CN1250255C - Chinese herbal medicine combination for treating disease of disorder of bowels's function and its product - Google Patents

Abstract

The invention relates to a traditional Chinese medicine compound composition for treating intestinal dysfunction diseases such as a traditional Chinese medicine composition (irritable bowel syndrome, IBS), and a dosage form of the traditional Chinese medicine compound composition. The applicant believes that the common and primary cause of IBS is mental factors, and based on the principle of "holistic concept" and "treatment based on syndrome differentiation", it provides a traditional Chinese medicine composition for treating irritable bowel syndrome, including: Bupleurum bupleurum 6-15 grams, Radix Paeoniae Alba 5-20, Rhizoma Chuanxiong 3-10, Atractylodes Rhizoma 6-20, Poria 6-12 grams, Licorice 5-20 grams. Its dosage forms include: granules, capsules, tablets, oral liquids, injections, transdermal or transmucosal administration preparations, rectal administration preparations prepared by adding the extract of the composition directly or after purification and separation with appropriate pharmaceutical excipients. Suppository This regimen has demonstrated unique effects and advantages in the treatment of IBS, and has a good prospect.

Description

Traditional Chinese medicine composition and preparation thereof for treating intestinal dysfunction

technical field

The invention relates to a traditional Chinese medicine compound composition for treating irritable bowel syndrome (irritable bowel syndrome, IBS) and other intestinal dysfunction diseases, and a preparation of the traditional Chinese medicine compound composition.

Background technique

Irritable bowel syndrome (IBS) is a common non-organic intestinal dysfunction disease of the digestive tract, with clinical characteristics of chronic recurrent attacks. The clinical symptoms are abdominal discomfort (abdominal pain, bloating) and abnormal intestinal motility, such as changes in bowel habits (diarrhea or constipation), abnormal stool properties (loose stools, mucus stools, or hard stools), and increased frequency of bowel movements. Existence or intermittent attacks, pathological examination mostly no specific intestinal inflammatory lesions. At present, there is no effective treatment for this disease, so it is one of the common refractory diseases in clinical practice. Studies have shown that the prevalence of IBS in European and American countries is about 20%, the annual new incidence rate is 1-2%, and the male to female ratio is about 1:3. According to relevant literature reports in our country, IBS accounts for 1/3 of gastrointestinal specialist outpatient visits and about 15% of the total population. Because the symptoms recur and persist for a long time, the impact on the patient's life and the inconvenience brought to the work are quite obvious, and the cost of various examinations and treatments is even more considerable. Modern medicine believes that the disease is closely related to the nervous system, endocrine system and immune regulation system. Due to the high incidence of IBS, foreign pharmaceutical companies are scrambling to develop new drugs, but so far, the treatment methods are limited, and there is no specific drug to cure the disease. Moreover, most of the drugs start from relaxing intestinal smooth muscle, stimulating and antagonizing neurotransmitters, and anti-anxiety, and their effects are limited. They are often aimed at treating single symptoms such as diarrhea or constipation, and mainly focus on the regulation of intestinal microecology, anti-depression, Prokinetic drug therapy, calcium channel antagonist and astringent therapy, etc. At present, most commonly used clinical medicines are used to relieve certain symptoms, such as SEMECDA (SEMECDA) for abdominal pain and diarrhea of irritable bowel syndrome; gastrointestinal prokinetic drugs commonly used for the treatment of constipation symptoms mainly include domperidone (domperidone, domperidone) ) is a peripheral nerve dopamine receptor antagonist, and cisapride (cisapride, prepulsid, Prepulsid) is a new type of gastrointestinal prokinetic drug, which completes the prokinetic effect through multiple actions of different 5-hydroxytryptamine (5-HT) receptors. power action. Tegashirol maleate is a new type of chemical drug developed by Novartis Pharmaceuticals for the treatment of irritable bowel syndrome. Its indications are symptoms such as abdominal pain, abdominal discomfort and constipation in patients with irritable bowel syndrome. Tegathiaro has no cardiotoxicity of cisapride, and has fewer side effects than cisapride. In recent years, the serotonin receptor blocker, alosetron, which has been on the market in recent years, treats diarrhea-based irritable bowel syndrome (D-IBS). Studies have shown that there are gender differences. Although the above types of drugs can alleviate some symptoms of irritable bowel syndrome, they have disadvantages such as irreversible cure, large side effects, obvious individual differences, and high treatment costs in application. However, since the onset of this disease involves multiple aspects of spirit, diet, and individual quality, there are one-sidedness and limitations in clinical application, which cannot meet the clinical requirements.

IBS has been recognized as a psychosomatic disease and is a multifactorial syndrome that involves biological and social psychology (including tension, patient's personality and behavior) and other factors in its etiology and pathogenesis. It has been proved that the pathogenesis of IBS is related to mental factors, changes in intestinal dynamics, improper diet, changes in colon secretion and absorption, and intestinal flora imbalance.

In ancient Chinese medical literature, there have been a large number of descriptions and records of the etiology and pathogenesis, symptoms and signs, prevention and treatment of IBS. The principles of "holistic concept" and "treatment based on syndrome differentiation" of TCM theory have obvious advantages in the treatment of such diseases. The basic research of IBS found that IBS is caused by the dysfunction of the central nervous system and autonomic nerves, which can cause intestinal motility and secretion dysfunction. Abnormal intestinal motility and visceral hypersensitivity in IBS patients are one of the important pathophysiological basis of IBS pathogenesis. The theory of traditional Chinese medicine believes that this disease is caused by "spleen deficiency and liver excess". Spleen deficiency is easily caused by liver wood insults, qi stagnation, and abnormal ascending and descending, resulting in diarrhea or constipation. my country's traditional Chinese medicine medical units have used traditional Chinese medicine to carry out a lot of exploration and practice on IBS. A lot of work has been done on the dialectical classification of IBS, treatment principles, integration of traditional Chinese and Western medicine, etc., and good results have been achieved. For the IBS type, the dialectical treatment is based on the principles of soothing the liver and relieving depression, suppressing the intestines and stopping diarrhea; achieve real results. It has been reported that the treatment of IBS can be combined with physical therapy, acupuncture, abdominal massage, hot compress or ultrashort wave, etc., which has a certain effect. The combination of traditional Chinese medicine and western medicine is also effective in treating IBS by using compound Chinese medicine together with astemizole and vitamin C.

Contents of the invention

The present invention focuses on formulating prescriptions according to the overall concept of traditional Chinese medicine, and provides a method for treating irritable bowel syndrome by comprehensively considering multiple factors in the pathogenesis of the syndrome based on the principles of "holistic concept" and "treatment based on syndrome differentiation". A traditional Chinese medicine compound composition for diseases such as intestinal dysfunction, and a preparation of the preparation of the traditional Chinese medicine compound composition. The main clinical manifestations of IBS are diarrhea, constipation, abdominal pain, alternating diarrhea and constipation; accompanied by anorexia, fatigue, weight loss, poor sleep quality, irritability, etc. Modern medicine is divided into diarrhea type, constipation type, alternating type. Based on years of clinical treatment and scientific research, the relevant applicants of this project start from the theory of traditional Chinese medicine and believe that the common and primary cause of IBS is mental factors. The onset or aggravation of patients often occurs when they are nervous, depressed, and irritable. It belongs to the pathogenic category of "seven emotions" in traditional Chinese medicine. , fire consumes body fluid, body fluid is lost and transfused into cloth, which cannot moisten the large intestine, resulting in dysfunction of the spleen. Constipation is often seen clinically, accompanied by anorexia, abdominal distension, nervousness, irritability, dry mouth, and insomnia. If the disease is not controlled and the course of the disease is protracted, it will lead to weak spleen and stomach, weak transportation and transformation, and insufficient source of Qi and blood biochemistry. Clinically, diarrhea and constipation are often seen alternately. At the end of the course of the disease, it can be seen clinically that abdominal pain occurs in the morning, borborygmus, diarrhea, accompanied by cold body and cold limbs, sore waist, pale tongue with white coating, and deep thready pulse. Therefore, based on the theory of liver-spleen imbalance, the principles of soothing the liver and regulating qi, invigorating the spleen and clearing the intestines, nourishing yin and promoting movement, and basic prescriptions that have been clinically verified are summarized.

The basic formula of the traditional Chinese medicine composition for the treatment of intestinal dysfunction includes:

Bupleurum 6-15 grams

Paeoniae Alba 5-20 grams

Chuanxiong 3-10 grams

Atractylodes 6-20 grams

Poria cocos 6-12 grams

Licorice 5-20 grams.

Further optimize the above scheme: the recommended dosage of the basic prescription is:

Bupleurum 8-12 grams

Paeoniae Alba 9-12 grams

Chuanxiong 5-9 grams

Atractylodes 9-15 grams

Poria cocos 6-12 grams

Licorice 6-15 grams.

The above basic prescriptions can be directly used clinically without adding other components. That is: the composition of the composition is the above formula. At the same time, other components can also be added on the basis of the above-mentioned basic prescription, and the components that can be added include any one or more of the following two types of drugs:

1: Codonopsis, ebony, aurantium, windproof, tangerine peel, heterophylla, cassia twig, cohosh, nutmeg, schisandra.

2: Astragalus, ginseng, kudzu root, uncaria, angelica, jujube, ginger, Cyperus cyperi, pinellia, turmeric.

For example: when used for different degrees of diarrhea, constipation, abdominal pain, diarrhea and constipation alternately, 6 grams of woody fragrance can be added;

For diarrhea, abdominal pain, constipation, alternating diarrhea and constipation, accompanied by different degrees of obvious symptoms of weight loss and poor sleep, add one of the following component combinations on the basis of the basic prescription: (1), add Pseudostellaria 10 ～18 grams, or, (2), 10～18 grams of Radix Pseudostellariae, 6 grams each of tangerine peel and citrus aurantium; or (3), 6 grams to 9 grams of tangerine peel, or (4), 9 grams of Scutellaria baicalensis, 9 grams of Codonopsis pilosula, Citrus aurantium 6 grams, Cimicifuga 3 grams, or (5), orange peel, Codonopsis 6 grams each.

For abdominal distension, abdominal pain, accompanied by obvious constipation and irritability, you can add: 6 grams of Fangfeng, 6 grams of nutmeg, 9 grams of kudzu root, and 6 grams of Schisandra.

For diarrhea or constipation, accompanied by obvious abdominal pain, chills, etc., add one of the following component combinations on the basis of the basic prescription: (1), 9 grams of black plum, 3 grams of Coptis chinensis, 3 grams of cassia twig, 6 grams of Radix Pseudostellaria; or (2), 12 grams of nutmeg, 6 grams of tangerine peel, 6 grams of cinnamon sticks, and 3 grams of coptis; or (3), 9 grams of cinnamon sticks, 6 grams of tangerine peel, and 3 grams of turmeric.

For diarrhea and constipation alternately accompanied by obvious abdominal distension, anorexia, and emaciation, you can add: Codonopsis 18g, Bellflower 9g, Coptidis 3g, Muxiang 3g, Hawthorn 3g, Divine Comedy 3g, Citrus aurantium 3 grams of tangerine peel and 3 grams of tangerine peel.

Modern dosage forms of the above traditional Chinese medicine composition include:

1. Granules, capsules, tablets, oral liquids, injections (subcutaneous, blood vessel, intramuscular administration), transdermal or transmucosal administration preparations prepared by adding the above extracts directly or after purification and separation with appropriate pharmaceutical excipients , suppositories for rectal administration.

2. Granules, capsules, tablets, preparations for transdermal or transmucosal administration, and suppositories for rectal administration prepared by adding appropriate pharmaceutical excipients to the above drugs.

3. Granules, capsules, tablets, preparations for transdermal or transmucosal administration, and suppositories for rectal administration prepared by combining the above extracts directly or after purification and separation with the directly pulverized drug.

The scope of indications of the composition: gastrointestinal dysfunction of humans or other general mammals. include:

1. Irritable bowel syndrome (bowel dysfunction) induced by mental factors.

2. Irritable bowel syndrome (bowel dysfunction) induced by food or inflammation

3. The main clinical manifestations of IBS are diarrhea, constipation, abdominal pain, alternating diarrhea and constipation; accompanied by anorexia, fatigue, weight loss, poor sleep quality, irritability, etc. Modern medicine is divided into diarrhea type and constipation type. The main manifestations of clinical symptoms are irregular abdominal pain, abdominal distension, diarrhea, changes in stool properties and increased frequency of defecation. Exclude other intestinal organic diseases: exclude thyroid disease, diabetes, kidney disease, cardiovascular disease, hematopoietic system disease, ulcerative colitis, Crohn's disease, chronic dysentery, peptic ulcer, chronic hepatitis, anal disease, etc., to prevent false positives . Generally, it has the following characteristics: (1) abdominal pain before defecation, relieved after defecation; (2) intestinal peristalsis significantly increased during abdominal pain; (3) constipation or diarrhea; (4) generally good general condition or accompanied by systemic neurosis. (5) The spontaneous peristalsis of the colon is abnormal and the intestinal sensitivity is increased. (6) visceral hyperalgesia, etc.

4. Other related diseases include: functional bowel disorder (functional diarrhea, functional constipation), acute and chronic functional abdominal pain or bloating or accompanied by gastric symptoms, periodic abdominal pain or bloating, functional dyspepsia, stomach pain Discomfort etc.

The animal pharmacodynamics research result of this composition is as follows:

Pharmacodynamic Study 1 Effects on defecation and body weight recovery and motilin in spleen-deficiency model animals.

Animal Pharmacology Research Results:

(1) Effects on the recovery of defecation and body weight and motilin in spleen-deficiency model animals

Experimental Materials

1.1 Experimental drugs: self-prepared prescription (bupleurum bupleuri 10g, white peony root 9g, chuanxiong 6g, heterophylla 6g, atractylodes macrocephala 9g, poria cocos 9g, licorice 6g). The concentrated solution is decocted twice according to the requirements of the prescription drug, and concentrated to 1 g crude drug/ml (medium dose) and 3 g crude drug/ml (high dose) after precipitation with an appropriate amount of ethanol, and stored at 5°C for later use;

1.2 Experimental animals: SD adult rats, 180-220g.

2 Experimental methods

2.1 Group experiment

对照组：取健康大鼠10只，腹腔注射生理盐水适量，连续10天。并于每日9:00、16:00灌服生理盐水各2ml。连续20天，记录观察。

Control group: 10 healthy rats were injected with an appropriate amount of normal saline intraperitoneally for 10 consecutive days. And at 9:00 and 16:00 every day, 2ml of normal saline was given. For 20 consecutive days, record observations.

模型制备：取大鼠腹腔注射利血平注射液0.5mg kg-1 d-1。连续10天。于每日9:00、16:00灌服生理盐水各2ml。

Model preparation: Rats were intraperitoneally injected with reserpine injection 0.5 mg kg-1 d-1. 10 consecutive days. At 9:00 and 16:00 every day, 2ml of normal saline was administered.

自然恢复组：取模型大鼠10只，于每日9:00、16:00灌服生理盐水各2ml。连续10天。

Natural recovery group: 10 model rats were taken and fed with 2ml of normal saline at 9:00 and 16:00 every day. 10 consecutive days.

自拟方低剂量组：取模型大鼠10只，于每日9:00、16:00灌服自拟方浓缩液(1g/ml)各2ml，连续10天。

Self-made prescription low-dose group: 10 model rats were taken, and each 2ml of self-made prescription concentrated solution (1g/ml) was fed at 9:00 and 16:00 every day for 10 consecutive days.

High-dose self-preparation group: 10 model rats were given 2ml each of the self-preparation concentrated solution (3g/ml) at 9:00 and 16:00 every day for 10 consecutive days.

阳性药物对照组：取模型大鼠10只，于每日9:00、16:00以1g Kg-1剂量灌服思密达混悬液，连续10天。

Positive drug control group: 10 model rats were taken and fed with 1 g Kg-1 suspension of Smecta at 9:00 and 16:00 every day for 10 consecutive days.

2.2 Result Judgment Index

Observation of the model status: After the injection of reserpine, the model rats gradually developed different degrees of diarrhea and perianal contamination. By the tenth day, all groups had a lot of loose stools and decreased appetite.

指标选择：记录各组动物体重、食量、粪便等情况。选择动物食量、体重、恢复正常排便的时间等症状和体征为判断指标。结果见表1，表2。另取胃动素(MTL)为辅助判断指标。同时观察胃肠组织的粘膜损伤情况。各组动物实验结束后禁食16小时，断头处死，取肠液、血浆、空肠、下丘脑组织冷冻保存，按试剂盒方法测定MTL，结果见表3。取胃肠组织，肉眼、光镜、透射电镜观察粘膜损伤情况，结果见表4。

Index selection: Record the animal body weight, food intake, feces and other conditions of each group. Animal food intake, body weight, time to return to normal defecation and other symptoms and signs were selected as judgment indicators. The results are shown in Table 1 and Table 2. In addition, motilin (MTL) was used as an auxiliary judgment index. At the same time, the mucosal injury of gastrointestinal tissue was observed. Animals in each group were fasted for 16 hours after the experiment, and then killed by decapitation. The intestinal juice, plasma, jejunum, and hypothalamus tissues were collected for cryopreservation. MTL was determined according to the kit method. The results are shown in Table 3. Gastrointestinal tissues were collected, and the mucosal damage was observed with the naked eye, light microscope, and transmission electron microscope. The results are shown in Table 4.

2.4 Data processing

Two-group t-test was used for statistical analysis between the means.

3 results

The middle and high dose self-preparation group and the positive drug control group can significantly improve the body weight (P<0.05) and appetite (P<0.05) of the model animals, while the self-preparation group has a significant improvement compared with the positive drug control group (P<0.05). ) (Table 1, Table 2). Both the middle and high dose self-made prescription groups and the positive drug control group can improve the symptoms of animal defecation disorders, and the self-made prescription group has a faster onset of effect than Smecta (Table 3). The middle and high dose self-preparation groups can significantly increase the MTL content in body fluids and tissues of model animals (P<0.05) (Table 4). Both the middle and high dose self-prepared prescription groups and the positive drug control group can significantly restore the damage of the model drugs to the gastrointestinal mucosal cells (Table 5).

The results of this study showed that the animal model had obvious symptoms such as diarrhea, loose stool, sticky stool, decreased appetite, body weight, and MTL. However, there was no obvious damage to the gastrointestinal mucosa before and after the treatment. Self-made formula and Smecta can significantly improve the general condition (body weight, food intake, and defecation) of reserpine-treated model rats (P<0.05), and self-made formula can significantly increase the MTL content in body fluids and tissues of model animals (P<0.05 ); Compared with the Smecta control group, the self-prepared prescription treatment group had significant advantages in terms of general condition, normal defecation recovery days, and MTL (P<0.05). Compared with the Smecta control group, the self-prepared prescription treatment group had significantly improved defecation recovery days, body weight, and MTL (P<0.05). Therefore, as a drug for the treatment of IBS, it is beneficial to the recovery of patients.

(2) Research on the pharmacodynamic site of the regulation of gastrointestinal motility.

Method: The isolated intestinal tube was used to observe the effect of different extraction parts of the self-prepared formula on the movement of isolated small intestine of rabbits.

Material 11 Experimental Drug The self-prepared drug was decocted twice, 30 minutes/time, filtered, centrifuged, concentrated, extracted with different organic solvents, and separated into water to extract the alcohol-soluble part, chloroform part, chloroform part 1, and chloroform Part 2, ethyl acetate part, ethyl acetate part 1, ethyl acetate part 2, ethyl acetate part 3, n-butanol part 1, n-butanol part 2, n-butanol insoluble part, prepared with distilled water during the test Use in appropriate concentration.

Schematic diagram of the separation of different chemical sites

13 Animals New Zealand rabbits, weighing 20-2.5kg.

14 Methods The isolated small intestine of rabbits was prepared according to the method in the literature, and the table-top automatic balance recorder was used to record the movement curve, and the changes of the intestinal movement curve before and after administration were observed: ①Compared the influence of each extraction part of the self-made prescription on the spontaneous activity of the duodenum, Calculate the percentage of inhibition of intestinal contraction range 5 minutes after administration. ②Based on the tonic contraction induced by barium chloride (BaCl ₂ , 20% 0.1ml), the antagonism of each sample was observed, and the percentage of inhibition of intestinal tension was calculated. ③ Observing the antagonism of the sample on the basis of the obvious inhibition caused by adrenaline hydrochloride (0.1ml) on the isolated small intestine, and calculating the increase rate of the intestinal contraction amplitude caused by the drug.

2 results

2.1 Effects on spontaneous activity of duodenum in rabbits

The self-prepared water extract and the water-extracted alcohol-soluble part had an inhibitory effect on the spontaneous activity of the isolated duodenum in rabbits, showing a decrease in the contraction amplitude, frequency and tension. When the dose is small, the main performance is that the contraction range is reduced, and the frequency and tension change are not obvious. The inhibition percentages of the above doses on intestinal contraction range were 69.0±27.3% (n=10) and 81.4±12.0% (n=10). The ethyl acetate part, chloroform part and n-butanol extraction part of the self-prepared formula have inhibitory effects on the spontaneous activity of the duodenum, and the effect is similar to that of the water extract, mainly manifested in the reduction of the contraction range. When the dose is larger, the frequency decreases and the tension decreases slightly, and the intensity of the action is related to the dose. Comparing the three, the effects of ethyl acetate and chloroform are equivalent, while the effects of n-butanol are weaker. The n-butanol-insoluble part had no significant effect on the spontaneous motility of the duodenum.

2.2 Antagonize the effect of acetylcholine and barium chloride

The self-prepared water extract (35mg/ml) and the water-extracted alcohol-soluble part (35mg/ml) all have obvious antagonistic effects on the tonic contraction of the intestine caused by acetylcholine and barium chloride, mainly manifested as a significant decrease in tension. The antagonism percentages to acetylcholine were 66.9±11.3% (n=10), 70.1±9% (n=10); the antagonism rates to barium chloride were 53.4±11.2% (n=10), 48.5±9.6% (n=10). The ethyl acetate part, chloroform part and n-butanol part of the self-made formula all have obvious antagonistic effects on the tonic contraction of the intestine caused by acetylcholine. Comparing the three, the chloroform part has the same strength as the ethyl acetate part, and the effect of the n-butanol part is weaker.

Chloroform part 1, chloroform part 2, ethyl acetate part 1, and ethyl acetate part 2 have obvious antagonism effects on acetylcholine and barium chloride, and the action strength is significantly stronger than that of chloroform part or ethyl acetate part. Ethyl acetate site 3 had no such effect. The n-butanol part 2 has an obvious antagonistic effect on the intestinal tonic contraction induced by acetylcholine and barium chloride, but the intensity is weaker than that of the chloroform part or ethyl acetate part.

2.3 Anti-adrenaline effect

The water extract, n-butanol fraction, and n-butanol insoluble fraction of the self-made prescription all showed certain antagonism on the obvious inhibition of isolated small intestine caused by adrenaline, and the antagonism rates were 23.8±8.4%, 13.5±53%, and 12.7± 4.7% (n=10), the main performance is that after adding the test drug, the contraction range has a certain increase. Ethyl acetate, chloroform, and water-extracted alcohol-soluble parts have no anti-adrenaline effect.

The n-butanol site 1 showed a strong antagonistic effect on the obvious inhibition of isolated small intestine induced by adrenaline, and the effect strength was significantly stronger than that of the n-butanol site. The n-butanol fraction 2 has no antagonistic effect on epinephrine-induced significant inhibition of the isolated small intestine.

3 Discussion Self-made prescriptions are clinically used in different degrees of gastrointestinal motility disorders (expressed as hyperactivity or weakening of gastrointestinal motility). We use a combination of chemical separation and pharmacodynamic research for research. The results preliminarily showed that the chloroform extraction part, ethyl acetate part, n-butanol part and water extract of the self-prepared formula had inhibitory effects on the spontaneous activity of the isolated small intestine of rabbits. Based on the tonic contraction of the isolated small intestine induced by acetylcholine or barium chloride, the above-mentioned parts all have antagonistic effects, among which the chloroform part and the ethyl acetate part have stronger effects. The n-butanol insoluble part has no obvious effect on the spontaneous activity of the small intestine or on the action of acetylcholine and barium chloride. On the basis of epinephrine-induced significant inhibition of the isolated small intestine, except for n-butanol, which has a certain anti-adrenaline effect, the other parts have no such effect.

Chloroform fraction 1, chloroform fraction 2, ethyl acetate fraction 1, and ethyl acetate fraction 2, which were further separated from each effective fraction, exhibited stronger antagonistic effects on intestinal tonic contraction induced by acetylcholine and barium chloride; the refined fraction n-Butanol site 1 was more strongly antagonistic to epinephrine-induced apparent inhibition of the isolated small intestine.

               Table 1 Changes in food intake of animals in each group after treatment

^* P<0.05vs natural recovery group, aP<0.05vs positive drug control group

Table 2 Changes in body weight of animals in each group

^* P<0.05vs natural recovery group, aP<0.05vs positive drug control group

Table 3 Observation of defecation status group Time for stool to return to normal (days) control group natural recovery group 11 Self-prepared high-dose group 5 Self-prepared prescription middle dose group 5 positive drug control group 7

Table 4 Changes of MTL content in animal body fluids and tissues group Plasma ng/L Intestinal fluid ng/L Hypothalamusng/L Jejunum tissue ng/L In the control group, the self-prepared high dose of natural recovery group 231.14±77.28168.75±31.40255.08± 624.05±29.47483.57±41.26610.39± 32.94±2.1820.17±5.4028.62± 59.72±5.0541.62±4.9155.21± Self-prepared formula in the dosage group Positive drug control group in the middle dosage group 29.59 ^* 220.61±51.42 ^* 192.31±27.93 ^* 46.29 ^* 654.96±30.51 ^* 499.35±38.16 3.66 ^* 30.57±7.04 ^* 18.73±5.17 7.27 ^* a68.40±4.25 ^* a38.61±3.19

^* P<0.05vs natural recovery group; aP<0.05vs positive drug control group

Table 5 Observation of gastrointestinal mucosal injury group the naked eye Light microscopy Electron microscopy Control group Natural recovery group Natural recovery group Self-made prescription High-dose group Self-made prescription Medium-dose group Positive drug control group normal normal normal normal normal normal normal normal normal normal normal normal Normal mucosal epithelial cells are loosely arranged, a small amount of exfoliated mucosal epithelial cells are arranged loosely, a small amount of exfoliated mucosal epithelial cells are close to the control group, no exfoliated mucosal epithelial cells are close to the control group, non-exfoliated mucosal epithelial cells are close to the control group, and no exfoliation

clinical use observation

Irritable bowel syndrome (IBS) is a common non-organic disease of the digestive tract. The clinical symptoms are irregular abdominal pain, bloating, diarrhea, changes in stool properties and increased frequency of defecation. There is no ideal treatment. The current clinical medicines for treating IBS are basically aimed at the relief of a certain symptom, such as painkillers (such as calcium ion antagonists), antidiarrheal medicines, and gastrointestinal motility medicines. In view of the situation that there is no specific drug that can cure IBS, the principle of comprehensive treatment should be adopted for the treatment of IBS. The invention provides a compound composition of traditional Chinese medicine (Bupleurum 10 grams, Radix Paeoniae Alba 9 grams, Ligusticum Chuanxiong 6 grams, Radix Pseudostellariae 6 grams, Atractylodes Rhizoma 9 grams, Poria cocos 9 grams, Radix Glycyrrhizae 6 grams). Diarrhea; sweet and light to support the spleen, nourishing yin and assisting the treatment principles to formulate prescriptions. On the basis of TCM theory and pharmacological experiments, according to our clinical observation, it is used for the treatment of IBS and other gastrointestinal disorders, and the effect is better. The result is as follows:

Choice of control drug:

In recent years, there have been many cases of clinical reports using Smecta to treat IBS to achieve good results. Smecta can improve various symptoms of IBS, especially in terms of stool frequency and stool properties. After taking the medicine, the symptoms can be quickly relieved and Improvement, most patients can return to normal stool after 3-4 days.

Case selection criteria:

Select 50 patients with irritable bowel syndrome with a course of more than 1 month. Case selection: According to the selection criteria for irritable bowel syndrome cases formulated by the Chengdu National Symposium on Chronic Diarrhea in 1986. In all cases, organic diseases were excluded by blood routine, stool routine, liver function, blood sugar, B-ultrasound of liver, gallbladder and pancreas, fiber colonoscopy or intestinal barium contrast. The clinical manifestations are mainly diarrhea, accompanied by abdominal distension, borborygmus, abdominal pain, which can be relieved after defecation.

Healing:

Among the cases, there were 33 males and 17 females; they were divided into a treatment group of 40 cases and a control group of 10 cases. The two groups were similar in gender, age, and clinical manifestations and were comparable. Treatment group: One dose per day with self-prepared prescription. After 2 weeks of treatment, the symptoms improved twice a day, and then used for another 2 weeks. The clinical manifestations after 4 weeks were used as the basis for judging the curative effect. Control group: Smecta 3 grams once, 3 times a day, the course of treatment is the same as before. It is a non-random grouping. After 4 weeks of treatment, the blood routine and liver function will be checked. During the treatment, the patients will be followed up once a week to understand the changes in symptoms, the characteristics and frequency of defecation, and check the routine of stool.

Efficacy evaluation

Markedly effective: Diarrhea stopped, accompanied by obvious relief of symptoms. Effective: The diarrhea was obviously relieved, and the bowel movements were 2 times a day, accompanied by the improvement of the symptoms. Invalid: Does not meet the above criteria.

result observation

Self-preparation group: 40 cases, 21 cases (52.5%) were markedly effective, 12 cases (30%) were effective, 7 cases (17.5%) were ineffective, and the total effective rate was 82.5%. Of the 20 cases in the control group, 5 cases were markedly effective (25%), 7 cases were effective (35%), 8 cases were ineffective (40%), and the total effective rate was 60%. The curative effect of the self-made prescription is higher than that of Smecta, and the fastest onset of self-made prescription treatment is 5 days. The curative effect was stable for 3 weeks, indicating that the symptoms of abdominal pain and discomfort were significantly reduced, and the intestinal function was improved (including the reduction of stool frequency and urgency, and the improvement of stool shape), and the symptom improvement appeared within the first four weeks of medication and was maintained throughout the medication period. Prolonging the course of treatment for ineffective cases could not improve the curative effect. No obvious adverse reactions were observed in the two groups of medications, and there was no change in blood routine and liver function after treatment.

The composition has shown unique effects and advantages in treating IBS, and the development of modern Chinese medicine for treating IBS from the clinically proven prescriptions of traditional Chinese medicines has a solid foundation and good prospects in line with my country's national conditions.

Detailed ways

Example 1: 9 grams of Bupleuri, 9 grams of Radix Paeoniae Alba, 6 grams of Rhizoma Chuanxiong, 9 grams of Atractylodes Rhizome, 9 grams of Poria cocos, and 6 grams of licorice.

Example 2: Bupleurum bupleuri 10 grams, Radix Paeoniae Alba 9, Rhizoma Chuanxiong 6, Atractylodes macrocephala 6, Poria cocos 6 grams, licorice 3 grams.

Example 3: Bupleurum bupleuri 12 grams, Radix Paeoniae Alba 9, Rhizoma Chuanxiong 6, Radix Pseudostellariae 10, Atractylodes macrocephala 6, Poria cocos 3, licorice 5 grams.

Example 4: 18 Radix Pseudostellariae, 15 Radix Paeoniae Alba, 15 Rhizoma Chuanxiong, 10 grams Bupleurum, 15 Atractylodes Rhizome, 9 grams Poria, and 9 grams Licorice.

Example 5: Bupleurum bupleuri 12 grams, Radix Paeoniae Alba 9, Rhizoma Chuanxiong 6, Radix Pseudostellariae 10, Atractylodes macrocephala 6, Poria cocos 3, and licorice 5 grams. Tangerine peel 6, Citrus aurantium 6. )

Example 6: 10 grams of Bupleuri, 15 grams of Radix Paeoniae Alba, 5 grams of Rhizoma Chuanxiong, 20 grams of Atractylodes Rhizome, 15 grams of Poria cocos, and 8 grams of licorice.

Example 7: Bupleurum bupleuri 10 grams, Radix Paeoniae Alba 15 grams, Rhizoma Chuanxiong 5, Atractylodes macrocephala 20 grams, Poria cocos 15 grams, licorice 8 grams. Tangerine peel.

Example 8: Bupleurum bupleuri 12, Scutellaria baicalensis 9, Codonopsis 9, Licorice 6, Citrus aurantium 6, Radix Paeoniae Alba 12.

Example 9: Bupleurum 9 grams, Radix Paeoniae Alba 18 grams, Atractylodes macrocephala 12, Poria cocos 6 grams, licorice 9 grams. Chenpi 9

Example 10: Atractylodes macrocephala 9, Radix Paeoniae Alba 6, Chenpi 6, Codonopsis 6, Licorice 4.5, Poria cocos 3.

Example 11: Atractylodes Rhizoma 12, Radix Paeoniae Alba 9, Fangfeng 6, Nutmeg 6, Evodia Evodia 6, Schisandra chinensis 6, Licorice 3, Poria cocos 9.

Example 12: Radix Paeoniae Alba 15, Radix Glycyrrhizae 9, Poria cocos 6, Prunus ebony 9, Coptis chinensis 3, Guizhi 3, Pseudostellaria 6.

Example 13: Radix Paeoniae Alba 20, Glycyrrhizae 9, Guizhi 9, Atractylodes macrocephala 9, Poria cocos 9, Tangerine peel 6, Curcuma 3.

Example 14: Codonopsis 18, Atractylodes macrocephala 9, Poria cocos 9 grams, licorice 6 grams. Bellflower 9, Coptis 3, Woody 3, Hawthorn 3, Divine Comedy 3, Citrus aurantium 3, Tangerine peel 3.

Example 15: Radix Paeoniae Alba 18, Atractylodes macrocephala 15, Nutmeg 12, Rhizoma Chuanxiong 6, Tangerine Peel 6, Licorice 6, Guizhi 3, Coptis 3.

Claims (2)

1. A traditional Chinese medicine composition for the treatment of irritable bowel syndrome, characterized in that the composition is composed of the following raw materials: Bupleurum 8-12 grams Paeoniae Alba 9-12 grams Chuanxiong 5-9 grams Atractylodes 9-15 grams Poria cocos 6-12 grams Licorice 6-15 grams Pseudostellaria 10-18 grams. 2. A dosage form of the traditional Chinese medicine composition for treating irritable bowel syndrome according to claim 1, comprising: Granules, capsules, tablets, oral liquids, injections, transdermal or transmucosal administration preparations, suppositories for rectal administration prepared by adding the extract of the composition directly or after purification and separation with appropriate pharmaceutical excipients, or Granules, capsules, tablets, preparations for transdermal or transmucosal administration, suppositories for rectal administration, or Granules, capsules, tablets, preparations for transdermal or transmucosal administration, suppositories for rectal administration prepared directly or after the extract of the composition is directly or purified and separated and combined with the directly pulverized drug.