Traditional Chinese medicine composition for treating irritable bowel syndrome, preparation method and application thereof

Abstract

The application belongs to the field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating irritable bowel syndrome, a preparation method and application thereof. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 10-15 parts of plantago, 10-20 parts of buzhaye, 5-10 parts of costus, 10-15 parts of atractylodes, 3-5 parts of coptis, 10-15 parts of fructus aurantii, and 10-15 parts of pot marigold. Animal experiments show that the traditional Chinese medicine composition can obviously reduce diarrhea, visceral hypersensitivity and depression phenotype of IBS-D model rats, thereby indicating that the traditional Chinese medicine composition can effectively treat irritable bowel syndrome.

Description

TECHNICAL FIELD

[0001] The application belongs to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating irritable bowel syndrome and a preparation method and application thereof. BACKGROUND

[0002] Irritable bowel syndrome (IBS) is one of functional gastrointestinal diseases with repeated abdominal pain and accompanied by abnormal defecation or defecation habit change. IBS is one of the most common functional gastrointestinal diseases in clinic, which does not endanger life, but affects the work and life of patients to a certain extent, and causes serious decline of the quality of life of patients. According to epidemiological investigation, IBS affects 9% to 23% of the global population. Diarrhea-predominant irritable bowel syndrome (IBS-D) is a main clinical subtype of IBS, accounting for about 60% of all IBS, and has the characteristics of high incidence and repeated difficult recovery. In addition to physiological abnormal symptoms such as abdominal pain, diarrhea and abdominal distension, IBS-D patients also often have psychological abnormal symptoms such as depression and anxiety.

[0003] At present, the drugs for treating IBS in clinic mainly include drugs for regulating intestinal movement, drugs for correcting visceral sensory abnormalities, drugs for improving central emotion and other drugs such as gastrointestinal microecological preparations and cholecystokinin, which are mainly symptomatic treatment. Among them, the calcium antagonist pinaverium bromide is relatively widely used, which can relieve diarrhea symptoms to a certain extent. However, western medicine treats the symptoms but not the root cause, and the clinical treatment effect is often unsatisfactory.

[0004] Traditional Chinese medicine has unique advantages in the treatment of IBS due to multi-target effect and small side effects. IBS belongs to the category of "abdominal pain", "diarrhea" and "constipation" in traditional Chinese medicine, and is one of the advantage diseases of traditional Chinese medicine prevention and treatment. In recent years, research reports on the intervention of traditional Chinese medicine therapy in IBS and other functional gastrointestinal diseases are frequently seen in the international community. Tongxie Yaofang (90g of white atractylodes, 60g of white peony root, 45g of dried tangerine or orange peel and 60g of wind-preventing) is widely used in the treatment of IBS as a basic prescription in clinic, and has achieved certain clinical efficacy. In addition, there are also some clinical experience prescriptions obtained by adding and subtracting on the basis of it. However, the traditional Chinese medicine prescriptions in the prior art are almost focused on improving the physiological abnormal symptoms such as abdominal pain, diarrhea and abdominal distension of IBS patients, and the improvement of the psychological abnormal symptoms such as depression and anxiety of IBS patients, especially IBS-D patients, is not obvious. Therefore, it is necessary to develop a traditional Chinese medicine composition which can not only effectively improve the physiological abnormal symptoms such as abdominal pain, diarrhea and abdominal distension of IBS patients, but also effectively improve the psychological abnormal symptoms such as depression and anxiety of IBS patients, especially IBS-D patients, to meet the medication needs in clinic. SUMMARY

[0005] The first object of the present application is to provide a Chinese medicine composition for treating irritable bowel syndrome, the second object of the present application is to provide a preparation method of the Chinese medicine composition, and the third object of the present application is to provide an application of the Chinese medicine composition.

[0006] According to the first aspect of the present application, a Chinese medicine composition for treating irritable bowel syndrome is provided, and the raw material composition of the Chinese medicine composition includes 10-15 parts of Plantago asiatica L., 10-20 parts of Microcos paniculata L., 5-10 parts of Aucklandia lappa Decne., 10-15 parts of Atractylodes lancea (Thunb.) DC., 3-5 parts of Coptis chinensis Franch., 10-15 parts of Citrus aurantium L., and 10-15 parts of Potentilla chinensis Ser.

[0007] The present application considers that the diarrhea type irritable bowel syndrome is located in the intestine, and is closely related to the spleen and stomach. The weak spleen and stomach is caused by long-term illness, improper emotion, diet disorder, improper living, overwork and internal injury, etc. The weak spleen and stomach causes the dysfunction of transportation and transformation, and cannot transport and transform the fine essence of food and drink, so that the food and drink are not separated, and diarrhea occurs. The dysfunction of the spleen and stomach and the stagnation of liver qi are the main pathogenesis of the disease, so the treatment method is to soothe the liver and invigorate the spleen, and to separate and stop diarrhea.

[0008] The present application takes Plantago asiatica L. as the monarch drug, clears heat and diuresis, separates the urine, and makes the water and liquid out of the urine. Microcos paniculata L. is used as the ministerial drug, clears heat and removes dampness, invigorates the spleen and resolves phlegm, and assists the Plantago asiatica L. in separating the urine. Aucklandia lappa Decne. is used to promote qi and stop pain, soothe the liver and invigorate the spleen. Aucklandia lappa Decne. has a pungent and fragrant flavor, and is good at promoting the stagnated qi of the spleen and stomach, so it is the main drug for promoting qi and stopping pain. Atractylodes lancea (Thunb.) DC. dries dampness and invigorates the spleen, dispels wind and resolves stagnation, and can transport and transform the water and dampness in the middle jiao. A small amount of Coptis chinensis Franch. is added to clear heat and remove dampness, and to raise the spleen yang, so as to increase the function of thickening the intestine and stopping diarrhea. Citrus aurantium L. breaks qi and eliminates accumulation, removes dampness and resolves phlegm. Potentilla chinensis Ser. clears heat and resolves toxicity, and stops diarrhea. The combination of the above drugs can clear heat, remove dampness, stop diarrhea to treat the symptoms, and invigorate the spleen and soothe the liver to treat the root.

[0009] The raw materials of the present application are as follows:

[0010] Plantago asiatica L.: the dried whole grass of Plantago asiatica L. or Plantago depressa Willd.

[0011] Microcos paniculata L.: the dried leaf of Microcos paniculata L.

[0012] Aucklandia lappa Decne.: the root of Aucklandia lappa Decne.

[0013] Atractylodes lancea (Thunb.) DC.: the dried rhizome of Atractylodes lancea (Thunb.) DC. or Atractylodes chinensis (DC.) Koidz.

[0014] Huanglian: Dried rhizome of Coptis chinensis Franch., Coptis deltoidea C. Y. et Hsiao or Coptis teeta Wall. of Coptis.

[0015] Citrus: Dried young fruit of Citrus aurantium L. and its cultivated varieties or Citrus sinensis Osbeck of Rutaceae.

[0016] Patrinia: Dried whole plant of Potentilla chinensis Ser. of Rosaceae.

[0017] In some embodiments, the raw material composition includes, by weight: 15 parts of Plantaginis Herba, 10 parts of Buxuriae Folium, 10 parts of Radix Aucklandiae, 10 parts of Radix Atractylodis, 3 parts of Coptidis Rhizoma, 10 parts of Citri Fructus, and 10 parts of Potentillae Herba.

[0018] In some embodiments, pharmaceutically acceptable adjuvants can also be added.

[0019] In some embodiments, the dosage form of the traditional Chinese medicine composition is a decoction, granules, powder, tablet, pill or capsule.

[0020] According to a second aspect of the present application, a preparation method of the traditional Chinese medicine composition for treating irritable bowel syndrome is provided, and includes the following steps:

[0021] The raw materials are soaked in 8-12 times of water by weight for 20-40 minutes, and then heated to boiling, and kept at a slight boil for 1-2 hours. The filtrate is obtained by filtering and repeating the decoction of the residue 1-2 times.

[0022] According to a third aspect of the present application, the traditional Chinese medicine composition for treating irritable bowel syndrome is used for preparing a medicine for treating irritable bowel syndrome. Specifically, the symptoms of irritable bowel syndrome include diarrhea and / or visceral hypersensitivity and / or depression.

[0023] In some embodiments, the irritable bowel syndrome is diarrhea-predominant irritable bowel syndrome.

[0024] The beneficial effects of the present application include:

[0025] Animal experiments show that the traditional Chinese medicine composition of the present application can significantly reduce the diarrhea, visceral hypersensitivity and depression of IBS-D model rats, thus indicating that the traditional Chinese medicine composition of the present application can effectively treat irritable bowel syndrome. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1is the general state observation and body weight growth rate of each group of rats.

[0027] Figure 2 is the fecal water content of each group of rats, and the figure is compared with the normal group, ### P<0.001, compared with the model group, *** P<0.001.

[0028] Figure 3 is the behavioral evaluation result of the central stay time of each group of rats in the open field, and the figure is compared with the normal group, # P<0.05, compared with the model group, * P<0.05. DETAILED DESCRIPTION

[0029] The application will be further described in detail below in conjunction with specific examples, but the embodiments of the application are not limited thereto. The materials involved in the following examples can be obtained from commercial channels.

[0030] Example 1

[0031] The traditional Chinese medicine decoction for treating irritable bowel syndrome of this example is prepared from the following components: 15g of plantain, 10g of buzhaye, 10g of costus, 10g of atractylodes, 3g of coptis, 10g of immature bitter orange fruit, and 10g of pot marigold.

[0032] The preparation method thereof comprises the following steps:

[0033] The raw materials are added to 10 times the weight of water and soaked for 30 minutes, then heated to boiling and kept at a slight boil for 1 hour, filtered, and the filter residue is repeatedly decocted once, and the filtrates are combined to obtain the traditional Chinese medicine decoction.

[0034] The traditional Chinese medicine decoction prepared in this example is one dose, and one dose is about 150mL.

[0035] Example 2

[0036] The traditional Chinese medicine decoction for treating irritable bowel syndrome of this example is prepared from the following components: 15g of plantain, 10g of buzhaye, 10g of costus, 10g of atractylodes, 3g of coptis, 10g of immature bitter orange fruit, and 10g of pot marigold.

[0037] The preparation method thereof comprises the following steps:

[0038] The raw materials are weighed according to the ratio, 8 times the weight of ddH2O is added, boiled twice for 1 hour each time, filtered, the filtrates are combined to obtain the extract, and then the extract is concentrated to 1.22g of crude drug / mL using a vacuum rotary evaporator.

[0039] Example 3

[0040] The traditional Chinese medicine decoction for treating irritable bowel syndrome of the embodiment is prepared from the following components: 12g of plantain, 12g of Rubus corchorifolius L.f., 9g of costus root, 12g of atractylodes, 3g of Coptis chinensis Franch, 12g of immature bitter orange fruit, and 12g of pot marigold.

[0041] The preparation method is the same as that of Embodiment 1.

[0042] Embodiment 4

[0043] The traditional Chinese medicine decoction for treating irritable bowel syndrome of the embodiment is prepared from the following components: 15g of plantain, 15g of Rubus corchorifolius L.f., 10g of costus root, 15g of atractylodes, 3g of Coptis chinensis Franch, 15g of immature bitter orange fruit, and 15g of pot marigold.

[0044] The preparation method is the same as that of Embodiment 1.

[0045] Embodiment 5

[0046] The traditional Chinese medicine decoction for treating irritable bowel syndrome of the embodiment is prepared from the following components: 10g of plantain, 20g of Rubus corchorifolius L.f., 5g of costus root, 10g of atractylodes, 5g of Coptis chinensis Franch, 13g of immature bitter orange fruit, and 12g of pot marigold.

[0047] The preparation method is the same as that of Embodiment 1.

[0048] Next, in order to verify the treatment effect of the traditional Chinese medicine composition for treating irritable bowel syndrome of the present application on irritable bowel syndrome, the following animal experiments are performed.

[0049] I. Experimental animals

[0050] 40 Wistar rats (male, 6-8 weeks old, weighing 160-220g) were purchased from Guangdong Medical Laboratory Animal Center (Guangzhou, China, approval number: SCXK(YUE)2018-0002), and were raised in an SPF environment (temperature 22±2℃, humidity 50±10%), and food and water were provided.

[0051] II. Grouping

[0052] The 40 Wistar rats were randomly divided into four groups, 10 rats in each group, and were marked as normal group (i.e. Control group), model group (i.e. IBS-D group), traditional Chinese medicine group (i.e. Chinese herbal compound group), and positive drug pinaverium bromide group (i.e. Pinaverium Bromide group) respectively.

[0053] III. Modeling method

[0054] IBS-D model was prepared by the combined method of 4% acetic acid enema + restraint stress. The specific modeling method was as follows: first, 4% acetic acid enema was performed, 24 h before the experiment, the rats were fasted but not water deprived, after ether anesthesia, a silicone tube connected to a syringe was inserted into the anus (about 8 cm from the anus), 1 mL of 4% acetic acid was injected into the colon, the silicone tube was slowly pulled out, the anus was pressed with the hand and the tail of the rat was lifted for 30 s, then 1 mL of 0.01 mol / L PBS solution was used to flush the colon. The rats were put back into the cage to freely eat and drink, and restraint stress was performed on the 7th day after acetic acid enema. The rats were placed in a restraint bag which limited the movement of the body but did not affect their breathing, and after 2-3 h, the rats were taken out of the restraint bag and put into the feeding cage. The acetic acid enema was performed once, and the restraint stress was performed once a day until the end of the experiment.

[0055] The rats in the model group, the traditional Chinese medicine group and the positive drug pinaverium bromide group were modeled according to the above modeling method, and the rats in the normal group were normally bred.

[0056] Four, administration

[0057] Fourteen days after the 4% acetic acid enema and restraint stress, the traditional Chinese medicine group was administered with the traditional Chinese medicine decoction prepared in Example 2, once a day, 1 mL each time, for 2 weeks of continuous administration;

[0058] The positive drug pinaverium bromide group was given pinaverium bromide tablets (Deshu), which was dissolved in water (0.003 g / mL) and administered, once a day, 1 mL each time, for 2 weeks of continuous administration;

[0059] The normal group and the model group were administered with 0.9% normal saline, once a day, 1 mL each time, for 2 weeks of continuous administration.

[0060] During the administration period, the normal group was normally bred every day, and the model group, the traditional Chinese medicine group and the positive drug pinaverium bromide group continued to be restrained every day according to the above method, and no acetic acid enema was performed.

[0061] Five, evaluation index

[0062] (1) General index determination and body weight gain rate

[0063] The morphological changes of the rats were observed, including changes in fur color, activity, appearance, activity, feces, etc.; the body weight change and defecation of the rats were measured every week.

[0064] (2) Abdominal wall withdrawal reflex (AWR) score

[0065] AWR experiment is the most widely used method to evaluate visceral hypersensitivity in rats. On the first day after the end of administration, the abdominal withdrawal reflex of rats in each group was detected by using a colon manometer. Before detection, the anus of the rat was gently touched, and after defecation, a balloon coated with paraffin oil was inserted into the anus for 8 cm, and the tube connected to the balloon was fixed at the root of the rat's tail. After the rat was calm, the balloon was inflated slowly to a pressure of 20, 40, 60 and 80 mmHg, and the response of the abdominal wall to the balloon expansion stimulation in the intestinal cavity was observed within 20 s. The AWR score was scored according to the AWR scoring standard. The scoring standard is shown in Table 1.

[0066] Table 1 AWR scoring standard

[0067]

[0068]

[0069] (3) Determination of fecal water content

[0070] The feces of all rats were collected on the day after the end of administration, and the feces of rats were collected with a centrifuge tube, weighed and recorded on a microbalance, and then placed in an oven for 4 h. After that, it was weighed and recorded again. The water content of feces (%) = (weight of feces before drying - weight of feces after drying) / weight of feces before drying x 100%.

[0071] (4) Evaluation of rat open field behavior

[0072] The open field test is often used as a behavioral test to evaluate anxiety and depression. The central area residence time is used as an indicator to evaluate the spontaneous activity and anxiety and depression of rats. The open field test was performed on the first day after the end of administration. In the experiment, the rats were placed in the middle of the open field test area, and the rats were allowed to move freely for 5 min. After each rat was operated, the feces and urine were cleaned, and the inside of the open field box was cleaned with 75% ethanol to eliminate odors and prevent interference with the behavior of the next rat. The central residence time (s) of each rat was recorded for data statistics.

[0073] Six, experimental results

[0074] (1) General condition and body weight gain rate

[0075] The general state of rats in each group and the body weight gain rate are shown in Figure 1 Figure 1 ​It can be seen that compared with the normal group, after enema with 4% acetic acid and restraint stress, the model group rats reduced spontaneous activity, sluggish, like to curl up and huddle, messy hair, easily startled by sound, perianal pollution, continuous discharge of light brown unformed stool, with a small amount of mucus. Compared with the model group, the stool shape of the rats in the traditional Chinese medicine group and the positive drug group was slightly formed, the spontaneous activity increased, and the hair color was slightly shiny. Compared with the normal group, the model group rats significantly slowed down the weight gain, which was most obvious in the first week of modeling, and then the weight showed a slow growth trend. Compared with the model group, the weight gain of the rats in the traditional Chinese medicine group increased compared with the model group, showing a slow growth trend.

[0076] (2) Abdominal withdrawal reflex (AWR) score

[0077] The abdominal withdrawal reflex (AWR) score of rats in each group is shown in Table 2.

[0078] Table 2 Abdominal withdrawal reflex (AWR) score of rats in each group

[0079]

[0080] Note: ① 20mmHg, 40mmHg, 60mmHg, 80mmHg data normality test P(Shapiro-Wilk) <0.05, not in normal distribution, use M(P25, P75) to represent, use non-parametric test Kruskal-Wallis H method for multiple independent samples pairwise comparison, P value is corrected by Bonferroni. ② The number of rats initially included in each group n=10, due to the mortality during the experiment process and intragastric administration, therefore the number of rats finally included in IBS-D model and counted in each group n=5. ③ Compared with the normal group, # P<0.05; compared with the model group, * P<0.05.

[0081] As can be seen from Table 2, compared with the normal group, the AWR score of the model group rats under 80mmHg pressure was significantly increased, and the difference was statistically significant; compared with the model group, the AWR score of the rats in the traditional Chinese medicine group under 80mmHg pressure was significantly decreased, and the difference was statistically significant. Therefore, the traditional Chinese medicine composition of the present application can significantly reduce the visceral hypersensitivity of IBS-D model rats.

[0082] (3) Fecal water content

[0083] During the modeling period, rats induced by acetic acid enema combined with restraint stress all had unformed stool, and the diarrhea rate was 100%.

[0084] After the administration was completed, the fecal water content of rats in each group was Figure 2As shown in the figure, NC refers to the normal group. Compared with the normal group, ### P<0.001, compared with the model group, *** P<0.001. From Figure 2 It can be seen that compared with the normal group, the fecal water content of the model group is significantly increased; compared with the model group, the fecal water content of the traditional Chinese medicine group and the positive drug group is significantly reduced. It shows that the traditional Chinese medicine composition of the present application can significantly reduce the diarrhea symptoms and fecal water content of the IBS-D model rats.

[0085] (4) Open field behavior evaluation of rats

[0086] The open field central residence time behavior evaluation results of rats in each group are shown in Figure 3 As shown in the figure, compared with the normal group, # P<0.05, compared with the model group, * P<0.05. From Figure 3 It can be seen that compared with the normal group, the open field central residence time of the model group rats is significantly increased, indicating that the depression degree of IBS-D rats under chronic restraint stress is increased and the desire to explore is reduced. Compared with the model group, the open field central residence time of the traditional Chinese medicine group rats is significantly decreased, indicating that the traditional Chinese medicine composition of the present application can effectively improve the depression degree of IBS-D model rats.

[0087] In summary, the traditional Chinese medicine composition of the present application can significantly reduce the diarrhea, visceral hypersensitivity and depression phenotype of IBS-D model rats, which suggests that the traditional Chinese medicine composition of the present application can effectively treat irritable bowel syndrome.

[0088] The above only describes some embodiments of the present application. For those skilled in the art, without departing from the concept of the present application, several modifications and improvements can be made, which are all within the protection scope of the present application.

Claims

1. A Chinese medicine composition for treating diarrhea-type irritable bowel syndrome, characterized in that: The medicine is prepared from the following raw materials in parts by weight: 10-15 parts of plantain, 10-20 parts of buzia leaves, 5-10 parts of costus root, 10-15 parts of atractylodes, 3-5 parts of coptis root, 10-15 parts of immature bitter orange and 10-15 parts of potentilla.

2. The Chinese medicine composition for treating diarrhea-predominant irritable bowel syndrome according to claim 1, characterized in that: The medicine is prepared from the following raw materials in parts by weight: 15 parts of plantain, 10 parts of scutellaria baicalensis leaves, 10 parts of costus root, 10 parts of atractylodes, 3 parts of coptis root, 10 parts of immature bitter orange and 10 parts of potentilla.

3. The Chinese medicine composition for treating diarrhea-predominant irritable bowel syndrome according to claim 1 or 2, characterized in that: Pharmaceutically acceptable excipients may also be added.

4. The Chinese medicine composition for treating diarrhea-predominant irritable bowel syndrome according to claim 1 or 2, characterized in that: The dosage form of the Chinese medicine composition is decoction, granules, powder, tablets, pills or capsules.

5. The method for preparing the Chinese medicine composition for treating diarrhea-predominant irritable bowel syndrome according to any one of claims 1 to 4, characterized in that: When the dosage form of the Chinese medicine composition is a decoction, the preparation method thereof comprises the following steps: The raw materials are added into 8-12 times of water by weight and soaked for 20-40 minutes, then heated to boiling and kept slightly boiling for 1-2 hours, filtered, and the residue is repeatedly decocted 1-2 times, and the filtrate is combined to obtain the product.

6. Use of the traditional Chinese medicine composition for treating diarrhea-predominant irritable bowel syndrome according to any one of claims 1 to 4 in the preparation of a medicament for treating diarrhea-predominant irritable bowel syndrome.

7. The use according to claim 6, characterized in that Improve diarrhea and / or visceral hypersensitivity and / or depression in diarrhea-predominant irritable bowel syndrome.

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