CN1313130C - Medicine composition for treating stomachache, its preparation method and uses - Google Patents

Abstract

The invention relates to a pharmaceutical composition for treating stomach pain, which is composed of Bupleurum radix, Radix Paeoniae Alba, Coptidis Rhizoma, Evodia rutaecarpa, Rhizoma Cyperi, Woody Fragrance, Rhizoma Chuanxiong, Rhubarb, Corydalis Corydalis, Faluohai, Citrus aurantium, Rehmannia glutinosa, Cortex Moutan, Scallop made of raw materials. The pharmaceutical composition of the present invention soothes the liver and harmonizes the stomach, regulates qi and activates blood circulation, clears heat and relieves pain, and is used for disharmony between the liver and the stomach, stagnant heat blocking the collaterals, causing epigastric pain, belching, acid regurgitation, noisy, poor diet, dryness and irritability, Dry mouth, bitter mouth, etc., as well as gastric ulcer and chronic superficial gastritis with the above syndromes, can resist inflammation, relieve pain, directly kill Helicobacter pylori, have a high cure rate and low recurrence rate, and have a wide range of application values.

Description

A pharmaceutical composition for treating stomachache, preparation method and application thereof

technical field

The invention relates to a pharmaceutical composition for treating stomach pain, in particular to a pharmaceutical composition for treating stomach pain prepared from plants and Chinese herbal medicines, as well as a preparation method and application of the pharmaceutical composition of the invention.

Background technique

Stomach pain is a common disease frequently-occurring disease. Some diseases of modern medicine all have stomach pain symptoms, such as chronic superficial gastritis and peptic ulcer (stomach ulcer) etc. all have stomach pain symptoms. It has many pathogenic factors. Looking at its symptoms, traditional Chinese medicine believes that stomach pain is caused by liver qi invading the stomach, disharmony between liver and stomach, qi stagnation and blood stasis.

From the above analysis, it can be seen that stomachache is a complex disease, and it is difficult to treat it with only one or two medicines. This is also one of the reasons why there are few Western medicines for radically curing stomachache. Generally, Western medicine is mostly used to relieve pain, but its dependence and side effects cannot be ignored.

In addition, with the acceleration of the pace of modern life, the enhancement of competition consciousness, irregular diet, emotions and other factors have become the most important factors for the onset of gastric pain and peptic ulcer, and the clinical incidence rate is as high as 40%. Regarding the treatment of peptic ulcer, no matter international or domestic, synthetic drugs or Chinese patent medicines are facing a specific problem, that is, the cure rate is low and the recurrence rate is high, so improving the cure rate of peptic ulcer and reducing its recurrence rate are the problems key.

At present, research reports have confirmed that Helicobacter pylori is the pathogenic bacteria of chronic gastritis and gastric ulcer, and is closely related to the onset of gastric ulcer and gastritis. The use of antibiotics is the main treatment for Helicobacter pylori infection, but this single treatment has poor curative effect and is prone to drug resistance. Although the effective rate of combined drugs is high, but the side effects are large, some special patients cannot use it. Therefore, it is particularly important to explore the role of traditional Chinese medicine in the treatment of Helicobacter pylori infection, which belongs to the category of "evil qi" invasion in Chinese medicine.

At present, there is no ideal drug for the treatment of peptic ulcer. At present, whether international or domestic, there are four main categories of drugs:

* Anti-acid effect, increase gastric mucosal barrier function

*Acid secretion blockers

* Antispasmodics

*Gastric motility drugs

Due to the complex and different causes of the disease, although the above four types of drugs each have their advantages, they are not ideal in eliminating symptoms, promoting healing, and reducing recurrence. So develop a kind of Chinese medicine preparation that can anti-inflammatory, analgesic, directly kill Helicobacter pylori, the cure rate of stomachache is high, and recurrence rate is low, be the result of all expectations. The traditional Chinese medicine for the treatment of stomachache sold on the market mainly contains the following formulations:

1. Sanchaku, Jiulixiang, Scutellaria, Two-faced Acupuncture, Woody Fragrance, Poria, Paeoniae Alba, Rehmannia glutinosa

2. Sanyaku, Scutellaria, Gurixiang, Two-sided Acupuncture, Woody Fragrance, Poria, Paeoniae Alba, Rehmannia;

3. Codonopsis pilosula, Atractylodes macrocephala (stir-fried), aconite (produced), cinnamon, yam, black plum, amomum, tangerine peel, psoralen, hawthorn (stir-fried), astragalus, cistanche (produced);

4. Codonopsis, Radix Scrophulariae, Polygonatum (steamed), Atractylodes macrocephala (stir-fried), ebony, dodder, tangerine peel, yam, dried ginger, hawthorn, northern ginseng;

5. Woody, amomum, Atractylodes macrocephala, tangerine peel, poria, pinellia (made), Cyperus cyperi (made with vinegar), citrus aurantium (fried), cardamom (hulled), Magnolia officinalis (made with ginger), patchouli, licorice;

6. Astragalus, Tian Qi, bezoar, pearl layer powder, etc.;

7. Red ginseng, fragrant tea, citrus aurantium (stir-fried);

8. Twenty-three flavors such as roasted astragalus, cinnamon, evodia, salvia, corydalis, sliced turmeric, three-edge, curcuma, coptis, woody, aurantium, black medicine;

9. Hericium erinaceus culture extract, cuttlefish, corydalis, white peony root, Cyperus cyperi, licorice.

All of these Chinese patent medicines can not fully meet the requirements of anti-inflammatory, analgesic, direct killing of Helicobacter pylori, high cure rate of stomach pain and low recurrence rate.

The pharmaceutical composition of the present invention has remarkable curative effect on stomach pain caused by disharmony between liver and stomach, blood stasis and heat obstructing collaterals, and has low recurrence rate.

Anti-peptic ulcer test results show that the pharmaceutical composition of the present invention has obvious inhibitory effect and protective effect on acute gastric ulcer in stress responsiveness and pyloric ligation type rats (P＜0.05～0.01); Gastric ulcer has obvious antagonism effect namely therapeutic effect (P＜0.01); Reserpine type and indomethacin type rat gastric ulcer and gastric mucosa damage all have obvious inhibitory effect namely protective effect (former P＜0.01, latter P<0.05).

The test result of Helicobacter pylori shows that the pharmaceutical composition of the present invention has obvious antibacterial effect on Helicobacter pylori.

Clinical tests have proved that the total effective rate of the pharmaceutical composition of the present invention for gastric pain is 98%, and the effective rate and cure rate are 74%. Tests have shown that the pharmaceutical composition of the present invention has significant curative effect and unique effect on treating liver-stomach disharmony, stasis-heat blocking collateral epigastric pain, and has a relatively high cure rate and Lower recurrence rate.

The pharmaceutical composition of the present invention has a unique mechanism of action. It can resist inflammation, analgesia and sedation, and can directly kill Helicobacter pylori. There is no resistance to antibiotics or the like.

Contents of the invention

The purpose of the present invention is to provide an anti-inflammation, analgesic, directly kill Helicobacter pylori, a pharmaceutical composition for the treatment of gastric pain with high cure rate and low recurrence rate.

Another object of the present invention is to provide a preparation method of the pharmaceutical composition for treating stomach pain.

Another object of the present invention is to provide the application of the pharmaceutical composition for treating gastric pain in the treatment of acute gastric ulcer, chronic gastric ulcer, drug-induced gastric ulcer and gastric mucosal injury, as well as drugs for inhibiting gastric emptying and gastric juice secretion.

The technical solution of the present invention is based on the understanding of the mechanism of epigastric pain in traditional Chinese medicine, and with reference to the inventor's many years of experience, screened out soothing the liver and harmonizing the stomach, regulating qi and activating blood, clearing away heat and relieving pain, and used for liver and stomach disharmony, blood stasis and heat blocking collaterals. Epigastric pain, belching, acid regurgitation, noisy, poor diet, dryness and irritability, dry mouth and bitter mouth, etc., as well as the pharmaceutical composition for gastric ulcer and chronic superficial gastritis.

The raw material of the pharmaceutical composition of the present invention contains the following medicines in parts by weight: 4-27 parts of Bupleurum, 4-24 parts of Radix Paeoniae Alba, 2-18 parts of Coptidis Rhizoma, 2-18 parts of Evodia Evodia, 6-36 parts of Rhizoma Cyperi, 6-36 parts, 4-27 parts of Rhizoma Chuanxiong, 2-18 parts of Rhubarb, 9-54 parts of Corydalis Corydalis, 13-72 parts of Faluohai, 8-45 parts of Zhishi, 8-45 parts of Dihuang, 4-27 parts of Moutan Cortex , Allium 9-54 parts.

The preferred proportioning range by weight of the formula for preparing the pharmaceutical composition of the present invention is: 4-6 parts of Bupleuri, 4-6 parts of Radix Paeoniae Alba, 2-5 parts of Coptis Rhizoma, 2-4 parts of Evodia rutaecarpa, 6-8 parts of Cyperus cyperi , Woody 6-8 parts, Chuanxiong 4-6 parts, Rhubarb 2-4 parts, Corydalis 9-11 parts, Faluohai 13-15 parts, Citrus aurantium 8-10 parts, Rehmannia glutinosa 8-10 parts, Moutan bark 4 -6 parts, 9-10 parts of scallion

The optimal weight ratio of the pharmaceutical composition of the present invention is: 5.4 parts of Bupleurum, 5.4 parts of Radix Paeoniae Alba, 3.6 parts of Coptidis Rhizoma, 3.6 parts of Evodia rutaecarpa, 7.2 parts of Rhizoma Cyperi, 7.2 parts of Muxiang, 5.4 parts of Chuanxiong, and 3.6 parts of Rheum , 10.8 parts of Yanhusuo, 14.4 parts of Faluohai, 9 parts of Citrus aurantium, 9 parts of Rehmannia glutinosa, 5.4 parts of Moutan bark, and 10.8 parts of Xibai.

The raw materials of the pharmaceutical composition of the present invention may also contain traditional Chinese medicines for regulating qi.

The qi regulating traditional Chinese medicine in the pharmaceutical composition of the present invention may be 9-45 parts by weight of Toosendan.

The above pharmaceutical composition may further contain a pharmaceutically acceptable carrier.

The pharmaceutical composition of the present invention is injection, tablet, capsule, pill, solution, suspension, emulsion.

The pharmaceutical composition of the invention can be used in medicines for treating acute gastric ulcer, chronic gastric ulcer, drug-induced gastric ulcer and gastric mucosal damage, and inhibiting gastric emptying function and gastric juice secretion function.

The preparation method of the pharmaceutical composition of the present invention is to take Rhizoma Cyperi, Rhizoma Chuanxiong, Citrus Fructus Citrus Fructus Citrus Fructus Citrus Fructus Aurantii, Cortex Cortex Moutan, and Cortex Moutan, and together with Evodia Evodia, steam distillation to extract volatile oil, and the medicinal liquid after distillation is reserved for later use; -Cyclodextrin inclusion complex; the medicinal residue after extracting the volatile oil, together with Faluohai, Xiebai, Rhubarb, and Rehmannia glutinosa, decocted with water for 2-3 times, filtered, combined the filtrate, merged with the above-mentioned medicinal solution after extracting the volatile oil, and reduced Concentrate under pressure, add ethanol to make the alcohol content 60%-80%, let it stand after stirring, filter, recover ethanol from the filtrate, and concentrate under reduced pressure to obtain a concentrated medicinal solution; take Bupleurum, Coptidis Rhizome, Radix Paeoniae Alba, and Corydalis Corydalis to grind, Use 60%-80% ethanol to heat and reflux twice, the first time is 1.5-3 hours, the second time is 0.5-1.5 hours, filter, combine the extracts, recover ethanol, and concentrate under reduced pressure, and concentrate the drug after precipitation with the above alcohol The liquids were combined, dried under reduced pressure and vacuum to obtain a dry paste; the dry paste was crushed into fine powder, mixed with the above-mentioned β-cyclodextrin inclusion compound of volatile oil and the remaining Corydalis fine powder, made into granules with ethanol, dried, and granulated.

The preferred preparation method of the pharmaceutical composition of the present invention is to take Rhizoma Cyperi, Rhizoma Chuanxiong, Fructus Citrus Fructus Citrus Fructus Citrus Fructus Aurantii, Cortex Cortex Moutan, and Cortex Moutan, and together with Evodia Evodia, steam distillation extracts volatile oil, and the medicinal liquid after distillation is reserved for future use; β-cyclodextrin inclusion; extract volatile oil from medicinal residues together with Faluohai, Xiebai, Rhubarb, and Rehmannia glutinosa, add 6.4 times the amount of water equivalent to the crude drug, decoct twice, the first time for 2 hours, and the second time for 1 hour , filter and combine the filtrate, combine with the above-mentioned medicinal solution after extracting volatile oil, concentrate under reduced pressure to a relative density of 1.05 to 1.10 (50°C), add ethanol to make the alcohol content 70%, leave it for 12 hours after stirring, filter After filtration, the filtrate reclaims ethanol, and concentrates under reduced pressure to a relative density of 1.30-1.38 (50° C.) to obtain a concentrated medicinal solution; take Bupleurum Radix, Coptidis Rhizome, Radix Paeoniae Alba, and Corydalis Corydalis, and heat and reflux twice with 70% ethanol. 2 hours for the second time, 1 hour for the second time, filter, combine the extracts, recover ethanol, and concentrate under reduced pressure to a relative density of 1.30-1.38 (50°C), combine with the above-mentioned concentrated medicinal solution after alcohol precipitation, and reduce the concentration below 80°C. Vacuum drying to obtain a dry paste; the dry paste is crushed into a fine powder, mixed with the above-mentioned β-cyclodextrin inclusion compound of volatile oil and the remaining Corydalis fine powder, made into granules with ethanol, dried below 70°C, and granulated.

The Bupleurum chinense DC described therein is the dry root of the Umbelliferae plant Bupleurum chinense DC. It is mainly produced in Liaoning, Hebei, Henan and other places, and the northern Bupleurum is the best.

Coptis chinensis is the dry rhizome of Coptis chinensis Franch and Coptis deltoidea C.V.Cheng et Hsiao. It is mainly produced in Sichuan and other places, and chicken feet are the best.

Cyperus Cyperus is the dry rhizome of Cyperus rotundus L., a sedge plant. Mainly produced in Shandong, Zhejiang, Hunan, Henan and other places, vinegar Cyperus is the best.

Radix Paeoniae Alba is the dry root of Paeonia lactiflora Pall. Mainly produced in Zhejiang, Anhui, Sichuan and other places.

Faluohai is the dry root and rhizome of Angelica apaensis Shanet yuan, a plant belonging to the genus Angelica of Umbelliferae. Mainly produced in Yunnan, Sichuan and other places.

Citrus aurantium is the dry young fruit of Citrus aurantium L. and its cultivars or sweet orange Citrus sinensis Osbeck of the Rutaceae plant. It is mainly produced in Fujian, Shaanxi, Guangxi and other places, and it is better to stir-fry citrus aurantium with bran.

Rhubarb is the dry root and rhizome of Rheum palamatum L., Rheumtanguticum Maxim ex Balf or medicinal Rheum officinale Baill. Mainly produced in Qinghai, Gansu and other places.

Corydalis yanhusuo is the dry tuber of Corydalis yanhusuo W.T. It is mainly produced in Zhejiang and other places, and Yanhusuo with vinegar is the best.

Chuanxiong is the dried rhizome of Ligusticum chuanxiong Hort, an umbrella plant. Mainly produced in Sichuan and other places.

Rehmannia glutinosa is the fresh or dried tuber of Rehmannia glutinosa Libosch. Mainly produced in Henan and Hebei.

Cortex Moutan is the dried root bark of Peaonia suffruticosa Andr., a plant of Ranunculaceae. Mainly produced in Henan.

Evodia rutaecarpa (Juss.) Benth, Evodia rutaecarpa (Juss.) Benth.var.officinalis (Dode) Huang or Evodia rutaecarpa, (Juss.) Benth.var.bodinieri (Dode) Huang's dried nearly ripe fruit. It is mainly produced in Shaanxi and Hebei, and it is better to make Evodia rutaecarpa.

Allium macrostemon Bge. is the dried bulb of the plant Allium macrostemon Bge. Mainly produced in Liaoning and Hebei.

Woody is the dry root of Aucklandia lappa Kecne. Mainly produced in Yunnan, Guangxi, Sichuan and other places.

In the formula of the present invention, Bupleurum and Radix Paeoniae Alba are king. Bupleurum, Radix Paeoniae Alba are bitter, pungent, slightly cold, enter the liver and gallbladder meridian. Soothe the liver, relieve stagnation and clear away heat. "The Classic" states that Bupleurum "maintains confidantes, removes qi in the intestines." It has the function of regulating qi. "On the Properties of Medicine" Yun Bupleurum (clear) "Hot Qi... lowers the Qi to eliminate food." "Records" pointed out: "Bupleurum, the medicine of the intestines and stomach, the therapeutic effects mentioned in the "Classic" are all in the stomach and intestines. Its smell is light and clear, and it can clear stagnant qi in the stubborn soil, so its power is so." "" "Materia Medica Zheng" says "Bupleurum, those who use this use it to cool and calm the heat of the liver." However, the yin of the liver body is used for yang, and Bupleurum is used, and the yin medicine Baishao is also used. Paeoniae Alba is bitter and slightly cold, nourishes blood and restrains yin, softens the liver and relieves pain. "Southern Yunnan Materia Medica" says that white peony root "eliminates spleen heat, relieves abdominal pain...retracts liver pain." Taking into account the use, the power of regulating the liver and soothing the liver is stronger. Liver level then all diseases can be resolved. Therefore, the two medicines are the king medicine altogether.

Cyperus pungent, sweet, bitter, flat, enters the Liver Meridian, regulates qi, relieves depression and relieves pain, and cures mainly disharmony between the liver and stomach, stagnation of qi, fullness in the chest and abdomen, distending pain in the ribs, etc. "Southern Yunnan Materia Medica" states that it "regulates the qi in the blood, opens the depression qi and regulates all qi. Widens the food, relieves vomiting, harmonizes the stomach, and eats." Pain, accumulation of stagnation, fullness." "Yi Lin Zhuan Yao. Medicinal Properties" pointed out that Rhizoma Cyperi "replenishes the liver and breaks depression, and is suitable for Qi and blood. Woody incense enters the spleen, stomach, liver meridian, promotes the circulation of qi and relieves pain, regulates the middle and guides stagnation, and mainly treats fullness in the chest and hypochondrium, and pain in the abdomen and abdomen. "Yuehuazi" says that it "cures all qi in the heart", "invigorates the spleen and eliminates food". "Supplement to Materia Medica Yanyi" says that Muxiang "promotes liver meridian qi." Zhu Danxi said "it is suitable for people with stagnant qi." Chuanxiong, pungent in taste, enters the liver meridian, promotes blood circulation and removes blood stasis, promotes qi circulation, relieves stagnation and relieves pain. Li Shizhen said, "Qiuxiong is poor, the qi medicine in the blood, the liver is suffering, and the pungent is tonic... the pungent is scattered, so it is suitable for those with stagnant qi." Chuanxiong treats chest and abdominal pain. Helps monarch medicine soothe the liver and regulate qi because of its relieving depression. Chuanxiong promotes blood circulation and removes blood stasis, so it is more suitable for treating blood stasis caused by qi stagnation. Therefore, it is also a medicine for ministers. Because of stagnant heat in the liver and stomach, Coptis chinensis and Evodia rutaecarpa (the meaning of Zuojin Wan) are used to soothe the liver and clear away heat. "Suwen. Zhizhenyao Dalun" says that "all reverses and rushes belong to fire, and all vomiting and sourness belong to heat." Therefore, Coptis chinensis is used for bitter cold, clearing away heat, reducing adverse reactions and relieving vomiting, but it is not Zuojin pill, it is used Evodia rutaecarpa relieves stagnation and dissipates stagnation, warms the stomach and lowers qi, reduces adverse reactions, and treats fullness. To help Bupleurum soothe the liver. Therefore, the five flavors of medicine are ministerial medicines.

Citrus aurantium dispels qi and eliminates stagnation, and is generally not used alone. If it is used together with Chai Hu, it can strengthen its function of soothing the liver and regulating qi. "Compendium" states that Citrus aurantium "probably has the function of benefiting qi... the flow of qi will relieve swelling, and the flow of qi will relieve pain." Scallop also enters the Stomach Meridian, regulates qi, widens the chest, dissipates stagnation and relieves pain, controls chest and abdominal distension, abdominal pain, and helps the power of Bupleurum, Rhizoma Cyperi and Woody to regulate qi and relieve pain, so it is an adjuvant drug.

In this prescription, although the dosage of Bupleurum is more than that of Citrus Citrifolia, and the amount of Faluohai and Xiebai is slightly smaller, but the functions in this prescription are more and more comprehensive than that of promoting blood circulation, while the functions of other medicines are relatively single. , so use it for the king. There are seven cold and cool products in the prescription, and six are warm drugs. Combination of cold and warm medicines not only treats mixed cold and heat symptoms, but also assists each other to avoid hurting stomach qi again. Therefore, this prescription is properly compatible, and all the medicines have the effects of soothing the liver and relieving depression, regulating qi and harmonizing the stomach, promoting blood circulation and relieving pain.

In order to better understand the essence of the present invention, the animal experiment and clinical pharmacological experiment and results of the pharmaceutical composition of the present invention will be used to illustrate its excellent effect in treating stomach pain.

Get 5.4 parts by weight of Bupleurum, 5.4 parts by weight of Radix Paeoniae Alba, 3.6 parts by weight of Coptidis Rhizome, 3.6 parts by weight of Evodia rutaecarpa, 7.2 parts by weight of Cyperus Cyperi, 7.2 parts by weight of Muxiang, 5.4 parts by weight of Rhizoma Chuanxiong, 3.6 parts by weight of Rhubarb, 10.8 parts by weight of Corydalis Corydalis, 14.4 parts by weight of Faluohai, 9 parts by weight of Citrus aurantium, 9 parts by weight of Rehmannia glutinosa, 5.4 parts by weight of Cortex Moutan, 10.8 parts by weight of Allium scallions, and all raw materials are 1008 grams in total. Then Cyperus cyperi, Chuanxiong, Citrus aurantii, Cortex chinensis, Moutan cortex are smashed, together with Evodia rutaecarpa, steam distilled to extract the volatile oil, and the distilled liquid is reserved for later use; the volatile oil is clathrated with β-cyclodextrin; the volatile oil is extracted The final medicinal residues are mixed with Faluohai, Xiebai, rhubarb, and rehmannia root, decocted twice with water, filtered, and combined with the filtrate, combined with the above-mentioned medicinal liquid after extracting volatile oil, concentrated under reduced pressure, and added ethanol to make the alcohol content 70% %, after stirring, stand still, filter, recover ethanol from the filtrate, and concentrate under reduced pressure to obtain a concentrated medicinal solution; take Bupleurum, Coptidis Rhizoma, Radix Paeoniae Alba, and Corydalis Corydalis, and heat and reflux twice with 70% ethanol for 2 hours for the first time , the second time for 1 hour, filtered, combined extracts, reclaimed ethanol, and concentrated under reduced pressure, combined with the concentrated medicinal solution after alcohol precipitation, and dried under reduced pressure in vacuum to obtain a dry paste. The dry paste is crushed into fine powder, mixed evenly with the above-mentioned β-cyclodextrin inclusion compound of volatile oil and the remaining Corydalis fine powder, made into granules with ethanol, dried, granulated, packed into capsules, and made into 1000 granules for later use.

According to the clinical application of the drug, in accordance with the requirements of "pharmacodynamic research of traditional Chinese medicine for the treatment of epigastric pain" in the "Guidelines for Pharmacological Research of New Drugs of Traditional Chinese Medicine", and referring to the requirements of "pharmacodynamic research of traditional Chinese medicine for the treatment of peptic ulcer", the The main pharmacodynamics of the drug has been experimentally studied, and the effects of the drug on acute gastric ulcer, chronic gastric ulcer, drug-induced gastric ulcer or gastric mucosal damage, and gastric function (including gastric excretion) were observed. empty function and gastric juice secretion function) and the impact on Helicobacter pylori and the analgesic effect.

experiment material

(1) Drugs

1. Test drug: The pharmaceutical composition of the present invention is provided by Beijing Huaerfu Pharmaceutical Company. The experimental drug powder contains 10.18g of crude drug per gram, and it is prepared into the required concentration with distilled water before use.

2. Positive control drug, other drugs and reagents:

Qizhi Weitong Granules, produced by the Third Pharmaceutical Factory of Benxi, Liaoning Province, batch number 961106.

Acetic acid, product of Beijing Chemical Plant, batch number 840913.

Reserpine injection, product of Beijing No. 4 Pharmaceutical Factory, batch number 930612.

Indomethacin powder, product of Beijing Fuqiang Pharmaceutical Factory, batch number 960214.

Phenol red, produced by the Academy of Military Medical Sciences, batch number 901203.

Neostigmine methylsulfate injection, a product of China Xinyi Pharmaceutical Factory, batch number 960124.

Helicobacter pylori strains, Helicobacter pylori NCTC11639 standard strain, provided by the Institute of Epidemiology and Microbiology, Chinese Academy of Preventive Medicine; Helicobacter pylori 990409 clinical isolates, isolated and identified by the Air Force Aviation Medical Research Institute of the Chinese People's Liberation Army.

Sodium pentobarbital, repackaged by Beijing Purchasing and Supply Station of China Pharmaceutical Company, batch number 861209.

(2) Experimental animals

1. Mice, Kunming species, first grade, half male and half male, body weight 18-22g, certificate of conformity is Jingdong Guanzi No. 01-3064. Provided by Animal Center of China Academy of Traditional Chinese Medicine.

2. Rats, Wistar species, first grade, half male and half male, body weight 150-220g, the certificate of conformity is Medical Dynamic Zi No. 013084. Provided by the Animal Center of Capital Medical University.

(3) Instruments

721 Spectrophotometer, produced by Shanghai Third Analytical Instrument Factory,

UV-754 spectrophotometer, produced by Shanghai Third Analytical Instrument Factory.

Method and Results

(1) Anti-peptic ulcer test

1. Anti-acute gastric ulcer test

1. Effect of pharmaceutical composition of the present invention on rat stress gastric ulcer

Table 1 Effect of the pharmaceutical composition of the present invention on rat stress gastric ulcer (X ± SD) group Dose (g crude drug/Kg) Number of animals (only) Ulcer index (mm) Inhibition rate(%) Control group Pharmaceutical composition of the present invention Pharmaceutical composition of the present invention Pharmaceutical composition of the present invention 6.3 (equivalent to 5 times the clinical human dosage) 3.2 (equivalent to 2.5 times the clinical human dosage) 1.6 (equivalent to 1.25 times the clinical human dosage) 881010 11.88±3.527.63±2.45 ^* 8.10±1.20 ^** 8.70±3.56 ^* 35.7931.7926.74

Compared with the control group: ^* P<0.05, ^** P<0.01

As can be seen from the table, the ulcer index of each dosage group of the pharmaceutical composition of the present invention, that is, the millimeter number of the ulcer length summation, is all significantly lower than the normal saline control group (P＜0.05～P＜0.01), and the inhibition percentage is also in a corresponding change. It shows that the pharmaceutical composition of the present invention has obvious inhibitory effect on rats' water immersion stress gastric ulcer, that is, the pharmaceutical composition of the present invention has a protective effect on the formation of rat gastric ulcer caused by water immersion stress response method.

2. Effect of pharmaceutical composition of the present invention on rat pylorus-ligated gastric ulcer

Table 2 Effect of the pharmaceutical composition of the present invention on rat pylorus-ligated gastric ulcer (X ± SD) group Dose (g crude drug/Kg) Number of animals (only) Ulcer index (mm) Inhibition rate(%) Control group pharmaceutical composition of the present invention Qizhi Weitong Granules 6.3 (equivalent to 5 times the clinical human dosage) 6.8 (equivalent to 5 times the clinical human dosage) 101010 11.66±4.644.44±4.52 ^* 5.46±3.76 ^* 61.9653.20

Compared with the control group: ^* P<0.05, ^** P<0.01

As can be seen from the table, the ulcer area of the dosage group of the pharmaceutical composition of the present invention is all less than the normal saline control group, similar to the Qizhi Weitong Granules group, and also slightly lower than the Qizhi Weitong Granules group; the inhibition percentage is also correspondingly changed. The dosage group of the pharmaceutical composition is also slightly higher than that of the Qizhi Weitong Granules group. Illustrate that the pharmaceutical composition of the present invention has a better protective effect on the formation of rat gastric ulcer caused by rat pyloric ligation, and has a certain dose-effect relationship, wherein the pharmaceutical composition dosage group of the present invention is slightly better than Qi stagnation Stomach pain granules.

2. Anti-chronic gastric ulcer test

3. Effect of pharmaceutical composition of the present invention on rat acetic acid burning type gastric ulcer

Table 3 The effect of pharmaceutical composition of the present invention on rat acetic acid burning type gastric ulcer (X ± SD)

group Dose (g crude drug/Kg) Number of animals (only) Ulcer index (mm) Inhibition rate(%) Control group Pharmaceutical composition of the present invention Pharmaceutical composition of the present invention Pharmaceutical composition of the present invention 6.3 (equivalent to 5 times the clinical human dosage) 3.2 (equivalent to 2.5 times the clinical human dosage) 1.6 (equivalent to 1.25 times the clinical human dosage) 8788 77.00±10.4353.43±14.00 ^** 43.00±23.45 ^** 40.88±15.98 ^** 30.6144.1646.92

Compared with the control group: ^* P<0.05, ^** P<0.01

As can be seen from the table, the ulcer index of each dosage group of the pharmaceutical composition of the present invention is the mean value of the longest diameter and the shortest diameter of the ulcer all lower than the normal saline control group (P < 0.01); the ulcer healing percentage is also in a corresponding change. It shows that the pharmaceutical composition of the present invention has obvious antagonistic effect on rat gastric ulcer caused by acetic acid cauterization, that is, the pharmaceutical composition of the present invention has therapeutic effect on rat gastric ulcer caused by acetic acid cauterization.

3. Anti-drug-induced gastric ulcer and gastric mucosal injury test

4. Effect of the pharmaceutical composition of the present invention on rat reserpine type gastric ulcer and mucosal injury

Table 4 Effect of pharmaceutical composition of the present invention on rat reserpine type gastric ulcer and mucosal injury (X ± SD) group Dose (g crude drug/Kg) Number of animals (only) Ulcer index (mm) Inhibition rate(%) Control group Pharmaceutical composition of the present invention Pharmaceutical composition of the present invention Pharmaceutical composition of the present invention Qizhi Weitong Granule 6.3 (equivalent to 5 times the clinical human dosage) 3.2 (equivalent to 2.5 times the clinical human dosage) 1.6 (equivalent to 1.25 times the clinical human dosage) 6.8 (equivalent to 5 times the clinical human dosage) 1099109 2.57±0.740.81±0.47 ^** △△43.00±23.45 ^** △△##40.88±15.98 ^** △△39.71±24.21 ^** 30.6144.1646.9248.42

Compared with the control group: ^** P<0.01, compared with Qizhi Weitong Granule: △△P<0.01

Each dosage group of pharmaceutical composition of the present invention compares: ##P＜0.01

As can be seen from the table, the ulcer index of each dosage group of pharmaceutical composition of the present invention is the summation of lesion area all obviously lower than normal saline matched group (P＜0.01), wherein middle dosage group is the most obvious, is better than small dosage group (P＜0.01) ), the above-mentioned effect is similar to that of Qizhi Weitong Granules, but the intensity of each dosage group of the pharmaceutical composition of the present invention is significantly higher than that of Qizhi Weitong Granules (P<0.01); the inhibition percentage also changes accordingly. Illustrate that the pharmaceutical composition of the present invention has obvious inhibitory effect on rat reserpine-type gastric ulcer and gastric mucosal injury, that is to say, it has obvious protective effect on the formation of rat gastric ulcer and gastric mucosal injury caused by reserpine, Its action intensity has a certain relationship with the drug dosage, and both of them are stronger than Qizhi Weitong Granules.

5. Effect of the pharmaceutical composition of the present invention on rat indomethacin type gastric ulcer and gastric mucosal injury

Table 5 Effect of the pharmaceutical composition of the present invention on rat indomethacin type gastric ulcer and gastric mucosal injury (X ± SD) group Dose (g crude drug/Kg) Number of animals (only) Disease degree (points) Inhibition rate(%) Control group Pharmaceutical composition of the present invention Pharmaceutical composition of the present invention Pharmaceutical composition of the present invention 6.3 (equivalent to 5 times the clinical human dosage) 3.2 (equivalent to 2.5 times the clinical human dosage) 1.6 (equivalent to 1.25 times the clinical human dosage) 1010910 3.10±2.181.30±0.95 ^* 1.11±1.05 ^* 1.30±1.06 ^* 58.0664.0658.06

Compared with the control group: ^* P<0.05

It can be seen from the table that the degree of lesion in each dose group of the pharmaceutical composition of the present invention is significantly lower than that of the normal saline control group (P<0.05); the inhibition percentage also changes accordingly. Illustrate that the pharmaceutical composition of the present invention has obvious inhibitory effect on rat indomethacin type gastric ulcer and gastric mucosal injury, that is to say, the pharmaceutical composition of the present invention has obvious effect on the formation of rat gastric ulcer and gastric mucosal injury caused by indomethacin. protective effect.

summary

Anti-peptic ulcer test 1, 2, 3, 4, 5 experimental research results illustrate that the pharmaceutical composition of the present invention has obvious inhibitory effect on the formation of acute gastric ulcer in rats caused by stress response method and pyloric ligation. It has obvious antagonism effect on chronic gastric ulcer in rats caused by acetic acid cauterization, that is, therapeutic effect, and promotes ulcer healing; it also has effect on the formation of gastric ulcer and gastric mucosal damage in rats induced by reserpine and indomethacin. The obvious inhibitory effect is the protective effect. Thereby, the effect of the pharmaceutical composition of the present invention on the treatment of epigastric pain (gastric ulcer, gastritis), syndrome of stagnation of the liver turning into heat, and syndrome of invading the stomach due to rebellion has been confirmed, and the partial mechanism of its action has been explained.

(2) Stomach function test

1. Gastric emptying test

6. Effect of the pharmaceutical composition of the present invention on the gastric emptying function of normal mice

Table 6 Effects of the pharmaceutical composition of the present invention on the gastric emptying function of normal mice (X ± SD) group Dose (g crude drug/Kg) Number of rats (only) Residual amount of phenol red (mm) Control group Pharmaceutical composition of the present invention Pharmaceutical composition of the present invention Pharmaceutical composition of the present invention 9.14.62.3 810109 31.5±16.0 ^* 54.2±23.0 ^* 53.1±17.0 ^* 48.7±23.0

Compared with the control group: ^* P<0.05, ^** P<0.01

It can be seen from the table that the residual amount of phenol red in each dose group of the pharmaceutical composition of the present invention is greater than that in the normal saline control group, and there is a significant difference between the large and middle dose groups (P<0.05). It shows that the pharmaceutical composition of the present invention can slow down the gastric emptying speed of normal mice, that is, has a certain inhibitory effect on the gastric emptying function.

7. Effect of the pharmaceutical composition of the present invention on the gastric emptying function of mice with hyperactive gastric emptying

Table 7 Effect of the pharmaceutical composition of the present invention on the gastric emptying function of mice with hyperactive gastric emptying (X±SD) group Dose (g crude drug/Kg) Number of rats (only) Residual amount of phenol red (mm) Normal control group Model control group Pharmaceutical composition of the present invention Pharmaceutical composition of the present invention Pharmaceutical composition of the present invention Qizhi Weitong Granules 9.14.62.39.8 109101088 44.5±10.027.1±11.0 ^* 47.5±15.0△△44.1±14.0△△35.7±28.044.8±15.0△

Compared with normal control group: ^* P＜0.05

Compared with the model control group: △△P<0.01

It can be seen from the table that compared with the normal saline control group, only the model control group has a significant difference (P<0.05), indicating that the modeling is successful. Compared with the model control group, the phenol red residue in the stomach of each dose group of the pharmaceutical composition of the present invention is greater than that of the model control group, wherein there is a significant difference between the large and medium dose groups (P＜0.01), and its effect is similar to that of stagnation of qi and stomachache. Granules are similar, and the strength of action is stronger than Qizhi Weitong Granules. It shows that the pharmaceutical composition of the present invention has obvious inhibitory effect on neostigmine-induced hypergastric function in mice, that is, can obviously slow down the gastric emptying speed of mice with hypergastric emptying function.

2. Gastric juice analysis

8. Effect of the pharmaceutical composition of the present invention on the function of gastric juice secretion in rats

Table 8 Effects of the pharmaceutical composition of the present invention on the secretion of gastric juice in rats (X ± SD) group Dose (g crude drug/Kg) Number of rats (only) Gastric juice volume (ml) Total acidity (mmol/L) Total acid output (umol/L) Pepsin activity (u/ml) Control group Pharmaceutical composition of the present invention Pharmaceutical composition of the present invention Pharmaceutical composition of the present invention 6.33.21.6 128910 6.25±2.174.30±1.75 ^* △△4.77±2.55△△4.90±1.86△△ 126.24±20.56106.84±12.73 ^* △115.73±16.14△118.9±15.67△△ 397.55±175.85231.75±86.64 ^* △△305.50±146.44△△297.38±127.35△△ 1.46±0.171.02±0.36 ^** 1.15±0.33 ^* 1.39±0.37△△

Compared with the control group: ^* P<0.05, ^** P<0.01

As can be seen from the table, the amount of gastric juice, total acidity, and total enzyme discharge of each dosage group of the pharmaceutical composition of the present invention are all lower than normal saline matched group, wherein there is significant difference (P＜0.05) in the large dosage group; It was lower than that of normal saline control group, and there was a significant difference between large and medium dose groups (P<0.01 P<0.05). It shows that the pharmaceutical composition of the present invention has a certain inhibitory effect on the secretion function of gastric juice (including gastric juice, gastric acid, pepsin, etc.) in rats.

summary

Gastric function test 6,7 experimental research results illustrate that the pharmaceutical composition of the present invention can slow down the gastric emptying speed of normal mice, that is, the gastric emptying function of normal mice has a certain inhibitory effect, while gastric emptying The slowing effect of the gastric emptying speed of mice with hyperempty function is more obvious, that is, it has a more obvious inhibitory effect on the gastric emptying function of mice with hyperfunction of gastric emptying; and the pharmaceutical composition of the present invention can reduce The amount of gastric juice, total acidity and total acid excretion in rats can reduce the activity of pepsin, that is, it has a certain inhibitory effect on the gastric secretion function of rats. Thereby, the partial action and mechanism of the pharmaceutical composition of the present invention in treating epigastric pain (gastric ulcer, gastritis), liver stagnation and heat transformation, and rebellious stomach invasion are also described.

(3) Other tests

1. Helicobacter pylori test

9. Observation of the antibacterial effect of the pharmaceutical composition of the present invention on Helicobacter pylori

① Experimental results of agar dilution method

Table 9 The inhibitory effect of pharmaceutical composition of the present invention on standard strain Helicobacter pylori drug Inhibitory effect 50 25 12.5 6.25 3.12 1.56(mg/ml) The pharmaceutical composition of the present invention is Qizhi Weitong Granules 13/130/13 13/130/13 6/130/13 0/130/13 0/130/13 0/130/13

Note: The denominator is the number of experiments, and the numerator is the number of complete inhibition

Table 10 The inhibitory effect of pharmaceutical composition of the present invention on clinical isolate Helicobacter pylori drug Inhibitory effect 50 25 12.5 6.25 3.12 1.56(mg/ml) The pharmaceutical composition of the present invention is Qizhi Weitong Granule 13/130/13 13/130/13 6/130/13 0/130/13 0/130/13 0/130/13

Note: The denominator is the number of experiments, and the numerator is the number of complete inhibition

It can be seen from Table 9 and Table 10 that the pharmaceutical composition of the present invention has obvious inhibitory effects on both the standard strain and the clinically isolated strain of Helicopylori. Thirteen experiments showed that when the concentration of the pharmaceutical composition of the present invention was above 25mg/ml, it could stably and completely inhibit Helicobacter pylori. complete inhibition, so under the experimental conditions, the minimum inhibitory concentration of the pharmaceutical composition of the present invention to Helicobacter pylori should be 25mg/ml. Qizhiweitong granule has no obvious inhibitory effect on Helicobacter pylori in the concentration range of 1.56-50mg/ml.

② Experimental results of test tube method

Table 11 The inhibitory effect of pharmaceutical composition of the present invention on standard strain Helicobacter pylori drug Inhibitory effect 50 25 12.5 6.25 3.12 1.56(mg/ml) The pharmaceutical composition of the present invention is Qizhi Weitong Granule 3/30/3 3/30/3 1/30/3 0/30/3 0/30/3 0/30/3

Note: The denominator is the number of experiments, and the numerator is the number of complete inhibition

Table 12 The inhibitory effect of the pharmaceutical composition of the present invention on the clinical isolation of Helicobacter pylori drug Inhibitory effect 50 25 12.5 6.25 3.12 1.56(mg/ml) The pharmaceutical composition of the present invention is Qizhi Weitong Granules 3/30/3 3/30/3 2/30/3 0/30/3 0/30/3 0/30/3

Note: The denominator is the number of experiments, and the numerator is the number of complete inhibition

It can be seen from Table 11 and Table 12 that the pharmaceutical composition of the present invention has obvious inhibitory effects on standard strains and clinical isolates of Helicobacter pylori. When the concentration of the pharmaceutical composition of the present invention is more than 25mg/ml, three repeated experiments all completely inhibit Helicobacter pylori, and when the concentration is 12.5mg/ml, there is also a certain inhibitory effect. The minimum inhibitory effect of the pharmaceutical composition of the present invention on Helicobacter pylori The bacterial concentration (MIC) was 25mg/ml. Under the same conditions as the pharmaceutical composition of the present invention, the Qizhiweitong granule has no obvious inhibitory effect on Helicobacter pylori.

summary

In this experiment, the inhibitory effect of the pharmaceutical composition of the present invention and Qizhi Weitong Granule on Helicobacter pylori was compared by agar dilution method and test tube method. The experimental results show that the pharmaceutical composition of the present invention has a significant inhibitory effect on the standard strain NCTC11639 of Helicobacter pylori and the clinical isolate 990409. Under the experimental conditions, the minimum inhibitory concentration of the pharmaceutical composition of the present invention is 25mg/ml. However, when the concentration of Qizhi Weitong Granules is within the range of 1.56-50 mg/ml, no obvious inhibitory effect on the standard strain NCTC11639 and the clinical isolate 990409 of Helicobacter pylori was found. It shows that the inhibitory effect of the pharmaceutical composition of the present invention on Helicobacter pylori is significantly stronger than that of Qizhiweitong granule.

2. Analgesic test

10. Effect of the pharmaceutical composition of the present invention on the analgesic effect in mice

Table 13 The impact of the pharmaceutical composition of the present invention on the analgesic effect in mice group Dose (g crude drug/Kg) Number of rats (only) Number of twists (times) Reduction rate (%) Control group Pharmaceutical composition of the present invention Pharmaceutical composition of the present invention Pharmaceutical composition of the present invention 9.14.62.3 10101010 17.70±9.215.60±4.72 ^** 7.10±5.11 ^** 11.30±6.17 68.3659.8928.44

Compared with the control group: ^** P＜0.01

As can be seen from the table, the number of writhing times of mice in each dosage group of the pharmaceutical composition of the present invention is all lower than that of the matched group, wherein there is a significant difference (P＜0.01) in the large and middle dose groups; the number of times of writhing in mice also shows a corresponding relation. It shows that the pharmaceutical composition of the present invention has obvious inhibitory effect on the pain-writhing response of mice caused by acetic acid stimulation, that is, the pharmaceutical composition of the present invention has obvious analgesic effect on mice.

summary

Helicobacter pylori test result shows that pharmaceutical composition of the present invention has obvious inhibitory action to Helicobacter pylori, i.e. bacteriostasis, and gastric ulcer, gastritis are relevant with Helicobacter pylori infection, therefore, this item of pharmaceutical composition of the present invention The effect can further confirm that the medicine can cure epigastric pain (stomach ulcer, gastritis) syndrome of stagnation of the liver and turning into heat, rebellious violation of the stomach.

Phase III clinical trials (multicenter, randomized, single-blind, controlled trial analysis)

Researcher:

Hospital in charge of clinical research: The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine

Main hospitals for clinical research:

Affiliated Hospital of Liaoning University of Traditional Chinese Medicine

The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine

Affiliated Hospital of Shandong University of Traditional Chinese Medicine

Ministry of Health China-Japan Friendship Hospital

The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine

The First Affiliated Hospital of Guiyang College of Traditional Chinese Medicine

Test start date: November 2002-October 2003

Main efficacy indicators:

Gastric ulcer: gastric ulcer size, stage, epigastric pain degree, frequency, time, epigastric tenderness degree

Chronic superficial gastritis: acute inflammation, chronic inflammation, degree of epigastric pain, frequency, time, degree of epigastric tenderness

Secondary efficacy indicators: heating, acid regurgitation, noisy, poor diet, nausea and vomiting, restlessness and irritability Test population:

A total of 411 cases of epigastric pain (gastric ulcer, chronic superficial gastritis) who met the inclusion criteria belonged to the syndrome of liver-stomach disharmony and stasis-heat blocking collaterals. The treatment group consisted of 310 cases, including 108 cases of gastric ulcer and 202 cases of chronic superficial gastritis (2 cases dropped out); the control group included 101 cases, including 36 cases of gastric ulcer and 65 cases of chronic superficial gastritis (1 case dropped out).

Dosing regimen:

Treatment group: pharmaceutical composition capsule of the present invention, oral, each 4 (0.29g grain), every day 3 times

Control group: Hericium Hericium Jianweiling Capsules (50 bottles, production batch number: 020901), approval number: Z14020754, produced by Bawang Pharmaceutical Co., Ltd., orally, 4 capsules each time (0.34g capsules), daily 3 times

Duration of treatment: six weeks

Drugs that have a therapeutic effect on gastric ulcer and chronic superficial gastritis are not allowed to be used during the test.

Single-blind experiment:

The comparison medicine Hericium Head Jianweiling Capsules and the pharmaceutical composition of the present invention are both No. 0 capsules, and their appearance, shape, color, weight, etc. are all very similar. The usage and dosage of the two medicines are also 4 capsules each time. 3 times. After the two drugs are replaced with the same outer packaging, it is suitable for single-blind clinical trials. The pharmaceutical composition of the present invention, Hericium Hericium Jianweiling Capsules, is coded by researchers at the Drug Clinical Research Base of the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, and named as the pharmaceutical composition capsule No. 1 of the present invention, and the pharmaceutical composition of the present invention. Material Capsule II, and is responsible for labeling.

evaluation standard:

Effectiveness evaluation index:

Refer to "Guiding Principles for Clinical Research of New Chinese Medicines for Treating Peptic Ulcer" and "Guiding Principles for Clinical Research of New Chinese Medicines for Treating Chronic Superficial Gastritis".

(1) TCM syndrome curative effect standard

1. Clinical recovery: all clinical symptoms and signs disappear, and the curative effect index after treatment is ≥95%.

2. Significantly effective: clinical symptoms and signs are significantly improved, 75% ≤ curative effect index < 95%

3. Effective: improvement of clinical symptoms and signs, 30% ≤ curative effect index < 75%

4. Ineffective: no improvement in clinical symptoms and signs, efficacy index <30%

Note:

(2) Criteria for judging the curative effect of gastroscopy for gastric ulcer

1. Clinical recovery: gastric ulcer completely disappeared (in S1 or S2 stage), local mild redness, no obvious edema.

2. Significantly effective: the gastric ulcer basically disappeared (in the H2 stage), and there was still obvious inflammation.

3. Effective: the gastric ulcer surface is reduced by more than 50% (at H1 stage).

4. Ineffective: the reduction of gastric ulcer surface is less than 50%.

(3) Criteria for judging the curative effect of chronic superficial gastritis

1. Clinical recovery: clinical symptoms and signs disappear completely, acute inflammation disappears through gastroscopy and pathological examination, and chronic inflammation reaches mild (if there is bile reflux, it must disappear after treatment). (That is, if the curative effect index of TCM syndrome is ≥95%, the acute inflammation disappears, and if one of the mild chronic inflammations is not achieved, the curative effect judgment will be lowered by one level)

2. Markedly effective: the clinical symptoms and signs are significantly improved (reduced by 2 grades), the acute inflammation in gastroscopy and pathological examination basically disappears, and the chronic inflammation is alleviated by 1. (Those with bile reflux will be significantly relieved after treatment). (i.e., 75% ≤ TCM syndrome curative effect index < 95%, acute inflammation disappears substantially, and chronic inflammation alleviates I. If there is one item not reached, the curative effect judgment is reduced by 1 grade)

3. Effective: clinical symptoms and signs are improved (reduced by 1 grade), the range of mucosal lesions in gastroscopy and pathological examination is reduced by more than 12, and acute inflammation and chronic inflammation are alleviated by 1. (Those with bile reflux should be relieved after treatment). (that is, 30%≤Chinese medicine syndrome curative effect index＜75%, gastroscopy and pathological examination mucosal lesion scope dwindle more than 12, and acute inflammation, chronic inflammation alleviate 1.

4. Ineffective: Although the symptoms improved after treatment, the gastroscopy and pathological examination did not change much from before treatment, and the above-mentioned standards could not be reached.

Safety indicators:

Blood, urine, stool routine, heart, liver, kidney function

Observation of clinical symptoms:

Physical adverse reactions and gastrointestinal reactions

Statistical analysis method:

According to the nature of clinical trial data (measurement data, classification data and grade data), choose the appropriate statistical analysis method. The X2 test or the exact probability method was used for classified data; the normality test and the homogeneity of variance test were carried out for the measurement data first, and the t-test was used for the comparison of the means of two samples if the requirements were met, and the paired t-test was used for the comparison before and after itself; two samples were used for those who did not meet the requirements Wilcoxon sum test was used for comparison of means, and Wilcoxon paired sum test was used for self-post comparison; Wilcoxon sum test (correction) for two-sample comparison or Kruskal-Wallis test for multi-group comparison was used for graded data.

Enrollment of subjects:

A total of 419 subjects were randomly divided into groups, 316 in the treatment group and 103 in the control group. In the treatment group, 308 cases completed the entire course of treatment, and 2 cases dropped out during the treatment process; in the control group, 100 cases completed the entire course of treatment, and 1 case dropped out during the treatment process. After completing the treatment, there were 6 cases in the treatment group and 2 cases in the control group who did not meet the selection criteria of the subjects and were regarded as excluded cases (see Table 49 for reasons of exclusion).

Efficacy results:

1. Comparison of total curative effect:

1.1 Comparison of curative effect of TCM syndromes between the two groups (PP analysis) group clinical recovery Significant efficiency Efficient total effective rate therapy group 25.65% 32.79% 37.01% 95.45% control group 14.0% 14.0% 61% 89.00%

The difference between the two groups was significant.

1.2 Comparison of curative effect of gastric ulcer endoscopy between the two groups (PP analysis, no patients with gastric ulcer dropped out halfway) group clinical recovery Significant efficiency Efficient total effective rate therapy group 56.48% 19.44% 19.44% 95.37% control group 33.33% 25.0% 27.78% 86.11%

The difference between the two groups was significant.

1.3 Comparison of curative effect of chronic superficial gastritis between two groups (PP analysis) group clinical recovery Significant efficiency Efficient total effective rate therapy group 17.0% 41.5% 36.5% 95.0% control group 10.94% 25.00% 48.44% 84.35%

The difference between the two groups was significant.

1.4 Comparison of curative effect of chronic superficial gastritis between two groups (ITT analysis) group clinical recovery Significant efficiency Efficient total effective rate therapy group 16.83% 41.09% 36.14% 94.06% control group 10.77% 24.62% 49.23% 84.62%

The difference between the two groups was significant.

The above results suggest that the total clinical curative effect of the treatment group on gastric ulcer and chronic superficial gastritis is better than that of the control group.

2. Comparison of clinical symptoms, signs, and efficacy of gastroscopy:

Comparison of clinical symptoms, signs, and gastroscopy improvement: the number of epigastric pains in the treatment group was significantly reduced, the pain time was significantly shortened, the degree of epigastric pain was significantly reduced, and the symptoms of poor diet, acid regurgitation, and irritability were significantly improved. The size and number of ulcers were significantly reduced, and the pathological HP histological grade of patients with chronic superficial gastritis was significantly reduced. Compared with the control group, the differences were significant. After treatment, there was no significant difference in the improvement of epigastric tenderness, heating, and noisy symptoms, the activity of chronic superficial gastritis pathological examination, and the histological grade of chronic inflammation between the two groups.

Comparison of disappearance rates of clinical symptoms, signs, and gastroscopy examinations: disappearance rates of ulcers, epigastric pain, epigastric tenderness, poor diet, heating, acid regurgitation, noise, irritability, dry mouth, bitter mouth, etc. The normalization rate of active histological grading of superficial gastritis pathological examination was higher than that of the control group, and the difference was significant compared with the control group. However, there was no significant difference between the two groups of chronic superficial gastritis pathological examination HP, chronic inflammation histological grading and grading normalization rate.

The above results suggest that the curative effect of clinical symptoms, signs and gastroscopic examination in the treatment group is better than that in the control group.

3. Multi-center effect analysis:

In order to eliminate the influence of the confounding factors of the center effect of different hospitals on the comparison of the total curative effect between the two groups, the Cochran-Mantel-Haenszel statistical analysis was performed by SAS software, and the center effect was corrected. The results of central effect analysis for the treatment of gastric ulcer showed that QCMH=6.7465, P=0.0094, and the difference was significant. This is consistent with the result of comparing the curative effects of the two groups after combining the data of the two hospitals (P=0.01). The center effect analysis results of treating chronic superficial gastritis showed that QCMH=11.3044, P=0.0008, and the difference was significant. This is consistent with the result of comparing the curative effects of the two groups after merging the data of the 6 hospitals (P=0.001). The results suggest that the curative effect of the pharmaceutical composition of the present invention in Phase III clinical trials in treating patients with gastric ulcer and chronic superficial gastritis is better than that of the control drug.

14. Conclusion:

The results of randomized single-blind controlled trials show that the pharmaceutical composition of the present invention has good clinical curative effect in the treatment of epigastric pain (gastric ulcer, chronic superficial gastritis) patients, and can obviously improve the symptoms of gastric ulcer and chronic superficial gastritis. The clinical symptoms, signs and gastroscopy results were better than those of the control group. It can be used for the treatment of patients with epigastric pain (gastric ulcer, chronic superficial gastritis) caused by liver-stomach disharmony and blood stasis blocking collaterals. During the course of treatment, no obvious damage to the heart, liver, kidney function and blood system was found, and the clinical application is safe.

Discussion and conclusion

In this study, a randomized single-blind controlled trial method was used for clinical trials, and a total of 411 case report forms were received, including 411 qualified subjects (3 cases dropped out midway). 310 cases in the treatment group (108 cases of gastric ulcer and 202 cases of chronic superficial gastritis), 101 cases of matched group (36 cases of gastric ulcer and 65 cases of chronic superficial gastritis); 405 cases of outpatients (306 cases of treatment group, 99 cases in the control group), 6 cases of inpatients (4 cases in the treatment group, 2 cases in the control group); TCM syndromes were all syndromes of liver-stomach disharmony, blood stasis and heat blocking collaterals.

Comparability test showed that there was no significant difference between the two groups in terms of age, sex, course of disease, nature of epigastric pain, frequency, time, tenderness and other clinical symptoms, tongue condition and pulse condition. There was no significant difference in the number, size and staging of gastric ulcers by gastroscopy before treatment between the two groups. There was no significant difference in the pathological diagnosis of HP grade, activity grade, and chronic inflammation grade between the two groups of patients with chronic superficial gastritis before treatment. It suggested that the main factors affecting the prognosis of the two groups were balanced.

Comparison of clinical symptoms, signs, and efficacy of gastroscopy:

Comparison of clinical symptoms, signs, and gastroscopy improvement: the number of epigastric pains in the treatment group was significantly reduced, the pain time was significantly shortened, the degree of epigastric pain was significantly reduced, and the symptoms of poor diet, acid regurgitation, and irritability were significantly improved. The size and number of ulcers were significantly reduced, and the pathological HP histological grade of patients with chronic superficial gastritis was significantly reduced. Compared with the control group, the differences were significant. After treatment, there was no significant difference in the improvement of epigastric tenderness, heating, and noisy symptoms, the activity of chronic superficial gastritis pathological examination, and the histological grade of chronic inflammation between the two groups.

Comparison of disappearance rates of clinical symptoms, signs, and gastroscopy examinations: disappearance rates of ulcers, epigastric pain, epigastric tenderness, poor diet, heating, acid regurgitation, noise, irritability, dry mouth, bitter mouth, etc. The normalization rate of active histological grading of superficial gastritis pathological examination was higher than that of the control group, and the difference was significant compared with the control group. However, there was no significant difference between the two groups of chronic superficial gastritis pathological examination HP, chronic inflammation histological grading and grading normalization rate.

The above results suggest that the curative effect of clinical symptoms, signs and gastroscopic examination in the treatment group is better than that in the control group.

The results of center effect analysis showed that although the clinical effects of several hospitals were not consistent, there may be the influence of center effect confounding factors. In order to eliminate the influence of the confounding factors of the center effect of different hospitals on the comparison of the total curative effect between the two groups, the Cochran-Mantel-Haenszel statistical analysis was performed by SAS software, and the center effect was corrected. The results of central effect analysis for the treatment of gastric ulcer showed that QCMH=6.7465, P=0.0094, and the difference was significant. This is consistent with the result of comparing the curative effects of the two groups after combining the data of the two hospitals (P=0.01). The center effect analysis results of treating chronic superficial gastritis showed that QCMH=11.3044, P=0.0008, and the difference was significant. This is consistent with the result of comparing the curative effects of the two groups after merging the data of the 6 hospitals (P=0.001).

The above center effect analysis results suggest that the phase III clinical trial of the pharmaceutical composition of the present invention has a better curative effect on treating gastric ulcer and chronic superficial gastritis than the control drug.

In summary, the results of 411 randomized single-blind controlled trials in this study show that the pharmaceutical composition of the present invention has a good clinical effect in treating epigastric pain (gastric ulcer, chronic superficial gastritis) patients, and can obviously improve gastric The clinical symptoms, signs and gastroscopy results of patients with ulcer and chronic superficial gastritis were better than those of the control group. It can be used for the treatment of patients with epigastric pain (gastric ulcer, chronic superficial gastritis) caused by liver-stomach disharmony and blood stasis blocking collaterals. During the course of treatment, no obvious damage to the heart, liver, kidney function and blood system was found, and the clinical application is safe.

Detailed ways

Several embodiments of the present invention will be described below, but the content of the present invention is not limited thereto at all.

Example 1

Get 5.4 parts by weight of Bupleurum Bupleurum, 5.4 parts by weight of Radix Paeoniae Alba, 3.6 parts by weight of Coptidis Rhizoma, 3.6 parts by weight of Evodia rutaecarpa, 7.2 parts by weight of Cyperus Cyperi, 7.2 parts by weight of Muxiang, 5.4 parts by weight of Rhizoma Chuanxiong, 3.6 parts by weight of Rhubarb, and 10.8 parts by weight of Corydalis Corydalis 14.4 parts by weight, Faluohai 14.4 parts by weight, 9 parts by weight of Citrus aurantii, 9 parts by weight of Rehmannia glutinosa, 5.4 parts by weight of Cortex Moutan, 10.8 parts by weight of Scallion, all raw materials are 1008 grams altogether. Then Cyperus cyperi, Chuanxiong, Citrus aurantii, Cortex chinensis, Moutan cortex are smashed, together with Evodia rutaecarpa, steam distilled to extract the volatile oil, and the distilled liquid is reserved for later use; the volatile oil is clathrated with β-cyclodextrin; the volatile oil is extracted The final medicinal residues are mixed with Faluohai, Xiebai, rhubarb, and rehmannia root, decocted twice with water, filtered, and combined with the filtrate, combined with the above-mentioned medicinal liquid after extracting volatile oil, concentrated under reduced pressure, and added ethanol to make the alcohol content 70% %, after stirring, stand still, filter, recover ethanol from the filtrate, and concentrate under reduced pressure to obtain a concentrated medicinal solution; take Bupleurum, Coptidis Rhizoma, Radix Paeoniae Alba, and Corydalis Corydalis, and heat and reflux twice with 70% ethanol for 2 hours for the first time , the second time for 1 hour, filter, combine the extracts, recover ethanol, and concentrate under reduced pressure, combine with the above-mentioned concentrated medicinal solution after alcohol precipitation, and dry under reduced pressure in vacuum to obtain a dry paste. The dry paste is crushed into fine powder, mixed with the above-mentioned β-cyclodextrin inclusion compound of volatile oil and the remaining Corydalis fine powder, made into granules with ethanol, dried, sized, and packed into capsules to make 1000 granules.

Example 2

Get 5.4 parts by weight of Bupleurum Bupleurum, 5.4 parts by weight of Radix Paeoniae Alba, 3.6 parts by weight of Coptidis Rhizoma, 3.6 parts by weight of Evodia rutaecarpa, 7.2 parts by weight of Cyperus Cyperi, 7.2 parts by weight of Muxiang, 5.4 parts by weight of Rhizoma Chuanxiong, 3.6 parts by weight of Rhubarb, and 10.8 parts by weight of Corydalis Corydalis 14.4 parts by weight, Faluohai 14.4 parts by weight, 9 parts by weight of Citrus aurantii, 9 parts by weight of Rehmannia glutinosa, 5.4 parts by weight of Cortex Moutan, 10.8 parts by weight of Scallion, all raw materials are 1008 grams altogether. Then Cyperus cyperi, Chuanxiong, Citrus aurantii, Cortex chinensis, Moutan cortex are smashed, together with Evodia rutaecarpa, steam distilled to extract the volatile oil, and the distilled liquid is reserved for later use; the volatile oil is clathrated with β-cyclodextrin; the volatile oil is extracted The final medicinal residues are mixed with Faluohai, Xiebai, rhubarb, and rehmannia root, decocted twice with water, filtered, and combined with the filtrate, combined with the above-mentioned medicinal liquid after extracting volatile oil, concentrated under reduced pressure, and added ethanol to make the alcohol content 70% %, after stirring, stand still, filter, recover ethanol from the filtrate, and concentrate under reduced pressure to obtain a concentrated medicinal solution; take Bupleurum, Coptidis Rhizoma, Radix Paeoniae Alba, and Corydalis Corydalis, and heat and reflux twice with 70% ethanol for 2 hours for the first time , the second time for 1 hour, filter, combine the extracts, reclaim ethanol, and concentrate under reduced pressure, combine with the concentrated medicinal solution after alcohol precipitation, and dry under reduced pressure to obtain a dry paste, which is pulverized into fine powder and mixed with the above-mentioned The β-cyclodextrin inclusion compound of volatile oil and the remaining Corydalis fine powder, starch, magnesium stearate, and sodium carboxymethyl starch are mixed evenly, and made into granules with ethanol, and the soft material is granulated with a 14-mesh nylon sieve, and dried for 20 minutes. Whole grains, mixed for 20 minutes, pressed into 1000 pieces, made into tablets.

Example 3

Get 5.4 parts by weight of Bupleurum, 5.4 parts by weight of Radix Paeoniae Alba, 3.6 parts by weight of Coptidis Rhizome, 3.6 parts by weight of Evodia rutaecarpa, 7.2 parts by weight of Cyperus Cyperi, 7.2 parts by weight of Muxiang, 5.4 parts by weight of Rhizoma Chuanxiong, 3.6 parts by weight of Rhubarb, 10.8 parts by weight of Corydalis Corydalis, 14.4 parts by weight of Faluohai, 9 parts by weight of Citrus aurantium, 9 parts by weight of Rehmannia glutinosa, 5.4 parts by weight of Cortex Moutan, 10.8 parts by weight of Allium scallions, and all raw materials are 1008 grams in total. Then Cyperus cyperi, Chuanxiong, Citrus aurantii, Cortex chinensis, Moutan cortex are smashed, together with Evodia rutaecarpa, steam distilled to extract the volatile oil, and the distilled liquid is reserved for later use; the volatile oil is clathrated with β-cyclodextrin; the volatile oil is extracted The final medicinal residues are mixed with Faluohai, Xiebai, rhubarb, and rehmannia root, decocted twice with water, filtered, and combined with the filtrate, combined with the above-mentioned medicinal liquid after extracting volatile oil, concentrated under reduced pressure, and added ethanol to make the alcohol content 70% %, after stirring, stand still, filter, recover ethanol from the filtrate, and concentrate under reduced pressure to obtain a concentrated medicinal solution; take Bupleurum, Coptidis Rhizoma, Radix Paeoniae Alba, and Corydalis Corydalis, and heat and reflux twice with 70% ethanol for 2 hours for the first time , the second time for 1 hour, filter, combine the extracts, recover ethanol, and concentrate under reduced pressure, combine with the above-mentioned concentrated medicinal solution after alcohol precipitation, and dry under reduced pressure in vacuum to obtain a dry paste. The dry paste is crushed into fine powder, mixed with the above-mentioned β-cyclodextrin inclusion compound of volatile oil and the remaining Corydalis fine powder, and made into granules with ethanol, and the soft material is granulated with a 14-mesh nylon sieve, dried for 20 minutes, granulated, total Mix for 20 minutes, put into aluminum foil bags, 250 bags, and make granules.

Example 4

Get 5.4 parts by weight of Bupleurum, 5.4 parts by weight of Radix Paeoniae Alba, 3.6 parts by weight of Coptidis Rhizome, 3.6 parts by weight of Evodia rutaecarpa, 7.2 parts by weight of Cyperus Cyperi, 7.2 parts by weight of Muxiang, 5.4 parts by weight of Rhizoma Chuanxiong, 3.6 parts by weight of Rhubarb, 10.8 parts by weight of Corydalis Corydalis, 14.4 parts by weight of Faluohai, 9 parts by weight of Citrus aurantium, 9 parts by weight of Rehmannia glutinosa, 5.4 parts by weight of Cortex Moutan, 10.8 parts by weight of Allium scallions, and all raw materials are 1008 grams in total. Then Cyperus cyperi, Chuanxiong, Citrus aurantii, Cortex chinensis, Moutan cortex are smashed, together with Evodia rutaecarpa, steam distilled to extract the volatile oil, and the distilled liquid is reserved for later use; the volatile oil is clathrated with β-cyclodextrin; the volatile oil is extracted The final medicinal residues are mixed with Faluohai, Xiebai, rhubarb, and rehmannia root, decocted twice with water, filtered, and combined with the filtrate, combined with the above-mentioned medicinal liquid after extracting volatile oil, concentrated under reduced pressure, and added ethanol to make the alcohol content 70% %, after stirring, stand still, filter, recover ethanol from the filtrate, and concentrate under reduced pressure to obtain a concentrated medicinal solution; take Bupleurum, Coptidis Rhizoma, Radix Paeoniae Alba, and Corydalis Corydalis, and heat and reflux twice with 70% ethanol for 2 hours for the first time , the second time 1 hour, filter, combine the extracts, recover ethanol, and concentrate under reduced pressure, melt the mixed fatty acid glycerides, control the temperature at 50°C (range 40-60°C), add the crushed extract, and circulate and stir For 40 minutes (range 30-60 minutes), the water bath is kept warm to about 45°C (40-50°C), filled, the temperature is kept at 37-39°C, and frozen to shape. Made into a suppository.

Example 5

Get 5.4 parts by weight of Bupleurum, 5.4 parts by weight of Radix Paeoniae Alba, 3.6 parts by weight of Coptidis Rhizome, 3.6 parts by weight of Evodia rutaecarpa, 7.2 parts by weight of Cyperus Cyperi, 7.2 parts by weight of Muxiang, 5.4 parts by weight of Rhizoma Chuanxiong, 3.6 parts by weight of Rhubarb, 10.8 parts by weight of Corydalis Corydalis, 14.4 parts by weight of Faluohai, 9 parts by weight of Citrus aurantium, 9 parts by weight of Rehmannia glutinosa, 5.4 parts by weight of Cortex Moutan, 10.8 parts by weight of Allium scallions, and all raw materials are 1008 grams in total. Then Cyperus cyperi, Chuanxiong, Citrus aurantii, Cortex chinensis, Moutan cortex are smashed, together with Evodia rutaecarpa, steam distilled to extract the volatile oil, and the distilled liquid is reserved for later use; the volatile oil is clathrated with β-cyclodextrin; the volatile oil is extracted The final medicinal residues are mixed with Faluohai, Xiebai, rhubarb, and rehmannia root, decocted twice with water, filtered, and combined with the filtrate, combined with the above-mentioned medicinal liquid after extracting volatile oil, concentrated under reduced pressure, and added ethanol to make the alcohol content 70% %, after stirring, stand still, filter, recover ethanol from the filtrate, and concentrate under reduced pressure to obtain a concentrated medicinal solution; take Bupleurum, Coptidis Rhizoma, Radix Paeoniae Alba, and Corydalis Corydalis, and heat and reflux twice with 70% ethanol for 2 hours for the first time , the second time for 1 hour, filter, combine the extracts, recover ethanol, and concentrate under reduced pressure, combine with the above-mentioned concentrated medicinal solution after alcohol precipitation, and dry under reduced pressure in vacuum to obtain a dry paste. The dry paste is crushed into fine powder, mixed with the above-mentioned β-cyclodextrin inclusion compound of volatile oil and the remaining Corydalis fine powder, ground with carboxymethylcellulose sodium mucilage, and mixed with lemon essence to make a suspension, namely Get oral solution.

Claims (6)

1. A pharmaceutical composition for the treatment of stomach pain, characterized in that its raw materials contain the following medicines in parts by weight: 4-6 parts of Bupleurum, 4-6 parts of Radix Paeoniae Alba, 2-5 parts of Coptis Rhizoma, 2-4 parts of Evodia rutaecarpa, Fu 6-8 parts, Muxiang 6-8 parts, Chuanxiong 4-6 parts, Rhubarb 2-4 parts, Corydalis 9-11 parts, Faluohai 13-15 parts, Citrus aurantium 8-10 parts, Rehmannia glutinosa 8-10 parts 4-6 parts of Moutan Cortex, 9-10 parts of Scallion White; The preparation method of described pharmaceutical composition comprises the following steps: Take Rhizoma Cyperi, Rhizoma Chuanxiong, Fructus Citrus Citrus Fructus Citrus Fructus Aurantium, Cortex Cortex Moutan, Cortex Moutan, and distill together with Evodia rutaecarpa to extract the volatile oil, and the distilled liquid is reserved for later use; the volatile oil is clathrated with β-cyclodextrin; the dregs after extracting the volatile oil are mixed Add water to decoct 2-3 times, filter, combine the filtrate, combine with the above-mentioned medicinal solution after extracting volatile oil, concentrate, add ethanol and stir, let stand, filter, and recover ethanol from the filtrate , and concentrated to obtain a concentrated medicinal solution; take Bupleurum, Coptis Rhizoma, Radix Paeoniae Alba, and Corydalis Corydalis, pulverize them, heat and reflux twice with ethanol, combine the extracts, recover ethanol, concentrate, combine with the above-mentioned concentrated medicinal solution, and dry to obtain a dry paste; The paste is crushed into fine powder, mixed with the above-mentioned β-cyclodextrin inclusion compound of volatile oil, remaining fine powder of Corydalis Corydalis, and other pharmaceutically acceptable carriers to prepare a pharmaceutical composition. 2. The pharmaceutical composition according to claim 1, characterized in that its raw materials contain the following medicines in parts by weight: 5.4 parts of Bupleurum, 5.4 parts of Radix Paeoniae Alba, 3.6 parts of Coptis Rhizoma, 3.6 parts of Evodia rutaecarpa, 7.2 parts of Vinegaria Cyperus, 7.2 parts of woody fragrance, 5.4 parts of Chuanxiong, 3.6 parts of rhubarb, 10.8 parts of vinegar corydalis, 14.4 parts of faluohai, 9 parts of bran fried aurantium, 9 parts of rehmannia, 5.4 parts of Moutan bark, and 10.8 parts of scallion. 3. The pharmaceutical composition according to claim 1 or 2, characterized in that the pharmaceutical composition is injection, tablet, capsule, pill, solution, suspension, emulsion. 4. The pharmaceutical composition according to claim 1 or 2 is effective in treating acute gastric ulcer, chronic gastric ulcer, drug-induced gastric ulcer and gastric mucosal injury, inhibiting gastric emptying function and gastric juice secretion, soothing liver and stomach, regulating qi and activating blood circulation , clearing heat and relieving pain, epigastric pain, gastric ulcer, and chronic superficial gastritis. 5. A method for preparing the pharmaceutical composition described in claim 1 or 2, characterized in that it takes Rhizoma Cyperi, Rhizoma Chuanxiong, Fructus Citrus Fructus Citrus Fructus Citrus Fructus Aurantii, Cortex Cortex Moutan, smashes them, together with Evodia Evodia, extracts by steam distillation The volatile oil, and the distilled medicinal liquid is kept for later use; the volatile oil is clathrated with β-cyclodextrin; the medicinal residue after extracting the volatile oil is decocted with Faluohai, Xiebai, rhubarb, and rehmannia root for 2-3 times, filtered, Combine the filtrate, combine with the above-mentioned medicinal solution after extracting the volatile oil, concentrate under reduced pressure, add ethanol to make the alcohol content 60%-80%, stand still after stirring, filter, recover ethanol from the filtrate, and concentrate under reduced pressure to obtain concentrated medicine liquid; take Bupleurum, Coptis Rhizoma, Radix Paeoniae Alba, and Corydalis Corydalis and grind them, heat and reflux twice with 60%-80% ethanol, the first time for 1.5-3 hours, the second time for 0.5-1.5 hours, filter, combine the extracts, and recover Ethanol, concentrated under reduced pressure, combined with the above-mentioned concentrated medicinal solution after alcohol precipitation, and dried under reduced pressure to obtain a dry paste; the dry paste was crushed into fine powder, and mixed with the above-mentioned β-cyclodextrin inclusion compound of the above-mentioned volatile oil and the remaining Corydalis fine powder , made into granules with ethanol, dried, and granulated. 6. method according to claim 5, it is characterized in that described method is to get Rhizoma Cyperi, Rhizoma Chuanxiong, Fructus Citrus Fructus Aurantii, Cortex Cortex Moutan, break into pieces, together with Evodia Evodia, steam distillation extracts volatile oil, and after distillation Keep the medicinal solution for later use; the volatile oil is clathrated with β-cyclodextrin; the medicinal dregs after extracting the volatile oil are mixed with Faluohai, Xiebai, rhubarb, and rehmannia, add 6.4 times the amount of water equivalent to the crude drug, and decoct twice, the first time 2 hour, the second time for 1 hour, filter and combine the filtrate, combine with the above-mentioned medicinal solution after extracting volatile oil, concentrate under reduced pressure to a relative density of 1.05 to 1.10 at 50°C, add ethanol to make the alcohol content 70%, after stirring Stand still for 12 hours, filter, recover ethanol from the filtrate, and concentrate under reduced pressure to a relative density of 1.30 to 1.38 at 50°C to obtain a concentrated medicinal solution; take Bupleurum, Coptidis Rhizome, Radix Paeoniae Alba, and Corydalis Corydalis and heat to reflux with 70% ethanol 2 times, 2 hours for the first time, 1 hour for the second time, filter, combine the extracts, recover ethanol, and concentrate under reduced pressure to a relative density of 1.30-1.38 at 50°C, and combine with the above-mentioned concentrated medicinal solution after alcohol precipitation, Dry under reduced pressure and vacuum below 80°C to obtain a dry paste; the dry paste is crushed into fine powder, mixed with the above-mentioned β-cyclodextrin inclusion compound of volatile oil and the remaining Corydalis fine powder, made into granules with ethanol, dried below 70°C, and granulated .