WO2021213230A1

WO2021213230A1 - Application of traditional chinese medicine composition in preparation of drug for treating or preventing fatty liver disease

Info

Publication number: WO2021213230A1
Application number: PCT/CN2021/087271
Authority: WO
Inventors: 吴铁; 袁孟峰; 王嘉豪; 麦龙儿
Original assignee: Ng Tit
Priority date: 2020-04-23
Filing date: 2021-04-14
Publication date: 2021-10-28
Also published as: CN112007123B; CN112007123A

Abstract

An application of a traditional Chinese medicine composition in the preparation of a drug for treating or preventing fatty liver disease. The traditional Chinese medicine composition is prepared from gardenia, poria, salvia, cortex lycii, radix pseudostellariae, fructus amomi, raw malt, and semen raphani. The described traditional Chinese medicine composition can treat or prevent fatty liver disease, treating and/or preventing non-alcoholic fatty liver disease in particular.

Description

Application of traditional Chinese medicine composition in preparing medicine for treating or preventing fatty liver disease

Technical field

The invention relates to the field of medicine, in particular to the application of a traditional Chinese medicine composition in the preparation of a medicine for treating fatty liver.

Background technique

Non-alcoholic fatty liver disease (NAFLD) refers to the excessive deposition of fat in liver cells caused by alcohol and other clear liver damage factors. NAFLD is a common liver disease, and global health concerns are increasing, with an estimated global prevalence of 25.2%. It includes a wide spectrum of diseases, from simple steatosis to non-alcoholic steatohepatitis (NASH), which may lead to advanced fibrosis, liver cirrhosis or its related complications, and hepatocellular carcinoma. In Western countries, people's observation and research on NAFLD are the most common, with a prevalence of 24-46%. Recently, with the improvement of living standards and changes in lifestyle and eating habits, the prevalence of NAFLD in Asia is also increasing rapidly. The meta-analysis conducted by Li et al. found that the combined prevalence of NAFLD in mainland China was 20.1%. According to reports, the prevalence of NAFLD exceeds 40% in Chinese cities such as Beijing, Shanghai and Hong Kong, as well as other Asian cities. These data indicate the importance of NAFLD, which is the main cause of chronic liver diseases in Asia (except chronic hepatitis B). However, the pathogenesis of NAFLD has not been fully elucidated, and there is a lack of effective treatment for NAFLD.

In recent years, the treatment of non-alcoholic fatty liver disease with traditional Chinese medicine has attracted more and more attention. The treatment of traditional Chinese medicine has a wide range of clinical applications and multi-channel therapeutic effects; it has the characteristics of inhibiting inflammation, protecting the liver and lowering enzymes. Traditional Chinese medicine can treat diseases with multiple approaches, multiple targets, and multiple links from a holistic perspective, and at the same time, have small adverse reactions, providing new ideas for the treatment of NAFLD.

Therefore, it is necessary to develop a new traditional Chinese medicine composition for the preparation of drugs for the treatment or prevention of fatty liver disease.

Summary of the invention

In view of the above technical status, the purpose of the present invention is to provide a new traditional Chinese medicine composition in the preparation of the treatment or prevention of fatty liver disease of the application It is composed of ginseng, Amomum villosum, raw malt and vegetable servings.

In the present invention, as one of the embodiments, the fatty liver disease is non-alcoholic fatty liver disease.

The invention also provides an application of the composition in the preparation of treatment or prevention of steatosis.

In the present invention, as one of the embodiments, the steatosis is steatosis caused by a high-fat diet.

In the application of the present invention, the amount of the Chinese medicine composition administered to an adult subject is: 5-10g/day (calculated as a Chinese medicine pill). As an exemplary illustration, the amount of the Chinese medicine composition administered to an adult subject may be 5g/day. Daily, 6g/day, 7g/day, 8g/day, 9g/day, and 10g/day Chinese medicine pills of the present invention.

The present invention also provides a traditional Chinese medicine composition for the above application. The traditional Chinese medicine composition, by weight, consists of 1.25-1.55 parts of Gardenia, 1.25-1.46 parts of Poria, 0.925-1.31 parts of Salvia miltiorrhiza, and 1.1-1.5 parts of Digupi It consists of 1.37 parts, 0.925-1.08 parts of Taizishen, 0.55-0.68 parts of Amomum villosum, 3 parts of raw malt, and 1 part of Caifuzi.

As one of the embodiments, the traditional Chinese medicine composition of the present invention is composed of 1.55 parts of Gardenia, 1.46 parts of Poria, 1.31 parts of Salvia miltiorrhiza, 1.37 parts of Radix Geophylla, 1.08 parts of Radix Ginseng, 0.68 parts of Amomum villosum, and 3 parts of raw malt by weight. It consists of 1 serving and 1 serving of Caifuzi.

As one of the embodiments, the traditional Chinese medicine composition of the present invention is composed of 1.25 parts of Gardenia, 1.25 parts of Poria, 0.925 parts of Salvia miltiorrhiza, 1.1 parts of Radix Geophylla, 0.925 parts of Radix Ginseng, 0.55 parts of Amomum villosum, and 3.0 parts of raw malt by weight. It is composed of 1.0 servings and 1.0 servings of Caifuzi.

The present invention also provides a method for preparing a traditional Chinese medicine composition, the method comprising:

(1) The prescription ratio Zhongdan participated in the extraction of gardenia with 80% ethanol for 2 times, the first time was 5 times the amount of 80% ethanol for 2 hours, the second time was 4 times the amount of 80% ethanol for 1.5 hours, filtered , The dregs are collected in a separate container for use; the two filtrates before and after are combined, and ethanol is recovered under reduced pressure to a clear ointment with a relative density of about 1.20 (70°C) for use;

(2) Crush 1/10 of the prescription amount of Poria cocos through a 100-mesh sieve to sift out the fine powder, and the remaining coarse particles will be used separately;

(3) Add 7 times the amount of water to decoction for 2 hours, filter, and collect the filtrate by adding 7 times the amount of water and pulverized coarse grains of Poria cocos and Poria cocos in the prescription proportions of Zhongsheng malt, Digupi, Laifuzi and Prince Edward The slag will be collected separately for later use;

(4) Add 8 times the amount of water to extract the volatile oil of Amomum villosum in the prescription ratio for 2 hours, and collect the volatile oil for later use; the filtrate of Amomum villosum and the medicine residue are collected in a separate container for use;

(5) Combine the dregs obtained above, add 5 times the amount of water to decoct for 1.5 hours, filter, and collect the filtrate; then combine with the filtrate in steps (3) and (4), and concentrate under reduced pressure to a relative density of about 1.20 Clear ointment: Combine the obtained clear ointment with salvia miltiorrhiza and gardenia alcohol extraction ointment, mix well, concentrate to a thick paste with a relative density of about 1.40, dry under reduced pressure, and pulverize into fine powder extract;

(6) Mix and dry the fine extract powder, Amomum villosum volatile oil and sterilized Poria powder to obtain.

The present invention also provides a preparation containing the traditional Chinese medicine composition of the present invention. The preparation is composed of the traditional Chinese medicine composition and pharmaceutical excipients. As one of the embodiments, the excipients include but are not limited to beta cyclodextrin, corn Starch, talc, or a combination of two or more of them.

In the present invention, as one of the embodiments, the preparation includes but is not limited to pills, dripping pills, capsules or granules.

A person skilled in the art prepares the traditional Chinese medicine composition of the present invention and including but not limited to the above-mentioned auxiliary materials in the present invention into pills, drop pills, capsules or granules based on common knowledge in the field and conventional preparation methods.

As one of the embodiments, the preparation is preferably a pill; as one of the embodiments, the auxiliary materials of the pill are betacyclodextrin, corn starch and talc.

As one of the embodiments, the present invention further provides a preparation method of the pill. The preparation method of the preparation includes:

(2) Crush 1/10 of the prescription amount of Poria in the prescription through a 100-mesh sieve to sift out the fine powder, and the remaining coarse particles will be used separately;

(3) Add 7 times the amount of water to decoction for 2 hours, filter, and collect the filtrate by adding 7 times the amount of water and pulverized coarse grains of Poria cocos and Poria cocos in the prescription proportions of Zhongsheng malt, Digupi, Laifuzi and Prince Edward The slag is collected by another device for later use;

(4) Add 8 times the amount of water to extract the volatile oil of Amomum villosum in the prescription ratio for 2 hours, collect the volatile oil, and clathrate it with beta cyclodextrin to obtain the Amomum villosum volatile oil beta cyclodextrin inclusion compound for later use; Amomum villosum filtrate Collect separately from the medicine residue for later use;

(5) Combine the dregs obtained above, add 5 times the amount of water to decoct for 1.5 hours, filter, and collect the filtrate; then combine with the filtrate obtained in steps (3) and (4), and concentrate under reduced pressure to a relative density of about 1.20 (70 ℃) clear ointment; combine the obtained clear ointment with salvia miltiorrhiza and gardenia alcohol extraction ointment, mix, and concentrate to a thick paste with a relative density of about 1.40 (70°C), dry under reduced pressure, and pulverize into fine powder extract. Can;

(6) The fine powder of extract, the inclusion compound of Amomum villosum volatile oil beta cyclodextrin and the fine sterilized Poria powder are made into pellets with honey water (refined honey: water = 1:3), dried, and corn starch and talc are used. Powder coating, ready to go.

Experiments have proved that the traditional Chinese medicine composition of the present invention has significant therapeutic and/or preventive effects on the treatment of non-alcoholic fatty liver disease, and has a good synergistic effect.

Description of the drawings

Figure 1 shows the body weight changes of mice fed a high-fat diet treated with Chinese medicine pills of the present invention.

Figure 2 shows the changes in serum total cholesterol levels of mice fed a high-fat diet treated with Chinese medicine pills of the present invention.

Figure 3 shows the changes in serum triglyceride levels of mice fed a high-fat diet treated with Chinese medicine pills of the present invention.

Figure 4 is a representative histological image (H&E, 200 times magnification) of mouse liver tissue, which shows different degrees of steatosis.

A. 0% steatosis; B. 5-10% steatosis; C. 60% steatosis; D. 90% steatosis.

Detailed ways

The present invention further illustrates the present invention through the following examples and experimental examples, and is not intended to limit its scope.

Preparation of Chinese medicine composition

Example 1

1) Chinese medicine composition formula (in parts by weight):

2) Preparation method:

Example 2

1) Chinese medicine formula (in parts by weight):

2) Preparation method:

Preparation of Chinese medicine composition pills

Example 3

1) Chinese medicine composition formula (in parts by weight)

2) Accessories (in parts by weight)

Beta cyclodextrin 0.04

Corn starch 3% (based on the amount of the total blend)

Talc 0.8% (based on the amount of the total blend)

3) Preparation method

(6) The fine powder of extract, the volatile oil beta cyclodextrin of Amomum villosum, and the fine sterilized Poria powder are made into pellets with honey water (refined honey: water = 1:3), dried, and made into 1000 g. Coated with corn starch and talcum powder, ready to be obtained.

Example 4

1) Chinese medicine composition

2) Accessories (in parts by weight)

Beta cyclodextrin 0.04

Corn starch 3% (based on the amount of the total blend)

Talc 0.8% (based on the amount of the total blend)

3) Preparation method

Test example 1

Samples and reagents:

The Chinese medicine pill of the present invention was prepared according to Example 3;

High-fat food: (HFD Research Diets, New Brunswick, NJ; catalog number D12492), which has a fat content of 60%;

Low-fat control diet (LFD; Research Diets; catalog number D12492), the fat content is only 10%.

Animal model and research design

Five-week-old C57BL/6J male mice were used as animal models to simulate human metabolic abnormalities. All mice are kept in a pathogen-free environment, with temperature (22±2°C), humidity (40-60%), and a light-dark cycle of 12:12 hours. All mice were fed ad libitum. After 7 days of acclimatization to the standard food environment, the mice were randomly assigned: fed a high-fat diet (HFD; Research Diets, New Brunswick, NJ; catalog number D12492) with a fat content of 60%; or its corresponding low The fat control diet (LFD; Research Diets; catalog number D12492) has a sucrose content that matches HFD, but the fat content is only 10%.

The mice were divided into different groups according to diet and intervention (Table 1). For all groups, the mice were first fed LFD or HFD for 10 weeks, and then for 8 weeks of intervention (using traditional Chinese medicine pills or water (as a placebo)).

Table 1 Diet and treatment plan of different groups of mice

*Dose definition: normal=46.2mg/50g mice; low dose=half the normal dose (23.1mg/50g mice); high dose=two times the normal dose (92.4mg/50g mice)

Each group consisted of 10 mice. Group 1 consisted of LFD-fed mice (n=10), which was used as a low-fat normal control. Group 2 is a model control with HFD-fed mice (n=10). Groups 3, 4, and 5 are HFD-fed mice, respectively, with different doses (low, normal or high doses) of the Chinese medicine pill of the present invention.

The normal dose is determined to be 46.2mg Chinese medicine pills/50g mice. Traditional Chinese medicine pills are prepared in a form suspended in water and administered by oral gavage every day. The high dose is set to twice the normal dose (92.4mg Chinese medicine pill/50g mouse), and the low dose is set to half the normal dose (23.1mg/50g mouse). As a placebo, control mice without intervention were given water equivalent to the volume of Chinese medicine pills.

The mice were weighed every week, and the dosage of Chinese medicine pills (or water) for each mouse was based on body weight. Chinese medicine pills were administered for 8 weeks.

At baseline, (before TCM pill treatment/placebo), 50 μL of blood was collected from the tail vein. At the end of the experiment (after 8 weeks of intervention), the mice were sacrificed, and blood and liver tissue were collected for analysis. All animal experiments were carried out in accordance with the Laboratory Animal Use Guidelines of the Teaching and Research Committee on the Use of Live Animals of the University of Hong Kong.

Biochemical analysis

The ALT/GPT Liqui-UV assay and the AST/GOT Liqui-UV assay (both from Stanbio Laboratory, Boerne, TX) were used to evaluate serum ALT and AST, respectively. The LiquiColor triglyceride and cholesterol LiquiColor assays (both from Stanbio Laboratory) were used to analyze serum triglycerides and total cholesterol.

Histological analysis

The liver tissue specimens were fixed in 10% formalin buffer, embedded in paraffin, cut into 5 μm thick, and stained with hematoxylin and eosin. The degree of steatosis was assessed by a pathologist who did not understand the experimental design and was based on the system described by Kleiner et al. (Hepatology 2005; 41:1313-21). Fat changes are expressed as the percentage of fatty degeneration cells and are classified as described previously: no steatosis (<5% fat change); low-grade steatosis (fat change is 5-33%); moderate steatosis (>33 -66% fat change); and severe steatosis (>66% fat change).

Statistical analysis was performed using SPSS 25.0 (SPSS, Chicago, Illinois). Continuous variables are expressed as mean±standard error of mean (SEM), and analyzed using Student's t test or one-way ANOVA test. The categorical variables were analyzed using chi-square test or Fisher's exact test. P<0.05 was considered statistically significant.

Experimental result

Baseline characteristics

Before feeding different diets, the mice assigned to LFD and HFD had comparable body weights (22.5±0.3g and 22.1±0.1g, respectively; P=0.331). In the 0th week of intervention (baseline) (ie, after 10 weeks of differential diet and before the administration of Chinese medicine pills), the mice fed with HFD (average body weight: 44.1±0.5g) were higher than those fed with LFD (average body weight). : 29.9±0.6g; P<0.001) is much heavier. After 10 weeks of diet, the average weight change of LFD-fed mice was 7.4±0.6g, while the average weight change of HFD-fed mice was 22.0±0.5g (P<0.001).

The serum total cholesterol level of HFD-fed mice (129.6±3.5mg/dL) was significantly higher than that of LFD-fed mice (79.1±8.4mg/dL; P<0.001), and the serum glycerol of HFD-fed mice The triester level (76.0±6.1 mg/dL) was higher than that of LFD-fed mice (41.4±3.8 mg/L; P=0.052).

Then designated mice fed by HFD to receive different doses of Chinese medicine pills (or water as a placebo control). At baseline (the beginning of the Chinese medicine pill treatment), the body weight, serum total cholesterol and triglycerides of the different HFD-fed mice receiving different treatments were well balanced and comparable (Table 2).

Table 2. Baseline characteristics of different groups of mice

LFD: low-fat diet; HFD: high-fat diet

Effect of Chinese medicine pill of the present invention on fatty liver mice induced by high-fat diet

Average weight

At the end of the experiment, the average body weight of the HFD-fed control mice (group 2) was 49.2±0.68 g, which was 14.8% heavier than the baseline (before treatment) body weight. At the end of the treatment, the weight gain of the control mice fed with HFD was significantly greater than that of the control mice fed with LFD (group 1), and the average body weight of the latter increased by 3.3% (P=0.041). The body weight of HFD-fed mice (average increase: 5.1-12.0%) that received Chinese medicine pills also increased. The weight gain of each treatment group was slightly lower than that of the HFD placebo group, but the difference in weight change was not statistically significant. No dose effect on weight change was observed in the Chinese medicine pill group (Figure 1); the experimental results showed that the Chinese medicine pill of the present invention effectively reduced the weight gain effect of high-calorie diet in mice, and has corresponding effective prevention or treatment effect.

Total cholesterol level

In LFD-fed control mice, total cholesterol levels at the end of treatment increased by 16.9% (compared to baseline), while HFD-fed placebo mice increased by 57.7% in total cholesterol at the end of treatment (P= 0.073). For mice treated with traditional Chinese medicine pills (Figure 2), the average increase in total cholesterol levels at the end of low, normal, and high-dose Chinese medicine pills treatment was 39.4%, 14.6%, and 7.9%, respectively. The P values (compared to placebo) were 0.388, 0.075 and 0.049, respectively. Overall, by comparing the placebo group and the three dose groups of traditional Chinese medicine pills, the dose effect of serum total cholesterol can be observed (P=0.043); the experimental results show that traditional Chinese medicine pills effectively reduce the high-calorie diet in mice. Cholesterol-increasing effects have corresponding effective preventive or therapeutic effects.

Serum triglyceride level

Compared with baseline, the serum triglyceride levels of LFD-fed mice increased by 6.5% by the end of the experiment. The average increase in serum triglycerides of LFD-fed mice was significantly less than that of HFD-fed placebo-controlled mice (a 35.0% increase compared to baseline; P = 0.022). In all mice treated with traditional Chinese medicine pills, serum triglycerides decreased at the end of the treatment. The average reduction of triglycerides in mice treated with low-dose, normal-dose and high-dose Chinese medicine pills was 4.2%, 11.2% and 18.6% (compared to the placebo group, all P<0.05; Figure 3). Mice treated with traditional Chinese medicine pills observed a dose-dependent decrease in serum triglyceride levels (P=0.006); the experimental results showed that traditional Chinese medicine pills effectively reduced the increase in serum triglycerides caused by high-calorie diet in mice, and had a corresponding effect. Effective prevention or treatment.

Serum ALT and AST

At the end of the treatment period, the average serum ALT and AST values of LFD-fed control mice were 17.6±7.8 U/L and 69.3±5.9 U/L, which were lower than those of HFD-fed placebo mice (ALT: 55.8 ±11.0 U/L; P = 0.013 and AST: 128.3 ± 23.1 U/L; P = 0.035). Compared with the placebo group, the ALT and AST contents of the mice treated with Chinese medicine pills were lower, although the difference was not statistically significant, and no dose effect was observed (Table 3); ALT and AST are commonly used clinically Liver damage indicators. The experimental results show that Chinese medicine pills effectively reduce the liver damage caused by high-calorie diet in mice, and have corresponding effective preventive or therapeutic effects.

Table 3. Liver enzyme levels of mice in different groups at the end of the experiment

*P<0.05 relative to the control group (group 2)

ALT: alanine aminotransferase; AST: aspartate aminotransferase

Degree of liver steatosis

Table 4: The degree of hepatic steatosis of the liver at the end of the experiment.

No steatosis (fat-changed cells <5%); low-grade steatosis (fat-changed cells 5-33%); moderate steatosis (fat-changed cells> 33-66%); severe steatosis (fat-changed cells> 66 %).

At the end of the experiment, the fat changes of all LFD-fed control mice were less than 5% (no steatosis), while 9 out of 10 placebo mice (90%) fed with HFD had severe steatosis (The remaining mice suffer from moderate steatosis). Overall, of the 30 mice treated with traditional Chinese medicine pills, 15 (50%) had severe steatosis, while 7 (23.3%) had no steatosis or low-grade steatosis. The proportion of mice with severe steatosis treated with traditional Chinese medicine pills was significantly lower than that of placebo mice fed with untreated HFD (P=0.025). The representative histological results are shown in Figure 4; the experimental results show that the traditional Chinese medicine pills effectively reduce the effect of high-calorie diet on the accumulation of fat in the liver of mice (ie, fatty liver), and have corresponding effective preventive or therapeutic effects.

Claims

An application of a traditional Chinese medicine composition in the preparation of a medicine for treating or preventing fatty liver disease. The traditional Chinese medicine composition is composed of gardenia, poria, salvia, root bark, ginseng, Amomum villosum, raw malt and Caifuzi.
The application according to claim 1, wherein the fatty liver disease is non-alcoholic fatty liver disease.
The use of the composition according to claim 1 in the preparation of a medicine for treating or preventing steatosis.
The use according to claim 3, wherein the steatosis is steatosis caused by a high-fat diet.
The application according to claim 1, wherein the dosage of the traditional Chinese medicine composition is 5-10 g/day.
A Chinese medicinal composition according to claim 1, characterized in that the Chinese medicinal composition, by weight, comprises 1.25-1.55 parts of Gardenia, 1.25-1.46 parts of Poria, 0.925-1.31 parts of Salvia miltiorrhiza, and 1.1-1.5 parts of Digupi It consists of 1.37 parts, 0.925-1.08 parts of Taizishen, 0.55-0.68 parts of Amomum villosum, 3 parts of raw malt, and 1 part of Caifuzi.
The traditional Chinese medicine composition according to claim 6, characterized in that, by weight, the traditional Chinese medicine composition consists of 1.55 parts of Gardenia, 1.46 parts of Poria, 1.31 parts of Danshen, 1.37 parts of Digu Bark, 1.08 parts of Pseudostellariae, by weight, It is composed of 0.68 parts of Amomum villosum, 3 parts of raw malt, and 1 part of Caifuzi.
The traditional Chinese medicine composition according to claim 6, wherein the traditional Chinese medicine composition is composed of 1.25 parts of Gardenia, 1.25 parts of Poria, 0.925 parts of Salvia miltiorrhiza, 1.1 parts of Radix Digupi, 0.925 parts of Radix Pseudostellariae, by weight, It consists of 0.55 parts of Amomum villosum, 3.0 parts of raw malt, and 1.0 part of Caifuzi.
The preparation method of the traditional Chinese medicine composition according to any one of claims 6 to 8, wherein the method comprises:

(1) The prescription ratio Zhongdan participated in the extraction of gardenia with 80% ethanol for 2 times, the first time was 5 times the amount of 80% ethanol for 2 hours, the second time was 4 times the amount of 80% ethanol for 1.5 hours, filtered , The dregs are collected in a separate container for use; the two filtrates before and after are combined, and ethanol is recovered under reduced pressure to a clear ointment with a relative density of about 1.20 (70°C) for use;

(2) Crush 1/10 of the prescription amount of Poria cocos through a 100-mesh sieve, and sift out the fine powder, and the remaining coarse particles will be used separately;

(3) Add 7 times the amount of water to decoction for 2 hours, filter, and collect the filtrate by adding 7 times the amount of water and pulverized coarse grains of Poria cocos and Poria cocos in the prescription proportions of Zhongsheng malt, Digupi, Laifuzi and Prince Edward The slag will be collected separately for later use;

(4) Add 8 times the amount of water to extract the volatile oil of Amomum villosum in the prescription ratio for 2 hours, and collect the volatile oil for later use; the filtrate of Amomum villosum and the medicine residue are collected in a separate container for use;

(5) Combine the dregs obtained above, add 5 times the amount of water to decoct for 1.5 hours, filter, and collect the filtrate; then combine with the filtrate in steps (3) and (4), and concentrate under reduced pressure to a relative density of about 1.20 Clear ointment: Combine the obtained clear ointment with salvia miltiorrhiza and gardenia alcohol extraction ointment, mix well, concentrate to a thick paste with a relative density of about 1.40, dry under reduced pressure, and pulverize into fine powder extract;

(6) Mix and dry the fine extract powder, Amomum villosum volatile oil and sterilized Poria powder to obtain.
A preparation containing the traditional Chinese medicine composition according to any one of claims 6 to 8 or the traditional Chinese medicine composition prepared according to the method of claim 9, wherein the preparation is composed of a traditional Chinese medicine composition and pharmaceutical excipients, wherein the excipients It is beta cyclodextrin, corn starch, talc, or a combination of two or more of them.
The preparation according to claim 10, wherein the preparation comprises a pill, dripping pill, capsule or granule.
The preparation according to claim 11, wherein the preparation is a pill.
The method for preparing a pill according to claim 11, wherein the method comprises:

(1) The prescription ratio Zhongdan participated in the extraction of gardenia with 80% ethanol for 2 times, the first time was 5 times the amount of 80% ethanol for 2 hours, the second time was 4 times the amount of 80% ethanol for 1.5 hours, filtered , The dregs are collected in a separate container for use; the two filtrates before and after are combined, and ethanol is recovered under reduced pressure to a clear ointment with a relative density of about 1.20 (70°C) for use;

(2) Crush 1/10 of the prescription amount of Poria cocos through a 100-mesh sieve to sift out the fine powder, and the remaining coarse particles will be used separately;

(3) Add 7 times the amount of water to decoction for 2 hours, filter, and collect the filtrate. The slag will be collected separately for later use;

(4) Add 8 times the amount of water to extract the volatile oil of Amomum villosum in the prescription ratio for 2 hours, collect the volatile oil, and clathrate it with beta cyclodextrin to obtain the Amomum villosum volatile oil beta cyclodextrin inclusion compound for later use; Amomum villosum filtrate Collect the dregs in a separate container for later use;

(5) Combine the dregs obtained above, add 5 times the amount of water to decoct for 1.5 hours, filter, and collect the filtrate; then combine with the filtrate in steps (3) and (4), and concentrate under reduced pressure to a relative density of about 1.20 Clear ointment: Combine the obtained clear ointment with salvia miltiorrhiza and gardenia alcohol extraction ointment, mix well, concentrate to a thick paste with a relative density of about 1.40, dry under reduced pressure, and pulverize into fine powder extract;

(6) The fine powder of extract, the inclusion compound of Amomum villosum volatile oil beta cyclodextrin and the fine sterilized Poria powder are made into pellets with honey water (refined honey: water = 1:3), dried, and corn starch and talc are used. Powder coating, ready to go.