WO2013155995A1

WO2013155995A1 - Red yeast and kudzu root pharmaceutical composition for regulating blood lipids and preparation method therefor

Info

Publication number: WO2013155995A1
Application number: PCT/CN2013/074534
Authority: WO
Inventors: 段震文; 郭树仁; 刘曦
Original assignee: 北京北大维信生物科技有限公司
Priority date: 2012-04-20
Filing date: 2013-04-22
Publication date: 2013-10-24
Also published as: CN103372051B; CN103372051A

Abstract

A pharmaceutical composition that regulates blood lipid regulation and comprises red yeast and kudzu root. The composition uses the lovastatin concentration as the quality control indicator. A pharmaceutical composition that lowers blood sugar, and comprises red yeast, kudzu root, and mulberry bark.

Description

Red korea root drug combination for regulating blood lipid and preparation method thereof

The invention relates to a pharmaceutical composition and a preparation method thereof, in particular to a pharmaceutical composition prepared by using a traditional Chinese medicine compound as a raw material and a preparation method thereof, and belongs to the field of traditional Chinese medicine. Background technique

The modern lifestyle has led to an increase in the intake of high-protein, high-cholesterol, and high-sugar foods in people's foods, leading to a marked increase in the incidence of hyperlipidemia. Hyperlipidemia is a pre-existing atherosclerosis and has a significant correlation with the incidence of cerebrovascular disease. Hyperlipidemia is also an important factor in inducing coronary heart disease, arteriosclerosis, fatty liver, diabetes, and obesity. Therefore, prevention and treatment of hyperlipidemia plays an important role in the prevention of cardiovascular and cerebrovascular diseases. It is very necessary to research and develop safe and effective blood lipid regulating drugs and health foods.

Hyperlipidemia refers to excessively high total cholesterol (TC) and/or triglyceride (TG) or high density lipoprotein cholesterol (HDL-C) in the blood. Clinically divided into: hypercholesterolemia (increased serum TC), hypertriglyceridemia (increased serum TG), mixed hyperlipidemia (increased TC, TG), low high density lipoprotein Blood (lower serum HDL-C levels).

The serum TC level in our population is significantly lower than that in the high-risk population of western coronary heart disease. Through a sample survey of 49,252 permanent residents of 18 provinces, autonomous regions and municipalities directly under the Central Government in China: The prevalence of dyslipidemia in 18-year-old residents in China is 18.6%. The prevalence of hypercholesterolemia was 2.9 %; the marginal rate of cholesterol was 3.9 %; the prevalence of hypertriglyceridemia was 11.9%; The rate is 7.4%. The abnormal types of blood lipid metabolism in our country are mainly high triglyceride and low-density lipoproteinemia, which is different from the high-cholesterolemia in western population. It is necessary to find a hypolipidemic drug for the abnormal type of lipid metabolism in Chinese people.

Summary of the invention

SUMMARY OF THE INVENTION It is an object of the present invention to provide a pharmaceutical composition for regulating blood lipids (especially for treating hypertriglyceridemia) and a process for the preparation thereof; and an object of the present invention is to provide a pharmaceutical use of the pharmaceutical composition.

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

The composition of the drug substance of the pharmaceutical composition of the present invention is:

Red yeast 1 to 5 parts by weight Pueraria 1 to 5 parts by weight;

The drug substance composition of the pharmaceutical composition of the present invention is preferably:

Red yeast 2 parts by weight Pueraria 4 weights t;

Red yeast 4 parts by weight Pueraria 2 weights t;

Red yeast 1 part by weight Pueraria 4 weight t parts;

Red yeast 4 parts by weight Pueraria 1 weight t parts;

The pharmaceutical composition of the present invention can be formulated into a clinically acceptable oral preparation according to a conventional method by adding a conventional excipient, including but not limited to a pill, a powder, a tablet, a granule, a capsule, or an oral liquid preparation.

Preferably, the red yeast in the drug substance of the above pharmaceutical composition may be ordinary red yeast or functional red yeast rice.

Ordinary red yeast rice is red yeast rice (also known as red yeast rice, red yeast rice, red rice, and glutinous rice) which is inoculated on rice by Monascus anka Nakazawa et Sato. It can be purchased from the market or it can be prepared according to the method of GB 4926-2008.

The functional red yeast rice can be prepared by using a commercially available product or by the following method: (The preparation method is China) Patent No. 97116744. 3, 97103970. 4 The content of claim 1. (1), preparation of culture solution: consists of glycerin (or wort or potato juice), a mixture of sugar and yeast (or beef extract or peptone) and water, of which glycerin (or wort or potato juice) accounts for 2~7 %, sugar accounts for 2~6 %, peptone 0~3 %, yeast powder accounts for 0~3 %, beef cream 0~3 %, a small amount of antifoaming agent into soybean oil or peanut oil 2~4%. 0〜5. 0。 The pH is 3. 0~5. 0. (2), per 100 g of glutinous rice, add 30~80 ml of culture solution, high temperature steam (12 灭菌 sterilized. After the temperature is cooled to below 40 ° ,, inoculate the strain of Monascus. The strain of Monascus is selected from the following One or more of the three strains: Aspergillus oryzae, the preservation number is CGMCC No. 0315; the red mold fungus, the preservation number is CGMCC No. 0316; the koji koji, the deposit number is CGMCC No. 0317, Fermentation culture at 15 to 35 ° C for more than 9 days, the strain can be cultured into a liquid strain or a solid strain. (3), the culture is sterilized at a temperature of 60 to 121 ° C, and the pressure is reduced by 60. Drying at ~80 °C to obtain functional red yeast rice.

The preparation method of the pharmaceutical composition of the present invention may also be the following method:

Preparation of Monascus extract I and Pueraria extract II, extract I and extract II according to a conventional method, adding conventional excipients, to prepare a clinically acceptable oral preparation, including but not limited to pills, powders, tablets, granules , capsules, oral liquid preparations;

The red yeast extract I can be prepared by any of the following methods:

A, red koji 1 part by weight, each time adding 2~10 parts by volume of 50~90% ethanol, methanol or ethyl acetate, heating under reflux for 1-3 hours, extracting 2~3 times; extracting the filtrate, combining the filtrate, recycling The solvent is concentrated to 55~60 ° C to measure the relative density of 0. 95~1. 06 thick paste, obtained extract I;

B, red koji 1 part by weight, each time adding 2~10 parts by volume of 50~90% ethanol, methanol or ethyl acetate heated under reflux for 1~3 hours, extracting 2~3 times; extracting the filtrate, combining the filtrate, recovering the solvent Concentrating to a concentration of 0. 95~1. 06, concentrated in a concentration of 0. 5~2. 0 times deionized water mixed, room temperature or refrigerated for 2 to 12 hours, centrifuge, The precipitate was collected and dried to obtain extract I;

The Pueraria lobata extract II is prepared by the following method:

1 part by weight of Radix Puerariae, each time adding 4~20 parts by volume of water or ethanol and refluxing for 1~3 hours, extracting 2~4 times, filtering the extract, combining the filtrate, recovering the solvent, and concentrating into a thick paste; Item II.

Preferably, the method A described in the preparation method of the present invention comprises: taking 1 part by weight of red yeast medicine, adding 3 parts by volume of 75% ethanol and refluxing for 3 hours, and extracting the extract; and adding the residue to 2 parts by volume of 75% ethanol and refluxing for 2 hours. The extract is filtered, the filtrate is combined twice, and the ethanol is removed under reduced pressure. The concentrated extract is adjusted to a density of 0. 95~1.

The method B described in the preparation method of the present invention is preferably: 1 part by weight of Monascus var. var. var. var. var. var. var. var. var. var. var. var. var. var. var. var. var. var. var. var. The liquid was filtered, the filtrate was combined twice, and the ethanol was evaporated under reduced pressure. The concentration was adjusted to 55-60 ° 0. The relative density was 0.95 to 1. 06, and the mixture was mixed with 1 time deionized water, and allowed to stand at room temperature or in a refrigerated place. hour. After centrifugation, the precipitate was collected, dried at 80 ° C for 8 small tests, and pulverized through a 60 mesh sieve to obtain Extract I.

The Pueraria lobata extract II described in the preparation method of the present invention is preferably prepared by the following method: 1 part by weight of Radix Puerariae, each time adding 12 parts by volume of 70% or 40% ethanol for heating for 1 to 3 hours, extracting 2 to 3 times, extracting The liquid was filtered, and the filtrate was combined, and the solvent was collected, and concentrated to 55 to 60 ° C to measure a relative density of 0.95 to 1. 06 thick paste;

The relationship of parts by weight per part by volume of the present invention is: gram per milliliter. The red yeast rice of the present invention may be a common red yeast medicine, or may be a commercially available functional red yeast rice or a high content red yeast rice.

The pharmaceutical composition of the present invention, red yeast and puerarin, is compatible with each other, and synergistic effect is produced. With dehumidification, blood circulation Hey, the effect of spleen and digestion. The pharmaceutical composition of the present invention is capable of lowering total cholesterol in blood, increasing high-density lipoprotein, lowering low-density lipoprotein content, and particularly exhibiting a lowering of triglyceride, and can significantly treat hypertriglyceridemia. The preparation process of the invention is reasonable, which not only improves the content of the active ingredient lovastatin in the red yeast rice, but also retains the active ingredients of each drug in the prescription, and fully exerts the effects of each drug. The preparation of the invention has the content of lovastatin as a quality control index, and the preparation quality is stable and controllable.

Another object of the present invention is to provide a hypoglycemic pharmaceutical composition, a process for the preparation thereof, and a pharmaceutical use for providing the pharmaceutical composition.

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

1 to 5 parts by weight of koji, 1 to 5 parts by weight of pueraria, 1 to 5 parts by weight of mulberry white.

1 part by weight of red yeast rice, 1 part by weight of pueraria, 1 part by weight of mulberry white.

The preparation method of the pharmaceutical composition of the present invention may be as follows:

Preparing red yeast extract I, Pueraria extract II and mulberry extract III, extracting extract I, extract II and extract III according to a conventional method, adding conventional excipients to prepare a clinically acceptable oral preparation, including but It is not limited to pills, powders, tablets, granules, capsules, oral liquid preparations.

The red yeast extract I can be prepared by any of the following methods:

A, red koji 1 part by weight, each time adding 2~10 parts by volume of 50~90% ethanol, methanol or ethyl acetate, heating under reflux for 1-3 hours, extracting 2~3 times; extracting the filtrate, combining the filtrate, recycling The solvent is concentrated to 55~60 ° C to measure the relative density of 0. 95~1. 06 thick paste, to obtain extract I;

B, red koji 1 part by weight, each time adding 2~10 parts by volume of 50~90% ethanol, methanol or ethyl acetate heated under reflux for 1~3 hours, extracting 2~3 times; extracting the filtrate, combining the filtrate, recovering the solvent Concentrating to a concentration of 0. 95~1. 06, concentrated in a concentration of 0. 5~2. 0 times deionized water mixed, room temperature or refrigerated for 2 to 12 hours, centrifuge, Collecting the precipitate and drying to obtain the extract I;

The Pueraria lobata extract II is prepared by the following method:

1 part by weight of Radix Puerariae, each time adding 4~20 parts by volume of water or ethanol and refluxing for 1~3 hours, extracting 2~4 times, filtering the extract, combining the filtrate, recovering the solvent, and concentrating into a thick paste; Substance II;

The mulberry bark extract III can be prepared by any of the following methods:

C, mulberry white medicinal material 1 part by weight, each time add 8~12 parts by volume of water to boil for 1~3 hours, extract 2~3 times, extract the filtrate, combine the filtrate, concentrate to 55~60 °C a thick paste of 0. 95~1. 06; dried, obtained extract III;

D, mulberry white medicinal material 1 part by weight, each time add 8~12 parts by volume of water to boil for 1~3 hours, extract 2~3 times, extract the filtrate, combine the filtrate, concentrate, and centrifuge. The cation exchange resin was eluted with 3 to 8 column volumes of 0.25 to 1 mol/L aqueous ammonia solution, concentrated, and dried. Extract III was obtained.

Preferably, the method A described in the preparation method of the present invention comprises: taking 1 part by weight of red yeast medicine, adding 3 parts by volume of 75% ethanol and refluxing for 3 hours, and extracting the extract; adding the residue to 2 parts by volume of 75% ethanol and refluxing for 2 hours. 5的稠膏,得提取物 I; The extract is obtained by adding the filtrate to the filtrate, and the ethanol is removed under reduced pressure to a concentration of 0. 95~1.

The method B described in the preparation method of the present invention is preferably: 1 part by weight of red yeast medicine, and 3 parts by volume of 75% The alcohol was refluxed for 3 hours, and the extract was filtered; the residue was added to 2 parts by volume of 75% ethanol and refluxed for 2 hours. The extract was filtered, and the filtrate was combined twice. The ethanol was recovered under reduced pressure and concentrated to 55-60°. 95~1. 06, add 1 times deionized water to the concentrate, mix and mix at room temperature or refrigerate for 8 hours. Centrifugation, collecting the precipitate, drying at 80 ° C for 8 hours, crushing through a 60 mesh sieve to obtain extract I;

The Pueraria lobata extract II described in the preparation method of the present invention is preferably prepared by the following method: 1 part by weight of Radix Puerariae, and each time adding 12 parts by volume of 70% or 40% ethanol for heating for 1 to 3 hours, and extracting 2 to 3 times, The extract is filtered, the filtrate is combined, the solvent is recovered, and concentrated to 55-60 ° C to measure the relative density of 0. 95~1. 06 thick paste; extract II; The C method described in the preparation method of the present invention is preferably: The mulberry white medicinal material 1 part by weight, each time adding 10 parts by volume of water to be boiled for 2 hours, extracted 2 times, the extract is filtered, the filtrate is combined, and concentrated to 55~60 ° C to measure the relative density of 0. 95~ 1. 06 Thick paste; dried, extract III;

The D method described in the preparation method of the present invention is preferably: 1 part by weight of mulberry white medicinal material, and each time 10 parts by volume of water is boiled and extracted for 2 hours, extracted twice, the extract is filtered, the filtrate is combined, concentrated, and centrifuged. The cation exchange resin was eluted with 6 column volumes of 0.5 mol/L aqueous ammonia solution, concentrated, and dried. Extract III was obtained.

The relationship of parts by weight per part by volume of the present invention is: gram per milliliter.

The pharmaceutical composition of the invention has the synergistic effect of red yeast, puerarin and mulberry white skin, and has the effect of lowering blood sugar. The preparation process of the invention is reasonable, and the content of the active ingredient lovastatin in the red yeast rice is improved, and the active ingredients of each drug in the prescription are retained, and the effects of each drug are fully exerted. The preparation of the invention has the content of lovastatin as a quality control index, and the preparation quality is stable and controllable. The effects of the present invention are demonstrated by pharmacodynamic experiments below.

Experimental Example 1 Effect of the pharmaceutical composition of the present invention on hypertriglyceridemia in a high-fat feeding model mouse

1. Experimental materials:

(1) Preparation of test drugs:

Red yeast extract preparation: The preparation method is the same as the preparation method of extract I in Example 4.

Pueraria lobata extract preparation: The preparation method is the same as the preparation method of extract II in Example 4.

Preparation of compound medicine: See Example 4 for the preparation method.

All the above drugs were prepared by adding 1% CMC before use to make lml (liquid) l (raw drug).

(2) Preparation of high-fat emulsion: cholesterol 10g, lard 40g, sodium cholate 2g, propylthiouracil lg, Tween-80 lml, propylene glycol 15ml, distilled water added to 100ml

(3), reagent: Triglyceride (TG) kit, Beijing Zhongsheng North Control Biotechnology Co., Ltd.

(4), Animals: ICR mice, male, weighing 25~30g, purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd.

(5), instrument: Versa max tunable (Molecular Devices), centrifuge: (Anke LXJ-

Π Β).

2, methods and results

(1), Methods: 60 ICR mice were taken and served for 5 days. After confirming the health, the mice were randomly divided into 6 groups, 10 in each group. Blank control group, high fat model group (ig high fat emulsion 20ml/kg. d ten water), positive control group (ig high fat emulsion 20ml/kg. d ten fenofibrate 300mg/kg), red yeast group (ig High fat emulsion 20ml/kg. d + red yeast concentrate), pueraria group (ig high fat emulsion 20ml/kg. d + puerarin concentrate), compound group (ig high fat emulsion 20ml/kg. d ten compound thick Shrinkage). High fat milk and its blank solution at 8:30 am; water supply, positive by group at 15:30 in the afternoon Reference drug, each test drug, and the like. The cells were administered continuously for 20 days, and blood was taken at the 21st day. Plasma was prepared by anticoagulation with EDTA. The triglyceride content was determined by the kit method.

(2) The results are shown in Table 1.

Table 1 Effect of Chinese herbal compound composition on TG in high-fat mice (X±SD, mg/dl) High-fat milk volume (ml/kg) n (only) Triglyceride (r

(g original medicine / kg body weight)

Blank to control

20 (water) 10

Group 146±30.2

High fat model

20 10

Group 243±51.7ΔΔ

Positive control

300mg/kg 20 10

Group 110±25.3

Red song group 20 20 10 175±30.2*

Pueraria group 20 20 10 173±52.5

Compound group 20 20 10 150±37.9**

Eighth eight compared with the blank control group (t test), P <0.01; *, ** indicates comparison with the high fat model group (t test), P <0.05, 0.01

Red yeast rice, radix puerariae and compound can reduce the serum TG content in high fat milk model mice. However, in the same dose, the red yeast group was 31% lower than the model group, the puerarin group was 29% lower than the model group, and the compound group was 38% lower than the model group. The TG of the compound group was lower than that of the red yeast group and Pueraria. group. It shows that the traditional Chinese medicine compound composition has a more obvious effect of lowering TG in blood. Experimental Example 2 Effect of the pharmaceutical composition of the present invention on hypertriglyceridemia in a high fat diet-fed model mouse

1. Experimental materials:

(1) Preparation of test drugs:

Red yeast extract preparation: The preparation method is the same as the preparation method of extract I in Example 5.

Pueraria lobata extract preparation: The preparation method is the same as the preparation method of extract II in Example 5.

Preparation of compound medicine: See Example 5 for the preparation method.

All the above drugs were prepared by adding 1% CMC before use to make lml (liquid) / g (raw drug).

(2) Preparation of high fat emulsion: Same as Experimental Example 1.

(3), reagent: same as experimental example 1.

(4) Animals: ICR mice, male, weighing 25~30g, purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd.

(5), Instrument: Same as Experimental Example 1.

2, methods and results

(1), Method: Same as Experimental Example 1.

(2) The results are shown in Table 2.

Table 2 Effect of Chinese herbal compound composition on TG in high-fat mice (X±SD, mg/dl) 别^^, high-fat milk volume (ml/kg) n (only) triglyceride (mg,

(g original medicine / kg body weight) Blank control

20 (water) 10

Group 146±30.2

High fat model

20 10

Group 243±51.7ΔΔ

Positive control

300mg/kg 20 10

Group 110±25.3

Red song group 20 20 10 168±35.6*

Pueraria group 20 20 10 190±47.9

Compound group 20 20 10 146±32.7**

Red yeast rice, radix puerariae and compound can reduce the serum TG content in high fat milk model mice. However, in the same dose, the red yeast group was 31% lower than the model group, the Pueraria group was 22% lower than the model group, and the compound group was 40% lower than the model group. The TG of the compound group was lower than that of the red yeast group and Pueraria. group. It shows that the traditional Chinese medicine compound composition has a more obvious effect of lowering TG in blood. Experimental Example 3 Effect of the pharmaceutical composition of the present invention on hypertriglyceridemia in a high fat diet-fed model mouse

1. Experimental materials:

(1) Preparation of test drugs:

Red yeast extract preparation: The preparation method is the same as the preparation method of extract I in Example 6.

Pueraria lobata extract preparation: The preparation method is the same as the preparation method of extract II in Example 6.

Preparation of compound medicine: See method example 6

(2) Preparation of high fat emulsion: Same as Experimental Example 1.

(3), reagent: same as experimental example 1.

(5), Instrument: Same as Experimental Example 1.

2, methods and results

(1), Method: Same as Experimental Example 1.

(2) The results are shown in Table 3.

Table 3 Effect of Chinese herbal compound composition on TG in high-fat mice (X±SD, mg/dl) High-fat milk volume (ml/kg) n (only) Triglyceride (r

(g original medicine / kg body weight)

Blank to control

20 (water) 10

Group 146±30.2

High fat model

20 10

Group 243±51.7ΔΔ

Positive control

300mg/kg 20 10

Group 110±25.3

Red song group 20 20 10 173±36.4* Pueraria group 20 20 10 188 ±46.9

Compound group 20 20 10 142±33.5**

Red yeast rice, radix puerariae and compound can reduce the serum TG content in high fat milk model mice. However, in the same dose, the red yeast group was 29% lower than the model group, the Pueraria group was 23% lower than the model group, and the compound group was 42% lower than the model group. The TG of the compound group was lower than that of the red yeast group and Pueraria. group. It shows that the traditional Chinese medicine compound composition has a more obvious effect of lowering TG in blood. Experimental Example 4 Experimental study on the hypolipidemic effect of the pharmaceutical composition of the present invention

1. Experimental materials:

(1), drugs

Preparation of compound medicine: See Example 4 for the preparation method.

All the above drugs are prepared by adding 1% CMC before use to make lml (liquid) l (raw drug).

(2) Animals: Wistar male rats weighing 150-200 g. Purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd.

(3), high fat feed: cholesterol 2%, sodium cholate [pig] 0.5%, lard 15% (homemade), propyl thiouracil 0.2 basal powder 82.3%. The lard was melted in a 40 ° C water bath. Sodium cholate, cholesterol, and propylthiouracil are pulverized and mixed with a pulverizer, and the base is mixed, and then the melted lard is added and mixed well. Add a total of lOOOOg of raw material to 50ml of water and mix well. Press it into a block with a dough press (one cake per 30 g of mixed material). Dry and sterilize to get high fat.

(4), reagent: Triglyceride (TG) kit, Beijing Zhongsheng Beikong Biotechnology Co., Ltd.

(5), Instruments: Instruments: Versa max tunable, Molecular Devices, Centrifuge: (Anke LXJ-IIB).

2, methods and results

(1), hyperlipidemia modeling:

Fifty rats were divided into a blank control group (10) and a high-fat model (40), which were given normal basal support and high-fat support for 4 weeks. Fasting on the evening of the 28th, the next morning to cut the tail to take blood. Plasma was prepared by anticoagulation with EDTA. The triglyceride content was determined by the kit method. The results are shown in Table 2.

(2), Method: The normal basal rats were fed as a blank control group: continue to feed the normal basal feeding, and 1% CMC aqueous solution was administered by daily gavage; the high-fat model animals were randomly divided into 4 groups according to the blood lipid TG level. High-fat model group: fed high-fat diet, 1% CMC aqueous solution was administered intragastrically every day; Red yeast group: Red yeast extract was administered by daily gavage, the dosage was 20g (original medicine) / kg body weight; The Pueraria lobata extract was administered by daily gavage, and the dose was 20 g (original medicinal material) / kg body weight; Compound group: The traditional Chinese medicine compound extract of the present invention was administered by gavage every day, and the dose was 20 g (original medicinal material) / kg body weight. Continuous feeding for 4 weeks, fasting for 12 hours after the last administration, and taking blood at the end of the next morning. Plasma was prepared by anticoagulation with EDTA. The triglyceride content was determined by the kit method.

(3) The results are shown in Table 4.

Table 4 Effect of Chinese herbal compound composition on blood lipid content (X Shi SD, mg/dl)

Group dose of n (only) triglyceride (mg / dl) (g original medicine / kg body weight)

Blank control group 10 126±28.8

High fat model group 10 218±48.6ΔΔ

Red yeast group 20 10 169±40.1* Pueraria group 20 10 178±45.3 Compound group 20 10 134±33.5** Eighth eight indicates comparison with blank control group (t test), P<0.01; *, ** indicates high fat Model group comparison (t test), P<0.05, 0.01

The results showed that both Hongqu and Fufang could reduce the serum TG content in high TG model rats induced by high-fat feeding. Compared with the model group, the difference was significant P<0.05 and extremely significant difference. <0.01. From the percentage of TG reduction: At the same dose, the red yeast group was 22% lower than the model group, the puerarin group was 18% lower than the model group, and the compound group was 39% lower than the model group. It is larger than the red yeast group and the puerarin group. It shows that the traditional Chinese medicine compound composition has a more obvious effect of lowering TG in blood. Experimental Example 5 Experimental study on the hypolipidemic effect of the pharmaceutical composition of the present invention

1. Experimental materials:

(1), drugs

Preparation of compound medicine: See Example 5 for the preparation method.

(3), high fat feed: the same as experimental example 4.

(4), reagent: same as experimental example 4.

(5), Instrument: Same as Experimental Example 4.

2, methods and results

(1), hyperlipidemia modeling: the same as experimental example 4.

(2) Experimental method: Same as experimental example 4.

(3), the results are shown in Table 5

Table 5 Effect of Chinese herbal compound composition on blood lipid content (X±SD, mg/dl) Group (only) Triglyceride (mg/dl)

(g original medicine / kg body weight)

Blank to control group 1100 112266±±2288..88

High fat model group 10 218±48.6ΔΔ

Red yeast group 20 10 150±36.8* Pueraria group 20 10 176±49.5 Compound group 20 10 138±35.4** Eight eight indicates comparison with blank control group (t test), P<0.01; *, ** indicates high fat Model group comparison (t test), P<0.05, 0.01 The results showed that both Hongqu and Fufang could reduce the serum TG content in high TG model rats induced by high-fat feeding, compared with the model group, the significant difference was P<0.05 and the extremely significant difference was P<0.01. In this experiment, the Pueraria group had a decreasing trend, but the statistical difference was not obvious. From the percentage of TG reduction: At the same dose, the red yeast group was 31% lower than the model group, the puerarin group was 19% lower than the model group, and the compound group was 37% lower than the model group. It is larger than the red yeast group and the puerarin group. It shows that the traditional Chinese medicine compound composition has a more obvious effect of lowering blood TG. Experimental Example 6 Experimental study on the hypolipidemic effect of the pharmaceutical composition of the present invention

1. Experimental materials:

(1), drugs

Preparation of compound medicine: See Example 6 for the preparation method.

(3), high fat feed: the same as experimental example 4.

(4), reagent: same as experimental example 4.

(5), Instrument: Same as Experimental Example 4.

2, methods and results

(1), hyperlipidemia modeling: the same as experimental example 4.

(2) Experimental method: Same as experimental example 4.

(3), the results are shown in Table 6

Table 6 Effect of Chinese herbal compound composition on blood lipid content (X±SD) Group (only) Triglyceride (mg/dl)

(g original medicine / kg body weight)

Blank to control group 1100 112266±±2288..88

High fat model group 10 218±48.6ΔΔ

Red yeast group 20 10 146±36.1** Pueraria group 20 10 169±40.9* Compound group 20 10 130±35.4** Eight-eighth comparison with blank control group (t test), P<0.01; *, ** indicates Comparison of high fat model group (t test), P<0.05, 0.01

The results showed that Hongqu, Gegen and Fufang could reduce the serum TG content in high TG model rats induced by high-fat feeding. Compared with the model group, the significant difference was P<0.05 and extremely significant difference. <0.01. From the percentage of TG reduction: At the same dose, the red yeast group was reduced by 33% compared with the model group, the puerarin group was reduced by 22% compared with the model group, and the compound group was reduced by 40% compared with the model group; It is larger than the red yeast group and the puerarin group. It shows that the traditional Chinese medicine compound composition has a more obvious effect of lowering TG in blood. Experimental Example 7 Experimental study on the hypolipidemic effect of the pharmaceutical composition of the present invention 1. Experimental materials:

(1), drugs

Preparation of red yeast extract: 1 part by weight of Hongqu and 1 part by weight, added with 6 parts by volume of 75% ethanol, and refluxed for 3 hours, and the extract was filtered; the residue was added to 6 parts by volume of 75% ethanol and refluxed for 2 hours, and the extract was filtered. The filtrate was combined twice, and ethanol was recovered under reduced pressure, and concentrated to a concentration of 55 to 60 ° 0 to determine a relative density of 0.95 to 1.06. Spray dried.

Preparation of Pueraria lobata extract: Take 1 part by weight of Radix Puerariae, and add 6 parts by volume of 75% ethanol for reflux for 3 hours, and extract the extract; the filter residue is added to 6 parts by volume of 75% ethanol for reflux for 2 hours, and the extract is filtered. The filtrate was combined twice, and ethanol was recovered under reduced pressure, and concentrated to a concentration of 55 to 60 ° 0 to determine a relative density of 0.95 to 1.06. Spray dried.

Preparation of compound medicine: See Example 7 for the preparation method.

Each of the above drugs was prepared by adding 1% CMC to 1 ml (liquid) / _g (raw drug).

(3), high fat feed: the same as experimental example 4.

(4) Reagents: total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (LDL-C), determined by Beijing Zhongsheng Beikong Biotechnology Co., Ltd. kit .

(5), instrument: Instrument: Versa max tunable, Molecular Devices, centrifuge: (AnkeLXJ- ΠΒ

2, methods and results

(1), hyperlipidemia modeling: the same as experimental example 4.

(2) Experimental method: Same as experimental example 4.

(3), the results are shown in Table 7

Table 7 Effect of Chinese herbal compound composition on blood lipid content (X Shi SD) Group (g original medicine / kg n (only) TC HDL-C LDL-C

(mg/dl)

Body weight) (mg/dL) (mg/dL) (mg/dL) blank control group 10 143±28.9 120.11±21.13 42.97± 11.37 88.19± 14.16 high fat model group 10 230 + 49.3 ^ΔΔ 251.26±25.87 ^ΔΔ 30.51±11.81 ^Δ 230.17 ±20.52 ^Δ红曲组20 10 164 ±38.6* 129.22± 18.59** 40.09± 13.16* 146.89 ±28.98* Pueraria group 20 10 186±56.4 190.81±30.11* 35.58± 13.13 189.11 ±25.90 Compound group 20 10 150 ±34.5 ** 115.90± 18.15** 43.60± 14.87* 130.66± 13.47** Eighty-eight is compared with the blank control group (t test), P<0.01 _; *, ** indicates comparison with the high-fat model group (t test), P <0.05

The results showed that Hongqu, Gegen and Fufang could reduce the serum TG content in high TG model rats induced by high-fat feeding. Compared with the model group, the difference was significant P<0.05 and extremely significant difference. <0.01. From the TG reduction percentage: In the same dose, the red yeast group was 29% lower than the model group, the Pueraria group was 19% lower than the model group, and the compound group was 35% lower than the model group. It is larger than the red yeast group and the puerarin group. It shows that the traditional Chinese medicine compound composition has a more obvious effect of lowering blood TG.

From the results of TC, HDL-C and LDL-C, the Pueraria group has a significant effect on reducing TC (< 0.05), has a certain effect on lowering LDL-C, and increasing HDL-C. After the compound is compounded, the red color is enhanced. The decrease of TC and LDL-C in the song increased the effect of HDL-C (P<0.05 and <0.01). Experimental Example 8 Formulation Screening Experiment

1. Tested drugs: Water extracting and alcohol extracting sites, two monomeric compounds, and four effective extracts of 25 kinds of medicinal materials were screened, and one Chinese herbal medicine preparation and red yeast extract prepared on the market were compared. Into the compound. See Table 8 for details.

Among them, all the medicinal materials were tested for the combination of the water extract and the red yeast extract compound, the ethanol extract and the red yeast extract.

2, preparation method:

(1) Preparation of extract when A is a medicinal material:

• Water extraction method: A medicinal material 100g plus 8 times the amount of water, soaked for 30min, heated to boiling and kept slightly boiling for 30min;

100 mesh sieve filtration; filter residue added 5 times the amount of water, heated to boiling and kept slightly boiling for 20 min _; 100 mesh sieve filtration; the filtrate was combined, concentrated, and dried to obtain a water extract of the medicinal material.

• Ethanol extraction method: A medicinal material 100g plus 8 times 75% ethanol, soak for 30min, reflux extraction for 30min; 100 mesh sieve filtration; filter residue plus 5 times the amount of 75% ethanol, reflux extraction for 20min _; 100 mesh sieve filtration; Concentrated, dried, and obtained the ethanol extract of the medicine.

(2) Preparation of B red koji extract: Take 100g of red yeast koji, add 3 times 75% ethanol and reflux for 3 hours, and extract the extract; filter residue added to 2 times 75% ethanol reflux for 2 hours, extract filtration The filtrate was combined twice, and the ethanol was recovered under reduced pressure, concentrated, and dried to give a red yeast extract.

(3), preparation method of compound:

The water extract of A medicinal material prepared by the method of 2. (1) and the red yeast extract are combined to form a compound; or the ethanol extract of A medicinal material and the red yeast extract are combined to form a compound. Before use, it was made up to 100 ml with 0.5% aqueous sodium carboxymethylcellulose solution.

(4), a method for preparing a test compound when A is a commercially available extract

Take 25g of extract and add the extract of B medicine. (For the extraction method of B medicine, see 2. (2) above). Before use, 100 ml of 0.5% sodium carboxymethylcellulose aqueous solution was prepared.

(5), a method for preparing a test compound when A is a commercially available monomer

Take commercially available monomeric curcumin or matrine 3g (600mg/kg dose group), lg (200mg/kg dose group), 0.5g (100mg/kg dose group), and add B medicine extract (B medicine) For the extraction method, see 2. (2)) above. Before use, it was made up to 100 ml with 0.5% aqueous sodium carboxymethylcellulose solution.

(6), a method for preparing a test compound when A is a commercially available preparation

Take 75 capsules of Gynostemma pentaphyllum (equivalent to 1500 mg of Gynostemma pentaphyllum) and add the extract of B. (The extraction method of B drug is shown in 2. (2) above). Before use, it was made up to 100 ml with 0.5% aqueous sodium carboxymethylcellulose solution.

3, the experimental drug dose: are the following doses

(1), when A is a medicinal material, the dosage of the compound drug to be tested is:

The doses of A and B herbs are 20 g of medicinal material / k _g body weight (the concentration is 1 g of medicinal material / m 1 ), which is equivalent to 10 times of clinical dosage;

(2) When A is a commercially available extract (such as Salvia miltiorrhiza, Seabuckthorn, Ginkgo biloba), the dose of the compound to be tested is: A dose of 5 g of extract I kg body weight, dose of B containing drug is 20 g medicinal material / kg body weight (prepared concentration: compound A extract 0. 25 g / m 1, containing Bl g medicinal material / m 1);

(3) When A is a commercially available monomer (such as curcumin or matrine), the dose of the compound to be tested is: The dose containing A is 600~100mg monomer/kg body weight, and the dose containing B medicine is 20g medicine/kg body weight (preparation concentration: compound containing 30m g / m 1~5mg/ml, containing Bl g medicine) / m 1 )

(4) When A is a commercially available preparation, the dose of the compound to be tested is:

The dose of drug A is 300 mg/kg body weight and the concentration is 15 mg/ml; the dose containing drug B is 20 g drug I k g body weight (the concentration is 1 g drug / m 1 ).

4. Model establishment:

(1) Fructose-induced high TG mouse model:

Male ICR mice, about 30 g. Mice were dosed without fasting. The blank group and the model group were intragastrically administered with a 0.5% aqueous solution of sodium carboxymethylcellulose in a volume of 20 ml/kg, and the fenofibrate group (300 mg/kg) was given fenofibrate in an equal volume. Continuous administration for 3 days. On the 2nd to 3rd day, the water was forbidden for 24 hours, and the drinking water was replaced with 20% fructose solution for 20 hours. The blood was cut at 20 hours after administration. TG was measured. Plasma was prepared by anticoagulation with EDTA (centrifugation 2400 rpm X 10 min). The TG value was measured.

(2) Triton WR-1339 high TG mouse TG model

Triton WR-1339 (Sigma): A concentration of 50 mg/mL was prepared using 0.9% sodium chloride solution. It was administered at a dose of 250 mg/kg.

Male ICR mice, about 30 g. The blank group and the model group were administered with 0.5% CMC solution, the fenofibrate group was administered at a dose of 300 mg/kg, and the test drug was administered at a dose of 20 g/kg. TG was measured 2 days after continuous administration of i. g. On the third day, blood was taken from each group, i. g. was administered, i.v. was modeled (Triton 0. 05 ml/10 g was injected into the tail vein, and physiological saline was injected into the blank group), and blood was taken at 24 h after modeling to determine the TG value.

(3) Effects of TG on multiple doses of normal mice

Male ICR mice, about 30g. Mice were dosed without fasting. Blank control group to 20ml volume / k _g of orally administered 0.5% aqueous sodium carboxymethyl cellulose, fenofibrate positive drug group (300mg / kg) and each test drug administration group in equal volume of fenofibric Specifically, continuous administration for 4 days, blood was taken at the 5th tail. Plasma was prepared by anticoagulation with EDTA. The TG value was measured.

5. Mode of administration: i. g

6. Dosing volume: 20m 1 / k _g

7. Positive control drug: fenofibrate 300m g / k g body weight

8. Mathematical statistics: t test, P < 0. Q 5 has significant difference, P < 0. Q 1 has extremely significant difference

Primary screening of drug groups

Water extraction

Yam compound evening primrose oil complex

* * There is a trend 18.1% There is a trend 46.5%

Water extraction

Hawthorn compound

** 17.03⁄4 water extract

Chuanxiong compound

Yujin compound

Vine ** water extract

System of Shouwu

Alcohol

Water extraction trend 26.5% red peony compound

Alcohol

Salvia miltiorrhiza extract

Commercially available extracts ** Seabuckthorn extract

Commercially available extract Curcumin compound Commercial monomer * * Matrine compound Commercial monomer Toxicity Toxicity Gynostemma total glycosides

Commercially available preparation

Tablet compound

Note:

* indicates that TG was significantly lower than the model control group (P<0.05);

** indicates that TG was significantly reduced compared with the model control group (P<0.01);

"There was a trend" indicating that the TG value was lower than that of the model control group, but the t test was not statistically significant, indicating that the drug had a decreasing trend.

(1) Fructose model: Each group was compared with the model control group and repeated experiments were performed. The experimental results are summarized as follows:

**: Salvia miltiorrhiza, Gynostemma pentaphyllum, Alisma, Rhizoma Curcumae, Licorice, Hawthorn, Chuanxiong;

*: Curcumin, Seabuckthorn, Evening Primrose Oil, Shayuanzi, Sophora flavescens;

There are trends: Ginkgo biloba, Atractylodes, Sedum

(2), Triton model: Each group was compared with the model control group, and repeated experiments were carried out. The experimental results are summarized as follows:

**: turmeric, Sophora flavescens, Alisma, Rhizoma, Yujin

*: Gynostemma, Evening Primrose Oil, Pueraria,

There are trends: Ginkgo biloba, cooked rhubarb, sea buckthorn, milk thistle, capillaris, hawthorn, Chuanxiong, red oak

(3) After repeated administration of normal mice, the TG has a significantly reduced decrease: Second, the second stage of screening the above preferred drug regrouping (administration method, dosage, etc. are the same as above) (see Table 9)

Table 9 Summary of Compound Remarks for Drug Regrouping Screening

From the above results, it can be seen that different drug combinations show different results in reducing TG in various models, possibly due to different mechanisms of action. However, the end result is that it shows a better effect of reducing TG. Experimental Example 9: Experimental study on hypoglycemic effect of the pharmaceutical composition of the present invention

1. Experimental materials

(1) Male ICR mice, 22±2g, purchased from Beijing Huakangkang Biotechnology Co., Ltd.

(2) Bai Tangping: Batch number: BJ01063, Manufacturer: Bayer Health Care Co., Ltd.

(3) Metformin: Lot No.: 100624, Manufacturer: Beijing Shuanghe Pharmaceutical Co., Ltd.

(4) Compound drugs:

Red yeast extract I preparation: the preparation method of the extract I in the same manner as in the example 10;

Pueraria lobata extract II preparation: the preparation method of the extract of the same method as in Example 10;

Preparation of extract of Mulberry bark III: a method for preparing the extract of the same method as in Example 10;

Preparation of compound medicine: See Example 10 for the preparation method.

Each of the above drugs was prepared by adding 1% CMC (carboxymethyl cellulose) to 1 ml (liquid) / g (raw drug).

2, the experimental method

(1) Preparation and screening of streptozotocin (STZ) diabetic model mice

Male ICR mice, weighing 24-28 g, fasted overnight, were modeled by rapid tail vein injection of freshly prepared STZ solution at a dose of 140 mg/kg. The mice were given a free diet after modeling. After 2 weeks of modeling, the fasting blood glucose (white sky abdomen 3_4h) was measured using the American Johnson & Johnson blood glucose meter, and the fasting blood glucose above 11. ImM was selected as a successful model.

(2) Grouping, administration and index determination

Except for the blank control group, all the successful diabetic mice were divided into three groups: model group, Baitangping group and compound three dose groups. It is administered once a day by intragastric administration. The fasting blood glucose was measured once a week, the non-fasting blood glucose was measured in two weeks, and the fasting blood lipid level was measured periodically. The blood was collected at the end, and the related indicators such as glycated hemoglobin and ins were measured.

(3) Plasma sample preparation

Blood was taken from the tail vein of the surgical blade, and 20 μΐ or 10 μΐ of the blood was taken from Yantai Yongming. The mixture was mixed well with 10 μΐ of EDTA physiological saline solution (EDTA concentration was 0.15 g/10 ml), 3000 rpmX. Centrifuge at lOmin and take the supernatant for glucose determination.

(4) Sampling methods for fasting and non-fasting blood glucose

Fasting blood glucose: Each group of mice was fasted for 4 hours during the day to collect blood and determine fasting blood glucose. The mice were intragastrically administered for 3 hours after fasting, and 1 hour later, blood was taken from the tail vein to measure fasting blood glucose.

Non-fasting blood glucose: Each group of mice was intragastrically administered with the corresponding test drug at 9 am, and blood was taken from the tail vein 1 h after the administration to measure the non-fasting blood glucose.

(5) Method for measuring blood sugar:

Using the kit of Zhongsheng Beikong, take 2 μl of plasma, add 96-well plate, then add 300 μΐ of Zhongsheng Beikong reagent, and place it in Vers Luo X-plate reader for 10 min at 37 °C to determine 0D ₅ . ₅ values.

(6) Oral glucose tolerance test (0GTT)

The mice were fasted for 4 hours during the day, and the fasting blood glucose was measured by cutting the tail vein. Then, each test drug was given by ig. After half an hour, ig was given 2 g/kg of glucose solution (concentration was 20%, and the administration volume was 10 ml/ Kg), blood was taken at 0.5 h, 1 h and 2 h after glucose administration.

(7) Oral starch tolerance test

After the rats were fasted for 4 hours in the daytime, the fasting blood glucose was measured by cutting the tail vein, and then the medicated starch solution was administered ig, wherein the concentration of the starch solution was 0.15 g/ml, and the dosage volume was 20 ml/kg. The dose is 3 g/kg. Blood was taken at 0.5 h, 1 h, and 2 h of the starch solution, and blood glucose levels were measured.

(8) Determination of glycated hemoglobin

After fasting overnight mice were anesthetized with 50 mg/kg sodium pentobarbital, blood was drawn from the abdominal aorta. 5 ml/1 of EDTA physiological saline solution was taken out with a 2 ml syringe, and all air in the tube was removed, and the volume was adjusted to 0.2 ml. Then, the abdominal aorta was pumped to 1.2 ml, and the blood was thoroughly mixed with EDTA physiological saline solution. , placed in an ice water mixture. After the end of the test, centrifugation (3000 rpm X IOmin, 4 ° C), the upper layer of plasma was used for other indicators, and the lower cells were stored in a -4 ° C refrigerator.

The sample was thoroughly mixed with a vortex shaker, then 100 μΐ of blood cells were taken, 100 μΐ of physiological saline was added, and the mixture was thoroughly mixed with a vortex shaker, and then the Siemens glycated hemoglobin meter DCA vantage and its supporting kit (5035C) were used. ) Perform the measurement.

3, the experimental results

(1) Effect of continuous administration of compound on fasting blood glucose in STZ mice

Table 10 Effect of continuous administration of compound on fasting blood glucose in STZ mice

3w 5w 7w

Blank control 2.8+1.2" 4.2±1.1 4.8 soil 1.1 model control 32.3+3.3 33.4+3.5 32.9+5.4 Baitangping 20mg/kg 25.9 soil 7.2* 30.1+4.0 28.7 soil 7.1 Compound 20 g/kg 26.5±3.9"28.3+3.5" 27.6 soil 2.8

* <0.05 ** P<0.01, the drug-administered group compared with the model group; n=l l-12 From the above results, the fasting blood glucose of the STZ model mice at each time point was significantly higher than that of the blank control, indicating that the STZ was small Rats have significant hyperglycemia characteristics and have been very successful as a mouse model of diabetes.

Bai Tangping has a certain tendency to reduce the fasting blood glucose of model mice, which may be indirectly related to the inhibition of α-glucosidase by Bai Tangping. Explain that our test system is completely credible.

The compound prescription can reduce the fasting blood glucose of model mice at different time points at different time points, and has obvious statistical differences, indicating that the compound does have a clear effect on reducing fasting blood glucose in STZ mice.

(2) Effect of continuous administration of compound on the level of glycosylated hemoglobin (HbAl c) in STZ mice

Table 11 Effect of continuous administration of compound for 2 months on HbAlc levels in STZ mice Group dose HbAlc(<3⁄4) blank control 3.8±0.3

Model control 8.6 soil 1.0

Bai Tangping 20mg/kg 7.1+0.8"

Compound 20g/kg 7.3+0.7"

*, p<0.05, **, p<0.01, compared with the model control group, n=l l-12 From the above results, the glycosylated hemoglobin level of STZ mice was significantly higher than that of the blank control group, indicating that the model mice Blood glucose has been at a high level for a long time, indicating that the diabetic mouse model was successfully established.

Long-term administration of Baitangping in STZ model mice can significantly reduce the level of glycosylated hemoglobin in model mice, and there is a statistically significant difference, indicating that the administration of 2 months of Baitangping can maintain the blood glucose of the model mice continuously and smoothly. At a lower level, the entire test system is believed to be credible.

In reducing the level of glycated hemoglobin in model mice, the compound can significantly reduce the level of glycated hemoglobin in the model mice, which is statistically different, indicating that the compound can exert a sustained and stable effect on the blood sugar of STZ mice. From the above experimental results, the following conclusions can be drawn:

(1) The compound has a clear effect on reducing fasting blood glucose in STZ mice.

(2) The compound can significantly reduce the glycated hemoglobin level of the model mice, and exert a sustained and stable effect on the blood sugar of the model mice. detailed description: Example 1: Preparation of the pharmaceutical composition pellet of the present invention

6 kg of red yeast rice was taken, and 24 L of 80% ethyl acetate was added and heated under reflux for 2 hours, and extracted three times; the extract was filtered, the filtrate was combined, the solvent was recovered, and concentrated to a thick paste to obtain extract I.

Take radix radix lkg: Dilute with water 3 times, each time the volume is 10 times, 8 times, 8 times of its weight, and the boiling time is 2h, lh, lh. The filtrate was separately filtered, and the filtrate was combined and concentrated under reduced pressure to give the extract II.

The extracts I and II are added to the preparation auxiliary materials, and the clinically accepted dropping pills are prepared according to a conventional process. Example 2: Preparation of the pharmaceutical composition capsule of the present invention

4 kg of red yeast rice, adding 8 L of 90% ethanol and refluxing for 1 hour, filtering; adding 8 L of 90% ethanol and refluxing for 1 hour, filtering; combining the filtrate, recovering the solvent, and concentrating into a thick paste to obtain extract I.

Take radix radix lkg: add 15 times of its weight, extract 90% ethanol, reflux for 2h, filter; add 10 times 90% ethanol reflux for 1h, filter; combine the filtrate and concentrate to obtain extract II.

The extracts I and II are added to the preparation excipients, and the clinically accepted capsules are prepared according to a conventional process. Example 3: Preparation of oral liquid of pharmaceutical composition of the present invention

Take 1kg of red yeast medicine, add 4L of 50% ethanol and reflux for 3 hours, and extract the extract; filter residue by adding 2L of 50% ethanol and reflux for 3 hours, and extract the extract. The mixture is combined with two filtrates, and the ethanol is recovered under reduced pressure, and concentrated to 55~60 ° C. The relative density is 0. 95~1. 06. Add 0.2 volume of deionized water to the concentrate and mix for 12 hours. After centrifugation, the precipitate was collected to obtain a red yeast extract I.

5小时。 After extracting the roots of the roots of the genus 6g _g: 10 times the weight of 20% ethanol reflux extraction 1. 5h, filtration; adding 10 times 20% ethanol reflux extraction 1. 5h, filtration; the filtrate was combined, concentrated, to obtain extract II.

The extracts I and II are added to the preparation auxiliary materials, and a clinically accepted oral liquid is prepared according to a conventional process. Example 4: Preparation of granules of pharmaceutical composition of the present invention

Take red yeast lkg, add 4L of 80% ethanol each time and heat to reflux for 2 hours, extract 2 times; extract the filtrate, combine the filtrate, recover the solvent, concentrate to thick paste, and obtain extract I.

Take radix radicans 3k _g: add 10 times the volume of 50% ethanol and reflux for 2 times, the extraction time is 2h. The filtrate was separately filtered, and the filtrate was combined and concentrated under reduced pressure to give the extract II.

The extracts I and II are added to the preparation excipients, and the clinically accepted granules are prepared according to a conventional process. Example 5: Preparation of a pharmaceutical composition tablet of the present invention

2 kg of red yeast rice was added, and 6 L of 70% ethanol was added and heated under reflux for 3 hours, and filtered; 4 L of 75% ethanol was further added thereto and heated under reflux for 2 hours, and filtered; the filtrate was combined, the solvent was recovered, and concentrated to a thick paste to obtain an extract I.

Take the radix radicans lkg: add 8 times the volume of 75 times ethanol reflux extraction 2 times, the extraction time is lh. The filtrate was separately filtered, and the filtrate was combined and concentrated under reduced pressure to give the extract II.

Extracts I and II were added to the preparation excipients, and clinically accepted tablets were prepared according to a conventional procedure. Example 6: Preparation of the pharmaceutical composition capsule of the present invention

Take the red yeast medicine lkg, add 3L75 % ethanol reflux extraction for 3 hours, the extract is filtered; the filter residue is added to 2L75 % ethanol reflux extraction for 2 hours, and the extract is filtered. Combine the two filtrates, recover the ethanol under reduced pressure, and concentrate to 55~60 °C. Relative density 0. 95~1. 06. The mixture was mixed with 2.0 times volume of deionized water and allowed to stand for 8 hours. Centrifuge and collect the pellet. Extract I was obtained.

Take Pueraria lobata 1kg: Add 6 times of 7 times volume of 75 % ethanol to extract twice, and the extraction time is lh. The filtrate was separately filtered, and the filtrate was combined, concentrated under reduced pressure and dried to give extract II.

The extracts I and II are added to the preparation excipients, and a clinically accepted capsule is prepared according to a conventional process. Example 7: Preparation of the pharmaceutical composition capsule of the present invention

Take the red yeast medicine lkg, puerarin lkg into 6L75% ethanol reflux extraction for 3 hours, the extract is filtered; the filter residue is added to 6 parts by volume of 75 % ethanol for reflux for 2 hours, and the extract is filtered. The filtrate was combined twice, and the ethanol was recovered under reduced pressure, concentrated and dried. The preparation auxiliary is added, and a clinically accepted capsule is prepared according to a conventional process.

Example 8: Preparation of oral liquid of pharmaceutical composition of the present invention

10 kg of Hongqu and 10 kg of Radix Puerariae were added, and 120 L of 75 % ethanol was added to reflux for 3 hours, and the extract was filtered; the residue was added to 120 L of 75 % ethanol and refluxed for 2 hours, and the extract was filtered. The preparation excipients are added, and a clinically accepted oral liquid is prepared according to a conventional process.

Example 9: Preparation of soft capsule of pharmaceutical composition of the present invention

Take 1kg of red yeast medicine, add 3L755% ethanol reflux for 3 hours, extract the extract; filter residue by adding 2L75 % ethanol reflux extraction for 2 hours, extract the filtrate. The mixture is combined with two filtrates, and the ethanol is recovered under reduced pressure, and concentrated to 55~60 ° C. The relative density is 0. 95~1. 06. Add 0.2 volume of deionized water to the concentrate and mix for 8 hours. Centrifuge and collect the pellet. Extract I was obtained.

The extracts I and II are added to the preparation excipients, and a clinically accepted soft capsule is prepared according to a conventional process.

Example 10: Preparation of granules of pharmaceutical composition of the present invention

10 kg of red yeast medicine was taken, and refluxed for 3 hours by adding 30 L of 75% ethanol, and the extract was filtered; the residue was added to 20 L of 75% ethanol and refluxed for 2 hours, and the extract was filtered. The mixture is combined with two filtrates, and the ethanol is recovered under reduced pressure to a concentration of 55 to 60 ° C. Add 0.2 volume of deionized water to the concentrate and mix for 8 hours. Centrifuge and collect the pellet. Extract I was obtained.

Take Pueraria lobata 10k _g: add 60L of 75% ethanol and reflux for 2 times, the extraction time is lh. The filtrate was separately filtered, and the filtrate was combined, concentrated under reduced pressure and dried to give extract II.

Take 10 kg of mulberry white medicinal material, add 100 L of water and boil for 2 hours, extract twice, extract the extract, combine the filtrate, concentrate, and centrifuge. The cation exchange resin was eluted with 6 column volumes of 0.5 mol/L aqueous ammonia solution, concentrated, and dried to obtain extract III.

The extracts I, II, and III are added to the preparation excipients, and the clinically accepted granules are prepared according to a conventional process.

Claims

Rights request

A pharmaceutical composition having a blood lipid regulating effect, characterized in that the pharmaceutical composition of the pharmaceutical composition is: 1 part by weight of red yeast rice and 1 to 5 parts by weight of pueraria.

The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition of the pharmaceutical composition is any one of the following:

Red koji 2 heavy S parts 4 heavy t parts;

Red yeast 4 S S shares t;

Red yeast 1 S S shares 4 weights] t copies;

Red yeast 4 heavy" t shares 1 weight] t copies.

The pharmaceutical composition according to claim 1 or 2, wherein the pharmaceutical composition is produced by the following method: Step one, red yeast extract I preparation

Red yeast extract I is prepared by any of the following methods:

Step 2, Pueraria lobata extract II preparation

Pueraria radix 1 part by weight, add 4~20 parts by volume of water or ethanol each time and heat to reflux for 1~3 hours, extract

2 4 times, the extract is filtered, the filtrate is combined, the solvent is recovered, and concentrated into a thick paste; the extract II is obtained;

Step three, preparation

The extract I and the extract II are added to a conventional excipient according to a conventional method to prepare a clinically accepted pellet, powder, tablet, granule, capsule or oral liquid preparation.

The pharmaceutical composition according to claim 3, wherein the method A in the first step is: taking 1 part by weight of the red yeast medicine, adding 3 parts by volume of 75% ethanol and refluxing for 3 hours, and extracting the extract; The thick paste of the slag is obtained. The thick residue of the slag is obtained by adding 2 parts by volume of 75% ethanol and refluxing for 2 hours, and the extract is filtered, and the filtrate is combined, and the ethanol is evaporated to a concentration of 55. Extract I.

The pharmaceutical composition according to claim 3, wherein the method B in the first step is: 1 part by weight of red yeast medicine, and 3 parts by volume of 75% ethanol is added for reflux extraction for 3 hours, and the extract is filtered; The addition of 2 parts by volume of 75% ethanol was refluxed for 2 hours, and the extract was filtered, and the filtrate was combined, and the ethanol was evaporated under reduced pressure to give a relative density of 0. 95~1. Mix 1 time with deionized water, and leave it at room temperature or refrigerate for 8 hours. After centrifugation, the precipitate was collected, dried at 80 ° C for 8 hours, and pulverized through a 60 mesh sieve to obtain Extract I.

6. The pharmaceutical composition according to claim 3, wherein the second step is:

1 part by weight of Radix Puerariae, each time adding 12 parts by volume of 70% or 40% ethanol for 1 to 3 hours, extracting 2~3 times, filtering the extract, combining the filtrate, recovering the solvent, and concentrating to 55~60 °C Measure the relative density of 0. 95~1. 06 thick paste; get extract II.

The method for preparing a pharmaceutical composition according to claim 1 or 2, wherein the method is as follows: Step 1: Preparation of Monascus extract I

Red yeast extract I is prepared by any of the following methods:

A, red koji 1 part by weight, each time adding 2~10 parts by volume of 50~90% ethanol, methanol or ethyl acetate, heating under reflux for 1-3 hours, extracting 2~3 times; extracting the filtrate, combining the filtrate, recycling The solvent is concentrated to 55~60 ° C to measure the relative density of 0. 95~1. 06 thick paste, to obtain extract I; B, red koji 1 part by weight, each time adding 2~10 parts by volume of 50~90% ethanol, methanol or ethyl acetate heated under reflux for 1~3 hours, extracting 2~3 times; extracting the filtrate, combining the filtrate, recovering the solvent Concentrating to a concentration of 0. 95~1. 06, concentrated in a concentration of 0. 5~2. 0 times deionized water mixed, room temperature or refrigerated for 2 to 12 hours, centrifuge, Collecting the precipitate and drying to obtain the extract I;

Step 2, Pueraria lobata extract II preparation

Step three, preparation

The method for preparing a pharmaceutical composition according to claim 7, wherein the methods for preparing the red yeast extract I in the A and B methods are:

Method A: Take 1 part by weight of Monascus medicinal herbs, add 3 parts by volume of 75% ethanol and reflux for 3 hours, and extract the extract; filter residue added to 2 parts by volume of 75% ethanol and reflux for 2 hours, extract the filtrate, combine the two filtrates, reduce The extract of the thick paste obtained by the relative density of 0. 95~1. 06 thick extract I;

Method B: 1 part by weight of Monascus sinensis, 3 parts by volume of 75% ethanol was added to reflux for 3 hours, and the extract was filtered; the residue was added to 2 parts by volume of 75% ethanol and refluxed for 2 hours, the extract was filtered, and the filtrate was combined and decompressed. The ethanol was recovered and concentrated to a concentration of 55 to 60 ° 0. The relative density was 0.95 to 1. 06, and the mixture was mixed with 1 time of deionized water, and allowed to stand at room temperature or refrigerated for 8 hours. After centrifugation, the precipitate was collected, dried at 80 ° C for 8 hours, and pulverized through a 60 mesh sieve to obtain Extract I.

9. The method of preparing a pharmaceutical composition according to claim 7, wherein the preparation method of the Pueraria lobata extract II is:

The pharmaceutical composition according to claim 1 or 2, wherein the red yeast rice is ordinary red yeast or functional red yeast rice.

The pharmaceutical composition according to claim 1 or 2, wherein the pharmaceutical composition is added to a conventional excipient according to a conventional method to prepare a clinically acceptable pill, powder, tablet, granule, capsule or oral liquid. preparation.

The use of the pharmaceutical composition according to any one of claims 1 to 6 for the preparation of a medicament for treating hypertriglyceridemia.

A pharmaceutical composition having hypoglycemic action, characterized in that the pharmaceutical composition of the pharmaceutical composition is: 1 to 5 parts by weight of red yeast rice, 1 to 5 parts by weight of puerarin, and 1 to 5 parts by weight of mulberry white.

The pharmaceutical composition according to claim 13, wherein the pharmaceutical composition of the pharmaceutical composition comprises: 1 part by weight of red yeast rice, 1 part by weight of puerarin, and 1 part by weight of mulberry bark.

The pharmaceutical composition according to claim 13 or 14, wherein the pharmaceutical composition is produced by the following method:

Step one, red yeast extract I preparation

Red yeast extract I is prepared by any of the following methods:

B, red koji 1 part by weight, each time adding 2~10 parts by volume of 50~90% ethanol, methanol or ethyl acetate heated under reflux for 1~3 hours, extracting 2~3 times; extracting the filtrate, combining the filtrate, recovering the solvent Concentrating to a concentration of 0. 95~1. 06, concentrated in a concentration of 0. 5~2. 0 times deionized water mixed, room temperature or refrigerated for 2 to 12 hours, centrifuge, Collecting the precipitate and drying to obtain the extract I; Step 2, Pueraria lobata extract π preparation

Step 3: Preparation of Mulberry White Extract III

Red yeast extract I is prepared by any of the following methods:

C, mulberry white medicinal material 1 part by weight, each time add 8~12 parts by volume of water to boil for 1~3 hours, extract 2~3 times, extract the filtrate, combine the filtrate, concentrate to 55~60 °C a thick paste of 0. 95~1. 06; dried to obtain extract III;

D, mulberry white medicinal material 1 part by weight, each time add 8~12 parts by volume of water to boil for 1~3 hours, extract 2~3 times, extract the filtrate, combine the filtrate, concentrate, and centrifuge. The cation exchange resin was eluted with 3 to 8 column volumes of 0.25 to 1 mol/L aqueous ammonia solution, concentrated, and dried. Extract III;

Step four, the preparation

The pharmaceutical composition according to claim 15, wherein the method B in the step 1 is:

Method A: Take 1 part by weight of Monascus medicinal herbs, add 3 parts by volume of 75% ethanol and reflux for 3 hours, and extract the extract; filter residue added to 2 parts by volume of 75% ethanol and reflux for 2 hours, extract the filtrate, combine the two filtrates, reduce The extract of the thickened paste, the obtained extract I; the relative density of 0. 95~1. 06 thick extract, obtained extract I;

The pharmaceutical composition according to claim 15, wherein the second step is:

18. The pharmaceutical composition according to claim 15, wherein in the third step. The D method is:

5〜1。 C, mulberry white medicinal herbs 1 part by weight, each time adding 10 parts by volume of water to be extracted by boiling for 2 hours, extracted 2 times, the extract was filtered, the filtrate was combined, concentrated to 55~60 ° C measured relative density 0. 95~1 . 06 thick paste; dried to obtain extract III;

D. Mulberry white medicinal material 1 part by weight, each time 10 parts by volume of water is boiled and extracted for 2 hours, extracted twice, the extract is filtered, the filtrate is combined, concentrated, and centrifuged. The cation exchange resin was eluted with 6 column volumes of 0.5 mol/L aqueous ammonia solution, concentrated, and dried. Extract III was obtained.

The method for preparing a pharmaceutical composition according to claim 13 or 14, wherein the method is as follows: Step 1: Preparation of Monascus extract I

Red yeast extract I is prepared by any of the following methods:

Step 2, Pueraria lobata extract II preparation 1 part by weight of Radix Puerariae, each time adding 4~20 parts by volume of water or ethanol and refluxing for 1~3 hours, extracting 2~4 times, filtering the extract, combining the filtrate, recovering the solvent, and concentrating into a thick paste; Substance II;

Step 3: Preparation of Mulberry White Extract III

Red yeast extract I is prepared by any of the following methods:

Step four, the preparation

The method for preparing a pharmaceutical composition according to claim 19, wherein the methods of VIII and B in the step 1 are respectively:

The method for preparing a pharmaceutical composition according to claim 19, wherein the second step is: 1 part by weight of puerarin, and each step is added with 12 parts by volume of 70% or 40% ethanol to extract 1~3约的提取物II。 Extracted II, extracted 2 to 3 times, the extract was filtered, the filtrate was combined, the solvent was recovered, and concentrated to 55~60 ° C to measure the relative density of 0. 95~1. 06 thick paste;

The method for producing a pharmaceutical composition according to claim 19, wherein in the third step. The D methods are:

The pharmaceutical composition according to claim 13 or 14, wherein the red yeast rice is ordinary red yeast or functional red yeast rice.

24. Use of a pharmaceutical composition according to any one of claims 13 to 18 for the preparation of a medicament for lowering blood glucose.