relative density of 1.15 - 1.25 at 60 ° C, spray dried, or concentrated under reduced pressure until the relative density was 1.25 ° at 60 ° C. The extract of 1.35 is vacuum dried and pulverized through an 80 mesh sieve.

The hawthorn extract is prepared by the following method:

Take the hawthorn slices and extract twice with an aqueous solution of 60-80% by volume of ethanol. Add the solvent weight 6~10 times for the first time, and add 4~8 times the solvent weight for the second time. After flowing for 1~3 hours, the two extracts were combined, filtered, concentrated under reduced pressure to an extract having a relative density of 1.15 to 1.20 at 60 ° C, spray dried, or concentrated under reduced pressure to a relative density of 60 ° C. After measuring the 1.25 ~ 1.35 extract, vacuum drying, smashing through 80 mesh sieve, that is.

In the medicament of the present invention, the total glycosides of Gynostemma pentaphyllum are in accordance with the standards of the Ministry of Health, and the standard number is

WS ₃ -Z-006-93 (Z) to prepare.

Preferably, the medicament for treating coronary heart disease angina pectoris has the following parts: 20 parts of total flavonoids of puerarin, 6 parts of hawthorn extract, 2 parts of total glucosides of Gynostemma pentaphyllum, 25.4 parts of soybean oil or salad oil, 0.6 parts of beeswax 3 parts of hydrogenated palm oil, 1 part of soybean phospholipid, 0.05 part of disilicone oil, 40 parts of gelatin, 16 parts of glycerin, 40 parts of purified water and 0.08 parts of hydroxyphenylethyl ester.

The raw material of the hawthorn extract used in the above-mentioned medicine of the present invention is mainly a total flavonoid compound of hawthorn, mainly quercetin, vitexin, hyperoside, epicatechin, etc., having hypolipidemicemia, increasing coronary flow, Strong heart, blood pressure and other effects; Pueraria total flavonoids mainly contain daidzin, daidzein, puerarin, genistein, etc., have increased coronary blood flow, significant relaxation of vascular smooth muscle, reduce myocardial oxygen utilization and myocardial Oxygen consumption, anti-arrhythmia, improvement of peripheral circulation, hypoglycemia, blood lipids, blood pressure, etc.; Gynostemma saponins main components are Gynostemma saponins (Gyp) III, IV, sputum, sputum, and ginsenoside (Gin) -Rb^Rb^-Rd is exactly the same as -F ₂ , and ginsenoside Rd ₃ , K is isolated, and the rest are ginsenoside analogues, which have anti-aging, antihypertensive, hypolipidemic, hypoglycemic and the like effects. The above three flavor extracts are combined to exert a synergistic effect, and have a triple effect of expanding crown, reducing blood pressure, and lowering blood fat, and satisfying the treatment of coronary heart disease and angina pectoris according to the standard of TCM and blood stasis.

In another aspect, the present invention provides a method for preparing the above-mentioned medicine for treating coronary heart disease angina pectoris, the preparation method comprising the following steps:

(a) Preparation of the glue: First, dissolve the gelatin with an appropriate amount of purified water, inhale and swell, and place the glycerin, the remaining purified water, and the hydroxyphenylethyl ester in a plastic jar, heat to 70-80 ° C, and mix well. Add the expanded gelatin, stir it, melt it into a uniform gelatin, open the vacuum system of the sol tank, remove the bubbles in the gelatin solution, and dilute the water in the gelatin solution while heating until the viscosity is 28000~32000 mTorr. Put it in a stable rubber tank for heat preservation, spare;

(b) adding quantitative beeswax, hydrogenated palm oil to soybean oil or salad oil, and heating to 70-80 °C, the above two substances are completely dissolved in soybean oil or salad oil, cooled to 30~35 °C, added soybean phospholipid, fully stirred to make it uniform;

(c) Gradually add Gynostemma pentaphyllum, Hawthorn extract, Pueraria flavonoid powder, stir well, mix it, and grind it twice, add disilicone oil, let stand, vacuum, wait for bubbles in the liquid Basic removal

(d) using the glue obtained in the step (a) and the liquid solution obtained in the step (c) by using a pressing method, the thickness of the rubber is controlled to be 0.85 to 0.95 mm, and 580 mg per capsule is obtained;

Wherein, the total flavonoids of pueraria are prepared by the following method:

Take Pueraria lobata, crush into coarse powder, infiltrate with ethanol solution with 60%~80% volume by volume for 1 hour, then extract twice by reflux, use 6~10 times of solvent per time, and reflux 1~3 each time. In the hour, the two extracts were combined, filtered, concentrated under reduced pressure to a relative density of 1.15 - 1.25 at 60 ° C, spray dried, or concentrated under reduced pressure until the relative density was 1.25 ° at 60 ° C. The extract of 1.35 is vacuum dried and pulverized through an 80 mesh sieve.

Wherein, the hawthorn extract is prepared by the following method:

The above preparation method of the invention has the advantages of single controllable, short production cycle and low cost; the prepared product has exact curative effect, safe and non-toxic side effects, stable quality, convenient storage, and is more conducive to clinical application and application of the product, and has significant clinical significance. The economic significance of treatment.

In a specific embodiment of the invention, the method of preparing a medicament for treating coronary heart disease angina is as follows:

(1) Preparation of total flavonoids from Pueraria

Take Pueraria lobata, crush into coarse powder, infiltrate with 60%-80% ethanol aqueous solution for 1 hour, then reflux and extract twice, each time using the drug weight 6~10 times solvent, each reflux for 1-3 hours. Combine the two extracts, filter, concentrate under reduced pressure to a relative density of 1.15 ~ 1.25 (60 °C thermal measurement) extract, spray dry, or concentrate under reduced pressure to a relative density of 1.25 ~ 1.35 (60 °C thermal test) After the extract is vacuum dried and pulverized through an 80 mesh sieve, the total flavonoids of Pueraria lobata are obtained;

(2) Preparation of hawthorn extract:

Take the hawthorn slices and extract twice with 60%-80% ethanol aqueous solution. Add the solvent weight 6~10 times for the first time, add the drug weight 4~8 times the solvent for the second time, and return each time. After 1-3 hours, the two extracts were combined, filtered, concentrated under reduced pressure to an extract having a relative density of 1.15 to 1.20 (60 °C heat), spray dried, or concentrated under reduced pressure to a relative density of 1.25 to 1.35 ( 60 ° C thermal test) After the extract is vacuum dried and pulverized through an 80 mesh sieve, the hawthorn extract is obtained;

(3) Preparation of drugs for treating coronary heart disease with angina pectoris

(a) Preparation of the glue: First, dissolve the gelatin with an appropriate amount of purified water, inhale and swell, and place the glycerin, the remaining purified water, and the hydroxyphenylethyl ester in a plastic jar, heat to 70-80 ° C, and mix well. Add the expanded gelatin, stir it, melt it into a uniform gelatin, open the vacuum system of the sol tank, remove the bubbles in the gelatin solution, and dilute the water in the gelatin solution while heating until the viscosity is 28000~32000 mpo. Put it in a stable rubber tank for heat preservation, spare;

(b) adding quantitative beeswax and hydrogenated palm oil to soybean oil or salad oil, heating to 70-80 ° C, so that the above two substances are completely dissolved in soybean oil or salad oil, cooled to 30-35 ° C, added Soy lecithin, stir well to make it uniform;

(C) Gradually add Gynostemma pentaphyllum, Hawthorn extract, Pueraria total flavonoid powder, stir well, mix well, pass the colloid mill 2 times, add disilicone oil, let stand, vacuum, wait for the bubble in the liquid Remove

U) The glue obtained in the step (a) and the liquid solution obtained in the step (c) are pelletized by a pressing method, and the thickness of the rubber is controlled to be 0.85 to 0.95 mm, and 580 mg per pellet is obtained.

In the above preparation method, the Gynostemma total glycosides are in accordance with the standards of the Ministry of Health, and the standard number is

WS ₃ -Z-006-93 (Z) to prepare.

In still another aspect, the present invention also provides a method of treating coronary heart disease angina pectoris using the above medicament. Compared with the prior art, the present invention has at least the following beneficial effects:

The pueraria total flavonoid raw material in the medicament of the invention adopts the reflux method instead of the percolation method in preparation, the time is short, the pollution is small, the solvent consumption is small, the solvent can be recycled; and the experiment proves that compared with the prior art ZL03134404.6, The medicament of the invention has more outstanding effects in treating coronary heart disease and angina pectoris without any side effects.

In summary, the present invention has been subjected to a large number of experimental studies to compile the raw material extraction and preparation process, and at the same time enrich the active ingredients to a greater extent, thereby improving the bioavailability of the drug. The best way to implement the invention

The invention is illustrated by the following examples, which are intended to be illustrative of the invention and are not intended to limit the scope of the invention. Example 1

A proprietary Chinese medicine for treating coronary heart disease angina pectoris, the raw material weight components are: 4 parts of pueraria total flavonoids, 1 part of hawthorn extract, 0.4 parts of Gynostemma pentaphyllum, 5 parts of soybean oil, 0.1 part of beeswax, 0.4 Parts of hydrogenated palm oil, 0.2 parts of soybean phospholipid, 0.01 part of disilicone oil, 8 parts of gelatin, 3 parts of glycerin, 8 parts of purified water and 0.01 parts of hydroxyphenylethyl ester. The preparation method of the Chinese patent medicine comprises the following steps:

(1) Preparation of total flavonoids from Pueraria lobata:

Take Pueraria lobata, crush into coarse powder, infiltrate with 60% aqueous solution of ethanol for 1 hour, then extract twice by reflux, each time with 8 times the solvent weight of the drug, reflux for 2 hours each time, combine the two extracts, Filtered, concentrated under reduced pressure to a relative density of 1.16 (60 ° C thermal measurement) extract, spray dried, smashed through 80 mesh sieve, that is, the total flavonoids of Pueraria lobata;

(2) Preparation of hawthorn extract:

Take the hawthorn slices and extract twice with 80% ethanol solution by volume. Add the solvent of 6 times the weight of the drug for the first time, add the solvent of 4 times the weight of the drug for the second time, reflux for 2 hours each time, and combine twice. The extract is filtered, concentrated under reduced pressure to an extract having a relative density of 1.16 (60 ° C thermal measurement), spray dried, and pulverized through an 80 mesh sieve to obtain a hawthorn extract;

(3) Preparation of proprietary Chinese medicines:

(a) Preparation of the glue: First, dissolve the gelatin with an appropriate amount of purified water, inhale and swell, and place the glycerin, the remaining purified water, and the hydroxyphenylethyl ester in a plastic jar, heat to 70 ° C, mix well, add Expanded gelatin, stir, melt it into a uniform gelatin, open the vacuum system of the sol tank, remove the bubbles in the gelatin solution, and dilute the water in the gelatin solution while heating until the viscosity is 29000 mA, put the stabilizer Keep warm in the bucket, spare;

(b) adding quantitative beeswax and hydrogenated palm oil to soybean oil, heating to 70 ° C, completely dissolving the above two substances in soybean oil, cooling to 33 ° C, adding soybean phospholipid, stirring well to make it uniform;

(c) Gradually add Gynostemma pentaphyllum, Hawthorn extract, Pueraria flavonoid powder, stir well, mix well, pass the colloid mill 2 times, add disilicone oil, let stand, vacuum, wait for the bubble in the liquid Remove

U) The glue obtained in the step (a) and the liquid solution obtained in the step (c) are pelletized by a pressing method, and the thickness of the rubber is controlled to be 0.86 mm, and 580 mg per pellet is obtained. Example 2

A Chinese patent medicine for treating coronary heart disease and angina pectoris, the raw material weight composition thereof is: 6 parts of total flavonoids of pueraria, 2 parts of hawthorn extract, 0.7 parts of total glycosides of gynostemma, 9 parts of salad oil, 0.2 parts of beeswax, 0.6 parts of hydrogenated palm oil, 0.4 parts of soybean phospholipid, 0.02 parts of disilicone oil, 12 parts of gelatin, 5 parts of glycerin, 10 parts of purified water and 0.02 parts of hydroxyphenylethyl ester.

The preparation method of the Chinese patent medicine comprises the following steps:

(1) Preparation of total flavonoids from Pueraria lobata:

Take Pueraria lobata, crush into coarse powder, infiltrate with a 65% by volume aqueous solution of ethanol for 1 hour, then extract twice by reflux, each time with a drug weight of 6 times the amount of solvent, each reflux for 1.5 hours, combine two The second extract, filtered, concentrated under reduced pressure to a relative density of 1.28 (60 ° C thermal measurement) extract, vacuum dried, smashed through 80 mesh sieve, that is, the total flavonoids of Pueraria lobata;

(2) Preparation of hawthorn extract:

Take the hawthorn slices and extract twice with a 75% by volume aqueous solution of ethanol. Add the solvent of 7 times the amount of the drug for the first time, add the solvent of 6 times the weight of the drug for the second time, reflux for 2.5 hours each time, and combine twice. The extract is filtered, concentrated under reduced pressure to a relative density of 1.25 (60 ° C thermal measurement), vacuum dried, and pulverized through a 80 mesh sieve to obtain a hawthorn extract;

(3) Preparation of proprietary Chinese medicines:

(a) Preparation of the glue: First, dissolve the gelatin with an appropriate amount of purified water, inhale and swell, and place the glycerin, the remaining purified water, and the hydroxyphenylethyl ester in a plastic jar, heat to 73 ° C, mix well, and add Expanded gelatin, stir, melt it into a uniform gelatin, open the vacuum system of the sol tank, remove the bubbles in the gelatin solution, and dilute the water in the gelatin solution while heating until the viscosity is 30000 mPa, put the stabilizer Keep warm in the bucket, spare;

(b) adding a certain amount of beeswax and hydrogenated palm oil to the salad oil, heating to 76 ° C, completely dissolving the above two substances in the salad oil, cooling to 32 ° C, adding soybean phospholipid, stirring well to make it uniform;

(d) using the glue obtained in the step (a) and the liquid obtained in the step (c) by a pressing method, the thickness of the rubber is controlled at 0.90 mm, and 580 mg per tablet is obtained. Example 3

A proprietary Chinese medicine for treating coronary heart disease and angina pectoris, the raw material weight components are: 10 parts of total flavonoids of pueraria, 3 parts of hawthorn extract, 1 part of Gynostemma pentaphyllum, 14 parts of soybean oil, 0.3 parts of beeswax, 1 part of hydrogenated palm oil, 0.6 part of soybean phospholipid, 0.03 part of disilicone oil, 25 parts of gelatin, 8 parts of glycerin, 20 parts of purified water and 0.04 parts of hydroxyphenylethyl ester.

(1) Preparation of total flavonoids from Pueraria lobata:

Take Pueraria lobata, crush into coarse powder, infiltrate with a 75% by volume aqueous solution of ethanol for 1 hour, then extract twice by reflux, each time using a solvent weight of 7 times the amount of solvent, each reflux for 2.5 hours, and combine the two extracts. Filtered, concentrated under reduced pressure to a relative density of 1.25 (60 ° C thermal measurement) extract, spray dried, smashed through a 80 mesh sieve, that is, the total flavonoids of Pueraria lobata;

(2) Preparation of hawthorn extract:

Take the hawthorn slices and extract twice with 60% ethanol solution by volume. Add the first time. The weight of the drug is 9 times the amount of solvent, the second time plus the drug weight 5 times the amount of solvent, each reflux for 1.5 hours, the two extracts are combined, filtered, concentrated under reduced pressure to a relative density of 1.18 (60 ° C thermal measurement) dip After the paste is spray-dried and pulverized through an 80 mesh sieve to obtain a hawthorn extract;

(3) Preparation of proprietary Chinese medicines

(a) Preparation of the glue: First, dissolve the gelatin with an appropriate amount of purified water, inhale and swell, and place the glycerin, the remaining purified water, and the hydroxyphenylethyl ester in a plastic jar, heat to 77 ° C, mix well, and add Expanded gelatin, stir, melt it into a uniform gelatin, open the vacuum system of the sol tank, remove the bubbles in the gelatin solution, and dilute the water in the gelatin solution while heating until the viscosity is 28000 mPa, put the stabilizer Keep warm in the bucket, spare;

(b) adding quantitative beeswax and hydrogenated palm oil to soybean oil, heating to 74 ° C, completely dissolving the above two substances in soybean oil, cooling to 34 ° C, adding soybean phospholipid, stirring well to make it uniform;

U) The glue obtained in the step (a) and the liquid solution obtained in the step (c) are pelletized by a pressing method, and the thickness of the rubber is controlled to be 0.92 mm, and 580 mg per pellet is obtained. Example 4

A Chinese patent medicine for treating coronary heart disease and angina pectoris, the raw material weight components are: 15 parts of total flavonoids of pueraria, 4 parts of hawthorn extract, 1.5 parts of total glycosides of Gynostemma pentaphyllum, 20 parts of salad oil, 0.5 parts of beeswax, 1.5 parts of hydrogenated palm oil, 0.8 parts of soybean phospholipid, 0.04 parts of disilicone oil, 30 parts of gelatin, 12 parts of glycerin, 30 parts of purified water, and 0.06 parts of hydroxyphenylethyl ester.

(1) Preparation of total flavonoids from Pueraria lobata:

Take Pueraria lobata, crush into coarse powder, infiltrate with 80% aqueous solution of ethanol for 1 hour, then extract twice by reflux, each time with 9 times the solvent weight of the drug, reflux for 3 hours each time, combine the two extracts, Filtration, concentration under reduced pressure to a relative density of 1.32 (60 ° C thermal measurement) extract, vacuum drying, smashed through 80 mesh sieve, that is, the total flavonoids of Pueraria lobata;

(2) Preparation of hawthorn extract:

Take the hawthorn slices and extract them twice with a 65% by volume aqueous solution of ethanol. Add the solvent by 10 times the amount of the first time, add the solvent of 7 times the weight of the drug for the second time, reflux for 1 hour each time, and combine twice. The extract is filtered, concentrated under reduced pressure to a relative density of 1.32 (60 ° C thermal measurement), vacuum dried, and pulverized through a 80 mesh sieve to obtain hawthorn extract;

(3) Preparation of proprietary Chinese medicines (a) Preparation of the glue: First, dissolve the gelatin with an appropriate amount of purified water, inhale and swell, and place the glycerin, the remaining purified water, and the hydroxyphenylethyl ester in a plastic jar, heat to 78 ° C, mix well, and add Expanded gelatin, stir, melt it into a uniform gelatin, open the vacuum system of the sol tank, remove the bubbles in the gelatin solution, and dilute the water in the gelatin solution while heating until the viscosity is 30000 mPa, put the stabilizer Keep warm in the bucket, spare;

(b) adding a certain amount of beeswax and hydrogenated palm oil to the salad oil, heating to 73 ° C, completely dissolving the above two substances in the salad oil, cooling to 35 ° C, adding soybean phospholipid, stirring well, and making it uniform;

(c) Gradually add Gynostemma totalin, Hawthorn extract, Pueraria total flavonoid powder, stir well, mix well, pass the colloid mill 2 times, add disilicone oil, let stand, vacuum, wait for the bubble in the liquid Remove, spare,

U) The glue obtained in the step (a) and the liquid solution obtained in the step (c) are pelletized by a pressing method, and the thickness of the rubber is controlled to be 0.86 mm, and 580 mg per pellet is obtained. Example 5

A proprietary Chinese medicine for treating coronary heart disease and angina pectoris, the raw material weight components are: 20 parts of total flavonoids of pueraria, 6 parts of hawthorn extract, 2 parts of total glycosides of Gynostemma pentaphyllum, 25.4 parts of soybean oil, 0.6 parts of beeswax, 3 parts of hydrogenated palm oil, 1 part of soybean phospholipid, 0.05 part of disilicone oil, 40 parts of gelatin, 16 parts of glycerin, 40 parts of purified water and 0.08 parts of hydroxyphenylethyl ester.

(1) Preparation of total flavonoids from Pueraria lobata:

Take Pueraria lobata, crush into coarse powder, infiltrate with 70% aqueous solution of ethanol for 1 hour, then extract twice by reflux, each time with 8 times the solvent weight of the drug, reflux for 1 hour each time, combine the two extracts, Filtration, concentration under reduced pressure to a relative density of 1.20 (60 ° C thermal measurement), spray drying, smashed through 80 mesh sieve, that is, the total flavonoids of Pueraria lobata;

(2) Preparation of hawthorn extract:

Take the hawthorn slices and extract twice with 70% ethanol solution by volume. Add the solvent weight 8 times for the first time, add the solvent weight 6 times for the second time, reflux for 2 hours each time, combine twice. The extract is filtered, concentrated under reduced pressure to an extract having a relative density of 1.18 (60 ° C thermal measurement), spray dried, and pulverized through an 80 mesh sieve to obtain a hawthorn extract;

(3) Preparation of proprietary Chinese medicines

(a) Preparation of the glue: First, dissolve the gelatin with an appropriate amount of purified water, inhale and swell, and place the glycerin, the remaining purified water, and the hydroxyphenylethyl ester in a plastic jar, heat to 70 ° C, mix well, and add Expanded gelatin, stir, melt it into a uniform gelatin, open the vacuum system of the sol tank, remove the bubbles in the gelatin solution, and dilute the water in the gelatin solution while heating until the viscosity is 29000 Within a millipoise, put it in a stable rubber tank to keep it warm;

(b) adding a certain amount of beeswax and hydrogenated palm oil to the soybean oil, heating to 75 ° C, completely dissolving the above two substances in soybean oil, cooling to 32 ° C, adding soybean phospholipid, stirring well, and making it uniform;

(c) Gradually add Gynostemma totalin, Hawthorn extract, Pueraria total flavonoid powder, stir well, mix well, pass the colloid mill 2 times, add disilicone oil, let stand, vacuum, wait for the bubble in the liquid Remove

U) The glue obtained in the step (a) and the liquid solution obtained in the step (c) are pelletized by a pressing method, and the thickness of the rubber is controlled to be 0.88 mm, and 580 mg per pellet is obtained. Example 6

A Chinese patent medicine for treating coronary heart disease and angina pectoris, the raw material weight composition thereof is: 30 parts of total flavonoids of pueraria, 10 parts of hawthorn extract, 4 parts of total glycosides of Gynostemma pentaphyllum, 40 parts of salad oil, 1 part of beeswax, 4.5 parts of hydrogenated palm oil, 2 parts of soybean phospholipid, 0.1 part of disilicone oil, 70 parts of gelatin, 25 parts of glycerin, 80 parts of purified water and 0.15 parts of hydroxyphenylethyl ester.

(1) Preparation of total flavonoids from Pueraria lobata:

Take the Pueraria lobata, crush into a coarse powder, infiltrate with a 75% by volume aqueous solution of ethanol for 1 hour, then extract twice by reflux, each time using a solvent of 6 times the weight of the drug, refluxing for 1 hour each time, combining the two extracts, Filtration, concentration under reduced pressure to a relative density of 1.35 (60 ° C thermal measurement), vacuum drying, smashed through 80 mesh sieve, that is, the total flavonoids of Pueraria lobata,

(2) Preparation of hawthorn extract:

Take the hawthorn slices and extract twice with a 75% by volume aqueous solution of ethanol. Add the solvent with 9 times the weight of the drug for the first time, add the solvent with 8 times the weight of the drug for the second time, reflux for 2.5 hours each time, and combine twice. The extract is filtered, concentrated under reduced pressure to a relative density of 1.25 (60 ° C thermal measurement), vacuum dried, and pulverized through a 80 mesh sieve to obtain hawthorn extract;

(3) Preparation of proprietary Chinese medicines

(a) Preparation of the glue: First, dissolve the gelatin with an appropriate amount of purified water, inhale and swell, and place the glycerin, the remaining purified water, and the hydroxyphenylethyl ester in a plastic jar, heat to 80 ° C, mix well, and add Expanded gelatin, stir, melt it into a uniform gelatin, open the vacuum system of the sol tank, remove the bubbles in the gelatin solution, and dilute the water in the gelatin solution while heating, until the viscosity is 32000 mPa, put the stabilizer Insulation in the bucket, spare,

(b) adding a certain amount of beeswax and hydrogenated palm oil to the salad oil, heating to 76 ° C, completely dissolving the above two substances in the salad oil, cooling to 33 ° C, adding soybean phospholipid, stirring well, and making it uniform, (C) Gradually add Gynostemma pentaphyllum, Hawthorn extract, Pueraria total flavonoid powder, stir well, mix well, pass the colloid mill 2 times, add disilicone oil, let stand, vacuum, wait for the bubble in the liquid Remove, spare,

U) The glue obtained in the step (a) and the liquid solution obtained in the step (c) are pelletized by a pressing method, and the thickness of the rubber is controlled to be 0.86 mm, and 580 mg per pellet is obtained. Example 7

A Chinese patent medicine for treating coronary heart disease and angina pectoris, the raw material weight composition thereof is: 40 parts of total flavonoids of pueraria, 18 parts of hawthorn extract, 6 parts of total glycosides of Gynostemma pentaphyllum, 60 parts of soybean oil, 1.5 parts of beeswax, 6 parts of hydrogenated palm oil, 3 parts of soybean phospholipid, 0.2 part of disilicone oil, 90 parts of gelatin, 40 parts of glycerin, 100 parts of purified water and 0.3 parts of hydroxyphenylethyl ester.

(1) Preparation of total flavonoids from Pueraria lobata:

Take Pueraria lobata, crush into coarse powder, infiltrate with 80% aqueous solution of ethanol for 1 hour, then extract twice by reflux, each time with the drug weight 7 times the amount of solvent, each reflux for 1.5 hours, combine the two extracts, Filtered, concentrated under reduced pressure to a relative density of 1.25 (60 ° C thermal measurement) extract, spray dried, smashed through a 80 mesh sieve, that is, the total flavonoids of Pueraria lobata;

(2) Preparation of hawthorn extract:

Take the hawthorn slices and extract twice with 80% ethanol solution by volume. Add the solvent with 6 times the weight of the drug for the first time, add the solvent of 7 times the weight of the drug for the second time, reflux for 1.5 hours each time, and combine twice. The extract is filtered, concentrated under reduced pressure to an extract having a relative density of 1.16 (60 ° C thermal measurement), spray dried, and pulverized through an 80 mesh sieve to obtain a hawthorn extract;

(3) Preparation of proprietary Chinese medicines

(a) Preparation of the glue: First, dissolve the gelatin with an appropriate amount of purified water, inhale and swell, and place the glycerin, the remaining purified water, and the hydroxyphenylethyl ester in a plastic jar, heat to 72 ° C, mix well, and add Expanded gelatin, stir, melt it into a uniform gelatin, open the vacuum system of the sol tank, remove the bubbles in the gelatin solution, and dilute the water in the gelatin solution while heating until the viscosity is 31000 mPa, put the stabilizer Keep warm in the bucket, spare;

(b) adding a certain amount of beeswax and hydrogenated palm oil to the soybean oil, heating to 72 ° C, completely dissolving the above two substances in soybean oil, cooling to 35 ° C, adding soybean phospholipid, stirring well to make it uniform;

(d) using the glue obtained in the step (a) and the liquid obtained in the step (c) by a pressing method, The thickness of the rubber is controlled at 0.92mm, and 580mg per capsule is obtained. Example 8

A Chinese patent medicine for treating coronary heart disease and angina pectoris, the raw material weight composition thereof is: 50 parts of total flavonoids of pueraria, 24 parts of hawthorn extract, 8 parts of total glycosides of Gynostemma pentaphyllum, 80 parts of salad oil, 2.2 parts of beeswax, 8 parts of hydrogenated palm oil, 4 parts of soybean phospholipid, 0.3 parts of disilicone oil, 120 parts of gelatin, 60 parts of glycerin, 130 parts of purified water and 0.5 parts of hydroxyphenylethyl ester.

(1) Preparation of total flavonoids from Pueraria lobata:

Take the Pueraria lobata, crush into a coarse powder, infiltrate with a 60% aqueous solution of ethanol for 1 hour, and then extract twice by reflux, each time using a solvent of 9 times the weight of the drug, refluxing for 2.5 hours each time, combining the two extracts, Filtered, concentrated under reduced pressure to a relative density of 1.26 (60 ° C thermal measurement) extract, vacuum dried, smashed through 80 mesh sieve, that is, the total flavonoids of Pueraria lobata;

(2) Preparation of hawthorn extract:

Take the hawthorn slices and extract twice with 70% ethanol solution by volume. Add the solvent of 7 times the weight of the drug for the first time, add the solvent of 5 times the amount of the drug for the second time, reflux for 3 hours each time, and combine twice. The extract is filtered, concentrated under reduced pressure to a relative density of 1.28 (60 ° C thermal measurement), vacuum dried, and pulverized through a 80 mesh sieve to obtain a hawthorn extract;

(3) Preparation of proprietary Chinese medicines

(a) Preparation of the glue: First, dissolve the gelatin with an appropriate amount of purified water, inhale and swell, and place the glycerin, the remaining purified water, and the hydroxyphenylethyl ester in a plastic jar, heat to 75 ° C, mix well, and add Expanded gelatin, stir, melt it into a uniform gelatin, open the vacuum system of the sol tank, remove the bubbles in the gelatin solution, and dilute the water in the gelatin solution while heating until the viscosity is 28000 mPa, put the stabilizer Keep warm in the bucket, spare;

(b) adding a certain amount of beeswax and hydrogenated palm oil to the salad oil, heating to 78 ° C, completely dissolving the above two substances in the salad oil, cooling to 30 ° C, adding soybean phospholipid, stirring well to make it uniform;

U) The glue obtained in the step (a) and the liquid solution obtained in the step (c) are pelletized by a pressing method, and the thickness of the rubber is controlled to be 0.95 mm, and 580 mg per capsule is obtained. Example 9

A proprietary Chinese medicine for treating coronary heart disease and angina pectoris, the raw material weight component of which is: 60 parts of Ge Total flavonoids, 30 parts of hawthorn extract, 10 parts of Gynostemma pentaphyllum, 100 parts of soybean oil, 3 parts of beeswax, 10 parts of hydrogenated palm oil, 5 parts of soybean phospholipids, 0.5 parts of disilicone oil, 150 Parts of gelatin, 80 parts of glycerin, 150 parts of purified water, 0.8 parts of hydroxyethyl ester.

(1) Preparation of total flavonoids from Pueraria lobata:

Take Pueraria lobata, crush into coarse powder, infiltrate with a 65% by volume aqueous solution of ethanol for 1 hour, then extract twice by reflux, each time using a solvent weight of 10 times the amount of solvent, each reflux for 3 hours, and combine the two extracts. Filtration, concentration under reduced pressure to a relative density of 1.22 (60 ° C thermal measurement), spray drying, smash through 80 mesh sieve, that is, the total flavonoids of Pueraria lobata;

(2) Preparation of hawthorn extract:

Take the hawthorn slices and extract twice with 60% ethanol solution by volume. Add the solvent weight of the drug for 10 times for the first time, add the solvent of 6 times the weight of the drug for the second time, reflux for 1 hour each time, and combine twice. The extract is filtered, concentrated under reduced pressure to an extract having a relative density of 1.20 (60 ° C thermal measurement), spray dried, and pulverized through an 80 mesh sieve to obtain a hawthorn extract;

(3) Preparation of proprietary Chinese medicines

(a) Preparation of the glue: First, dissolve the gelatin with an appropriate amount of purified water, inhale and swell, and place the glycerin, the remaining purified water, and the hydroxyphenylethyl ester in a plastic jar, heat to 76 ° C, mix well, and add Expanded gelatin, stir, melt it into a uniform gelatin, open the vacuum system of the sol tank, remove the bubbles in the gelatin solution, and dilute the water in the gelatin solution while heating until the viscosity is 29000 mA, put the stabilizer Keep warm in the bucket, spare;

(b) adding a certain amount of beeswax and hydrogenated palm oil to the soybean oil, heating to 80 ° C, completely dissolving the above two substances in soybean oil, cooling to 32 ° C, adding soybean phospholipid, stirring well to make it uniform;

U) The glue obtained in the step (a) and the liquid solution obtained in the step (c) are pelletized by a pressing method, and the thickness of the rubber is controlled to be 0.94 mm, and 580 mg per pellet is obtained. The following examples further demonstrate the pharmaceutical effects of the present invention.

Example 10 The effect of the medicament of the present invention on acute myocardial ischemia induced by pituitrin in rats refers to Chen Qi et al., "Pharmacological Methodology of Traditional Chinese Medicine", People's Medical Publishing House, 1st edition, September 1993, by giving The drug prepared in the fifth embodiment of the present invention was administered by the method of the present invention. The drug of the present invention was observed to improve the myocardial ischemia by using the Glanxining soft capsule of the prior art ZL03134404.6 and the dispersible tablet of 200910024368.0. Test article Example 5 drug

The SD strain of the test animals weighed 180-220 g, half male and half female. Provided by the Experimental Animal Center of Xi'an Jiaotong University School of Medicine, Animal Quality Certificate No.: SYXK (Shaan) 2007-005.

Positive control drug Gelan Xinning soft gelatin, batch number: 20100525; Gelan Xinning dispersible tablets. Provided by Xi'an Qianhe Pharmaceutical Co., Ltd.

Blank Control Drug 0.9% Sodium Chloride Sterilization Injection Specification: 250 ml/bottle Physical Properties: Colorless Transparent Liquid Batch No.: 100121 National Pharmaceutical Standard H20023017 Xi'an Jingxi Shuanghe Pharmaceutical Co., Ltd.

Test room temperature 20 ~ 22 ° C Relative humidity: 60% - 70%

Test time October 6, 2010 ~ October 12

Method and result

Sixty rats were randomly divided into six groups, 10 in each group, half male and half female. Namely: blank control group (physiological saline lml/100g.d), Example 5 drug large, medium and small dose group (0.8g / kg.d, 0.4g / kg-d, 0.2g / kg-d), positive The drug control group (Glan Xinning soft capsule group 0.4g/kg.d, Gelan Xinning dispersible tablet 0.4g/kg.d). The rats in each group were intragastrically administered once a day for 7 days for 7 days. One hour after the last administration, rats were anesthetized with intraperitoneal injection of urethane lg / kg, fixed one by one, linked to chest lead II, and injected with pituitrin 0.5 u/kg (1 ml/kg). , in 10 seconds, the ECG-6511 electrocardiograph (experimental conditions: lmV=20mm paper speed 50mm/S, sensitivity 2, EMG open, HUM off), before and after injection of pituitary Two-lead ECG within 5 minutes (10, 20, 30, 45 seconds, 1, 3, 5 minutes). The myocardial ischemic negative rate and positive rate were recorded in rats. Positive myocardial ischemia occurs in the following testimony: ECG changes caused by vasopressin can be divided into two phases, phase I, injection of pituitary vasopressin for 5 ~ 30 seconds, J point increased above O.lmV; In the second phase, 30 seconds to 5 minutes after the injection, the T wave is low (less than 50% of the original T wave height), bidirectional, inverted or arrhythmia, and the heart rate is slowed down. It is judged to be positive for myocardial ischemia by one of the above-mentioned second-stage indications. The results are shown in Table 1 by X ² test.

Table 1 Effect on acute myocardial ischemia in rats (^士 s )

, number of rats, number of myocardial ischemia, myocardial ischemia (%)

(n) Negative positive number negative rate positive rate blank control group 10 2 8 20 80 high dose group 10 8 2 80 20** medium dose group 10 6 4 60 40 ** low dose group 10 5 5 50 50 * 葛兰Xinning Soft Gelatin Group 10 7 3 70 30** Gelan Xinning Dispersible Tablets 10 8 2 80 20** Note: Compared with the blank control group *P<0.05 ** P<0.01

The results showed that the improvement of acute myocardial ischemia in the large, medium and small doses of the drug of Example 5 was significantly different from that of the blank control group (P<0.05, PO.01). Prompt Example 5 The drug has an improved heart ischemia effect. Example 11 Effect of the Drug of the Invention on Coronary Flow of Isolated Rat Heart

By administering a drug solution of the drug prepared in Example 5 of the present invention to a rat, the prior art

ZL03134404.6's Gelan Xinning Softgel and 200910024368.0 Gelanxining Dispersible Tablets are used as a control to observe the effect of the drug of the present invention on improving coronary flow.

Test article Example 5 drug

The SD strain of the test animals weighed 180-220 g, half male and half female. Provided by the Experimental Animal Center of Xi'an Jiaotong University School of Medicine. Laboratory animal license number: SYXK (Shaan) 2007-005.

Blank Control Drug 0.9% Sodium Chloride Sterilization Injection Specification: 250 ml/bottle Physical Properties: Colorless Transparent Liquid Batch No.: 2010121 National Pharmaceutical Standard H20023017 Xi'an Jingxi Shuanghe Pharmaceutical Co., Ltd.

Test room temperature 20 ~ 22 ° C Relative humidity: 60% - 70%

Test time October 6, 2010 ~ October 12

Method and result

Sixty rats were randomly divided into 6 groups, namely: blank control group (normal saline lml/100g'd), and Example 5 drug large, medium and small dose groups (0.8 g/kg 'd, 0.4 g/kg). -d, 0.2g/kg-d), positive drug control group (Glan Xinning soft gelatin 0.4g/kg.d, Gelan Xinning dispersible tablet 0.4g/kg.d), each group was continuously intragastrically administered After 7 days of administration, after 60 minutes of the last administration, blood was taken and centrifuged at 3000 r/min for 20 minutes to separate the drug-containing serum, which was stored in a refrigerator at a low temperature and dissolved before use. Rat hearts were given 0.2 ml of drug-containing serum in each group. After Langendorf isolated heart perfusion method, after adjusting the constant temperature and constant pressure perfusion device, the rat brain was stunned with a wooden stick, the carotid artery was excised, the chest was opened, the heart was exposed, the happy bag was cut, and the aorta and other hearts were cut. Connected to the superior and inferior vena cava, pulmonary artery, pulmonary veins, place the heart in cold Colisec, gently squeeze the heart several times, discharge the remaining blood in the heart, quickly insert the aortic cannula into the aorta, ligature and fix, place In the constant temperature insulation, open the thermostatic oxygen-filled perfusate switch. The constant temperature Rockwell fluid enters the right atrium from the coronary heart, flows out from the end of the vena cava and pulmonary artery, and collects the effluent from the measuring cylinder. Clamp the apex with a frog heart clip, connect it to the two-channel physiological recorder through a tension transducer, stabilize for 15 minutes, then inject 0.2 ml of drug serum into the tee tube beside the cannula of the arterial cannula, first record The crown flow in the pre-dose, the crown flow at 1, 2, and 3 minutes after the drug was recorded, and the average value within 3 minutes after the drug was taken as the drug. After the measured value. After each administration of the drug, the heart is returned to normal, and then the second experiment is performed until the heart is no longer normal. For each drug, the perfusion device was washed 3 times with Rockwell's solution. After t test, the results are shown in Table 2.

Table 2 Effect on isolated coronary heart flow in rats (n=10)

Group dose coronary artery; quantity (m 1/min)

g /kg before the drug

Blank control group 7.35 ± 0.33 7.02 ± 0.28

High dose group 0.8 5.61士 1.14 6.54士 1.98 ** Medium dose group 0.4 5.22±0.38 6.461士 0.76** Low dose group 0.2 5.01±0.20 5.30士 0.30*

葛兰心宁软胶嚢 0.4 4.82士 0.60 5.70士 0.50*

葛兰心宁分散片组 0.4 4.93士 0.70 5.81士 0.65*

Note: compared with before and after self-administration *p<0.05, **p<0.01

The results showed that the large, medium and small doses of the drug in Example 5 significantly increased the coronary artery before administration (p<0.05, p<0.01). It is suggested that the large, medium and small doses of the drug of Example 5 have the effect of increasing the coronary flow rate; the drug of Example 5 is superior to the Glan Xinning soft capsule group and the Ge of the isolated heart in the same dose. Lan Xining disperses the film set. Example 12 Animal Acute Toxicity Test of the Drug of the Invention - J, Oral Administration of MTD Determination

Abstract: Example 5 The drug was administered intragastrically without LD50. The rats were intragastrically administered three times within 24 hours. The number of mice died within 7 days was observed, and the maximum tolerated dose of the mice was determined. The test results showed that the maximum tolerated dose of the drug of Example 5 for oral administration in mice was 20.6 g/kg'd, which was 355.2 times of the daily oral dose of clinical adults (the clinical adult daily oral dose was 3.48 g/ 60kg).

Test objective: To determine the acute toxicity and death of the drug of Example 5 after administration by a single administration of the drug.

Test time April 11, 2010 ~ April 20

1. Test materials

1.1 Test drug

Example 5 Drug, Example 5 The drug of Example 5 was slowly soaked with distilled water at 50 ° C until a solution of 48.26% (by weight) was obtained by a mouse gavage.

1.2 Test animals

Healthy ICR strains of mice, weighing 18 ~ 22g, male and female, were provided by the Experimental Animal Center of Xi'an Jiaotong University School of Medicine. Laboratory animal use license number: SYXK (Shaan) 2007-004.

2, test conditions Before and after administration, the experimental mice were divided into male and female, full-price pellet feed, free drinking water, room temperature

20 ° C ~ 25 ° C, laboratory relative humidity: 50% ~ 70%.

3. Test methods and results

3.1 Test 3 full method

Thirty mice, 10 in each group, divided into 3 groups, namely high, medium and low dose groups (0.4,

0.2, 0.1 ml/10 g) administered intragastrically 3 times/day, and the range of LD50 of the drug of Example 5 was predicted. The results showed that the LD50 could not be measured in the high measurement group, so the measurement of the LD50 of the drug in Example 5 was changed to the maximum concentration to the maximum tolerance in the maximum volume.

Thirty mice were taken, half male and half female. After 12 hours of fasting, the test article was given 3 times/day by the predicted 0.4 ml/10 g dose for 7 days.

3.2 Test results

The spontaneous activity of the mice decreased 24 hours after the administration of the test article, and the feeding and water intake decreased. On the second day, the spontaneous activity gradually became normal, and the abnormal mice activity, food intake, weight gain, and feces were not observed. The mice were all normal, and all the mice survived after the observation period.

After the observation period, all the mice were sacrificed and examined by naked eyes. No obvious pathological changes were found in the heart, liver, spleen, lung, kidney, testis/ovary, intestine and stomach of all important organs.

4, summary

Example 5 The maximum dose of the drug administered by gavage showed that: 30 mice had no obvious toxicity after administration, and there was no death within one week. Example 5 The maximum dose of mice administered by intragastric administration was 20.6 g / kg.d. If the oral dose of the drug is 3.48g/60kg.d, the daily dose of the drug in the mice is 355.2 [(20.6g/kg) 临床 (3.48g/60kg). )] times. Example 13 Clinical trial of the drug of the present invention

1 Test drug: Inventive Example 5 Drug, 0.58 g/granule.

2 Test purposes: To observe the efficacy and safety of the drug of Example 5 of the present invention in the treatment of coronary heart disease with angina pectoris.

3 test design

3.1 Controlled drug: Gelan Xinning Softgel, batch number 20100912, provided by Xi'an Qianhe Pharmaceutical Co., Ltd.

3.2 case selection

3.2.1 Case selection criteria Refer to "Guidelines for Clinical Research of New Drugs in Traditional Chinese Medicine" 2002 Edition

3.2.2 Inclusion of the standard of the case of heart and blood stasis syndrome: chest tingling, cramping, fixed, painful shoulder or arm inside, chest tightness, palpitations. The lips are dark and the veins are fine. One of the main symptoms of chest pain, chest tightness, other symptoms with 2 items and tongue supporters, can be included in the test cases. 3.2.3 Exclusion of case criteria

1) Those who have been diagnosed as coronary heart disease, other diseases other than myocardial infarction, severe neurosis, menopausal syndrome, and chest pain caused by cervical cancer.

2) Combined moderate to high blood pressure, severe cardiopulmonary insufficiency, severe arrhythmia, and hepatorenal hematopoietic system disorders.

3) If the medication is not prescribed, it is impossible to judge the efficacy or the data is incomplete.

3.3 Grouping and Governing

3.3.1 Grouping The selected 246 cases were randomly divided into an experimental group of 164 cases and a control group of 82 cases in a ratio of 2:1. The gender, age, condition, and duration of the two groups were comparable.

3.3.2 Treatment method The experimental group took the example 5 drugs, 2 capsules/time, times/d; the control group took Gulan Xinning soft capsule, 2 capsules/time, 3 times/d. The course of treatment is 4 weeks. Other treatments for coronary heart disease are generally discontinued during medication, and special additions must be recorded. Symptoms were observed once a week and ECG was recorded once every 2 weeks. Record adverse reactions at any time.

3.3.3 Statistical processing All measurement data, F, q, t test; count data, χ 2 test; clinical efficacy observation results using Ridit test.

3.4 Observation indicators

1) Time, frequency, extent, duration, predisposing factors and nitroglycerin intake of angina pectoris.

2) ECG examination.

3) Heart function check.

3.5 efficacy judgment criteria

The curative effect standard was formulated according to the "Guidelines for Clinical Research of New Chinese Medicine for Treating Angina Pectoris of Coronary Heart Disease". The main items evaluated were angina pectoris, electrocardiogram, and nitroglycerin arrest rate.

4. Results

Example 5 The total effective rate of the drug for coronary heart disease angina pectoris was 92.07%, and the Gelan Xinning soft capsule group

82.93% was significantly increased, P<0.05. Among them, the efficiency was 47.56% and 40.6%, respectively, and the difference was also significant, P<0.05. The effect of the drug of Example 5 on pain in patients with angina pectoris was reduced from (6.15±2.30) times per week to (4.26±2.13) times, and the duration of pain was (9.42±3.26) min and (6.11) before and after treatment. ±2.05) min, the difference was significant, P<0.05. See Table 3 and Table 4.

Table 3 Example 5 Clinical observation of the effect of drugs on patients with angina pectoris group number of markedly effective and effective total effective rate experimental group 164 78 ( 47.56 ) * 73 ( 44.51 ) 13 ( 7.92 ) * * 151 ( 92.07 ) * control group 82 33 ( 40.6 35 ( 42.68 ) 14 ( 17.07 ) 68 ( 82.93 )

* P<0.01, * P<0.05 Table 4 Effect of Example 5 drugs on pain in patients with angina pectoris (s) s Number of pains before and after treatment (week) Duration (minutes) 6.15 ± 2.30 before treatment * 9.42 ± 3.26 * 4.26 ± 2.13 after treatment 2.11 ± 2.05 Note: ** Ρ<0·01, *Ρ<0.05

Example 5 The effect of the drug on the electrocardiogram of patients with angina pectoris, the total effective rate of electrocardiogram was 51.83%, the total effective rate of Glan Xinning soft gelatin was 40.24%, the difference between the two was significant, Ρ<0.05 The difference was 15.24% and 9.76%. See Table 5.

Table 5 Example 5 The effect of the drug on the electrocardiogram of patients with angina pectoris. The number of group cases was markedly effective and effective. Total effective rate experimental group 164 25 ( 15.24) * 60 (36.59) 79 (48.18 ) 85 ( 51.83 ) * Control group 82 8 (9.76) 25 (30.49) 49 ( 59.76) 33 (40.24) Note: **Ρ<0·01, *Ρ<0.05

5 Test conclusion: Inventive Example 5, the drug was orally administered 2 capsules/time, 3 times/day, and taking 2 courses of treatment for treating coronary heart disease angina pectoris, the curative effect was better than that of Gelan Xinning soft capsule; no obvious adverse reactions were found in the experiment. .

Claims

Rights request

1. A medicament for treating angina pectoris of coronary heart disease, the medicament comprising the following parts by weight of raw materials or consisting of the following raw materials by weight:

4~60 parts of total flavonoids, 1~30 parts of hawthorn extract, 0.4~10 parts of Gynostemma pentaphyllum, 5~100 parts of soybean oil or salad oil, 0.1~3 parts of beeswax, 0.4~10 parts of hydrogenated palm oil, soybean phospholipid 0.2~5 parts, 0.01~0.5 parts of disilicone oil, 8~150 parts of gelatin, 3~80 parts of glycerin, 8~150 parts of purified water and 0.01~0.8 parts of hydroxyphenylethyl ester.

The medicine according to claim 1, wherein the total flavonoids of pueraria are prepared by the following method:

Take Pueraria lobata, crush into coarse powder, infiltrate with ethanol solution of 60%~80% by volume for 1 hour, then extract twice by reflux, each time with the weight of the drug 6~10 times solvent, each reflux 1~3 In the hour, the two extracts were combined, filtered, concentrated under reduced pressure to a relative density of 1.15 to 1.25 at 60 ° C, spray dried, or concentrated under reduced pressure until the relative density was 1.25 ° at 60 ° C. The extract of 1.35 is vacuum dried and pulverized through an 80 mesh sieve.

The medicine according to claim 1 or 2, wherein the hawthorn extract is prepared by the following method:

Take the hawthorn slices and extract them twice with an aqueous solution of 60-80% by volume of ethanol. Add the solvent weight 6~10 times for the first time, and add 4~8 times the solvent weight for the second time. After flowing for 1~3 hours, the two extracts were combined, filtered, concentrated under reduced pressure to an extract having a relative density of 1.15 to 1.20 at 60 ° C, spray dried, or concentrated under reduced pressure to a relative density of 60 ° C. After measuring the 1.25 ~ 1.35 extract, vacuum drying, smashing through 80 mesh sieve, that is.

The medicine according to any one of claims 1 to 3, wherein the medicine consists of the following raw materials by weight:

20 parts of total flavonoids of Radix Puerariae, 6 parts of hawthorn extract, 2 parts of Gynostemma pentaphyllum, 25.4 parts of soybean oil or salad oil, 0.6 parts of beeswax, 3 parts of hydrogenated palm oil, 1 part of soybean phospholipid, 0.05 part of diterpene silicone oil, 40 parts of gelatin , 16 parts of glycerin, 40 parts of purified water and 0.08 parts of hydroxyphenylethyl ester.

5. A method of preparing a medicament according to any one of claims 1 to 4, the method comprising the steps of:

(a) Preparation of the glue: First, dissolve the gelatin with an appropriate amount of purified water, inhale and swell, and place the glycerin, the remaining purified water, and the hydroxyphenylethyl ester in a plastic jar, heat to 70-80 ° C, and mix well. Add the expanded gelatin, stir it, melt it into a uniform gelatin, open the vacuum system of the sol tank, remove the bubbles in the gelatin solution, and dilute the water in the gelatin solution while heating until the viscosity is 28000~32000 mTorr. Put it in a stable rubber tank for heat preservation, spare; (b) adding quantitative beeswax and hydrogenated palm oil to soybean oil or salad oil, heating to 70-80 °C, completely dissolving the above two substances in soybean oil or salad oil, cooling to 30~35 °C, adding Soy lecithin, stir well to make it uniform;

(d) using the glue obtained in the step (a) and the liquid solution obtained in the step (c) by a pressing method, the thickness of the rubber is controlled to be 0.85 to 0.95 mm, and 580 mg per capsule is obtained.

The medicine according to claim 5, wherein the total flavonoids of pueraria are prepared by the following method:

Take Pueraria lobata, crush into coarse powder, infiltrate with 60%~80% ethanol aqueous solution for 1 hour, then reflux and extract twice, each time with the drug weight 6~10 times solvent, each reflux 1~3 In the hour, the two extracts were combined, filtered, concentrated under reduced pressure to a relative density of 1.15 to 1.25 at 60 ° C, spray dried, or concentrated under reduced pressure until the relative density was 1.25 ° at 60 ° C. The extract of 1.35 is vacuum dried and pulverized through an 80 mesh sieve.

The preparation method according to claim 5 or 6, wherein the hawthorn extract is prepared by the following method:

A method for treating coronary heart disease angina pectoris according to any one of claims 1 to 4.