Traditional Chinese medicine compound for treating chemotherapy-related diarrhea as well as preparation method and application of traditional Chinese medicine compound

Abstract

The invention relates to the technical field of traditional Chinese medicine compositions, in particular to a traditional Chinese medicine compound for treating chemotherapy-related diarrhea and a preparation method and application thereof. The traditional Chinese medicine compound is prepared from the following components in parts by weight: 15 to 30 parts of sun-dried ginseng, 20 to 30 parts of radix astragali seu hedysari, 15 to 20 parts of radix angelicae sinensis, 15 to 20 parts of rhizoma chuanxiong, 15 to 20 parts of radix paeoniae alba, 15 to 20 parts of roasted rhizoma atractylodis macrocephalae, 15 to 20 parts of poria cocos, 15 to 20 parts of radix angelicae, 15 to 20 parts of spina gleditsiae, 15 to 30 parts of flos lonicerae, 10 to 20 parts of radix glycyrrhizae preparata and 10 to 15 parts of radix platycodonis. Based on the compatibility relation of the traditional Chinese medicine compounds, the traditional Chinese medicine composition accords with the meaning of supporting the interior and expelling evil, has the effects of strengthening the body resistance to eliminate evil, strengthening the spleen and stomach, clearing heat and drying dampness, and promoting blood circulation to remove blood stasis, has no obvious liver and kidney toxicity, and can be effectively applied to treatment of chemotherapy-related diarrhea.

Description

Technical Field

[0001] The present application relates to the technical field of Chinese medicine compositions, and in particular to a Chinese medicine compound related to the treatment of chemotherapy-related diarrhea, and a preparation method and application thereof. Background Art

[0002] Chemotherapy is one of the effective methods for treating cancer. However, with the continuous promotion and application of chemotherapy drugs in tumor clinics, while improving the efficacy of cancer treatment, it also produces many toxic side effects on the human body, such as chemotherapy-induced diarrhea (CID). CID is one of the most common digestive complications of cancer patients during chemotherapy. The clinical manifestations are mainly nausea, vomiting, painless or mildly painful diarrhea, and projectile watery stools. These conditions may occur several to dozens of times a day and generally last for 5 to 7 days. Some patients may even last for 2 to 3 months. What's more, malnutrition, electrolyte disorders, renal insufficiency, hypovolemic shock, etc. may occur. These CID-related side effects seriously affect the therapeutic effect of chemotherapy drugs. Some of them may also lead to the adjustment, delay or even cessation of treatment plans, which in turn has a significant impact on the quality of life of cancer patients. Among the common chemotherapy drugs currently, irinotecan, capecitabine, 5-fluorouracil, cisplatin, methotrexate, etc., cause the highest diarrhea rate in patients. In addition, there is no clear mechanism to explain the occurrence and development of chemotherapy-related diarrhea. However, previous clinical studies have shown that some chemotherapy drugs induce intestinal epithelial cell division and apoptosis, and produce reactive oxygen species through oxidative stress, thereby inducing the upregulation of proinflammatory cytokines and causing inflammation, thereby damaging the intestinal mucosal barrier function and leading to inflammatory diarrhea in patients. In addition, chemotherapy drugs can also cause intestinal flora disorders and cause homeostasis disorders of the flora, thereby affecting the immune function of the intestine and inducing diarrhea in patients.

[0003] At present, there is no unified and effective treatment plan for chemotherapy-related diarrhea in clinical practice; however, Western medicine mainly focuses on symptomatic treatment plans such as reducing gastrointestinal motility and anti-infection. The drugs used mainly include opioids, anticholinergics, and somatostatin octreotide. Among these drugs, loperamide is the first choice for the treatment of CID. Loperamide directly acts on the opioid receptors of smooth muscle to prevent the release of acetylcholine and prostaglandins, thereby inhibiting intestinal motility to promote the reabsorption of glucose and water electrolytes to treat diarrhea. However, loperamide is prone to cause adverse reactions such as gastrointestinal spasm, delayed allergic reactions, and dysuria, and high doses may cause paralytic ileus. In addition, octreotide is a synthetic somatostatin peptide analog that has been shown to regulate the exocrine and endocrine functions of the gastrointestinal system and pancreas, but in clinical trials, octreotide has not significantly improved the efficacy of CID patients.

[0004] In addition, currently, traditional Chinese medicine, acupoint application, acupuncture and other therapies commonly used in traditional Chinese medicine have certain effects on CID patients, with few adverse reactions and high patient compliance. Therefore, how to develop a traditional Chinese medicine compound for CID is a technical problem that needs to be solved urgently. Summary of the invention

[0005] The present application provides a Chinese herbal compound related to the treatment of chemotherapy-related diarrhea, and a preparation method and application thereof, to solve the following technical problem: how to fill the gap in Chinese herbal compound drugs for the treatment of chemotherapy-related diarrhea.

[0006] In a first aspect, the present application provides a Chinese medicine compound related to the treatment of chemotherapy-related diarrhea, which comprises, by weight: Raw sun-dried ginseng: 15 to 30 portions, astragalus: 20 to 30 portions, angelica: 15 to 20 portions, chuanxiong: 15 to 20 portions, white peony: 15 to 20 portions, stir-fried atractylodes: 15 to 20 portions, poria: 15 to 20 portions, angelica dahurica: 15 to 20 portions, sapodilla thorn: 15 to 20 portions, honeysuckle: 15 to 30 portions, roasted licorice: 10 to 20 portions, platycodon: 10 to 15 portions.

[0007] Optionally, the Chinese medicine compound further comprises, by weight: Raw sun-dried ginseng: 25 to 30 portions, astragalus: 25 to 30 portions, angelica: 15 to 18 portions, chuanxiong: 15 to 18 portions, white peony: 15 to 18 portions, stir-fried atractylodes: 15 to 18 portions, poria: 15 to 18 portions, angelica dahurica: 15 to 18 portions, gleditsia thorn: 15 to 18 portions, honeysuckle: 15 to 18 portions, roasted licorice: 10 to 15 portions, platycodon: 10 to 15 portions.

[0008] Optionally, the Chinese medicine compound further comprises, by weight: Raw sun-dried ginseng: 30 parts, astragalus: 30 parts, angelica: 15 parts, chuanxiong: 15 parts, white peony: 15 parts, stir-fried atractylodes: 15 parts, poria: 15 parts, angelica dahurica: 15 parts, gleditsia thorn: 15 parts, honeysuckle: 15 parts, roasted licorice: 10 parts, platycodon: 10 parts.

[0009] In a second aspect, the present application provides a method for preparing the Chinese medicine compound according to the first aspect, the method comprising: Adding raw sun-dried ginseng, astragalus, angelica, chuanxiong, white peony root, stir-fried atractylodes, tuckahoe, angelica dahurica, thorn of Gleditsia sinensis, honeysuckle, roasted licorice and platycodon grandiflorum into distilled water for soaking, and then decocting and filtering to obtain decoction filtrate; The decoction is first heated and then concentrated under reduced pressure to obtain a Chinese medicine compound liquid.

[0010] Optionally, the steps of adding raw sun-dried ginseng, astragalus, angelica, chuanxiong, white peony root, stir-fried atractylodes, tuckahoe, angelica dahurica, thorn of Gleditsia sinensis, honeysuckle, roasted liquorice and platycodon grandiflorum to distilled water for soaking respectively, and then decocting and filtering to obtain a decoction filtrate comprises the following steps: Adding raw sun-dried ginseng, astragalus, angelica, chuanxiong, white peony root, stir-fried atractylodes, tuckahoe, angelica dahurica, thorn of Gleditsia sinensis, honeysuckle, roasted liquorice and platycodon grandiflorum to distilled water for soaking respectively to obtain a mixture; The mixture is subjected to a second heating and a third heating, and then filtered to obtain a decoction liquid and a filter residue, respectively; The filter residue and water are mixed, and then the second heating, the third heating and filtering are performed to obtain a decoction secondary liquid; The first decoction liquid and the second decoction liquid are combined to obtain a decoction filtrate.

[0011] Optionally, the first heating temperature is 70° C. to 80° C., and the first heating time is 5 min to 10 min; and / or, The second heating temperature is 110° C. to 120° C., and the second heating time is 8 min to 12 min; and / or, The temperature of the third heating is 80° C. to 90° C., and the time of the third heating is 45 min to 55 min.

[0012] Optionally, the soaking time is 25 minutes to 35 minutes.

[0013] Optionally, the volume ratio of the distilled water to the water is 2.0 to 3.0.

[0014] In a third aspect, the present application provides a Chinese medicine preparation related to the treatment of chemotherapy-related diarrhea, wherein the Chinese medicine preparation comprises the Chinese medicine compound described in the first aspect and a pharmaceutically acceptable carrier thereof; the Chinese medicine preparation comprises at least one of the following: Chinese herbal decoctions, Chinese herbal granules, Chinese herbal ointments, Chinese herbal capsules, Chinese herbal powders, Chinese herbal pills and Chinese herbal mixtures.

[0015] In a fourth aspect, the present application provides an application of a Chinese medicine compound, which includes using the Chinese medicine compound described in the first aspect or the Chinese medicine preparation described in the third aspect to prepare a drug for treating chemotherapy-related diarrhea.

[0016] The above technical solution provided by the embodiment of the present application has the following advantages compared with the prior art: The embodiment of the present application provides a Chinese medicine compound related to the treatment of chemotherapy-related diarrhea. The Chinese medicine compound includes, by weight: raw sun-dried ginseng: 15 to 30 parts, astragalus: 20 to 30 parts, angelica: 15 to 20 parts, chuanxiong: 15 to 20 parts, white peony: 15 to 20 parts, stir-fried atractylodes: 15 to 20 parts, poria: 15 to 20 parts, angelica: 15 to 20 parts, gleditsia thorn: 15 to 20 parts, honeysuckle: 15 to 30 parts, roasted licorice: 10 to 20 parts, and platycodon: 10 to 15 parts. According to the clinical experience of the inventors of the present application, combined with the pathogenesis of chemotherapy-related diarrhea, chemotherapy-related diarrhea has the main pathogenesis of "spleen and stomach deficiency" and local "dampness, stasis, heat" and other tangible evil, and the prescription is formulated by using the products of clearing away evil and coordinating with the products of strengthening the body. The ancient famous prescription for sores and ulcers, Tuoli Xiaodu San, is added and subtracted and reasonably matched. In the Chinese medicine compound, astragalus, raw sun-dried ginseng, white atractylodes, poria, and licorice are combined to strengthen the spleen and replenish qi and replenish vital energy, and then combined with angelica to take the combination of astragalus to replenish qi and blood, and Chuanxiong to replenish blood and promote blood circulation. The combination of the two can play the effect of nourishing blood and promoting blood circulation without damaging blood. In addition, the white peony root and angelica in the Chinese medicine compound can replenish blood, relieve urgency and stop abdominal pain, and the Chuanxiong in the Chinese medicine compound can promote qi and promote blood circulation, and It can target local stasis. In addition, the honeysuckle in the Chinese medicine compound can clear away heat and expel pathogenic factors without causing bitter and cold stagnation. The angelica dahurica in the Chinese medicine compound has a fragrant aroma and can also dry out dampness. The sapodilla thorn in the Chinese medicine compound can detoxify and expel pathogenic factors. In addition, the platycodon in the Chinese medicine compound is a navigation agent, and the combination with ginseng, atractylodes, poria and other products can not only enhance the function of expelling pathogenic factors, but also increase the function of stopping diarrhea. In summary, the Chinese medicine compound is consistent with the symptoms and the root causes, which can nourish the spleen and stomach to strengthen the body, and can also clear away pathogenic factors, promote blood circulation and remove blood stasis, clear away heat and dry dampness. In addition, through modern pharmacological research, the Chinese medicine compound of the present invention can achieve the purpose of treating chemotherapy-related diarrhea by regulating inflammatory factors and affecting changes in intestinal flora, thereby filling the gap in the current Chinese medicine compound in treating chemotherapy-related diarrhea. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the present application and, together with the description, serve to explain the principles of the present application.

[0018] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, for ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative labor.

[0019] Figure 1 A schematic flow chart of a method for preparing a Chinese medicine compound provided in an embodiment of the present application; Figure 2A detailed schematic diagram of a method for preparing a Chinese medicine compound provided in an embodiment of the present application; Figure 3 A comparison of mouse colon or jejunal pathological tissue provided in the examples of the present application, wherein: Figure 3 A is the statistical result of weight records of mice in each group. Figure 3 B is the statistical result of diarrhea scores of mice in each group. Figure 3 C is the tumor size results of each group of mice. Figure 3 D is the result graph of tumor growth rate of mice in each group. Figure 3 E is the statistical result of tumor volume of mice in each group. Figure 3 F is the statistical result of tumor weight of mice in each group; Figure 4 This is a diagram of the HE staining results of mouse tumor tissue provided in the examples of this application. DETAILED DESCRIPTION

[0020] In order to make the purpose, technical solution and advantages of the embodiments of the present application clearer, the technical solution in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of this application.

[0021] Various embodiments of the present application may be presented in the form of a range; it should be understood that the description in the form of a range is only for convenience and brevity and should not be understood as a rigid limitation on the scope of the present application; therefore, it should be considered that the range description has specifically disclosed all possible sub-ranges and single numerical values ​​within the range; for example, it should be considered that the range description from 1 to 6 has specifically disclosed sub-ranges, such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as single numbers within the range, such as 1, 2, 3, 4, 5 and 6, which applies regardless of the range; in addition, whenever a numerical range is indicated in this document, it is meant to include any cited numbers (fractions or integers) within the indicated range.

[0022] In this document, the terms including "including" and "including" mean "including but not limited to". Relational terms such as "first" and "second" are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. "And / or" describes the association relationship of associated objects, indicating that there can be three relationships. For example, A and / or B can mean: A exists alone, A and B exist at the same time, and B exists alone; where A and B can be singular or plural. "At least one" means one or more, and "plurality" means two or more; "at least one", "at least one of the following" or similar expressions refer to any combination of these items, including any combination of single or plural items; for example, "at least one of a, b, or c", or "at least one of a, b, and c" can all mean: a, b, c, ab (i.e. a and b), ac, bc, or abc, where a, b, and c can be single or plural. Unless otherwise specified, various raw materials, reagents, instruments and equipment used in this application can be purchased from the market or prepared by existing methods.

[0023] It should be noted that although TCM does not include a corresponding description of CID, based on the symptoms of CID patients and the understanding of the core pathogenesis of the disease, CID can be classified as "diarrhea" in TCM: cancer patients are weak and lack of vital energy, while chemotherapy drugs are bitter and cold, which can easily damage the spleen and stomach in the middle jiao. In addition, the chemotherapy toxicity is foul and turbid in nature, which stagnates in the body, obstructs the qi, disturbs the clear yang, and causes the middle jiao to be blocked, which lays the foundation for the early onset of CID; in addition, chemotherapy drugs are "harsh and aggressive" and will damage the qi and yin, causing intestinal The surface ischemia and necrosis, and there will be blood stasis blocking the meridians, depression and heat loss and body fluids. The three elements of dampness, stasis and heat are intertwined, occupying the middle jiao, blocking qi and blood for a long time, and pain when it is not smooth, which will aggravate the condition and produce variant syndromes; in addition, CID patients are often accompanied by emotional distress during the course of the disease, as the saying goes, "the earth is reached by wood, and the wood depends on the earth to cultivate it." In addition, liver qi is stagnant, and the spleen is weak and healthy, so diarrhea occurs; in addition, after chemotherapy, the positive energy is insufficient, the cancer toxins are not cleared, and the kidneys are affected by the disease for a long time. The kidneys control the two excretions, the spleen and kidney yang are weak, and the control is weak, so the two excretions are not controlled. Therefore, the inventors of this application believe that the basic pathogenesis of CID patients is mostly deficiency of the root and excess of the superficial, with phlegm dampness as the superficial and yang deficiency as the root. The mutual binding of dampness, stasis and heat and the obstruction of the intestinal network are the local pathogenesis of CID, and its location is in the intestines.

[0024] Since patients after chemotherapy have obvious gastrointestinal reactions such as diarrhea, abdominal distension, and vomiting, most of them are located in the spleen and stomach, and chemotherapy drugs cause damage to the intestinal mucosa and inflammatory reactions, just like forming "sores" on the surface of the intestine, resulting in damage to the spleen, abnormal body fluid metabolism, endogenous dampness, downward tendency of dampness, ischemia and necrosis of the intestinal surface, blood stasis blocking the meridians, depression and heat, and dampness, stasis and heat are intertwined. Therefore, the local pathogenesis of chemotherapy-related diarrhea is located in the intestines. Tuoli Xiaodusan is a famous ancient prescription for traditional Chinese medicine to treat surgical sores. The Chinese medicine compound of this application is innovatively used and improved Tuoli Xiaodusan for the characteristics of patients with chemotherapy-related diarrhea, and uses the characteristics of clearing and dispelling evil and strengthening the body in its prescription to reasonably improve the symptoms of abdominal pain and diarrhea in such patients. In addition, it has been confirmed by clinical practical application that the Chinese medicine compound can effectively improve the symptoms of chemotherapy-related diarrhea in patients, and can also affect inflammatory factors and intestinal flora, thereby achieving the therapeutic purpose of improving the quality of life of patients; in addition, it was observed during the treatment process that the Chinese medicine compound has almost no toxic and side effects.

[0025] The present application provides a Chinese medicine compound related to the treatment of chemotherapy-related diarrhea. The Chinese medicine compound comprises, by weight: Raw sun-dried ginseng: 15-30 portions, astragalus: 20-30 portions, angelica: 15-20 portions, chuanxiong: 15-20 portions, white peony: 15-20 portions, stir-fried atractylodes: 15-20 portions, tuckahoe: 15-20 portions, angelica dahurica: 15-20 portions, sapodilla thorn: 15-20 portions, honeysuckle: 15-30 portions, roasted licorice: 10-20 portions, platycodon: 10-15 portions; In these embodiments, in the Chinese medicine compound: raw sun-dried ginseng, also known as ginseng, is warm in nature, sweet and slightly bitter in taste; it enters the heart, lung, spleen, and kidney meridians, and has the effects of greatly replenishing vital energy, restoring pulse and strengthening deficiency, replenishing spleen and lung, and promoting body fluid and calming the mind. Pharmacological effects: it has bidirectional regulation, analgesia, and antipyretic effects on the central nervous system; it has cardiotonic, anti-ischemic, vasodilatory, and hypotensive effects on the cardiovascular system; it protects and stimulates hematopoietic function on the blood system, and has anti-coagulation and anti-thrombotic effects; it has corticotropin-like and gonadotropin-like effects on the endocrine system.

[0026] Astragalus is warm in nature, sweet in taste, and belongs to the lung and spleen meridians. It has the effects of replenishing qi and raising yang, consolidating the exterior and stopping sweating, promoting diuresis and reducing swelling, promoting body fluid and nourishing blood, relieving stagnation and relieving arthritis, expelling toxins and draining pus, and healing sores and promoting tissue regeneration. Pharmacological effects: It has the effects and effects of promoting nucleic acid metabolism; enhancing hematopoietic function; improving myocardial function and resisting myocardial infarction; having antioxidant, antiviral, anticancer effects, and improving renal function and renal tissue pathological changes.

[0027] Poria cocos is sweet, light, and neutral in nature. It enters the heart, lung, spleen, and kidney meridians and has the effects of promoting diuresis and eliminating dampness, strengthening the spleen and calming the mind. Pharmacological effects: It can prevent gastric ulcers, prevent and treat liver damage, and has anti-cancer effects; it can also accelerate heart rate, has diuretic and antibacterial effects, and can improve the body's immune ability.

[0028] Atractylodes macrocephala, bitter and sweet, warm in nature, enters the spleen and stomach meridians, has the effects of strengthening the spleen and replenishing qi, drying dampness and promoting diuresis, stopping sweating, and calming the fetus. Pharmacological effects: It has obvious and lasting antidiuretic effect; it has a two-way regulating effect on the gastrointestinal system and can resist gastric ulcers; it has antispasmodic, liver-protecting, and antibacterial effects.

[0029] Roasted Licorice root is sweet and warm in nature. It enters the heart, lung, stomach and spleen meridians. It has the effects of tonifying the spleen and stomach, replenishing qi and restoring pulse, relieving urgency and detoxifying, and harmonizing various medicines. Pharmacological action: It can treat arrhythmia and viral myocarditis.

[0030] White peony root is sweet and sour in taste and cold in nature. It enters the liver and spleen meridians and has the effects of nourishing blood and regulating menstruation, restraining yin and stopping sweating, softening the liver and relieving pain, and calming liver yang. Pharmacological effects: It has anti-inflammatory and anti-myocardial ischemia pharmacological effects. It has an inhibitory effect on the central nervous system and has the effects of antipyretic, cooling, calming and hypnotic.

[0031] Angelica sinensis is sweet, pungent and bitter in taste and warm in nature. It enters the liver, heart and spleen meridians and has the effects of nourishing blood, regulating menstruation and relieving pain, and moistening the intestines and relieving constipation. Pharmacological effects: It has the effects of reducing platelet aggregation and anti-thrombotic effects; promoting the function of the hematopoietic system; lowering blood lipids and resisting arteriosclerosis; anti-oxidation and scavenging free radicals; enhancing the function of the immune system; inhibiting the nervous system, relaxing tracheal smooth muscles, diuresis, and antibacterial effects.

[0032] Chuanxiong, pungent in taste and warm in nature, enters the liver, gallbladder and pericardium meridians, and has the effects of promoting blood circulation, promoting qi, dispelling wind and relieving pain. Pharmacological effects: It has an inhibitory effect on the heart; it can dilate blood vessels and lower blood pressure; it has a protective effect on myocardial and reperfusion injury; it has the effects of improving the blood system, diuresis, enhancing the immune system, and having anti-tumor and anti-radiation effects.

[0033] Platycodon grandiflorum is bitter and pungent in taste, neutral in nature, and belongs to the lung meridian. It has the effects of clearing the lungs, relieving sore throat, removing phlegm, and draining pus. Pharmacological effects: It has the effects of removing phlegm and relieving cough; it has the effects of anti-inflammatory, anti-ulcer, and vasodilating; it also has the effects of lowering blood sugar, sedation and analgesia, lowering body temperature, lowering cholesterol, anti-edema and diuresis.

[0034] Angelica dahurica is pungent and warm in nature. It enters the stomach, large intestine and lung meridians and has the effects of dispelling wind, drying dampness, reducing swelling and relieving pain. Pharmacological effects: It has an inhibitory effect on many bacteria; it has antipyretic, analgesic and anti-inflammatory effects; it also has the effects of shortening coagulation time, dilating coronary blood vessels and lowering blood pressure.

[0035] Gleditsia sinensis has a pungent taste and warm nature. It enters the liver and stomach meridians and has the effects of reducing swelling, expelling toxins, draining pus and killing insects. Pharmacological action: It has an inhibitory effect on Staphylococcus aureus and Catarrhalis.

[0036] Honeysuckle is cold in nature, sweet in taste, and enters the lung, heart, and stomach meridians. It has the effects of clearing away heat and detoxifying, cooling and dispersing wind-heat. Pharmacological effects: It has the effects of resisting pathogenic microorganisms, anti-toxic, anti-inflammatory, antipyretic, promoting phagocytic function of inflammatory cells, lowering blood lipids, central nervous system excitement, anti-fertility, preventing gastric ulcers, and stimulating the uterus.

[0037] In summary, the Chinese medicine compound related to the treatment of chemotherapy-related diarrhea provided in the embodiment of the present application uses Astragalus and raw sun-dried ginseng as the main medicines, which can achieve the effect of nourishing qi and blood; uses Poria, Atractylodes macrocephala, Angelica sinensis, and Ligusticum chuanxiong as the ministerial medicines, and then uses roasted licorice as the guiding medicine, and then uses white peony root, Atractylodes macrocephala, Angelica dahurica, Gleditsia sinensis, and Platycodon grandiflorum as the adjuvant medicines. Based on the compatibility relationship of these Chinese medicine compounds, it conforms to the meaning of "towards the inside and out of evil", has the effects of strengthening the body and eliminating evil, nourishing the spleen and stomach, clearing away heat and dampness, and promoting blood circulation and removing blood stasis, and has no obvious liver and kidney toxicity, and can be effectively applied to the treatment of chemotherapy-related diarrhea.

[0038] It should be noted that the purchased medicinal materials for this Chinese medicine compound all meet the standards of the Pharmacopoeia of the People's Republic of China.

[0039] In some optional embodiments, the Chinese medicine compound further comprises, by weight: Raw sun-dried ginseng: 25-30 portions, astragalus: 25-30 portions, angelica: 15-18 portions, chuanxiong: 15-18 portions, white peony: 15-18 portions, stir-fried atractylodes: 15-18 portions, tuckahoe: 15-18 portions, angelica dahurica: 15-18 portions, sapodilla thorn: 15-18 portions, honeysuckle: 15-18 portions, roasted licorice: 10-15 portions, platycodon: 10-15 portions; In some optional embodiments, the Chinese medicine compound further comprises, by weight: Raw sun-dried ginseng: 30 parts, astragalus: 30 parts, angelica: 15 parts, chuanxiong: 15 parts, white peony: 15 parts, stir-fried atractylodes: 15 parts, tuckahoe: 15 parts, angelica: 15 parts, sapodilla thorn: 15 parts, honeysuckle: 15 parts, roasted liquorice: 10 parts, platycodon: 10 parts; In these embodiments, the specific proportions of the Chinese medicine compound are refined, wherein raw sun-dried ginseng, chuanxiong, white peony root, astragalus, angelica, atractylodes, poria, honeysuckle, angelica dahurica, licorice, sapodilla thorn, and platycodon all have the effects of invigorating qi and activating blood circulation and clearing away heat and dampness. The Chinese medicine compound combines the functions of invigorating, supporting, and penetrating to achieve the treatment of both the symptoms and the root cause of chemotherapy-related diarrhea. In addition, honeysuckle has broad-spectrum antibacterial, antiviral, antipyretic and anti-inflammatory, and immunomodulatory effects. In addition, sapodilla thorn has multiple pharmacological activities such as anti-inflammatory, immunomodulatory, and anti-tumor. In addition, atractylodes has the function of adjusting gastrointestinal motility and can also repair ulcers to enhance the body's immune function.

[0040] Based on a general inventive concept, such as Figure 1 As shown, the present application embodiment provides a method for preparing the Chinese medicine compound, the method comprising: S1. respectively adding raw sun-dried ginseng, astragalus, angelica, chuanxiong, white peony root, stir-fried atractylodes, Poria, angelica dahurica, Gleditsia sinensis, honeysuckle, roasted licorice and platycodon to distilled water for soaking, then decocting and filtering to obtain a decoction filtrate; S2. The decoction is first heated, and then concentrated under reduced pressure to obtain a Chinese medicine compound liquid.

[0041] This method is a method for preparing the above-mentioned Chinese medicine compound. The specific composition of the Chinese medicine compound can refer to the above-mentioned embodiment. Since this method adopts part or all of the technical solutions of the above-mentioned embodiment, it at least has all the beneficial effects brought by the technical solutions of the above-mentioned embodiment, which will not be repeated here one by one.

[0042] It should be noted that the container used for soaking and decocting can be a casserole.

[0043] It should be noted that the reduced pressure concentration can be performed in a beaker.

[0044] like Figure 2 As shown, in some optional embodiments, the raw sun-dried ginseng, astragalus, angelica, chuanxiong, white peony root, stir-fried atractylodes, tuckahoe, angelica dahurica, thorn of Gleditsia sinensis, honeysuckle, roasted licorice and platycodon grandiflorum are respectively added to distilled water for soaking, and then decocted and filtered to obtain a decoction filtrate, comprising the steps of: S101. respectively, adding raw sun-dried ginseng, astragalus, angelica, chuanxiong, white peony root, stir-fried atractylodes, Poria, angelica dahurica, Gleditsia sinensis, honeysuckle, roasted licorice and platycodon to distilled water for soaking to obtain a mixture; S102. The mixture is subjected to a second heating and a third heating, and then filtered to obtain a decoction liquid and a filter residue, respectively; S103. The filter residue and water are mixed, and then the second heating, the third heating and filtering are performed to obtain a decoction secondary liquid; S104. The first decoction liquid and the second decoction liquid are combined to obtain a decoction filtrate; In these embodiments, the decoction process can use the second heating and the third heating methods, which can effectively decoct the effective components of the Chinese medicine compound, thereby obtaining a sufficient amount of decoction filtrate with Chinese medicine efficacy.

[0045] In some optional embodiments, the first heating temperature is 70° C. to 80° C., and the first heating time is 5 min to 10 min; and / or, The second heating temperature is 110° C. to 120° C., and the second heating time is 8 min to 12 min; and / or, The temperature of the third heating is 80°C to 90°C, and the time of the third heating is 45min to 55min; In these embodiments, the first heating temperature can be 70°C to 80°C, and the first heating time can be 5min to 10min, which can ensure that the decoction has sufficient heat to facilitate the subsequent decompression and concentration to proceed smoothly, thereby ultimately obtaining a Chinese medicine compound liquid with sufficient effective ingredients.

[0046] The second heating temperature can be 110°C to 120°C, and the second heating time can be 8min to 12min. In addition, the third heating temperature can be 80°C to 90°C, and the third heating time can be 45min to 55min. The effective components in the Chinese medicine compound can be effectively extracted by the first heating and the second heating.

[0047] The first heating temperature may be 70°C, 71°C, 72°C, 73°C, 74°C, 75°C, 76°C, 77°C, 78°C, 79°C or 80°C.

[0048] The first heating time can be 5 min, 6 min, 7 min, 8 min, 9 min or 10 min.

[0049] The second heating temperature may be 110°C, 111°C, 112°C, 113°C, 114°C, 115°C, 116°C, 117°C, 118°C, 119°C or 120°C.

[0050] The second heating time can be 8 min, 9 min, 10 min, 11 min or 12 min.

[0051] The third heating temperature may be 80°C, 81°C, 82°C, 83°C, 84°C, 85°C, 86°C, 87°C, 88°C, 89°C or 90°C.

[0052] The third heating time can be 45 min, 46 min, 47 min, 48 min, 49 min, 50 min, 51 min, 52 min, 53 min, 54 min or 55 min.

[0053] In some optional embodiments, the soaking time is 25 min to 35 min; In these embodiments, the soaking time can be 25 minutes to 35 minutes, which can promote the effective mixing of the Chinese medicines in the Chinese medicine compound with the distilled water, thereby facilitating the subsequent decoction and extraction process to ultimately effectively extract the effective components in the Chinese medicine compound.

[0054] The soaking time can be 25 min, 26 min, 27 min, 28 min, 29 min, 30 min, 31 min, 32 min, 33 min, 34 min or 35 min.

[0055] In some optional embodiments, the volume ratio of the distilled water to the water is 2.0 to 3.0; In these embodiments, the volume ratio of distilled water to water may be 2.0 to 3.0, and a double decoction method may be used to effectively extract effective components of the Chinese medicine compound from each Chinese medicine in the Chinese medicine compound.

[0056] The volume ratio of distilled water to water may be 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9 or 3.0.

[0057] Based on a general inventive concept, the embodiment of the present application provides a Chinese medicine preparation related to the treatment of chemotherapy-related diarrhea, wherein the Chinese medicine preparation comprises the Chinese medicine compound and a pharmaceutically acceptable carrier thereof; the Chinese medicine preparation comprises at least one of the following: Chinese herbal decoctions, Chinese herbal granules, Chinese herbal ointments, Chinese herbal capsules, Chinese herbal powders, Chinese herbal pills and Chinese herbal mixtures.

[0058] The Chinese medicine preparation is realized based on the above-mentioned Chinese medicine compound. The specific composition of the Chinese medicine compound can refer to the above-mentioned embodiment. Since the Chinese medicine preparation adopts part or all of the technical solutions of the above-mentioned embodiments, it has at least all the beneficial effects brought by the technical solutions of the above-mentioned embodiments, which will not be described one by one here.

[0059] Based on a general inventive concept, an embodiment of the present application provides an application of a Chinese medicine compound, which includes using the Chinese medicine compound or Chinese medicine preparation to prepare a drug for treating chemotherapy-related diarrhea.

[0060] This application is realized based on the above-mentioned Chinese medicine compound. The specific composition of the Chinese medicine compound can refer to the above-mentioned embodiment. Since this application adopts part or all of the technical solutions of the above-mentioned embodiment, it has at least all the beneficial effects brought by the technical solutions of the above-mentioned embodiment, which will not be described one by one here.

[0061] The present application is further described below in conjunction with specific examples. The experimental methods in the following examples that do not specify specific conditions are usually measured according to industry standards; if there are no corresponding industry standards, they are carried out according to common international standards, conventional conditions, or conditions recommended by the manufacturer. Example 1

[0062] A Chinese medicinal compound related to the treatment of chemotherapy-related diarrhea, comprising, by weight: Raw sun-dried ginseng: 30 parts, astragalus: 30 parts, angelica: 15 parts, chuanxiong: 15 parts, white peony: 15 parts, stir-fried atractylodes: 15 parts, poria: 15 parts, angelica dahurica: 15 parts, gleditsia thorn: 15 parts, honeysuckle: 15 parts, roasted licorice: 10 parts, platycodon: 10 parts.

[0063] like Figure 2 As shown, a method for preparing a Chinese medicine compound comprises: S101. respectively, adding raw sun-dried ginseng, astragalus, angelica, chuanxiong, white peony root, stir-fried atractylodes, Poria, angelica dahurica, Gleditsia sinensis, honeysuckle, roasted licorice and platycodon to distilled water for soaking to obtain a mixture; S102. The mixture is subjected to a second heating and a third heating, and then filtered to obtain a decoction liquid and a filter residue, respectively; S103. The filter residue and water are mixed, and then a second heating, a third heating and filtering are performed to obtain a decoction secondary liquid; S104. The first decoction liquid and the second decoction liquid are combined to obtain a decoction filtrate; S2. The decoction liquid is first heated, and then concentrated under reduced pressure to obtain a Chinese medicine compound liquid.

[0064] The first heating temperature is 70°C to 80°C, and the first heating time is 5min to 10min; The second heating temperature is 110°C to 120°C, and the second heating time is 8min to 12min; The temperature of the third heating is 80° C. to 90° C., and the time of the third heating is 45 min to 55 min.

[0065] The soaking time is 25min to 35min.

[0066] The volume ratio of distilled water to water is 2.0 to 3.0.

[0067] Comparative Example 1 Based on the contents disclosed in Example 1, the following operations are further performed: 5-Fluorouracil was used as the agent.

[0068] Related experiments and effect data: 1. Experimental animals and methods: 1. The experimental animals were male SPF BALB / c mice. After one week of adaptive feeding, they were randomly divided into 7 groups (8 mice in each group): normal group (control), blank group (blank), CID model group (CID), positive control group (Loperamide), Toli Disinfection Powder low-dose group (TLXD-Low), Toli Disinfection Powder medium-dose group (TLXD-Medium), and Toli Disinfection Powder high-dose group (TLXD-High).

[0069] 2. Dosage plan: Tori Disinfection Powder (raw sun-dried ginseng: 30g, astragalus: 30g, angelica: 15g, chuanxiong: 15g, white peony root: 15g, stir-fried atractylodes: 15g, poria: 15g, angelica dahurica: 15g, sapodilla thorn: 15g, honeysuckle: 15g, roasted licorice: 10g, platycodon: 10g), the purchased medicinal materials all meet the standards of the Pharmacopoeia of the People's Republic of China. Weigh the medicinal materials according to the formula, and then concentrate them to a solution containing 1g / mL of crude drug according to the preparation method of Example 1. Preparation of traditional Chinese medicine: Use Biso's original method to convert the animal dose, and calculate the dosage for mice by conversion. The daily oral gavage dose of Tori Disinfection Powder for mice is 0.4g / 10g body weight. The specific dosing operation is as follows: (1) Normal group: no tumor cells were inoculated, no 5-fluorouracil (5-FU) intraperitoneal infusion + 0.9% saline (0.2 mL / 10 g body weight) intragastric infusion; (2) Blank group: inoculated with tumor cells, no 5-fluorouracil (5-FU) intraperitoneal infusion + 0.9% saline (0.2 mL per 10 g body weight) intragastric infusion; (3) CID model group: inoculated with tumor cells, received 5-fluorouracil (5-FU) intraperitoneal infusion + 0.9% saline (0.2 mL / 10 g body weight) gavage; (4) Control group: inoculated with tumor cells, received intraperitoneal infusion of 5-fluorouracil (5-FU) + intragastric gavage of loperamide suspension (0.7 mg / kg body weight); (5) Tuoli Xiaodu San low-dose group: inoculated with tumor cells, received 5-fluorouracil (5-FU) intraperitoneal infusion + Tuoli Xiaodu San (0.2 g / 10 g body weight) gavage; (6) Tuoli Xiaodu San medium-dose group: inoculated with tumor cells, received 5-fluorouracil (5-FU) intraperitoneal infusion + Tuoli Xiaodu San (0.4 g / 10 g body weight) gavage; (7) Toli Disinfection Powder high-dose group: inoculated with tumor cells, received 5-fluorouracil (5-FU) intraperitoneal infusion + Toli Disinfection Powder (0.8 g / 10 g body weight) gavage.

[0070] 3. Tumor measurement and volume calculation: The longest diameter and short diameter of the tumor were measured before modeling, before treatment with Tori Disinfection Powder, and before sacrifice in each group, and the tumor volume was calculated according to the following formula: Tumor volume = long diameter × short diameter × short diameter × 1 / 2.

[0071] 4. During the experiment, the weight and fecal characteristics of the mice were observed and recorded every day, and the scores were scored according to the Bowen scoring standard: 0: normal feces; 1: mildly wet and soft feces (mild diarrhea); 2: unformed feces (moderate diarrhea); 3: watery feces (severe diarrhea). The mice were killed on the 10th day of the experiment to collect the colon and jejunum tissues of the mice. Pathological sections were then made of the intestinal tissues, and the intestinal pathological tissues were evaluated by hematoxylin-eosin (HE staining). The pathological tissue score = intestinal epithelial cell damage score + inflammatory cell infiltration score (as shown in Table 1).

[0072]

[0073] 5. Observation indicators: mouse body weight, diarrhea condition, and histopathological score.

[0074] 2. Experimental results: After the administration, the indexes listed in Table 1 were measured, and the experimental data were expressed as mean ± standard deviation (`X ± s), and statistical analysis was performed. The results are shown in Figure 3 and Figure 4 As shown: like Figure 3 As shown in A, the mice in the blank group gained weight compared with the control group, while the mice in the CID group lost weight compared with the blank group. In addition, the mice in the CID group significantly gained weight after being given low, medium, and high doses of Toli Xiaodusan (see Figure 2). Figure 3 The severity of diarrhea in the CID group was significantly higher than that in the blank group (as shown in A). Figure 3 In addition, the severity of diarrhea in the mice in the low, medium, and high dose groups of loperamide and Toli Xiaodusan was significantly lower than that in the CID mice (as shown in Figure 2A). Figure 3 In addition, the intervention of 5-fluorouracil can significantly reduce the tumor growth rate, tumor volume and weight of CID mice, while the treatment with medium and high doses of Tori Xiaodu San can further inhibit these indicators (as shown in Figure 2A). Figure 3 C to Figure 3 F).

[0075] The results of hematoxylin-eosin (HE) staining showed that the small intestine of the control group and the blank group had normal structure, while the small intestine of the CID group showed mucosal degeneration, necrosis, intestinal gland atrophy and inflammatory cell infiltration (such as Figure 4 In CID mice, the pathological changes shown by HE staining were alleviated, and the intestinal gland atrophy and inflammatory response were improved compared with the untreated group after treatment with loperamide, medium-dose and high-dose Toli Xiaodusan (as shown in Figure 2A). Figure 4 as shown).

[0076] In summary, the Chinese medicine compound related to the treatment of chemotherapy-related diarrhea provided in the embodiment of the present application uses Astragalus and raw sun-dried ginseng as the main medicines, which can achieve the effect of nourishing qi and blood; uses Poria, Atractylodes macrocephala, Angelica sinensis, and Ligusticum chuanxiong as the ministerial medicines, and then uses roasted licorice as the guiding medicine, and then uses white peony root, Atractylodes macrocephala, Angelica dahurica, Gleditsia sinensis, and Platycodon grandiflorum as the adjuvant medicines. Based on the compatibility relationship of these Chinese medicine compounds, it conforms to the meaning of "towards the inside and out of evil", has the effects of strengthening the body and eliminating evil, nourishing the spleen and stomach, clearing away heat and dampness, and promoting blood circulation and removing blood stasis, and has no obvious liver and kidney toxicity, and can be effectively applied to the treatment of chemotherapy-related diarrhea.

[0077] In addition, a Chinese medicine compound related to the treatment of chemotherapy-related diarrhea provided in the embodiment of the present application, based on existing pharmacological studies, astragaloside can increase the content of IL-17 and TNF-α in the colon tissue of mice, while reducing the content of TGF-β, so it can regulate the expression of Foxp3 and ROR-γt proteins and the balance of Th17 / Treg cells to inhibit the inflammatory response of colitis mice. In addition, ginseng can reduce the content of inflammatory cytokines IL-1β, IL-6, IL-17 and IFN-γ in the colon, and can also promote intestinal mucosal regeneration, reduce inflammatory response, and have an inhibitory effect on increased intestinal permeability and bacterial translocation. In addition, honeysuckle has broad-spectrum antibacterial, antiviral, antipyretic and anti-inflammatory, and immunomodulatory effects. And Gleditsia sinensis has multiple pharmacological activities such as anti-inflammatory, immunomodulatory, and anti-tumor. Atractylodes macrocephala has the function of adjusting gastrointestinal motility, and can also repair ulcers and enhance the body's immune function.

[0078] In addition, the application of a Chinese medicine compound related to the treatment of chemotherapy-related diarrhea provided in the embodiment of the present application can achieve systemic conditioning of the patient based on the holistic treatment of the Chinese medicine compound. In addition, the Chinese medicine compound is convenient to be prepared into a variety of dosage forms together with a variety of pharmaceutical carriers, which can improve the convenience of clinical use, and has the advantages of reliable efficacy, safe use and high patient dependence.

[0079] The above is only a specific implementation of the present application, so that those skilled in the art can understand or implement the present application. It will be apparent to those skilled in the art that various modifications to these embodiments are possible, and the general principles defined in the present application can be implemented in other embodiments without departing from the spirit or scope of the present application. Therefore, the present application will not be limited to these embodiments shown in the present application, but will conform to the widest scope consistent with the principles and novel features applied for by the present application.

Claims

1. A Chinese medicinal compound related to the treatment of chemotherapy-related diarrhea, characterized in that: In parts by weight, the Chinese medicine compound comprises: Raw sun-dried ginseng: 15 to 30 portions, astragalus: 20 to 30 portions, angelica: 15 to 20 portions, chuanxiong: 15 to 20 portions, white peony: 15 to 20 portions, stir-fried atractylodes: 15 to 20 portions, poria: 15 to 20 portions, angelica dahurica: 15 to 20 portions, sapodilla thorn: 15 to 20 portions, honeysuckle: 15 to 30 portions, roasted licorice: 10 to 20 portions, platycodon: 10 to 15 portions.

2. The Chinese medicinal compound according to claim 1, characterized in that: In parts by weight, the Chinese medicine compound further comprises: Raw sun-dried ginseng: 25 to 30 portions, astragalus: 25 to 30 portions, angelica: 15 to 18 portions, chuanxiong: 15 to 18 portions, white peony: 15 to 18 portions, stir-fried atractylodes: 15 to 18 portions, poria: 15 to 18 portions, angelica dahurica: 15 to 18 portions, gleditsia thorn: 15 to 18 portions, honeysuckle: 15 to 18 portions, roasted licorice: 10 to 15 portions, platycodon: 10 to 15 portions.

3. The Chinese medicinal compound according to claim 2, characterized in that: In parts by weight, the Chinese medicine compound further comprises: Raw sun-dried ginseng: 30 parts, astragalus: 30 parts, angelica: 15 parts, chuanxiong: 15 parts, white peony: 15 parts, stir-fried atractylodes: 15 parts, poria: 15 parts, angelica dahurica: 15 parts, gleditsia thorn: 15 parts, honeysuckle: 15 parts, roasted licorice: 10 parts, platycodon: 10 parts.

4. A method for preparing the Chinese medicinal compound according to any one of claims 1 to 3, characterized in that: The method comprises: Adding raw sun-dried ginseng, astragalus, angelica, chuanxiong, white peony root, stir-fried atractylodes, tuckahoe, angelica dahurica, thorn of Gleditsia sinensis, honeysuckle, roasted licorice and platycodon grandiflorum into distilled water for soaking, and then decocting and filtering to obtain decoction filtrate; The decoction is first heated and then concentrated under reduced pressure to obtain a Chinese medicine compound liquid.

5. The method according to claim 4, characterized in that The method comprises the following steps: adding raw sun-dried ginseng, astragalus, angelica, chuanxiong, white peony root, stir-fried atractylodes, tuckahoe, angelica dahurica, thorn of Gleditsia sinensis, honeysuckle, roasted liquorice and platycodon grandiflorum to distilled water for soaking, and then decocting and filtering to obtain a decoction filtrate. The method comprises the following steps: Adding raw sun-dried ginseng, astragalus, angelica, chuanxiong, white peony root, stir-fried atractylodes, tuckahoe, angelica dahurica, thorn of Gleditsia sinensis, honeysuckle, roasted liquorice and platycodon grandiflorum to distilled water for soaking respectively to obtain a mixture; The mixture is subjected to a second heating and a third heating, and then filtered to obtain a decoction liquid and a filter residue, respectively; The filter residue and water are mixed, and then the second heating, the third heating and filtering are performed to obtain a decoction secondary liquid; The first decoction liquid and the second decoction liquid are combined to obtain a decoction filtrate.

6. The method according to claim 5, characterized in that The first heating temperature is 70° C. to 80° C., and the first heating time is 5 min to 10 min; and / or, The second heating temperature is 110° C. to 120° C., and the second heating time is 8 min to 12 min; and / or, The temperature of the third heating is 80° C. to 90° C., and the time of the third heating is 45 min to 55 min.

7. The method according to claim 4, characterized in that The soaking time is 25 min to 35 min.

8. The method according to claim 4, characterized in that The volume ratio of the distilled water to the water is 2.0 to 3.

0.

9. A Chinese medicine preparation related to the treatment of chemotherapy-related diarrhea, characterized in that: The Chinese medicine preparation comprises the Chinese medicine compound according to any one of claims 1 to 3 and a pharmaceutically acceptable carrier thereof; the Chinese medicine preparation comprises at least one of the following: Chinese herbal decoctions, Chinese herbal granules, Chinese herbal ointments, Chinese herbal capsules, Chinese herbal powders, Chinese herbal pills and Chinese herbal mixtures.

10. An application of a Chinese medicine compound, characterized in that: The application includes using the Chinese medicine compound according to any one of claims 1 to 3 or the Chinese medicine preparation according to claim 9 to prepare a drug for treating chemotherapy-related diarrhea.

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