Traditional Chinese medicine composition for treating cancerous constipation as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention provides a traditional Chinese medicine composition for treating cancerous constipation and a preparation method and application of granules of the traditional Chinese medicine composition. The traditional Chinese medicine composition consists of the following components: 5-11 parts of wine-processed desert cistanche, 13-20 parts of angelica sinensis, 20-30 parts of astragalus membranaceus, 5-7 parts of radix achyranthis bidentatae, 3-6 parts of rhizoma alismatis, 1-3 parts of rhizoma cimicifugae and 1-10 parts of liquorice. The composition has the effects of warming the kidney, boosting essence, tonifying qi, generating blood and relaxing bowel, can improve mouse constipation induced by multiple factors such as tumors, opioid receptor agonists and chemotherapy, shortens the first defecation time, increases the defecation quantity and increases the water content of excrement. Most importantly, the composition can increase the content of the sterosterol-producing eubacteria in the intestinal flora and improve the intestinal environment; the release of nerve rank protein NRTN in serum is increased, and intestinal neurons are activated, so that the unique constipation treatment effect is achieved. Compared with a traditional water decoction, the composition particles are convenient to carry and store, the stability of a preparation process can be ensured, the loss of effective components is reduced, and the curative effect of the composition is enhanced.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating cancer-induced constipation and a preparation method and application of granules thereof. BACKGROUND

[0002] Constipation is one of the most common problems in cancer patients. Due to different diagnostic criteria and study populations, the incidence rate varies from 30% to 90%, especially in elderly patients and patients with advanced cancer. Constipation not only can destroy the treatment mentality and quality of life of cancer patients, but also can cause adverse consequences such as nausea and vomiting, anal fissure, hemorrhoids, intestinal obstruction, urinary retention and other complications, further aggravating the psychological distress of patients and causing anxiety. In addition, the direct and indirect medical expenses caused by constipation will also cause additional economic burden on patients and the medical insurance system.

[0003] The factors inducing constipation in cancer patients are various, including tumor mechanical obstruction, opioid-related and chemotherapy-induced. First, tumors in sites such as the colon and rectum can directly squeeze or block the intestinal lumen due to tumor occupation, causing intestinal obstruction and leading to feces unable to pass. In a recent large cohort study, constipation was also used as a marker for occult colon cancer, pancreatic cancer and ovarian cancer. Second, cancer patients often have cancer pain, and the first choice of drugs for the treatment of moderate to severe pain is opioids, but opioids can cause constipation by hindering the intestinal movement of cancer patients. Studies have reported that 59% of cancer patients receiving opioid analgesics will develop constipation, so opioids are also a major cause of secondary constipation in cancer patients. If opioid-related constipation cannot be effectively solved, it will also hinder the best pain treatment. Finally, chemotherapy, as a major means of treating cancer, can also easily cause constipation and other adverse reactions. Chemotherapy-related constipation is a type of constipation that occurs due to damage to the autonomic nervous system and enteric nervous system caused by chemotherapy, leading to intestinal dysfunction and reduced gastrointestinal motility. Studies have shown that the incidence of chemotherapy-related constipation in patients with advanced cancer is as high as 40% -90%. Although the factors inducing constipation are different throughout the whole process of cancer treatment, traditional Chinese medicine believes that constipation in cancer patients is mostly based on deficiency, with deficiency and excess mixed together, and deficiency constipation belongs to "yin knot" in traditional Chinese medicine theory. Treatment should start from the whole, follow the principle of "deficiency cannot be attacked, and supplement can be used to unblock", that is, tonifying qi and nourishing yin, regulating qi and unblocking stool. Clinical experience also shows that traditional Chinese medicine has good clinical efficacy in the treatment of cancer-induced constipation, and the treatment thought of traditional Chinese medicine syndrome differentiation and treatment has an irreplaceable position in improving the quality of life of patients, reducing the side effects of Western medicine treatment, and reducing the economic burden of patients.

[0004] Non-pharmacological measures for cancer-induced constipation include hydration and nutrition, improved defecation posture, abdominal massage, etc. However, these auxiliary means usually cannot significantly relieve symptoms and cannot replace drug therapy. In drug therapy, the first choice is laxatives, including osmotic laxatives (such as polyethylene glycol, lactulose or magnesium sulfate) and stimulant laxatives (senna, bisacodyl or sodium picosulfate). However, these laxatives can cause abdominal pain, diarrhea, and further cause electrolyte imbalance, dehydration, etc. in patients, and increase the burden of the body of cancer patients; long-term use may also cause a decrease in the function of the colon's autonomous peristalsis, and even cause colon melanosis; especially important is that they may not be effective for severe constipation induced by opioid drugs or chemotherapy. In addition, opioid receptor antagonists with peripheral effects (such as naldemedine, naloxegol and methylnaltrexone) can also prevent or alleviate opioid-related constipation. However, they can antagonize the analgesic effect of opioid drugs, leading to increased cancer pain; at the same time, these drugs are expensive and need to be strictly monitored for drug interactions. In summary, due to the very complex pathogenesis of cancer-induced constipation, which is often caused by multiple factors, the current treatment means is single and the effect is limited, and the overall concept and prevention-before-disease thought of traditional Chinese medicine are expected to provide new prevention / treatment options for cancer-induced constipation.

[0005] CN119837979A proposes a traditional Chinese medicine composition for treating constipation, which includes broad hawthorn, small sophora flower, white atractylodes, poria cocos, malt and dried tangerine peel, etc. The traditional Chinese medicine composition can increase the number of defecation of constipated mice and enhance the small intestine propulsion function of mice. CN119564800A discloses a traditional Chinese medicine composition for treating constipation and a preparation method thereof, which includes fuzi, evodia, epimedium, astragalus, ginseng, atractylodes, coix seed, citron fruit, areca nut, and licorice, etc. The composition can also regulate the balance of the stomach and intestines and relieve constipation symptoms. However, since the pathogenic factors of constipation in tumor patients are different from those of ordinary constipation, and are more complex and difficult than ordinary constipation, and these traditional Chinese medicine compositions do not take into account the deficiency of qi, blood, yin and yang when tumor patients have constipation, the traditional Chinese medicine compositions for ordinary constipation in the prior art are not suitable for the treatment of cancer-induced constipation; secondly, these compositions do not form a preparation process route suitable for industrial production, and cannot meet the extensive needs of tumor patients. SUMMARY

[0006] To solve the above technical problems in the prior art, the purpose of the present application is to provide a traditional Chinese medicine composition for treating cancer-induced constipation and a preparation method thereof, which has a good therapeutic effect on constipation induced by tumor mechanical obstruction, opioid drugs and chemotherapy.

[0007] To solve the above problems, the present application provides the following technical solutions: The first object of the present application is to provide a Chinese medicine composition for treating cancer-induced constipation, comprising the following raw materials in parts by weight: Herba Cistanche 5-11 parts, Radix Angelicae Sinensis 13-20 parts, Radix Astragali 20-30 parts, Radix Nelumbinis 5-7 parts, Rhizoma Alismatis 3-6 parts, Rhizoma Cimicifugae 1-3 parts, and Radix Glycyrrhizae 1-10 parts.

[0008] Further, the preferred raw material is in parts by weight as follows: Herba Cistanche 9 parts, Radix Angelicae Sinensis 15 parts, Radix Astragali 20 parts, Radix Nelumbinis 6 parts, Rhizoma Alismatis 4.5 parts, Rhizoma Cimicifugae 3 parts, and Radix Glycyrrhizae 5 parts.

[0009] The second object of the present application is to provide a preparation method of the Chinese medicine composition as described above, comprising the following steps: mixing the Chinese medicine composition with water, decocting to obtain a decoction; filtering and concentrating the decoction to obtain an extract.

[0010] Further, the preparation method as described above comprises the following steps: Step 1: decocting the raw materials as described above with water twice, adding 8 times of water in the first time and extracting for 2 hours, filtering, adding 6 times of water in the second time and extracting for 1 hour, filtering, and combining the two times of decoction; Step 2: concentrating the decoction under reduced pressure to an extract with a relative density of 1.26-1.30 (65℃±5℃); Optionally, the method further comprises: Step 3: taking the extract, adding an appropriate amount of dextrin, mixing, drying under reduced pressure and vacuum, and crushing and sieving to obtain dry extract powder; Step 4: taking the dry extract powder, granulating, drying to obtain the Chinese medicine composition granules.

[0011] The third object of the present application is to provide a Chinese medicine preparation, comprising the Chinese medicine composition as described above or prepared by the preparation method as described above, and optionally one or more pharmaceutically acceptable carriers.

[0012] Further, the Chinese medicine preparation is a gel, a cream, a tablet, a capsule, a powder, a mixture, a pill, a granule, a solution, a syrup, a decoction, a suppository, an aerosol, a plaster, an ointment, an injection, a spray, a liniment, a tincture, a wet compress, a paste or a lotion; and the pharmaceutically acceptable carrier is selected from at least one of a pharmaceutically acceptable solvent, a solubilizer, a cosolvent, an emulsifier, a coloring agent, a binder, a disintegrant, a filler, a lubricant, a wetting agent, an osmotic pressure regulator, a stabilizer, a glidant, a flavoring agent, a preservative, a suspending agent, a coating material, an aromatic agent, an anti-adhesion agent, an integrating agent, a penetration enhancer, a pH regulator, a buffer, a plasticizer, a surfactant, a thickening agent, a complexing agent, a humectant, an absorbent, a diluent, a flocculating agent and a deflocculating agent, a filtration aid, a release retardant, a high molecular skeleton material and a film-forming material.

[0013] Further, the traditional Chinese medicine preparation further comprises optionally one or more other drugs for treating constipation and / or cancer Further, the drug for treating cancer is an opioid drug or a chemotherapy drug.

[0014] A fourth object of the present application is to provide the use of the aforementioned traditional Chinese medicine composition, the aforementioned traditional Chinese medicine composition prepared by the aforementioned preparation method, or the aforementioned traditional Chinese medicine preparation in the preparation of a drug for preventing or treating constipation, wherein the constipation is at least one of constipation caused by abdominal tumor compression, constipation caused by an opioid drug, and constipation caused by a chemotherapy drug.

[0015] Further, the aforementioned traditional Chinese medicine composition, the aforementioned traditional Chinese medicine composition prepared by the aforementioned preparation method, or the aforementioned traditional Chinese medicine preparation does not cause abdominal distension and diarrhea.

[0016] Further, the aforementioned traditional Chinese medicine composition, the aforementioned traditional Chinese medicine composition prepared by the aforementioned preparation method, or the aforementioned traditional Chinese medicine preparation can increase the content of coprostanol-producing eubacteria in the intestinal flora, improve the intestinal environment, and exert its unique effect of treating constipation.

[0017] Further, the aforementioned traditional Chinese medicine composition, the aforementioned traditional Chinese medicine composition prepared by the aforementioned preparation method, or the aforementioned traditional Chinese medicine preparation can increase the release of neurotrophin NRTN in serum, activate intestinal neurons, and enhance the sensitivity to mechanical expansion, thereby exerting its unique effect of treating constipation.

[0018] Compared with the prior art, the present application has the following beneficial effects: (1) After surgery and repeated radiotherapy and chemotherapy, the body of a cancer patient is already weak, various pathogenic factors act on the human body, causing the deficiency of qi, blood, yin and yang, deficiency of qi leading to weakness, deficiency of blood and body fluid leading to dryness of the stomach and intestines, deficiency of the kidney leading to failure of opening and closing, turbid qi not descending, and constipation caused by the loss of moisture in the intestines; therefore, the treatment should be to warm the kidney and replenish essence, tonify qi and blood, and moisten the intestines to promote defecation.

[0019] In the prescription, Cistanche is the monarch drug, which is sweet and salty in nature and warm in property, and has the functions of warming the kidney and replenishing essence and blood, warming the waist and moistening the intestines, in line with the theory of "essence and blood being derived from the same source", and in line with the pathogenesis of cancer patients with kidney essence and yang qi being consumed due to long-term illness.

[0020] The ministerial drugs include Angelica sinensis, which tonifies blood and moistens the intestines to promote defecation, and Astragalus membranaceus, which tonifies qi and generates body fluid and lifts up yang and collapse; the combination of the two drugs tonifies both qi and blood in line with the theory of "qi being able to generate blood", improves the state of deficiency of qi and blood in cancer patients, and promotes defecation in cooperation, with Angelica sinensis moistening the intestines and Astragalus membranaceus tonifying qi to drive, thereby enhancing the cathartic effect of Cistanche.

[0021] The adjuvant Radix Cyathulae nourishes liver and kidney, strengthens waist and knees, promotes blood downward, promotes blood circulation, and removes kidney turbidity by promoting urination. The adjuvant Rhizoma Alpiniae Oxophyllae prevents stagnation of the tonifying drugs. The adjuvant Rhizoma Anemones Praecox is combined with the adjuvant Radix Cyathulae and the adjuvant Rhizoma Anemones Praecox to form a balance between ascending and descending, restore the qi movement of the middle energizer, and prevent stagnation of the tonifying drugs. The adjuvant Rhizoma Alpiniae Oxophyllae prevents the adjuvant Cistanche deserticola and the adjuvant Radix Angelicae Sinensis from causing greasy food and stomach discomfort, so that the whole prescription is tonifying without stagnation.

[0022] The adjuvant Rhizoma Anemones Praecox lifts clear yang, opens the cover of the cauldron, and promotes the ascending of clear qi to the spleen. When clear yang rises, turbid yin falls, and they complement each other to help defecation.

[0023] The adjuvant Radix Glycyrrhizae nourishes the spleen and harmonizes all the drugs.

[0024] The combination of all the drugs warms kidney and essence to treat the root cause, moistens the intestines to treat the symptoms, and is smart in drug use. The prescription has the characteristics of tonifying with purgation and descending with ascending, and has the combination characteristics of tonifying with defecation and descending with ascending.

[0025] (2) The pharmaceutical composition provided by the present application can not only prevent / treat tumor mechanical obstruction, opioid-related and chemotherapy-induced constipation, but also has certain anti-tumor effect by enhancing immune response. Compared with traditional purgative drugs, the scope of action is more extensive, which embodies the characteristics of comprehensive and synergistic treatment of traditional Chinese medicine.

[0026] (3) The composition of the present application can increase the content of coprostanol-producing eubacteria in the intestinal flora, improve the intestinal environment, increase the release of nerve growth protein NRTN in serum, activate intestinal neurons, and thus play its unique effect in treating constipation.

[0027] (4) Compared with other drug compositions with different proportions, the pharmaceutical composition provided by the present application does not cause abdominal distension risk when treating constipation.

[0028] (5) The preparation method of the pharmaceutical composition provided by the present application is easy to establish a standardized quality control system, and the preparation of granules can enhance the extraction efficiency of important components of the composition and reduce the loss rate of effective components. In addition, the granules are also convenient for cancer patients to take. BRIEF DESCRIPTION OF DRAWINGS

[0029] Figure 1 Effect of the composition of the present application on the intestinal flora of constipated mice, note: *P<0.05, ***P<0.001.

[0030] Figure 2 Effect of the composition of the present application on the coprostanol-producing eubacteria of constipated mice, note: ***P<0.001.

[0031] Figure 3 Effect of the composition of the present application on the coprostanol-producing eubacteria of constipated mice, note: ***P<0.001. DETAILED DESCRIPTION

[0032] The present application is further explained in connection with the following examples, which do not limit the application in any form.

[0033] Example 1 Preparation of the composition of the present application 1.1 Prescription

[0034] 1.2 Preparation method The above decoction pieces are decocted twice with water, 8 times the amount of water is added in the first decoction, and extracted for 2 hours, filtered, 6 times the amount of water is added in the second decoction, and extracted for 1 hour, filtered, and the two decoctions are combined; the medicinal liquid is concentrated under reduced pressure to a relative density of 1.26-1.30 (65℃±5℃) of the extract; Take the extract, add an appropriate amount of dextrin (220 g-400 g), mix well, reduce pressure and vacuum dry, crush, sieve, and dry extract powder is obtained; Take the dry extract powder, granulate, dry, size, and package 9 g / bag, and the composition of the present application is obtained.

[0035] Example 2 Effect of the composition of the present application on constipation of C57BL / 6J mice induced by mechanical obstruction of tumors (colon cancer) 1.1 Experimental materials (1) Experimental animals: 81 SPF male C57BL / 6J mice, weighing about 20 g, provided by Hangzhou Ziyuan Experimental Animal Technology Co., Ltd., license number SCXK (Zhejiang) 2024-0004.

[0036] Raising temperature: 25±2℃, relative humidity 60%±10%, 12 h cycle of light lamp illumination, all free to eat and drink. Mouse feed and bedding were purchased from Jiangsu Province Synergy Pharmaceutical Biological Engineering Co., Ltd.

[0037] (2) Experimental reagents: activated carbon, specification: 1 kg / bag, produced by Shanghai Aladdin Biochemical Technology Co., Ltd., used for preparing ink solution.

[0038] Blank control group: 0.9% sodium chloride injection, specification: 500 mL, 4.5 g / bottle, produced by Shijiazhuang Four Pharmaceutical Co., Ltd.

[0039] Positive control group: lactulose, specification: 15 ml*6 bags / box, produced by Abbott Biologicals B.V. (Netherlands) Co., Ltd.

[0040] The composition of the present application (thick extract): 9 parts (g, same below) of Jujuboside, 15 parts of Angelica sinensis, 20 parts of Astragalus membranaceus, 6 parts of Cyathula officinalis, 4.5 parts of Alisma orientale, 3 parts of Cimicifuga foetida, and 5 parts of Glycyrrhiza uralensis are proportioned, prepared according to the method of Example 1, and dissolved with normal saline before use.

[0041] Comparative composition 1 (thick paste): 12 parts of Herba Cistanche, 12 parts of Angelica sinensis, 18 parts of Radix Astragali, 8 parts of Radix Anemarrhena, 4.5 parts of Rhizoma Anemarrhena, 4 parts of Rhizoma Cimicifugae, and 4 parts of Radix Glycyrrhizae, and the preparation method and treatment method are the same as the composition group of the present application.

[0042] Comparative composition 2 (thick paste): 15 parts of Herba Cistanche, 9 parts of Angelica sinensis, 16 parts of Radix Astragali, 10 parts of Radix Anemarrhena, 4.5 parts of Rhizoma Anemarrhena, 4 parts of Rhizoma Cimicifugae, and 4 parts of Radix Glycyrrhizae, and the preparation method and treatment method are the same as the composition group of the present application.

[0043] Comparative composition 3 (thick paste): 18 parts of Herba Cistanche, 6 parts of Angelica sinensis, 14 parts of Radix Astragali, 12 parts of Radix Anemarrhena, 4.5 parts of Rhizoma Anemarrhena, 4 parts of Rhizoma Cimicifugae, and 4 parts of Radix Glycyrrhizae, and the preparation method and treatment method are the same as the composition group of the present application.

[0044] 1.2 Experimental scheme After receiving C57BL / 6J mice, the mice were first adaptively fed for 2-3 days, and after the mice were adapted to the environment, the mice were randomly divided into 9 groups, 9 mice in each group, namely a blank control group, an in-situ colon cancer modeling group, a positive control group, a low, medium and high dose group of the composition of the present application, a comparative composition 1 group, a comparative composition 2 group, and a comparative composition 3 group. During the adaptive feeding of the mice, the mice were caught and gavaged with an empty gavage device every day, and other operations such as gavage were performed to make the mice adapt to being caught and gavaged, so as to minimize the errors caused by factors such as catching stress.

[0045] Except for the blank control group, the other groups were intraperitoneally injected with anesthetic, and the mice were fixed in a supine position. The skin was sterilized with 75% ethanol. A transverse incision was made on the lower abdomen, and the skin-muscle-peritoneum layer was sequentially incised to expose the cecum. Then, an appropriate amount of luciferase-labeled MC-38 cell suspension (5×10 5 After the matrix was solidified, the cecum was returned, and the surgical incision was sutured. The skin was sterilized with iodophor cotton balls, and the mice were placed in a heating pad for warming and waiting for them to wake up. Then, the body surface state of the mice in each group was observed every day. When the mice in each group showed dry and hard feces, less defecation, decreased activity, and disheveled hair, it was considered that the modeling was successful.

[0046] Then, the low, medium and high dose treatment groups of the composition of the present application were given 6 g / kg, 9 g / kg and 12 g / kg (crude drug amount) of the suspension every day, the comparative composition 1, comparative composition 2 and comparative composition 3 treatment groups were given 12 g / kg (crude drug amount, corresponding to the high dose treatment of the composition of the present application) of the suspension every day, the positive control group of mice was given 2.5 g / kg of lactulose, and the volume of the drug was 0.4 mL. The blank control group and the model group were both given the same volume of normal saline by gavage.

[0047] After the end of modeling and drug administration, the mice were fasted for 16 h without water to empty the intestinal tract. Then each group of mice was given 0.5 ml of ink solution by gavage, and the mice were placed in a metabolic cage to resume normal diet immediately. Then close observation was carried out, and the first defecation time, 5 h defecation number and fecal water content were recorded.

[0048] All data were statistically analyzed using GraphPad Prism 8 software, expressed as "mean ± standard deviation", and statistically processed using Student's t-test analysis, with p<0.05 being statistically significant.

[0049] 1.3 Effect of the composition of the present application on constipation induced by colon cancer in mice 1.3.1 Effect of the composition of the present application on the general condition of mice with colon cancer-induced constipation Before modeling, the physiological state of each group of mice was good, showing active movement and clean and shiny hair.

[0050] After modeling and drug intervention, the blank control group maintained healthy signs, the mice had good hair luster, active movement, and typical brown cylindrical solid excrement; the model control group, the comparative composition 1 group, the comparative composition 2 group and the comparative composition 3 group of mice showed typical pathological characteristics, including dry and dull hair, partial inhibition of activity, less defecation and dry and hard feces; the positive control group and the low, medium and high dose groups of the composition of the present application still had clean and shiny hair, good activity, moist and normal-shaped defecation, and their overall physiological indicators were significantly better than those of the model control group.

[0051] 1.3.2 Effect of the composition of the present application on the growth of colon cancer The growth of colon cancer in each group was observed by animal live imaging. The experimental results are shown in Table 1. After the end of drug administration, the modeling group had a large light intensity, indicating that the colon cancer was successfully inoculated and rapidly grew.

[0052] At the same time, compared with the model group, the low, medium and high dose groups of the composition of the present application could reduce the bioluminescence intensity, indicating that the composition of the present application could inhibit tumor growth, which had a significant statistical significance (P<0.01, P<0.001). Compared with the model group, the bioluminescence intensity of the positive control group, the comparative composition 1 group, the comparative composition 2 group and the comparative composition 3 group of mice had no obvious change (P>0.05), indicating that the existing purgative (positive control group) had no tumor inhibition effect.

[0053] Table 1 Effect of the composition of the present application on the growth of colon cancer (n=9, mean ± standard deviation) Group Light intensity / p / sec / cm2 / sr Blank control group — Model control group 4.76E7±2.73E7 Positive control group 4.13E7±2.32E7 Low-dose group of the present composition 1.77E7±1.03E7** Medium-dose group of the present composition 1.92E7±9.21E6** High-dose group of the present composition 3.84E6±2.07E6*** Comparative composition 1 group 4.96E7±2.44E7 Comparative composition 2 group 4.84E7±2.72E7 Comparative composition 3 group 4.89E7±2.39E7 Note: compared with the model control group, **P<0.01, ***P<0.001.

[0054] 1.3.3 Effect of the composition of the present application on the first black stool time of the constipation mice induced by colon cancer The experimental results are shown in Table 2. After modeling, compared with the blank control group, the first black stool time of the model group mice was significantly prolonged, which had statistical significance (P<0.001), indicating that the modeling of the constipation model induced by colon cancer was successful.

[0055] At the same time after administration, compared with the model group, the first black stool time of the positive control group, the low, medium and high dose groups of the composition of the present application was significantly shortened, which had significant statistical significance (P<0.001). Compared with the model group, there was no significant change in the first black stool time of the mice in the comparative composition 1 group, the comparative composition 2 group and the comparative composition 3 group (P>0.05). The medium and high dose groups of the composition of the present application had no significant difference compared with the positive control group (P>0.05), indicating that the composition of the present application could significantly improve the gastrointestinal transit capacity of the constipation mice induced by colon cancer, and showed a certain dose-dependent property.

[0056] Table 2 Effect of the composition of the present application on the first black stool time of the constipation mice induced by colon cancer (n=9, mean ± standard deviation) Group Time of the first black stool / min Blank control group 61±4.6 Model control group 103 ± 9.2 ### ]] Positive control group 62±4.7*** Low-dose group of the present composition 72±3.4*** Medium-dose group of the present composition 60±4.6*** High-dose group of the present composition 59±3.5*** Comparative composition 1 group 104±6.2 Comparative composition 2 group 102±5.1 Comparative composition 3 group 105±8.1 Note: compared with the model control group, ***P<0.001; compared with the blank control group, ### P<0.001.

[0057] 1.3.4 Effect of the composition of the present application on the 5 h stool particle number of the constipation mice induced by colon cancer The experimental results are shown in Table 3. After modeling, compared with the blank control group, the 5 h stool particle number of the model group mice was significantly reduced, which had statistical significance (P<0.001), also indicating that the modeling of the constipation model induced by colon cancer was successful.

[0058] At the same time after administration, compared with the model group, the 5 h stool particle number of the positive control group, the low, medium and high dose groups of the composition of the present application was significantly increased, which had significant statistical significance (P<0.001). Compared with the model group, there was no significant change in the 5 h stool particle number of the mice in the comparative composition 1 group, the comparative composition 2 group and the comparative composition 3 group (P>0.05). The medium and high dose groups of the composition of the present application had no significant difference compared with the positive control group (P>0.05), indicating that the composition of the present application could significantly improve the gastrointestinal transit capacity of the constipation mice induced by colon cancer, and showed a certain dose-dependent property.

[0059] Table 3 Effect of the composition of the present application on the 5 h stool particle number of the constipation mice induced by colon cancer (n=9, mean ± standard deviation) Group Number of stool particles in 5 h / particle Blank control group 55±4 Model control group 32 ± 2 ### ]] Positive control group 54±4*** Low-dose group of the present composition 50±6*** Medium-dose group of the present composition 57±4*** High-dose group of the present composition 58±2*** Comparative composition 1 group 33±5 Comparative composition 2 group 34±5 Comparative composition 3 group 32±4 Note: compared with the model control group, ***P<0.001; compared with the blank control group, ### P<0.001.

[0060] 1.3.5 Effect of the composition of the present application on the fecal water content of mice with constipation induced by colon cancer The experimental results are shown in Table 4. After modeling, compared with the blank control group, the fecal water content of the mice in the model group was significantly reduced, which had statistical significance (P<0.001), and the colon cancer-induced constipation model was also successfully modeled.

[0061] At the same time after administration, compared with the model group, the fecal water content of the mice in the positive control group, the composition of the present application low, medium and high dose groups was significantly increased, which had significant statistical significance (P<0.01, P<0.001). Compared with the model group, there was no significant change in the time of the first black stool of the mice in the comparative composition 1 group, the comparative composition 2 group and the comparative composition 3 group (P>0.05). The medium and high dose groups of the composition of the present application had no significant difference compared with the positive control group (P>0.05), which indicated that the composition of the present application could moisten the intestines and promote water excretion, significantly improve the gastrointestinal transit capacity of mice with constipation induced by colon cancer, and showed a certain dose-dependent property.

[0062] Table 4 Effect of the composition of the present application on the fecal water content of mice with constipation induced by colon cancer (n=9, mean ± standard deviation) Group Moisture content of feces / % Blank control group 60.2±8.0 Model control group 41.5 ± 6.9 ### ]] Positive control group 60.9 ± 5.7 *** ]] Low-dose group of the present composition 50.8 ± 5.1 ** ]] Medium-dose group of the present composition 62.4 ± 5.2 *** ]] High-dose group of the present composition 64.8 ± 7.0 *** ]] Comparative composition 1 group 40.4±3.6 Comparative composition 2 group 42.0±6.7 Comparative composition 3 group 41.8±4.4 Note: compared with the model control group, **P<0.01, ***P<0.001; compared with the blank control group, ### P<0.001.

[0063] Example 3 Effect of the composition of the present application on constipation of C57BL / 6J mice induced by opioid drugs (loperamide) 1.1 Experimental materials (1) Experimental animals: 81 SPF male C57BL / 6J mice, weighing about 20 g, provided by Hangzhou Ziyuan Experimental Animal Technology Co., Ltd., license number SCXK (Zhejiang) 2024-0004.

[0064] The feeding temperature was 25±2 ℃, the relative humidity was 60%±10%, the 12 h period light lamp lighting, and all were free to eat and drink water. The mouse feed and bedding were purchased from Jiangsu Province Cooperation Pharmaceutical Biological Engineering Co., Ltd.

[0065] (2) Experimental reagents: loperamide hydrochloride, specification: 1 g / bottle, produced by Shanghai Aladdin Bio-Chem Technology Co., Ltd.

[0066] Activated carbon, specification: 1 kg / bag, produced by Shanghai Aladdin Bio-Chem Technology Co., Ltd.

[0067] Blank control group: 0.9% sodium chloride injection, specification: 500 mL; 4.5 g / bottle, produced by Shijiazhuang Four Pharmaceutical Co., Ltd.

[0068] Positive control group: lactulose, specification: 15 ml*6 bags / box, produced by Abbott Biologicals B.V. (Netherlands) Co., Ltd.

[0069] The composition (thick paste) of the present application: cistanche 9 parts, angelica 15 parts, astragalus 20 parts, cyathula 6 parts, alisma 4.5 parts, cimicifuga 3 parts, and licorice 5 parts are proportioned, prepared according to the method of Example 1, and dissolved with normal saline before use; Comparative composition 1 (thick paste): cistanche 12 parts, angelica 12 parts, astragalus 18 parts, cyathula 8 parts, alisma 4.5 parts, cimicifuga 4 parts, and licorice 4 parts, prepared and treated in the same way as the composition group of the present application.

[0070] Comparative composition 2 (thick paste): cistanche 15 parts, angelica 9 parts, astragalus 16 parts, cyathula 10 parts, alisma 4.5 parts, cimicifuga 4 parts, and licorice 4 parts, prepared and treated in the same way as the composition group of the present application.

[0071] Comparative composition 3 (thick paste): cistanche 18 parts, angelica 6 parts, astragalus 14 parts, cyathula 12 parts, alisma 4.5 parts, cimicifuga 4 parts, and licorice 4 parts, prepared and treated in the same way as the composition group of the present application.

[0072] 1.2 Experimental scheme After receiving C57BL / 6J mice, the mice were first adaptively fed for 2-3 days, and after the mice adapted to the environment, the mice were randomly divided into 9 groups, 9 mice in each group, namely blank control group, loperamide modeling group, positive control group, low, medium and high dose groups of the composition of the present application, comparative composition 1 group, comparative composition 2 group, and comparative composition 3 group. During the adaptive feeding of the mice, the mice were caught and gavaged with an empty gavage device every day, and other operations such as gavage were performed to make the mice adapt to being caught and gavaged, so as to minimize the errors caused by factors such as stress caused by catching.

[0073] In addition to the blank control group, each group was given 2.5 mg / kg of loperamide hydrochloride by gavage at 9:00 every day, and the blank control group was given normal saline at the same time every day. After 6 hours of gavage every day, the low, medium and high dose treatment groups of the composition of the present application were given 6 g / kg, 9 g / kg and 12 g / kg (crude drug amount) of the suspension, the comparative composition 1, comparative composition 2 and comparative composition 3 treatment groups were given 12 g / kg (crude drug amount, corresponding to the high dose of the composition of the present application) of the suspension, and the positive control group of mice was given 2.5 g / kg of lactulose by gavage, and the volume of the drug was 0.4 mL. The blank control group and the model group were given the same volume of normal saline by gavage.

[0074] During the modeling and drug administration process, the body surface state of each group of mice was observed every day. When the model group of mice showed dry and hard feces, less defecation, decreased activity and disheveled hair, it was considered that the modeling was successful. After the modeling and drug administration were completed, the mice were fasted for 16 hours without water to empty the intestinal tract. Then each group of mice was given 0.5 ml of ink solution by gavage, and the mice were placed in a metabolic cage and immediately returned to normal diet. Then close observation was carried out, and the first black feces time, 5-hour defecation number and feces water content were recorded.

[0075] All data were statistically analyzed using GraphPad Prism 8 software, expressed as "mean ± standard deviation", and statistically processed using Student's t-test analysis, with p<0.05 being statistically significant.

[0076] 1.3 Effect of the composition of the present application on loperamide-induced constipation in mice 1.3.1 Effect of the composition of the present application on the general condition of loperamide-induced constipation mice Before modeling, the physiological state of each group of mice was good, showing active movement and clean and shiny hair.

[0077] After modeling and drug intervention, the blank control group maintained healthy signs, the mice had good hair luster, active movement, and typical brown cylindrical solid excrement; the model control group, the comparative composition 1 group, the comparative composition 2 group and the comparative composition 3 group of mice showed typical pathological characteristics, including dry and dull hair, reduced activity, less defecation and dry and hard feces; the positive control group and the low, medium and high dose groups of the composition of the present application still had clean and shiny hair, good activity, moist and normal defecation, and their overall physiological indicators were significantly better than those of the model control group, indicating that the low, medium and high doses of the composition of the present application could significantly improve the physiological indicators of ordinary constipation mice.

[0078] 1.3.2 Effect of the composition of the present application on the first black feces time of loperamide-induced constipation mice The experimental results are shown in Table 5. After modeling, compared with the blank control group, the first black stool time of the model group mice was significantly prolonged, which had statistical significance (P<0.001), indicating that the model of loperamide-induced constipation was successfully modeled.

[0079] At the same time after administration, compared with the model group, the first black stool time of the positive control group, the low, medium and high dose groups of the composition of the present application was significantly shortened, which had significant statistical significance (P<0.001). Compared with the model group, there was no significant change in the first black stool time of the mice in the comparative composition 1 group, the comparative composition 2 group and the comparative composition 3 group (P>0.05). The medium and high dose groups of the composition of the present application had no significant difference compared with the positive control group (P>0.05), indicating that the composition of the present application can significantly improve the gastrointestinal transport capacity of loperamide-induced constipation mice, and shows a certain dose-dependent property.

[0080] Table 5 Effect of the composition of the present application on the first black stool time of loperamide-induced constipation mice (n=9, mean ± standard deviation) Group Time of the first black stool / min Blank control group 60±5.5 Model control group 102 ± 9.0 ### ]] Positive control group 59±4.7*** Low-dose group of the present composition 68±2.4*** Medium-dose group of the present composition 58±4.3*** High-dose group of the present composition 56±5.3*** Comparative composition 1 group 97±6.8 Comparative composition 2 group 101±7.2 Comparative composition 3 group 103±8.8 Note: compared with the model control group, ***P<0.001; compared with the blank control group, ### P<0.001.

[0081] 1.3.3 Effect of the composition of the present application on the 5 h stool particle number of loperamide-induced constipation mice The experimental results are shown in Table 6. After modeling, compared with the blank control group, the 5 h stool particle number of the model group mice was significantly reduced, which had statistical significance (P<0.001), also indicating that the model of loperamide-induced constipation was successfully modeled.

[0082] At the same time after administration, compared with the model group, the 5 h stool particle number of the positive control group, the low, medium and high dose groups of the composition of the present application was significantly increased, which had significant statistical significance (P<0.001). Compared with the model group, there was no significant change in the 5 h stool particle number of the mice in the comparative composition 1 group, the comparative composition 2 group and the comparative composition 3 group (P>0.05). The medium and high dose groups of the composition of the present application had no significant difference compared with the positive control group (P>0.05), indicating that the composition of the present application can significantly improve the gastrointestinal transport capacity of ordinary constipation mice, and shows a certain dose-dependent property.

[0083] Table 6 Effect of the composition of the present application on the 5 h stool particle number of loperamide-induced constipation mice (n=9, mean ± standard deviation) Group Number of stool particles in 5 h / particle Blank control group 52±9 Model control group 34 ± 4 ### ]] Positive control group 59±6*** Low-dose group of the present composition 49±7*** Medium-dose group of the present composition 59±5*** High-dose group of the present composition 59±3*** Comparative composition 1 34±5 Comparative composition 2 36±6 Comparative composition 3 33±3 Note: compared with the model control group, ***P<0.001; compared with the blank control group, ### P<0.001.

[0084] 1.3.4 Effect of the composition of the present application on the fecal water content of mice with loperamide-induced constipation The experimental results are shown in Table 7. After modeling, the fecal water content of the mice in the model group was significantly lower than that in the blank control group, with statistical significance (P<0.001), which also indicated that the loperamide-induced constipation model was successfully modeled.

[0085] At the same time after administration, the fecal water content of the mice in the positive control group, the low-, medium-, and high-dose groups of the composition of the present application was significantly higher than that in the model group, with significant statistical significance (P<0.01, P<0.001). Compared with the model group, the first black feces time of the mice in the comparative composition 1 group, the comparative composition 2 group, and the comparative composition 3 group had no significant change (P>0.05). The medium- and high-dose groups of the composition of the present application had no significant difference compared with the positive control group (P>0.05), which indicated that the composition of the present application could moisten the intestines and promote water excretion, significantly improve the gastrointestinal transit capacity of ordinary constipated mice, and showed a certain dose-dependent property.

[0086] Table 7 Effect of the composition of the present application on the fecal water content of mice with loperamide-induced constipation (n=9, mean ± standard deviation) Group Moisture content of feces / % Blank control group 63.8±4.7 Model control group 42.4 ± 7.0 ### ]] Positive control group 65.4 ± 8.6 *** ]] Low-dose group of the present composition 53.7 ± 7.4 ** ]] Medium-dose group of the present composition 66.5 ± 7.6 *** ]] High-dose group of the present composition 68.0 ± 9.1 *** ]] Comparative composition 1 group 41.2±2.7 Comparative composition 2 group 42.2±4.6 Comparative composition 3 group 43.1±6.6 Note: **P<0.01, ***P<0.001 compared with the model control group, and ### P<0.001 compared with the blank control group.

[0087] Example 4 Effect of the composition of the present application on C57BL / 6J mice with constipation induced by a chemotherapy drug (paclitaxel) 1.1 Experimental materials (1) Experimental animals: SPF-grade male C57BL / 6J mice, 81, weighing about 20 g, provided by Hangzhou Ziyuan Experimental Animal Technology Co., Ltd., license number SCXK (Zhejiang) 2024-0004.

[0088] The feeding temperature was 25±2℃, the relative humidity was 60%±10%, the 12 h period light lamp lighting, and all were free to eat and drink water. The mouse feed and bedding were purchased from Jiangsu Province Cooperation Pharmaceutical Biological Engineering Co., Ltd.

[0089] (2) Experimental reagents: paclitaxel, specification: 50 mg / bottle, produced by Shanghai Aladdin Bio-Chem Technology Co., Ltd.

[0090] Activated carbon, specification: 1 kg / bag, produced by Shanghai Aladdin Bio-Chem Technology Co., Ltd.

[0091] Blank control group: 0.9% sodium chloride injection, specification: 500 mL; 4.5 g / bottle, produced by Shijiazhuang Four Pharmaceutical Co., Ltd.

[0092] Positive control group: lactulose, specification: 15 ml*6 bags / box, produced by Abbott Biologicals B.V. (Netherlands) Co., Ltd.

[0093] The composition (thick paste) of the present application: 9 parts of cistanche, 15 parts of angelica, 20 parts of astragalus, 6 parts of cyathula, 4.5 parts of alisma, 3 parts of cimicifuga, and 5 parts of licorice are proportioned, prepared according to the method of Example 1, and dissolved with normal saline before use.

[0094] Comparative composition 1 (thick paste): 12 parts of cistanche, 12 parts of angelica, 18 parts of astragalus, 8 parts of cyathula, 4.5 parts of alisma, 4 parts of cimicifuga, and 4 parts of licorice are proportioned, and the preparation method and treatment method are the same as those of the composition group of the present application.

[0095] Comparative composition 2 (thick paste): 15 parts of cistanche, 9 parts of angelica, 16 parts of astragalus, 10 parts of cyathula, 4.5 parts of alisma, 4 parts of cimicifuga, and 4 parts of licorice are proportioned, and the preparation method and treatment method are the same as those of the composition group of the present application.

[0096] Comparative composition 3 (thick paste): 18 parts of cistanche, 6 parts of angelica, 14 parts of astragalus, 12 parts of cyathula, 4.5 parts of alisma, 4 parts of cimicifuga, and 4 parts of licorice are proportioned, and the preparation method and treatment method are the same as those of the composition group of the present application.

[0097] 1.2 Experimental scheme After receiving C57BL / 6J mice, the mice were first adaptively fed for 2-3 days, and after the mice adapted to the environment, the mice were randomly divided into 9 groups, 9 mice in each group, namely blank control group, paclitaxel modeling group, positive control group, low, medium and high dose groups of the composition of the present application, comparative composition 1 group, comparative composition 2 group, and comparative composition 3 group. During the adaptive feeding of the mice, the mice were caught and gavaged with an empty gavaging device every day, and other operations were performed, so that the mice could adapt to being caught and gavaged, in order to minimize the errors caused by factors such as catching stress.

[0098] Except for the blank control group, the other groups were intraperitoneally injected with 10 mg / kg paclitaxel once a week, and the blank control group was intraperitoneally injected with normal saline at the same time. The low, medium and high dose treatment groups of the composition of the present application were given 6 g / kg, 9 g / kg and 12 g / kg (crude drug amount) of the suspension every day, and the comparative composition 1, comparative composition 2 and comparative composition 3 treatment groups were given 12 g / kg (crude drug amount, corresponding to the high dose treatment of the composition of the present application) of the suspension every day. The positive control group of mice was given 2.5 g / kg of lactulose, and the volume of the drug was 0.4 mL. The blank control group and the model group were both gavaged with the same volume of normal saline.

[0099] During the process of modeling and administration, the surface state of each group of mice was observed every day. When the model group mice showed dry and hard feces, less defecation, decreased activity and disheveled hair, it represented the success of modeling. Subsequently, the mice were fasted for 16 h without water to empty the intestinal tract. Subsequently, each group of mice was administered with 0.5 ml of ink solution, and the mice were placed in a metabolic cage to immediately resume normal diet. Then, close observation was conducted, and the time of the first black feces, the number of defecation in 5 h and the water content of feces were recorded.

[0100] All data were statistically analyzed by using GraphPad Prism 8 software, and represented as "mean ± standard deviation". Student's t-test analysis was used for statistical processing, and p<0.05 was statistically significant.

[0101] 1.3 Effect of the composition of the present application on paclitaxel-induced constipation in mice 1.3.1 Effect of the composition of the present application on the general condition of paclitaxel-induced constipation mice Before modeling, the physiological state of each group of mice was good, which showed active movement and clean and lustrous hair.

[0102] After modeling and administration intervention, the blank control group maintained healthy signs, the hair of the mice remained good in luster, the movement was active, and the excretion was typical brown cylindrical solid; the model control group, the comparative composition 1 group, the comparative composition 2 group and the comparative composition 3 group of mice showed typical pathological characteristics, including dry and dull hair, partial inhibition of activity, less defecation and dry and hard feces; the positive control group and the low, medium and high dose groups of the composition of the present application still had clean and lustrous hair, good activity, moist and normal defecation, and the overall physiological indicators were significantly better than those of the model control group.

[0103] 1.3.2 Effect of the composition of the present application on the first black feces time of paclitaxel-induced constipation mice The experimental results are shown in Table 8. After modeling, compared with the blank control group, the first black feces time of the model group mice was significantly prolonged, which had statistical significance (P<0.001), indicating that the paclitaxel-induced constipation model was successfully modeled.

[0104] At the same time after administration, compared with the model group, the first black feces time of the positive control group, the low, medium and high dose groups of the composition of the present application was significantly shortened, which had significant statistical significance (P<0.001). Compared with the model group, the first black feces time of the comparative composition 1 group, the comparative composition 2 group and the comparative composition 3 group of mice had no obvious change (P>0.05). The medium and high dose groups of the composition of the present application had no significant difference relative to the positive control group (P>0.05). It is indicated that the composition of the present application can significantly improve the gastrointestinal transmission capacity of ordinary constipation mice, and shows a certain dose dependence.

[0105] Table 8 Effect of the composition of the present application on the first defecation time of paclitaxel-induced constipation mice (n = 9, mean ± standard deviation) Group Time of the first black stool / min Blank control group 59±5.4 Model control group 100 ± 10.0 ### ]] Positive control group 60±3.5*** Low-dose group of the present composition 70±4.2*** Medium-dose group of the present composition 58±3.4*** High-dose group of the present composition 57±4.3*** Comparative composition 1 group 102±7.0 Comparative composition 2 group 99±8.4 Comparative composition 3 group 103±10.4 Note: compared with the model control group, ***P < 0.001; compared with the blank control group, ### P < 0.001.

[0106] 1.3.3 Effect of the composition of the present application on the 5 h defecation particle number of paclitaxel-induced constipation mice The experimental results are shown in Table 9. After modeling, compared with the blank control group, the 5 h defecation particle number of the model group mice was significantly reduced, which had statistical significance (P < 0.001), and the paclitaxel-induced constipation model was also successfully modeled.

[0107] At the same time after administration, compared with the model group, the 5 h defecation particle number of the positive control group, the low-, medium- and high-dose groups of the composition of the present application was significantly increased, which had significant statistical significance (P < 0.001). Compared with the model group, the 5 h defecation particle number of the comparative composition 1 group, the comparative composition 2 group and the comparative composition 3 group had no obvious change (P > 0.05). The medium- and high-dose groups of the composition of the present application had no significant difference compared with the positive control group (P > 0.05), which indicated that the composition of the present application could significantly improve the gastrointestinal transit capacity of paclitaxel-induced constipation mice, and showed a certain dose-dependent property.

[0108] Table 9 Effect of the composition of the present application on the 5 h defecation particle number of paclitaxel-induced constipation mice (n = 9, mean ± standard deviation) Group Number of stool particles in 5 h / particle Blank control group 53±8 Model control group 30 ± 5 ### ]] Positive control group 52±6*** Low-dose group of the present composition 48±8*** Medium-dose group of the present composition 55±5*** High-dose group of the present composition 56±3*** Comparative composition 1 group 31±7 Comparative composition 2 group 31±6 Comparative composition 3 group 32±8 Note: compared with the model control group, ***P < 0.001; compared with the blank control group, ### P < 0.001.

[0109] 1.3.4 Effect of the composition of the present application on the fecal water content of paclitaxel-induced constipation mice The experimental results are shown in Table 10. After modeling, compared with the blank control group, the fecal water content of the model group mice was significantly reduced, which had statistical significance (P < 0.001), and the paclitaxel-induced constipation model was also successfully modeled.

[0110] Meanwhile, compared with the model group, the fecal water content of the positive control group, the low, medium and high dose groups of the composition of the present application was significantly increased, with significant statistical significance (P<0.01, P<0.001). Compared with the model group, there was no significant change in the first black stool time of the composition 1 group, the composition 2 group and the composition 3 group (P>0.05). The medium and high dose groups of the composition of the present application had no significant difference compared with the positive control group (P>0.05), indicating that the composition of the present application can moisten the intestines and promote water excretion, significantly improve the gastrointestinal transit capacity of paclitaxel-induced constipated mice, and show a certain dose-dependent effect.

[0111] Table 10 Effect of the composition of the present application on the fecal water content of paclitaxel-induced constipated mice (n=9, mean ± standard deviation) Group Moisture content of feces / % Blank control group 62.4±7.1 Model control group 43.6 ± 7.0 ### ]] Positive control group 62.5 ± 6.8 *** ]] Low-dose group of the present composition 52.6 ± 6.3 ** ]] Medium-dose group of the present composition 64.3 ± 6.5 *** ]] High-dose group of the present composition 66.9 ± 8.0 *** ]]> Comparative composition 1 group 42.4±1.6 Comparative composition 2 group 43.3±3.1 Comparative composition 3 group 44.7±6.2 Note: compared with the model control group, **P<0.01, ***P<0.001; compared with the blank control group, ### P<0.001.

[0112] Example 5 Effect of the composition of the present application and three comparative compositions on abdominal distension of C57BL / 6J mice 1.1 Experimental materials (1) Experimental animals: SPF male C57BL / 6J mice, 54, weighing about 20 g, provided by Hangzhou Ziyuan Experimental Animal Technology Co., Ltd., license number SCXK (Zhejiang) 2024-0004.

[0113] The feeding temperature was 25±2℃, the relative humidity was 60%±10%, the 12 h period light lamp illumination, and the mice were free to eat and drink water. The mouse feed and bedding were purchased from Jiangsu Province Cooperation Pharmaceutical Biological Engineering Co., Ltd.

[0114] (2) Experimental reagents: loperamide hydrochloride, specification: 1 g / bottle, produced by Shanghai Aladdin Bio-Chem Technology Co., Ltd.

[0115] Activated carbon, specification: 1 kg / bag, produced by Shanghai Aladdin Bio-Chem Technology Co., Ltd.

[0116] Blank control group: 0.9% sodium chloride injection, specification: 500 mL; 4.5 g / bottle, produced by Shijiazhuang Four Pharmaceutical Co., Ltd.

[0117] The composition of the present application (thick paste): cistanche 9 parts, angelica 15 parts, astragalus 20 parts, cyathula 6 parts, alisma 4.5 parts, cimicifuga 3 parts, and licorice 5 parts, which are matched and prepared according to the method of Example 1, and then dissolved with normal saline before use.

[0118] Comparative composition 1 (thick paste): 12 parts of Herba Cistanche, 12 parts of Angelica sinensis, 18 parts of Radix Astragali, 8 parts of Radix Anemarrhena, 4.5 parts of Rhizoma Anemarrhena, 4 parts of Rhizoma Cimicifugae, and 4 parts of Radix Glycyrrhizae, and the preparation method and treatment method are the same as those of the composition group of the present application.

[0119] Comparative composition 2 (thick paste): 15 parts of Herba Cistanche, 9 parts of Angelica sinensis, 16 parts of Radix Astragali, 10 parts of Radix Anemarrhena, 4.5 parts of Rhizoma Anemarrhena, 4 parts of Rhizoma Cimicifugae, and 4 parts of Radix Glycyrrhizae, and the preparation method and treatment method are the same as those of the composition group of the present application.

[0120] Comparative composition 3 (thick paste): 18 parts of Herba Cistanche, 6 parts of Angelica sinensis, 14 parts of Radix Astragali, 12 parts of Radix Anemarrhena, 4.5 parts of Rhizoma Anemarrhena, 4 parts of Rhizoma Cimicifugae, and 4 parts of Radix Glycyrrhizae, and the preparation method and treatment method are the same as those of the composition group of the present application.

[0121] 1.2 Experimental scheme After receiving C57BL / 6J mice, the mice were first adaptively fed for 2-3 days, and after the mice were adapted to the environment, the mice were randomly divided into 6 groups, 9 mice in each group, namely a blank control group, a model group, a composition group of the present application, a comparative composition 1 group, a comparative composition 2 group and a comparative composition 3 group. During the adaptive feeding of the mice, the mice were caught and operated with an empty gavage every day to make the mice adapt to being caught and gavage in order to minimize the errors caused by catching stress and other factors.

[0122] Except for the blank control group, the other groups were given 2.5 mg / kg of loperamide hydrochloride by gavage at 9:00 every day, and the blank control group was given normal saline by gavage at the same time every day. After 6 hours of gavage every day, the composition group of the present application was given 12 g / kg (crude drug amount) of suspension every day, and the comparative composition 1, comparative composition 2 and comparative composition 3 treatment groups were given 12 g / kg (crude drug amount) of suspension every day, and the volume of the drug was 0.4 mL. After two weeks of modeling, the composition groups continued to be given the corresponding crude drug amount by gavage for one week.

[0123] After the last gavage, the intestinal distension volume was measured by the drainage volume method: the mice were sacrificed by cervical dislocation, dissected, the abdominal cavity was opened, the mesentery was separated, the upper end was cut from the pylorus and the lower end was cut to the end of the ileocecal junction, and the intestine was completely taken out (before cutting, the air was prevented from leaking, and the two ends were tied with a thread), and immediately immersed in normal saline, the drainage volume was measured, and the intestinal distension volume of the mouse was recorded.

[0124] All data were statistically analyzed by GraphPad Prism 8 software, represented by "mean ± standard deviation", and statistically processed by Student's t-test analysis, P<0.05 was statistically significant.

[0125] 1.3 Effect of the composition of the present application and three comparative compositions on abdominal distension of mice 1.3.1 Effects of the composition of the present invention and three comparative compositions on the intestinal distension volume of mice The experimental results are shown in Table 11. Compared with the blank control group, the intestinal distension volume of the composition group of the present invention did not change significantly. However, compared with the blank control group, the intestinal distension volume of mice in the control composition 1 group, control composition 2 group, and control composition 3 group was significantly increased (P < 0.001). This indicates that the composition of the present invention does not cause abdominal distension as a side effect while treating constipation; while the control composition, with the same amount of raw herbs, changing the proportions of each ingredient not only fails to treat constipation more effectively, but also causes abdominal distension as a side effect. Table 11 Effects of the addition and subtraction of the composition of the present invention on the intestinal distension volume of mice (n=9, mean ± standard deviation) Group Intestinal distension volume / mL Blank control group 1.08±0.17 Model control group 1.11±0.20 Composition group of the present application 1.12±0.16 Comparative composition 1 group 1.47±0.16*** Comparative composition 2 group 1.55±0.19*** Comparative composition 3 group 1.73±0.10*** Note: Compared with the blank control group, ***P<0.001.

[0126] Example 7 Effect of the composition of the present invention on coprostinol-producing eubacteria in the intestine of loperamide-induced constipation mice (C57BL / 6J mice) 1.1 Experimental Materials (1) Experimental animals: 81 male SPF-grade C57BL / 6J mice, weighing about 20 g, provided by Hangzhou Ziyuan Experimental Animal Technology Co., Ltd., license number SCXK (Zhejiang) 2024-0004.

[0127] The rearing temperature was 25±2 ℃, and the relative humidity was 60%±10%. The mice were kept under 12-hour periodic fluorescent lighting and had free access to food and water. Mice feed and bedding were purchased from Jiangsu Xietong Pharmaceutical Biotechnology Co., Ltd.

[0128] (2) Experimental reagent: Loperamide hydrochloride, specification: 1 g / bottle, produced by Shanghai Aladdin Biochemical Technology Co., Ltd.

[0129] Fecal genomic DNA extraction kit, manufactured by Beijing Tiangen Biotech Co., Ltd.

[0130] Coprosterol-producing eubacteria, produced by the American Type Culture Collection (ATCC), cultured under sterile, anaerobic conditions using trypsin-containing soybean agar / broth with defibrinated sheep blood.

[0131] Blank control group: 0.9% sodium chloride injection, specification: 500 mL, 4.5 g / bottle, produced by Shijiazhuang No. 4 Pharmaceutical Co., Ltd.

[0132] The composition of this invention (thick paste) is prepared according to the method of Example 1, using the following proportions: 9 parts of Cistanche deserticola, 15 parts of Angelica sinensis, 20 parts of Astragalus membranaceus, 6 parts of Achyranthes bidentata, 4.5 parts of Alisma plantago-aquatica, 3 parts of Cimicifuga foetida, and 5 parts of Glycyrrhiza uralensis. It is dissolved in physiological saline before use.

[0133] Comparative composition 1 (thick paste): 12 parts of Cistanche deserticola, 12 parts of Angelica sinensis, 18 parts of Astragalus membranaceus, 8 parts of Achyranthes bidentata, 4.5 parts of Alisma plantago-aquatica, 4 parts of Cimicifuga foetida, and 4 parts of Glycyrrhiza uralensis. The preparation and processing methods are the same as those of the composition group of the present invention

[0134] Comparative Composition 2 (thick paste): 15 parts of Cistanche deserticola, 9 parts of Angelica sinensis, 16 parts of Astragalus membranaceus, 10 parts of Achyranthes bidentata, 4.5 parts of Alisma plantago-aquatica, 4 parts of Cimicifuga foetida, and 4 parts of Glycyrrhiza uralensis. The preparation and processing methods are the same as those of the composition group of the present

[0135] Comparative composition 3 (thick paste): 18 parts of Cistanche deserticola, 6 parts of Angelica sinensis, 14 parts of Astragalus membranaceus, 12 parts of Achyranthes bidentata, 4.5 parts of Alisma plantago-aquatica, 4 parts of Cimicifuga foetida, and 4 parts of Glycyrrhiza uralensis. The preparation and processing methods are the same as those of the composition group of the present invention

[0136] 1.2 Experimental Scheme 1.2.1 Effects of the composition of the present invention on the intestinal flora of loperamide-induced constipation in C57BL / 6J mice After receiving C57BL / 6J mice, they were first acclimatized for 2-3 days. Once the mice had adapted to the environment, they were randomly divided into 6 groups of 9 mice each: a blank control group, a model group, the composition group of this invention, control composition 1 group, control composition 2 group, and control composition 3 group. During the acclimatization period, the mice were handled and administered gavage using an empty gavage device daily to help them adapt to handling and gavage, minimizing errors caused by handling stress and other factors.

[0137] Except for the blank control group, all other groups were administered 2.5 mg / kg loperamide hydrochloride by gavage at 9:00 AM daily, while the blank control group was administered physiological saline by gavage at the same time daily. Six hours after daily gavage, the groups using the composition of this invention were administered a suspension of 12 g / kg (crude drug amount) by gavage daily, while the control groups (comparative composition 1, comparative composition 2, and comparative composition 3) were administered a suspension of 12 g / kg (crude drug amount) by gavage daily, with a dosage volume of 0.4 mL for all groups. During the modeling and drug administration process, the surface condition of the mice in each group was observed daily. Successful modeling was indicated when the model group mice exhibited dry, hardened feces, reduced defecation frequency, decreased activity, and disheveled fur.

[0138] After successful modeling, fecal samples from each group of mice were collected for microbial diversity sequencing analysis, as follows: (1) Preparation of fecal samples: After the experiment, feces from each mouse were collected, aliquoted and stored. Approximately 0.2 g of each sample was weighed using sterile plastic centrifuge tubes and stored in a -80 ℃ refrigerator.

[0139] (2) Fecal genomic DNA extraction: DNA was extracted from the fecal samples of each mouse using a fecal genomic DNA extraction kit and the quality was tested.

[0140] (3) PCR amplification and product purification: Using specific primers for the 16S rDNA gene, the V4 variable region of prokaryotic 16S rDNA in mouse fecal samples was amplified by PCR.

[0141] (4) Library preparation and detection: The species information of the sample is obtained by comparing it with known bacteria in the database.

[0142] (5) Sequencing: After mixing multiple libraries, the V4 variable region sequence of 16S rDNA was sequenced in high throughput to identify the intestinal flora of mice.

[0143] All data were analyzed using GraphPad Prism 8 software and expressed as mean ± standard deviation. Student's t-test was used for statistical analysis, and P < 0.05 was considered statistically significant.

[0144] 1.2.2 Effect of coprosterol-producing bacteria on loperamide-induced constipation in C57BL / 6J mice After receiving C57BL / 6J mice, they were first acclimatized for 2-3 days. Once the mice had adapted to the environment, they were randomly divided into three groups of nine mice each: a blank control group, a model group, and a single-bacterial colonization group. During the acclimatization period, the mice were handled and administered gavage using an empty gavage device daily to help them adapt to handling and gavage, minimizing errors caused by handling stress and other factors.

[0145] During the modeling period, coprostinol-producing eubacteria stored at -80 °C were collected daily and cultured anaerobically on trypsin-soybean agar containing defibrotic sheep blood under sterile and anaerobic conditions. After collecting the bacteria, they were diluted with sterile PBS to 5 million colonies / mL.

[0146] The model group and the single-bacterial colonization group were administered 2.5 mg / kg loperamide hydrochloride by gavage at 9:00 AM daily, while the control group was administered physiological saline by gavage at the same time each day. Six hours after gavage, the single-bacterial colonization group was administered bacterial solution (0.2 mL / 10 g) by gavage, while the control and model groups were administered the same volume of physiological saline by gavage. During the modeling and drug administration process, the surface condition of the mice in each group was observed daily. Successful modeling was indicated when the mice in the model group exhibited dry, hard feces, reduced defecation frequency, decreased activity, and disheveled fur. After modeling and drug administration, the mice were fasted for 16 hours but allowed free access to water to empty their intestines. Subsequently, each group of mice was administered 0.5 mL of ink solution by gavage and placed in a metabolic cage, immediately resuming a normal diet. Close observation was then maintained, and the time of the first black feces and the number of feces in the first 5 hours were recorded.

[0147] All data were analyzed by GraphPad Prism 8 software, expressed as "mean ± standard deviation", and statistically processed by Student's t-test analysis, P<0.05 was statistically significant.

[0148] 1.3 Effect of the composition of the present application on coprostanol-producing eubacteria in the intestinal tract of C57BL / 6J constipation mice induced by loperamide 1.3.1 Effect of the composition of the present application on intestinal flora of C57BL / 6J constipation mice induced by loperamide Firstly, the intestinal flora composition of mice in the blank control group, the model group, the composition of the present application group, the comparative composition 1 group, the composition 2 group and the comparative composition 3 group was analyzed by 16S rDNA analysis.

[0149] The microbial abundance of the sample can be evaluated by single sample comparison analysis (alpha diversity), and chao1 is an algorithm for analyzing sample alpha diversity. Chao1 can estimate the number of classification units in the sample, and a classification unit is a group of bacterial sequences with 97% similarity in the sample. The larger the chao1 index, the more bacterial species in the sample and the higher the abundance. The results are shown in Figure 1 Compared with the blank control group, the chao1 index of the mice in the model group was significantly reduced (P<0.001); compared with the model group, the chao1 index of the mice in the composition of the present application group was significantly increased (P<0.001); and compared with the model group, the chao1 index of the mice in the comparative composition 1 group, the comparative composition 2 group and the comparative composition 3 group had no obvious change (P>0.05). This indicates that constipation can reduce the abundance of intestinal flora in mice, and the composition of the present application can restore the reduced intestinal flora abundance in mice due to constipation.

[0150] Subsequently, Metastats difference analysis was used to detect the differences in the relative abundance of intestinal bacteria between each group. As shown in Figure 2 Compared with the blank control group, the relative abundance of coprostanol-producing eubacteria in the mice of the model group was significantly reduced (P<0.001); and compared with the model group, the relative abundance of coprostanol-producing eubacteria in the mice of the composition of the present application group was significantly increased (P<0.001); and compared with the model group, the relative abundance of coprostanol-producing eubacteria in the mice of the comparative composition 1 group, the comparative composition 2 group and the comparative composition 3 group had no obvious change (P>0.05). This indicates that constipation can reduce the abundance of coprostanol-producing eubacteria in the intestinal tract of mice, and the composition of the present application can restore the reduced abundance of coprostanol-producing eubacteria due to constipation.

[0151] To further confirm the effect of constipation and the composition of the present application on the relative abundance of coprostanols-producing Eubacterium, the 16S rDNA gene copy number of coprostanols-producing Eubacterium in the feces of mice in each group was detected by real-time quantitative PCR experiment. The detection results are shown in Table 6. Figure 3 As shown in Table 6, compared with the blank control group, the 16S rDNA gene copy number of coprostanols-producing Eubacterium in the model group mice was significantly reduced (P<0.001); and compared with the model group, the 16S rDNA gene copy number of coprostanols-producing Eubacterium in the mice of the composition of the present application group was significantly increased (P<0.001); and compared with the model group, the 16S rDNA gene copy number of coprostanols-producing Eubacterium in the mice of the comparative composition 1 group, the comparative composition 2 group and the comparative composition 3 group had no obvious change (P>0.05). This further indicates that constipation can cause the level of coprostanols-producing Eubacterium in the intestine of mice to decrease, and the composition of the present application can restore the level of coprostanols-producing Eubacterium reduced by constipation.

[0152] 1.3.2 Effect of coprostanols-producing Eubacterium on constipation induced by loperamide in C57BL / 6J mice 1.3.2.1 Effect of coprostanols-producing Eubacterium on the general condition of loperamide-induced constipation mice Before modeling, the physiological state of mice in each group was good, which was manifested as active movement and clean and lustrous hair.

[0153] After modeling intervention, the blank control group maintained healthy physical signs, the hair of mice remained good in luster, the movement was active, and the excrement was typical brown cylindrical solid; the model group mice showed typical pathological characteristics, including dry and dull hair, partial inhibition of activity, less defecation and dry and hard stool; the hair of the single bacterium colonization group was still clean and lustrous, the activity was good, the defecation was moist and normal in shape, and the overall physiological indicators were significantly better than those of the model group.

[0154] 1.3.2.2 Effect of coprostanols-producing Eubacterium on the first black stool time of loperamide-induced constipation mice The experimental results are shown in Table 12. After modeling, compared with the blank control group, the first black stool time of mice in the model group was significantly prolonged, which had statistical significance (P<0.001), indicating that the modeling of the loperamide-induced constipation model was successful. At the same time after administration, compared with the model group, the first black stool of mice in the single bacterium colonization group was significantly shortened, which had significant statistical significance (P<0.001). The above results indicate that the composition of the present application can further improve the constipation of mice by affecting the level of coprostanols-producing Eubacterium in the intestine of mice.

[0155] Table 12 Effect of coprostanols-producing Eubacterium on the first black stool time of loperamide-induced constipation mice (n=9, mean ± standard deviation) Group Time of the first black stool / min Blank control group 51±3.1 Model group 104 ± 2.5 ### ]] Single-bacterial colonization group 51±3.2*** Note: compared with the model group, ***P<0.001; compared with the blank control group, ### P<0.001.

[0156] 1.3.2.3 Effect of coprostanogen-producing eubacterium on 5 h defecation particle number of loperamide-induced constipation mice The experimental results are shown in Table 13. After modeling, compared with the blank control group, the 5 h defecation particle number of the model group mice was significantly reduced, with statistical significance (P<0.001), indicating that the loperamide-induced constipation model was successfully modeled. At the same time after administration, compared with the model group, the 5 h defecation particle number of the single bacterial colonization group mice was significantly increased, with significant statistical significance (P<0.001). The above results further indicate that the composition of the present application further improves the constipation of mice by affecting the level of coprostanogen-producing eubacterium in the intestinal tract of mice.

[0157] Table 13 Effect of coprostanogen-producing eubacterium on 5 h defecation particle number of loperamide-induced constipation mice (n=9, mean ± standard deviation) Group Number of stool particles in 5 h / particle Blank control group 53±7 Model group 32 ± 4 ### ]] Single-bacterial colonization group 58±8*** Note: compared with the model group, ***P<0.001; compared with the blank control group, ### P<0.001.

[0158] 1.4 Experimental conclusion The composition of the present application can increase the content of coprostanogen-producing eubacterium in the intestinal flora when treating constipation, improve the intestinal environment, and exert its unique effect of treating constipation.

[0159] Example 8 Effect of the composition of the present application on neurogranin in serum of loperamide-induced C57BL / 6J constipation mice 1.1 Experimental materials (1) Experimental animals: SPF grade male C57BL / 6J mice, 81, weighing about 20 g, provided by Hangzhou Ziyuan Experimental Animal Technology Co., Ltd., license number SCXK (Zhejiang) 2024-0004.

[0160] The feeding temperature was 25±2℃, the relative humidity was 60%±10%, the 12 h period light lamp illumination, and all were free to eat and drink water.

[0161] The mouse feed and bedding were purchased from Jiangsu Cooperation Pharmaceutical Biological Engineering Co., Ltd.

[0162] (2) Experimental reagents: loperamide hydrochloride, specification: 1 g / bottle, produced by Shanghai Aladdin Bio-Chem Technology Co., Ltd.

[0163] Recombinant human neurogranin, produced by abcam company.

[0164] Mouse Neural Rank Protein-Linked Immunosorbent Assay Kit, manufactured by Wuhan Huamei Biotechnology Co., Ltd.

[0165] Blank control group: 0.9% sodium chloride injection, specification: 500 mL, 4.5 g / bottle, produced by Shijiazhuang No. 4 Pharmaceutical Co., Ltd.

[0166] The composition of this invention (thick paste) is prepared according to the method of Example 1, using the following proportions: 9 parts of Cistanche deserticola, 15 parts of Angelica sinensis, 20 parts of Astragalus membranaceus, 6 parts of Achyranthes bidentata, 4.5 parts of Alisma plantago-aquatica, 3 parts of Cimicifuga foetida, and 5 parts of Glycyrrhiza uralensis. It is dissolved in physiological saline before use.

[0167] Comparative composition 1 (thick paste): 12 parts of Cistanche deserticola, 12 parts of Angelica sinensis, 18 parts of Astragalus membranaceus, 8 parts of Achyranthes bidentata, 4.5 parts of Alisma plantago-aquatica, 4 parts of Cimicifuga foetida, and 4 parts of Glycyrrhiza uralensis. The preparation and processing methods are the same as those of the composition group of the present invention

[0168] Comparative Composition 2 (thick paste): 15 parts of Cistanche deserticola, 9 parts of Angelica sinensis, 16 parts of Astragalus membranaceus, 10 parts of Achyranthes bidentata, 4.5 parts of Alisma plantago-aquatica, 4 parts of Cimicifuga foetida, and 4 parts of Glycyrrhiza uralensis. The preparation and processing methods are the same as those of the composition group of the present

[0169] Comparative composition 3 (thick paste): 18 parts of Cistanche deserticola, 6 parts of Angelica sinensis, 14 parts of Astragalus membranaceus, 12 parts of Achyranthes bidentata, 4.5 parts of Alisma plantago-aquatica, 4 parts of Cimicifuga foetida, and 4 parts of Glycyrrhiza uralensis. The preparation and processing methods are the same as those of the composition group of the present invention

[0170] 1.2 Experimental Scheme 1.2.1 Effect of the composition of the present invention on the rank protein of the nerve in loperamide-induced C57BL / 6J constipation mice After receiving C57BL / 6J mice, they were first acclimatized for 2-3 days. Once the mice had adapted to the environment, they were randomly divided into 6 groups of 9 mice each: a blank control group, a model group, the composition group of this invention, control composition 1 group, control composition 2 group, and control composition 3 group. During the acclimatization period, the mice were handled and administered gavage using an empty gavage device daily to help them adapt to handling and gavage, minimizing errors caused by handling stress and other factors.

[0171] Except for the blank control group, all other groups were administered 2.5 mg / kg loperamide hydrochloride by gavage at 9:00 AM daily, while the blank control group was administered physiological saline by gavage at the same time daily. Six hours after daily gavage, the groups using the composition of this invention were administered a suspension of 12 g / kg (crude drug amount) by gavage daily, while the control groups (comparative composition 1, comparative composition 2, and comparative composition 3) were administered a suspension of 12 g / kg (crude drug amount) by gavage daily, with a dosage volume of 0.4 mL for all groups. During the modeling and drug administration process, the surface condition of the mice in each group was observed daily. Successful modeling was indicated when the model group mice exhibited dry, hardened feces, reduced defecation frequency, decreased activity, and disheveled fur.

[0172] After the success of modeling, the mice in each group were taken blood from the eye socket, the serum was separated, and the content of Neurturin (NRTN) in the serum of mice in each group was detected by mouse Neurturin enzyme-linked immunoassay kit.

[0173] All data were statistically analyzed by GraphPad Prism 8 software, represented by "mean ± standard deviation", and statistically processed by Student's t-test analysis, P<0.05 was statistically significant.

[0174] 1.2.2 Effect of Neurturin on Loperamide-induced Constipation in C57BL / 6J Mice After receiving C57BL / 6J mice, first adaptive feeding for 2-3 days, after the mice adapt to the environment, the mice are randomly divided into 3 groups, 9 in each group, namely blank control group, model group, and recombinant Neurturin group. During the adaptive feeding of the mice, the mice are caught and gavage operation is performed every day to make the mice adapt to being caught and gavage in order to minimize the error caused by catching stress and other factors.

[0175] The model group and the recombinant Neurturin group were gavaged with 2.5 mg / kg of loperamide hydrochloride at 9:00 every day, and the control group was gavaged with normal saline at the same time every day. After 6 hours of gavage every day, the recombinant Neurturin group was injected with rNRTN intraperitoneally, and the control group and the model group were injected with the same volume of normal saline intraperitoneally. During the modeling and drug administration process, the body surface state of the mice in each group was observed every day. When the model group mice showed dry and hard feces, less defecation, decreased activity, and disheveled hair, it was considered that the modeling was successful. After the modeling and drug administration were completed, the mice were fasted for 16 hours without water to empty the intestinal tract. Then the mice in each group were gavaged with 0.5 mL of ink solution, and the mice were placed in a metabolic cage and immediately returned to normal diet. Then the first black feces time and 5-hour feces particle number were closely observed and recorded.

[0176] All data were statistically analyzed by GraphPad Prism 8 software, represented by "mean ± standard deviation", and statistically processed by Student's t-test analysis, P<0.05 was statistically significant.

[0177] 1.3 Effect of the composition of the present application on Neurturin in serum of C57BL / 6J constipation mice induced by loperamide 1.3.1 Effect of the composition of the present application on Neurturin in C57BL / 6J constipation mice induced by loperamide The effect of different contents of Astragalus membranaceus in the composition of the present application on the content of NRTN in the serum of each group of mice was determined. The effect of NRTN content in the serum of mice is shown in Table 14. Compared with the blank control group, the content of NRTN in the serum of mice in the model group was significantly reduced (P<0.001), indicating that the constipation induced by loperamide in mice could affect the content of NRTN; compared with the model group, the content of NRTN in the serum of mice in the composition of the present application group was significantly increased (P<0.001); compared with the model group, the content of NRTN in the serum of mice in the comparative composition 1 group, the comparative composition 2 group and the comparative composition 3 group had no obvious change (P>0.05). The results show that constipation can reduce the content of NRTN in the serum of mice, and the composition of the present application can restore the reduced content of NRTN in the serum of mice caused by constipation.

[0178] Table 14 Effect of Astragalus membranaceus in the composition of the present application on the content of NRTN in the serum of constipated mice (n=9, mean ± standard deviation) Group NRTN (pg / mL) Blank control group 185.14±12.90 Model group 62.48 ± 8.15 ### ]] Composition group of the present application 181.81±4.44*** Comparative composition 1 group 63.74±4.82 Comparative composition 2 group 61.99±6.97 Comparative composition 3 group 64.44±7.67 Note: compared with the model group, ***P<0.001; compared with the blank control group, ### P<0.001.

[0179] 1.3.2 Effect of recombinant neural order protein on loperamide-induced constipation in C57BL / 6J mice 1.3.2.1 Effect of recombinant neural order protein on the general condition of loperamide-induced constipated mice Before modeling, the physiological state of mice in each group was good, showing active movement and clean and lustrous hair.

[0180] After modeling intervention, the control group maintained healthy signs, the mice had good hair luster, active movement, and typical brown cylindrical solid excrement; the mice in the model group showed typical pathological characteristics, including dry and dull hair, partial inhibition of activity, less defecation, and dry and hard feces; the hair of the recombinant neural order protein group was still clean and lustrous, the activity was good, the defecation was moist and normal in shape, and the overall physiological indicators were significantly better than those of the model group.

[0181] 1.3.2.2 Effect of recombinant neural order protein on the first black stool time of loperamide-induced constipated mice The experimental results are shown in Table 15. After modeling, compared with the blank control group, the first black stool time of mice in the model group was significantly prolonged, which was statistically significant (P<0.001), indicating that the modeling of the loperamide-induced constipation model was successful. At the same time after administration, compared with the model group, the first black stool time of mice in the recombinant neural order protein group was significantly shortened, which was statistically significant (P<0.001). The above results show that the composition of the present application can further improve the constipation of mice by affecting the level of NRTN in the serum of mice.

[0182] Table 15 Effect of NRTN on the first black stool time of loperamide-induced constipation mice (n=9, mean ± standard deviation) Group Time of the first black stool / min Blank control group 52±3.8 Model group 102 ± 3.6 ### ]] Recombinant neuroepithelial protein group 51±5.1*** Note: compared with the model group, ***P<0.001; compared with the blank control group, ### P<0.001.

[0183] 1.3.2.3 Effect of recombinant neurturin on the 5 h defecation particle number of loperamide-induced constipation mice The experimental results are shown in Table 16. After modeling, compared with the blank control group, the 5 h defecation particle number of the model group mice was significantly reduced, with statistical significance (P<0.001), indicating that the loperamide-induced constipation model was successfully modeled. At the same time after administration, compared with the model group, the 5 h defecation particle number of the recombinant neurturin group mice was significantly increased, with significant statistical significance (P<0.001). The above results further indicate that the composition of the present application further improves the constipation of mice by affecting the level of neurturin in the serum of mice.

[0184] Table 16 Effect of NRTN on the 5 h defecation particle number of loperamide-induced constipation mice (n=9, mean ± standard deviation) Group 5 h defecation particle number / particle Blank control group 40±4 Model group 22 ± 3 ### ]] Recombinant neuroepithelial protein group 43±4*** Note: compared with the model group, ***P<0.001; compared with the blank control group, ### P<0.001.

[0185] 1.4 Experimental conclusion The composition of the present application can increase the release of serum neurturin NRTN when treating constipation, activate intestinal neurons, increase the sensitivity to mechanical expansion, and play its unique effect of treating constipation.

[0186] The above only describes the preferred embodiments of the present application, and it should be noted that for ordinary skilled persons in the art, without departing from the principles of the present application, a number of improvements and refinements can be made, and these improvements and refinements should be considered as the protection scope of the present application.

Claims

1. A traditional Chinese medicine composition for treating cancer-induced constipation, characterized in that, The raw medicinal materials include the following by weight: 5-11 parts of Jinyangrong, 13-20 parts of Danggui, 20-30 parts of Huangqi, 5-7 parts of Niuxi, 3-6 parts of Zexie, 1-3 parts of Shengma, and 1-10 parts of Gancao.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The preferred raw material weight ratio is 9 parts of Jinyangrong, 15 parts of Danggui, 20 parts of Huangqi, 6 parts of Niuxi, 4.5 parts of Zexie, 3 parts of Shengma, and 5 parts of Gancao.

3. The preparation method of the traditional Chinese medicine composition according to claim 1 or 2, characterized in that, The preparation method includes the following steps: mixing the traditional Chinese medicine composition with water, decocting to obtain a decoction; filtering and concentrating the decoction to obtain an extract.

4. The production method according to claim 3, characterized by, The method includes the following steps: Step one: decoct the raw medicinal materials according to the prescription amount with water twice, 8 times of water for the first time, extracting for 2 hours, filtering, 6 times of water for the second time, extracting for 1 hour, filtering, and combining the two water decoctions; Step two: concentrate the medicinal liquid under reduced pressure to an extract with a relative density of 1.26-1.30 (65℃±5℃); Optionally, the method further includes: Step three: take the extract, add an appropriate amount of dextrin, mix well, and dry under reduced pressure and vacuum to obtain a dry extract powder; Step four: take the dry extract powder, granulate, and dry to obtain the traditional Chinese medicine composition granules.

5. A traditional Chinese medicine preparation, characterized in that, The traditional Chinese medicine composition of claim 1 or 2 or the traditional Chinese medicine composition prepared by the preparation method of any one of claims 3-5, and optionally one or more pharmaceutically acceptable carriers.

6. The traditional Chinese medicine preparation according to claim 5, characterized in that, The traditional Chinese medicine preparation is a gel, a cream, a tablet, a capsule, a powder, a mixture, a pill, a granule, a solution, a syrup, a decoction, a suppository, an aerosol, a plaster, an ointment, an injection, a spray, a liniment, a tincture, a wet compress, a paste, or a lotion; and the pharmaceutically acceptable carrier is at least one selected from a pharmaceutically acceptable solvent, a solubilizer, a cosolvent, an emulsifier, a coloring agent, a binder, a disintegrant, a filler, a lubricant, a wetting agent, an osmotic pressure regulator, a stabilizer, a glidant, a flavoring agent, a preservative, a suspending agent, a coating material, an aromatic agent, an anti-adhesion agent, an integrating agent, a penetration enhancer, a pH regulator, a buffer, a plasticizer, a surfactant, a thickening agent, a complexing agent, a humectant, an absorbent, a diluent, a flocculating agent and a deflocculating agent, a filter aid, a release retardant, a high molecular backbone material, and a film-forming material.

7. The traditional Chinese medicine preparation according to claim 6, characterized in that, It also includes optionally one or more other drugs for treating constipation and / or cancer.

8. The traditional Chinese medicine preparation according to claim 7, characterized in that, The drug for treating cancer is an opioid drug or a chemotherapy drug.

9. Use of the traditional Chinese medicine composition of claim 1 or 2, the traditional Chinese medicine composition prepared by the preparation method of claim 3 or 4, or the traditional Chinese medicine preparation of any one of claims 5-8 in the preparation of a drug for preventing or treating constipation, characterized in that, The constipation is at least one of constipation caused by abdominal tumor compression, constipation caused by opioid drugs, and constipation caused by chemotherapy drugs.

10. Use according to claim 9, characterized in that, The drug for preventing or treating constipation does not cause abdominal distension and diarrhea.

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