Traditional Chinese medicine composition for treating diarrhea-type irritable bowel syndrome

Abstract

The invention relates to the technical field of traditional Chinese medicines, and discloses a traditional Chinese medicine composition for treating diarrhea-type irritable bowel syndrome. The traditional Chinese medicine composition comprises 4-16 g of codonopsis pilosula, 4-16 g of roasted rhizoma atractylodis macrocephalae, 3-12 g of fructus psoraleae, 2-8 g of galangal, 3-12 g of poria cocos, 4-16 g of white hyacinth bean, 2-8 g of elecampane, 3-12 g of corydalis tuber and 2-8 g of honey-fried licorice root. The traditional Chinese medicine composition provided by the invention has the effects of tonifying spleen, clearing damp, warming middle-jiao, stopping diarrhea and the like, and can obviously improve clinical symptoms of IBS-D patients and model animals, specifically, the clinical symptoms are improved, the water content of excrement is reduced, and visceral hypersensitivity is relieved.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a traditional Chinese medicine composition for treating diarrhea-predominant irritable bowel syndrome. Background Technology

[0002] Irritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder closely related to poor lifestyle and dietary habits, mental stress, and work-related tension. Clinically, it is characterized by recurrent episodes of abdominal pain, bloating, and discomfort, accompanied by abnormal bowel movements or changes in bowel habits. Based on clinical manifestations, IBS is usually classified into diarrhea-predominant, constipation-predominant, mixed, and indeterminate types, with diarrhea-predominant IBS-D being more common in my country. This disease is characterized by a prolonged course and high relapse rate, significantly impacting patients' quality of life and mental health.

[0003] The pathogenesis of IBS in modern medicine is not fully understood. Studies suggest that potential mechanisms may include visceral hypersensitivity, gastrointestinal motility abnormalities, brain-gut axis dysregulation, gut microbiota imbalance, and immune-neurological abnormalities caused by low-grade gut inflammation. Among these, gut microbiota dysbiosis is considered a key factor in the pathogenesis of IBS-D. Currently, Western medicine treatment for IBS-D mainly relies on drug therapy and non-drug therapy, but both have significant limitations.

[0004] Drug treatments vary in their focus, but most aim to alleviate a particular symptom or aspect, treating the symptoms rather than the root cause. This approach has limitations, as it targets only a single point of attack and cannot cover all the pathological mechanisms of IBS-D. For example, antidiarrheals target diarrhea symptoms, antispasmodics target spasmodic abdominal pain, antidepressants target mood and pain modulation, and probiotics regulate gut microbiota. However, none of these drugs can address the multi-faceted pathological changes of the disease. Specifically, while antispasmodics can relieve abdominal pain, their improvement on symptoms such as diarrhea is limited, and they have side effects. Antidiarrheals can relieve diarrhea, but they are ineffective for symptoms such as abdominal pain and intestinal hypersensitivity, and long-term use may lead to constipation. While probiotics can improve symptoms in some patients by regulating the gut microbiota, their efficacy varies significantly due to differences in strain selection and dosage, and they cannot address the core pathological mechanisms of IBS-D. Although antidepressants are effective for some patients, they mainly regulate neurotransmitters and fail to address deeper issues such as intestinal dysfunction and dysbiosis. At the same time, long-term use of many drugs may lead to side effects, or even drug resistance and drug dependence, making it difficult for patients to tolerate continuous treatment. In addition, some drugs, such as 5-HT receptor antagonists, have certain efficacy, but their use is limited due to side effects or drug resistance.

[0005] Non-pharmacological therapies primarily focus on lifestyle interventions, including dietary adjustments, exercise, and psychotherapy. While these interventions are relatively safe and can improve some symptoms, especially bloating and psychological stress, their effects are usually mild and vary from person to person. For example, a low-FODMAP diet can alleviate symptoms, but long-term adherence is poor and it is not universally applicable to all patients. Exercise and psychotherapy can improve overall health, but primarily address emotional issues such as anxiety and depression, with limited direct impact on bowel function. It is noteworthy that the improvement from lifestyle interventions is often less rapid and significant than that from medication. Different studies have shown significant individual differences and inconsistencies in the effects of dietary, exercise, and psychotherapy interventions, lacking high-quality, large-sample evidence-based data to support unified guidelines. Many patients only achieve partial relief and require medication to control all symptoms. In general, lifestyle adjustments focus on regulation, with limited improvement. They are more about reducing the risk of relapse and regulating the body's overall balance than a fundamental treatment for the cause of IBS-D. Due to the lack of direct action on the core mechanisms of the disease, lifestyle changes alone are unlikely to completely reverse the course of IBS-D.

[0006] In summary, most current Western medicine treatments for IBS-D can only temporarily relieve symptoms, and long-term treatment is highly dependent on these treatments, with a high relapse rate. Therefore, there is an urgent need to find new, effective, and safe treatment methods. Furthermore, there is a need for a multi-mechanism, multi-target treatment plan that can comprehensively regulate intestinal function, flora, and the neuroimmune system to fundamentally improve the symptoms and quality of life of IBS-D patients. Summary of the Invention

[0007] The traditional Chinese medicine composition provided in this application has the effects of strengthening the spleen and removing dampness, warming the middle and stopping diarrhea, and can significantly improve the clinical symptoms of IBS-D patients and model animals, specifically by improving weight loss, reducing fecal water content, and alleviating visceral hypersensitivity. Therefore, the traditional Chinese medicine composition provided in this application is expected to provide a new treatment method for the clinical diagnosis and treatment of IBS-D.

[0008] On one hand, the present invention provides a traditional Chinese medicine composition comprising 4-16g of Codonopsis pilosula, 4-16g of stir-fried Atractylodes macrocephala, 3-12g of Psoralea corylifolia, 2-8g of Alpinia officinarum, 3-12g of Poria cocos, 4-16g of Dolichos lablab, 2-8g of Aucklandia lappa, 3-12g of Corydalis yanhusuo, and 2-8g of prepared Glycyrrhiza uralensis.

[0009] Furthermore, the traditional Chinese medicine composition consists of 4-16g of Codonopsis pilosula, 4-16g of stir-fried Atractylodes macrocephala, 3-12g of Psoralea corylifolia, 2-8g of Alpinia officinarum, 3-12g of Poria cocos, 4-16g of Dolichos lablab, 2-8g of Aucklandia lappa, 3-12g of Corydalis yanhusuo, and 2-8g of prepared Glycyrrhiza uralensis.

[0010] Furthermore, in the formulation of the traditional Chinese medicine composition, the mass ratio of Codonopsis pilosula and stir-fried Atractylodes macrocephala is 1:1.

[0011] Furthermore, the formulation of the traditional Chinese medicine composition includes 8g of Codonopsis pilosula, 8g of stir-fried Atractylodes macrocephala, 6g of Psoralea corylifolia, 4g of Alpinia officinarum, 6g of Poria cocos, 8g of Dolichos lablab, 4g of Aucklandia lappa, 6g of Corydalis yanhusuo, and 4g of prepared Glycyrrhiza

[0012] Furthermore, the traditional Chinese medicine composition consists of 8g of Codonopsis pilosula, 8g of stir-fried Atractylodes macrocephala, 6g of Psoralea corylifolia, 4g of Alpinia officinarum, 6g of Poria cocos, 8g of Dolichos lablab, 4g of Aucklandia lappa, 6g of Corydalis yanhusuo, and 4g of prepared Glycyrrhiza uralensis.

[0013] Furthermore, the dosage form of the traditional Chinese medicine composition includes tablets, capsules, powders, pills, granules, oral liquids, syrups, or decoctions.

[0014] Furthermore, the dosage of the traditional Chinese medicine composition is 4.10-9.40 g / kg / day.

[0015] On the other hand, the present invention provides the application of the above-mentioned traditional Chinese medicine composition in the preparation of a medicament for treating diarrhea-predominant irritable bowel syndrome.

[0016] On the other hand, the present invention provides a traditional Chinese medicine preparation, the components of which include the above-mentioned traditional Chinese medicine composition and optionally one or more pharmaceutically acceptable excipients.

[0017] Further, the pharmaceutically acceptable excipients are selected from at least one of the following pharmaceutically acceptable solvents, solubilizers, co-solvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, flow aids, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesives, binding agents, penetration enhancers, pH adjusters, buffers, plasticizers, surfactants, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and anti-flocculation agents, filter aids, release inhibitors, polymeric framework materials, and film-forming materials.

[0018] The technical solution of this invention has the following advantages:

[0019] (1) The diseases and scope of the traditional Chinese medicine composition provided in this application are the current clinical "pain points".

[0020] Because the etiology of IBS-D is not fully understood and involves multiple factors, including intestinal motility disorders, visceral hypersensitivity, and gut microbiota imbalance, treatment is complex and difficult. Current Western medicine treatments for IBS-D include antispasmodics, antidiarrheals, antidepressants, and probiotics; however, these medications are mostly symptomatic treatments and rarely address the underlying cause. Furthermore, long-term use of Western medicines suffers from unstable efficacy, high dependence, significant side effects, and a high relapse rate after discontinuation.

[0021] The traditional Chinese medicine (TCM) composition used in this application consists entirely of natural Chinese herbs. This TCM composition exhibits unique advantages in the treatment of IBS-D, specifically including its emphasis on holistic regulation. It improves patient symptoms and constitution through multi-pathway and multi-target intervention, simultaneously acting on multiple systems such as the immune, nervous, endocrine, and gut microbiota. TCM intervention is significantly effective in relieving IBS-D symptoms such as diarrhea and abdominal pain, and reducing recurrence, with relatively few adverse reactions. The multi-target comprehensive efficacy of TCM's syndrome differentiation and treatment compensates for the shortcomings of single-action Western medicine, providing a safe and effective treatment option for IBS-D patients.

[0022] (2) The traditional Chinese medicine composition provided in this application makes it an ideal new option for the treatment of IBS-D through multi-target action.

[0023] Based on the core pathogenesis of IBS-D (spleen deficiency with dampness), this application developed this formula, with the main effects of strengthening the spleen, eliminating dampness, warming the middle jiao, and stopping diarrhea. The formula consists of Codonopsis pilosula, Atractylodes macrocephala, Psoralea corylifolia, Alpinia officinarum, Poria cocos, Dolichos lablab, Aucklandia lappa, Corydalis yanhusuo, and Glycyrrhiza uralensis (processed), which work together to strengthen the spleen and replenish qi, warm the middle jiao and resolve dampness, regulate qi and relieve pain, thereby specifically improving diarrhea symptoms caused by spleen deficiency and impaired digestion in IBS-D patients. This formula originates from clinical practice and has a solid foundation in traditional Chinese medicine theory. Preliminary application observations have also indicated its good efficacy in IBS-D (spleen deficiency with dampness syndrome), laying the foundation for further in-depth research. This formula originates from traditional Chinese medicine theory, combined with modern pharmacological research, and uses natural plant materials, meeting the modern demand for natural therapies and safe treatments. Its effects are mild, natural, and relatively non-toxic. Compared to chemical drugs, its metabolic process in the body is gentler, significantly reducing the risk of toxic side effects and adverse reactions. This formula has multiple effects, including regulating the spleen and stomach, removing dampness and turbidity, regulating qi and promoting blood circulation. It can also regulate intestinal flora, promote the proliferation of beneficial bacteria and inhibit the growth of harmful bacteria. It shows broad applicability in the treatment of IBS-D, providing a safer and more effective treatment method for clinical practice.

[0024] (3) The traditional Chinese medicine composition provided in this application is set with a principal drug ratio of 1:1 to improve efficacy.

[0025] In the traditional Chinese medicine composition provided in this application, Codonopsis pilosula and stir-fried Atractylodes macrocephala are combined in a 1:1 weight ratio as the principal herbs in the entire formula. The two herbs work synergistically, forming the core pillar of the entire formula. The formulation strategy of this traditional Chinese medicine composition embodies the principle of emphasizing both tonifying Qi and drying dampness: the aforementioned 1:1 weight ratio ensures a balanced and synergistic effect between the two fundamental therapeutic functions of Codonopsis pilosula ("tonifying Qi") and stir-fried Atractylodes macrocephala ("drying and eliminating dampness"), achieving the therapeutic effect of tonifying without stagnation and drying without damaging Yin, jointly restoring the core physiological function of the spleen in transportation and transformation; it also embodies the principle of balancing the ascending of clear Qi and the consolidation of Qi: Codonopsis pilosula can help the clear Yang ascend, while stir-fried Atractylodes macrocephala can astringe the sinking Qi. The two herbs, one ascending and one consolidating, reverse the core pathogenesis of diarrhea from different dimensions of action. This 1:1 weight ratio is a key technical feature for synergistic effect: compared to the conventional method of adjusting the dosage of Codonopsis pilosula or stir-fried Atractylodes macrocephala according to symptoms, this fixed ratio has been proven to produce the best synergistic effect, which is the core technical guarantee for maximizing the overall therapeutic effect of "strengthening the spleen and eliminating dampness".

[0026] (4) The mechanism of action of the traditional Chinese medicine composition provided in this application in treating diarrhea-predominant irritable bowel syndrome is related to the reshaping of the intestinal microecological balance.

[0027] Animal experiments further confirmed the therapeutic effect of this formula. In an IBS-D model induced by maternal-infant separation, restraint stress, and senna gavage in newborn mice, intervention with this formula significantly improved diarrhea symptoms and visceral hypersensitivity in mice. Specifically, the general condition of the model mice improved, and the trend of weight loss was alleviated; the severity of diarrhea was significantly reduced, fecal water content decreased, and diarrhea scores were significantly lower; the abdominal retraction response (AWR) score was significantly lower than that of the model group, indicating a reduction in visceral hypersensitivity symptoms. Experiments using NMS, RS, and senna gavage to construct an IBS-D mouse model also showed that this formula could significantly alleviate symptoms such as diarrhea and abdominal pain in mice and improve intestinal function. The above studies demonstrate that the traditional Chinese medicine composition provided in this application can effectively alleviate diarrhea and intestinal hypersensitivity in the IBS-D model and has a definite therapeutic effect.

[0028] Metagenomic analysis revealed the mechanism of action of this formula in regulating the gut microbiota. High-throughput sequencing comparing the gut microbiota structure before and after treatment showed that this formula could correct the gut microbiota dysbiosis in IBS-D model mice: increased gut microbial diversity and richness, and improved probiotic flora. Lactobacillus_johnsonii Relative abundance increased, harmful bacteria Heminiphilus_faecisThe gut microbiota composition was restored to a healthy state after suppression. Further mechanistic studies revealed that this formula can regulate the gut microbiota, specifically by increasing the abundance of probiotics, inhibiting the growth of harmful bacteria, and restoring the diversity and health of the gut microbiota, thereby improving the negative impact of gut microbiota imbalance on IBS-D. These results suggest that this formula exerts its therapeutic effect by regulating the gut microbiota, and that improving the gut microbiota is crucial for alleviating IBS-D symptoms. In conclusion, this formula can effectively suppress the intestinal symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D) and reduce visceral sensitivity. Its mechanism of action is related to regulating gut microbiota homeostasis, providing a new approach and strategy for targeted treatment of IBS-D. Attached Figure Description

[0029] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0030] Figure 1 This is a graph showing the Bristol score results of feces in each group of mice, where compared with the control group, P < 0.01; Compared with the model group, ##P < 0.01, #P < 0.05; Figure 2 This is a graph showing the fecal water content of each group of mice, with the result compared to the control group. P<0.01; compared with the model group, ##P<0.01, #P<0.05.

[0031] Figure 3 This is a graph showing the visceral sensitivity scores of mice in each group, with the results compared to the control group. P < 0.01; Compared with the model group, ##P < 0.01, #P < 0.05; Figure 4 The figure shows the effect of this formula on the alpha diversity of gut microbiota in IBS-D mice. Compared with the model group, #P<0.05. Figure 5 This is a graph showing the impact of the gut microbiota Beta diversity on IBS-D mice. Figure 6 This describes the effect of this formula on the species composition of the gut microbiota at the phylum level in IBS-D mice; Figure 7 This describes the effect of this formula on the species composition of the gut microbiota in IBS-D mice at the genus level. Figure 8 This describes the effect of this formula on the species composition of the gut microbiota in IBS-D mice at the species level. Figure 9 This figure shows the results of our analysis of the gut microbiota at the species level in IBS-D mice. In this figure, A represents the differentially expressed species by the Kruskal-Wallis rank-sum test, and B represents the differentially expressed species by the LEfSe discriminant analysis. Detailed Implementation

[0032] The following embodiments are provided to better understand the present invention, but the following embodiments do not constitute a limitation on the content and scope of protection of the present invention. Any product that is the same as or similar to the present invention, derived by any person under the guidance of the present invention or by combining the features of the present invention with other prior art, falls within the scope of protection of the present invention.

[0033] Unless otherwise specified, the experimental steps or conditions in the examples were performed in accordance with conventional experimental procedures and conditions in the art. Reagents or instruments whose manufacturers are not specified are all commercially available products.

[0034] Reagents and instruments used in the examples: Hematoxylin staining solution, eosin staining solution, hematoxylin differentiation solution and hematoxylin blueing solution were purchased from Wuhan Saiwei Company; Neutral formalin fixative and bovine serum albumin were purchased from Solarbio. Anhydrous ethanol was purchased from Sinopharm Group; Xylene was purchased from Shanghai Maclean; The magnetic bead method for extracting genomic DNA from soil and feces was purchased from Shanghai Meiji Biomedical Technology Co., Ltd. The agarose was purchased from Thermo Scientific. The NEXTFLEX Rapid DNA-Seq library preparation kit was purchased from Bioo Scientific.

[0035] Example 1. A traditional Chinese medicine composition for treating diarrhea-predominant irritable bowel syndrome. This embodiment provides a traditional Chinese medicine composition for treating diarrhea-predominant irritable bowel syndrome, which consists of 4-16g of Codonopsis pilosula, 4-16g of stir-fried Atractylodes macrocephala, 3-12g of Psoralea corylifolia, 2-8g of Alpinia officinarum, 3-12g of Poria cocos, 4-16g of Dolichos lablab, 2-8g of Aucklandia lappa, 3-12g of Corydalis yanhusuo, and 2-8g of prepared Glycyrrhiza uralensis.

[0036] The preparation method of the above-mentioned traditional Chinese medicine composition for treating diarrhea-predominant irritable bowel syndrome involves weighing the medicinal materials according to the formula ratio, adding 10 times the mass of purified water, and soaking for 2 hours. Then, the soaked medicinal materials are heated to boiling, maintained at a gentle boil for 1 hour, and filtered while hot, collecting the first filtrate. Next, 8 times the mass of purified water is added to the residue, heated to boiling, maintained at a gentle boil for 3 hours, filtered, and the second filtrate is collected. The two filtrates are combined, and the combined filtrate is concentrated to a relative density of 1.15 to obtain the traditional Chinese medicine composition.

[0037] Theoretical Basis: Diarrhea-predominant irritable bowel syndrome (IBS-D), based on its clinical characteristics, falls under the categories of "diarrhea" and "abdominal pain" in Traditional Chinese Medicine (TCM). The core pathogenesis of this disease is closely related to the function of the spleen and stomach. As Zhang Jiebin, a physician of the Ming Dynasty, stated, "The root of diarrhea lies in the spleen and stomach," emphasizing that the spleen governs the transformation and transportation of food and water. If the spleen's yang energy is damaged, its transformation and transportation functions are impaired, leading to dysfunction in the small intestine's transformation of food and separation of clear and turbid substances, resulting in disordered large intestine transmission, inability to separate clear and turbid substances, and thus diarrhea. Dampness is both an important pathogenic factor in this disease and a pathological product of spleen qi deficiency. Therefore, the occurrence of IBS-D is closely related to spleen deficiency and dampness excess. The TCM composition provided in this embodiment uses strengthening the spleen and eliminating dampness as the basic principle of treatment.

[0038] Explanation: Based on years of clinical practice and systematic research in traditional Chinese medicine theory, this embodiment believes that the core pathogenesis of diarrhea-predominant irritable bowel syndrome lies in the deficiency and cold of the middle jiao (middle burner), with spleen qi deficiency as the root cause and internal dampness accumulation as the manifestation. When the spleen is weak, the clear yang fails to ascend, leading to impaired transportation and transformation. The essence of food and water mixes with dampness and descends, resulting in diarrhea. The qi mechanism in the middle jiao is obstructed, causing pain due to stagnation, hence the abdominal pain and distension. Based on this pathogenesis, this invention provides a traditional Chinese medicine composition with the fundamental treatment principle of "strengthening the spleen, eliminating dampness, warming the middle jiao, and stopping diarrhea."

[0039] This traditional Chinese medicine composition consists of nine herbs: Codonopsis pilosula, stir-fried Atractylodes macrocephala, Psoralea corylifolia, Alpinia officinarum, Poria cocos, Dolichos lablab, Aucklandia lappa, Corydalis yanhusuo, and prepared Glycyrrhiza uralensis. The entire formula follows the principle of "principal, assistant, adjuvant, and guide," with rigorous rules and a clear approach.

[0040] The principal herbs (strengthening the spleen and replenishing qi, the key to treating the root cause) are Codonopsis pilosula and stir-fried Atractylodes macrocephala: Codonopsis pilosula is sweet and neutral in nature, and enters the spleen and lung meridians. It is a key herb for tonifying the middle jiao and replenishing qi, specializing in supporting the spleen and stomach, and replenishing the middle jiao qi. It can strengthen the spleen and stomach and promote the ascent of clear qi, which is the source of treating the root cause. Stir-fried Atractylodes macrocephala is bitter, sweet, and warm, and enters the spleen and stomach meridians. It is good at replenishing qi and strengthening the spleen, drying dampness and promoting diuresis. After stir-frying, its warming and drying properties are enhanced, focusing more on consolidating the middle jiao and removing internal dampness, making it an excellent product for strengthening the spleen and stopping diarrhea. After repeated clinical verification and experimental optimization, this invention establishes Codonopsis pilosula and stir-fried Atractylodes macrocephala in a 1:1 weight ratio as the principal herbs. The two complement each other, forming the core pillar of the entire formula: the formula emphasizes both tonifying qi and drying dampness. This ratio ensures the balance and synergy of the two fundamental treatment forces of "tonifying spleen qi" (Codonopsis pilosula) and "drying away dampness" (Atractylodes macrocephala), tonifying without causing stagnation and drying without harming yin, together restoring the spleen's core function of transportation and transformation; it also balances ascending yang and consolidating yang, with Codonopsis pilosula helping yang to rise and Atractylodes macrocephala consolidating yang to astringe downward, one ascending and one consolidating, reversing the pathogenesis of diarrhea from different dimensions; and it has a synergistic effect, compared to simply increasing the dosage of a single principal herb, the fixed ratio of 1:1 has been proven to produce the best synergistic effect, which is the key technical feature for maximizing the overall efficacy of "strengthening the spleen and removing dampness".

[0041] Assistant Herbs (Warming and Assisting the Middle Jiao, Strengthening the Principal Herb) – Psoralea corylifolia and Alpinia galanga: Psoralea corylifolia is bitter, pungent, and very warm, entering the kidney and spleen meridians. It has the effects of tonifying the kidney and strengthening yang, warming the spleen and stopping diarrhea. This formula takes advantage of its "tonifying fire to generate earth" principle, warming and tonifying the kidney's primordial yang to warm the spleen earth, fundamentally addressing the source of spleen cold, and providing warming power for the principal herb to strengthen the spleen. Alpinia galanga is pungent and hot, entering the spleen and stomach meridians. It excels at dispelling cold, warming the middle jiao, relieving pain, and stopping vomiting. Its pungent and hot nature directly targets the affected area, quickly relieving abdominal pain caused by cold stagnation in the middle jiao, and enhancing the overall warming and dispelling cold effect of the formula. The combination of the two herbs, one (Psoralea corylifolia) warms the kidney to warm the spleen, treating the root cause; the other (Alpinia galanga) warms the middle jiao to dispel cold, treating the symptoms, together assisting the principal herb and strengthening the effect of warming the middle jiao and stopping diarrhea.

[0042] The adjuvant herbs (resolving dampness and promoting qi circulation, addressing both symptoms and root causes) are: Poria cocos, white hyacinth bean, costus root, and corydalis rhizome. Poria cocos and white hyacinth bean: Together, they strengthen the spleen and resolve dampness. Poria cocos is sweet and bland, promoting diuresis and eliminating dampness through urination, embodying the ancient principle of "promoting urination to solidify stool." White hyacinth bean is sweet and warm, strengthening the spleen and resolving dampness without being overly drying, aiding digestion and harmonizing the middle jiao. These two herbs assist the principal herb in thoroughly clearing internal dampness. Costus root and corydalis rhizome: These two are key to harmonizing qi and blood. Costus root is pungent and bitter, effectively clearing stagnant qi in the spleen and stomach, making it an essential herb for promoting qi circulation and relieving pain. Corydalis rhizome is pungent and warm, able to move qi stagnation in the blood, specifically for promoting blood circulation and relieving pain. When these two herbs are combined, qi flows, blood flows, and blood flows, pain stops, effectively targeting the core symptoms of IBS-D: abdominal pain and bloating.

[0043] The guiding herb (harmonizing the other herbs) is prepared licorice root. Prepared licorice root is sweet and neutral in nature. On the one hand, it tonifies the spleen and stomach, assisting the principal herb in replenishing qi; on the other hand, it harmonizes the cold, hot, warm, and cool properties of the other herbs in the formula, allowing the entire formula to work synergistically without producing any imbalance. This is why it is the guiding herb.

[0044] The Codonopsis pilosula - stir - fried Atractylodes macrocephala in a 1:1 compatibility for the whole formula serves as the monarch drug, laying a solid foundation for strengthening the spleen and removing dampness; Psoralea corylifolia - Alpinia officinarum serves as the ministerial drug, providing the core impetus for warming the middle - jiao and dispelling cold; Poria cocos - Dolichos lablab are used as adjuvant drugs to transform dampness and promote the function of the spleen in transportation, and Aucklandia lappa - Corydalis yanhusuo promote qi circulation and activate blood circulation to relieve pain; finally, roasted Glycyrrhiza uralensis is used to harmonize all the drugs. The combination of these drugs can jointly achieve the effects of strengthening the spleen and replenishing qi, warming the middle - jiao and dispelling cold, transforming dampness and stopping diarrhea, promoting qi circulation and relieving pain, treating both the symptoms and the root causes, closely targeting the pathogenesis, and is an accurate treatment plan for diarrhea - predominant irritable bowel syndrome with spleen qi deficiency and internal retention of damp pathogens.

[0045] Experimental Example 1. Verification of the efficacy of a traditional Chinese medicine composition for treating diarrhea - predominant irritable bowel syndrome 1. Experimental animals Forty - eight healthy SPF - level C57BL / 6 mice, 2 days old, were purchased from Beijing Sparf Bioscience Co., Ltd. The experimental animal license number is SCKK (Beijing) 2019 - 0010. They were housed in a SPF - level animal breeding room of Mediconnect. The light in the breeding room alternates between day (12 h) and night (12 h), the temperature is 20 - 24 °C, and the relative humidity is 50% - 60%.

[0046] 2. Experimental drugs The experimental drugs were divided into a positive drug group, a traditional Chinese medicine group, a model group, and a blank group according to the experimental design. The grouping is as follows: Model group and blank group: Administered distilled water by gavage at a dose of 1 mL / 100 g body weight of the mouse, once a day, continuously for 2 weeks. <…>Positive drug group: Pinaverium bromide tablets (Naitenan, abbreviated as PBT) were purchased from the Western Pharmacy of Dongfang Hospital, Beijing University of Chinese Medicine (Fuyuan Medicine, 50 mg, batch number: H33036); According to the conversion of the body surface area of humans and mice to calculate the dosing dose, pinaverium bromide in the positive drug group was administered by gavage at a dose of 20 mg / kg / d, once a day, continuously for 2 weeks of treatment. Traditional Chinese medicine group: Provided by the granule pharmacy of Dongfang Hospital, Beijing University of Chinese Medicine. The traditional Chinese medicine group was divided into Traditional Chinese Medicine Group 1 - Traditional Chinese Medicine Group 8 according to different prescriptions, specifically as follows: Traditional Chinese Medicine Group 1 (core dose group): Administration method: Administered by gavage at a dose of 8.19 g / kg / d. Prescription: Codonopsis pilosula 8 g, stir - fried Atractylodes macrocephala 8 g, Psoralea corylifolia 6 g, Alpinia officinarum 4 g, Poria cocos 6 g, Dolichos lablab 8 g, Aucklandia lappa 4 g, Corydalis yanhusuo 6 g, roasted Glycyrrhiza uralensis 4 g.

[0047] Traditional Chinese Medicine Group 2 (Codonopsis pilosula: Atractylodes macrocephala = 2:1): Administration method: Administered by gavage at a dose of 9.40 g / kg / d. Prescription: Codonopsis pilosula 16 g, stir - fried Atractylodes macrocephala 8 g, Psoralea corylifolia 6 g, Alpinia officinarum 4 g, Poria cocos 6 g, Dolichos lablab 8 g, Aucklandia lappa 4 g, Corydalis yanhusuo 6 g, roasted Glycyrrhiza uralensis 4 g.

[0048] Three groups of traditional Chinese medicine (Codonopsis pilosula: Atractylodes macrocephala = 1:2): Administration method: Administer via gavage at a dose of 9.40 g / kg / day; Formula: Codonopsis pilosula 8g, stir-fried Atractylodes macrocephala 16g, Psoralea corylifolia 6g, Alpinia officinarum 4g, Poria cocos 6g, Dolichos lablab 8g, Aucklandia lappa 4g, Corydalis yanhusuo 6g, prepared Glycyrrhiza uralensis 4g.

[0049] Four groups of traditional Chinese medicine (Codonopsis pilosula: Atractylodes macrocephala = 1:1); Administration method: Administer via gavage at a dose of 9.40 g / kg / day; Formula: Codonopsis pilosula 12g, stir-fried Atractylodes macrocephala 12g, Psoralea corylifolia 6g, Alpinia officinarum 4g, Poria cocos 6g, Dolichos lablab 8g, Aucklandia lappa 4g, Corydalis yanhusuo 6g, prepared Glycyrrhiza uralensis 4g.

[0050] Five groups of traditional Chinese medicine (low-dose group): Administration method: Administer by gavage at a dose of 4.10 g / kg / day; Formula: Codonopsis pilosula 4g, stir-fried Atractylodes macrocephala 4g, Psoralea corylifolia 3g, Alpinia officinarum 2g, Poria cocos 3g, Dolichos lablab 4g, Aucklandia lappa 2g, Corydalis yanhusuo 3g, prepared Glycyrrhiza uralensis 2g.

[0051] Six groups of traditional Chinese medicine (high-dose group): Administration method: Administer via gavage at a dose of 16.38 g / kg / day; Formula: Codonopsis pilosula 16g, stir-fried Atractylodes macrocephala 16g, Psoralea corylifolia 12g, Alpinia officinarum 8g, Poria cocos 12g, Dolichos lablab 16g, Aucklandia lappa 8g, Corydalis yanhusuo 12g, prepared Glycyrrhiza uralensis 8g.

[0052] Seven groups of traditional Chinese medicine (including the optimized control group of auxiliary drugs): Administration method: Administer by gavage at a dose of 8.19 g / kg / day; Formula: Codonopsis pilosula 8g, stir-fried Atractylodes macrocephala 8g, Epimedium brevicornu 6g, dried ginger 4g, Poria cocos 6g, white hyacinth bean 8g, Aucklandia lappa 4g, Corydalis yanhusuo 6g, prepared licorice root 4g.

[0053] Eight groups of traditional Chinese medicine (positive control group): Administration method: Administer by gavage at a dose of 24.87 g / kg / day; Formula: Codonopsis pilosula 15g, Astragalus membranaceus 20g, Atractylodes macrocephala 15g, Poria cocos 15g, Dioscorea opposita 15g, Bupleurum chinense 10g, stir-fried Paeonia lactiflora 15g, prepared Glycyrrhiza uralensis 6g, Corydalis yanhusuo 15g, Dolichos lablab 20g, Lindera strychnifolia 6g, Citrus reticulata 12g.

[0054] 3. Animal grouping, model establishment, and drug administration Six mice were randomly selected as the control group and fed with normal feed. The remaining 60 mice were separated from their lactating mothers for 3 hours daily from 8:00 to 11:00 AM from day 4 to 21 postpartum, and weaned on day 22, completing the separation of newborns and their mothers. All groups of mice were fed normal feed and water until day 42. From day 43 to 52 postpartum, they received RS stimulation for 2 hours daily from 9:00 to 11:00 AM. From day 53 to 59 postpartum, they were given senna leaves by gavage (10 g / kg / d) daily to establish the IBS-D mouse model. After successful modeling, the 60 mice were randomly divided into a model group, a traditional Chinese medicine group (TCM group 1, TCM group 2, TCM group 3, TCM group 4, TCM group 5, TCM group 6, TCM group 7, and TCM group 8), and a positive control group, with 6 mice in each group.

[0055] 4. Observation Indicators and Methods (1) General condition of mice in each group Observe and record the mice's diet, activity level, mental state, fur condition, frequency and characteristics of defecation.

[0056] (2) Bristol score of feces in each group of mice Mouse feces were scored using the Bristol Stool Scale. Scoring criteria: 1 point: Separate, hard spheres, like nuts (difficult to pass); 2 points: Sausage-shaped, but with an uneven surface; 3 points: Sausage-shaped, but with cracks on the surface; 4 points: Smooth and soft, like a sausage or snake; 5 points: Soft clumps with clear edges (easy to pass); 6 points: Loose, flaky, with indistinct edges, pasty stool; 7 points: Watery stool, without solid lumps. Two trained researchers independently scored the fecal samples.

[0057] (3) Changes in fecal water content of mice in each group While collecting feces for the Bristol fecal score, fresh feces were quickly transferred to pre-weighed non-woven tea bags using disposable tweezers. The wet weight was immediately measured and recorded using an electronic scale. The tea bags containing feces were then placed in a dryer and dried until the feces were completely dry and of constant weight, and then weighed again. The weight of the tea bags was removed from the dry and wet weights, and the water content of the feces for each group of mice was calculated using the formula: Fecal water content (%) = (Wet weight - Dry weight) / Wet weight × 100%.

[0058] (4) Evaluation of visceral sensitivity Mice were anesthetized with isoflurane gas. A homemade balloon catheter coated with a small amount of liquid paraffin was slowly inserted into the mouse colon through the anus to a depth of approximately 1 cm. The catheter was secured to the mouse's tail with medical tape. The other end of the balloon catheter was connected to a homemade pressure measuring device, and air at different pressures (e.g., 20, 40, 60, 80 mmHg) was injected into the balloon at a uniform rate, with each pressure maintained for 30 seconds. The abdominal retraction reflex of the mice under different pressures was recorded. The AWR scoring criteria were as follows: 0 points, no response; 1 point, slight piloerection and slight contraction of abdominal muscles; 2 points, significant abdominal contraction but no hip elevation; 3 points, significant abdominal contraction and hip elevation. Each pressure stimulation was spaced 3 minutes apart to avoid intestinal fatigue.

[0059] (5) Metagenomics detection of changes in gut microbiota in IBS-D mice Two weeks after drug treatment, mice were gently immobilized in a supine position, and their abdomens were gently pressed to promote defecation. Fresh feces were collected using sterile forceps or in sterile culture dishes and immediately transferred to pre-frozen storage tubes. After flash freezing in liquid nitrogen, the feces were transferred to an ultra-low temperature freezer at -80°C for subsequent metagenomic sequencing.

[0060] 5. Statistical Analysis SPSS 22.0 software was used for statistical analysis of the data in each group. Quantitative data were expressed as mean ± standard deviation (X±S). One-way ANOVA was used for multiple groups, and the LSD test was used for pairwise comparisons between groups. A p-value < 0.05 was considered statistically significant. GraphPad Prism 8.0 software was used for graphing.

[0061] 6. Experimental Results (1) General condition of mice in each group After separation of mother and infant, restraint stress combined with senna leaf gavage, compared with the blank group, the mice showed decreased activity, duller fur, reduced appetite and poor mental state during the modeling period. After treatment, the mice's mental state improved and the luster of their back fur increased, all of which were better than the model group.

[0062] (2) Effect of this formula on the fecal Bristol score of IBS-D mice The Bristol fecal score was used to quantitatively evaluate mouse feces. Results showed that the feces of mice in the control group were mostly typical type 3 and 4, short and cylindrical, with a smooth and shiny surface, uniform texture, and no mucus adhesion. Compared with the control group, the fecal score of mice in the model group was significantly higher (P<0.01), with feces mostly showing type 6 (loose texture) or type 7 (watery texture), and some mice exhibiting perianal adhesion. Compared with the model group, after intervention with traditional Chinese medicine, the Bristol fecal score of mice significantly decreased (P<0.01), and the feces gradually returned to type 4 (smooth, soft cylindrical shape). The effects of traditional Chinese medicine groups 1 and 6 were the most significant. Figure 1 .

[0063] (3) Effect of this formula on fecal water content of IBS-D mice After separation of mother and infant, restraint stress combined with senna leaf gavage, the fecal water content of mice in the model group was significantly increased compared with the control group (P<0.01). After 2 weeks of drug treatment, the fecal water content of mice decreased in all groups (P<0.01), with the most significant effects observed in groups 1 and 6 of the traditional Chinese medicine treatment. Figure 2 .

[0064] (4) Effect of this formula on the visceral sensitivity score of IBS-D mice The mice were scored after their responses were observed under different pressures applied to the colon and rectum; higher sensitivity resulted in higher scores. Under all pressure levels, the model group scores were higher than the control group. However, after treatment with this formula, the scores of the herbal medicine groups 1, 2, 3, 4, and 6 were significantly lower than the model group under all pressure levels. Figure 3 .

[0065] (5) Analysis of gut microbiota in mice of each group Two weeks after drug treatment, feces were collected from mice in the blank group (Control group), model group (Model group), and traditional Chinese medicine group 1 (JPYCD group) for metagenomic sequencing.

[0066] 1) Analysis of gut microbiota diversity Alpha diversity analysis: As shown in the bar chart, compared with the blank group, the Alpha diversity Simpsoneven index in the model group did not differ significantly from that in the control group, but showed a decreasing trend (P > 0.05). After treatment with this formula, compared with the model group mice, the Simpsoneven index increased significantly (P < 0.05), and the bacterial abundance recovered, as shown in the bar chart. Figure 4 .

[0067] Beta diversity analysis: PCoA scoring plots can show the differences in the distribution and structure of fecal microorganisms among different groups of mice. The control group, model group, and traditional Chinese medicine group each showed clustering trends. The control group and traditional Chinese medicine group had close distribution distances and similar microbial structures, while the model group differed significantly from both the control group and the traditional Chinese medicine group, exhibiting dissimilar microbial structures. Figure 5 .

[0068] 2) Analysis of gut microbiota structure To clarify the effect of this formula on the fecal intestinal flora structure, changes in the intestinal flora structure of mice were observed at the phylum, genus, and species levels.

[0069] Species abundance at the phylum level, such as Figure 6The gut microbiota of mice in each group mainly consisted of Bacteroidetes, Firmicutes, Actinomycetota, and Campylobacterota. Compared with the control group, the relative abundance of Firmicutes increased in the model group, while the abundance of Bacteroidetes decreased slightly. After intervention with this treatment, the relative abundance of Firmicutes further increased, while the abundance of Bacteroidetes was lower than that of the control and model groups. In addition, the relative abundance of Verrucomicrobiota increased in the model group compared with the control group, while the abundance of this phylum in the intervention group returned to near the level of the control group. Other phyla, such as Thermodesulfobacteria, had low relative abundance in each group and the changes were small.

[0070] Species abundance at the genus level, such as Figure 7 Significant differences were observed in the gut microbiota structure among the groups of mice. The dominant bacterial genera included... Duncaniella, Bacteroides, Heminiphilus, Muribaculum and Paramuribaculum Etc. Compared to the control group, the model group showed improvements in several beneficial bacterial genera, such as... Muribaculum, Faecalibaculum and Roseburia The relative abundance of [the bacteria] decreased. After intervention with this formula, the gut microbiota structure showed a certain recovery trend, with the abundance of Lactobacillus increasing compared to both the model group and the control group. These results indicate that the intervention with this formula can regulate the composition of the gut microbiota at the genus level in IBS-D model mice, partially reversing the dysbiosis caused by the model.

[0071] Species abundance at the species level, such as Figure 8 Significant differences were found in the abundance of major species in the gut microbiota of mice across the groups. Compared with the control group, the abundance of major species in the model group was significantly higher. Faecalibaculum_rodentium The abundance of decreased significantly; while Heminiphilus_faecis The abundance of probiotics increased significantly. This treatment showed a significant gut microbiota regulation effect after intervention. Lactobacillus_johnsonii The abundance of [the bacteria] was significantly increased compared to both the model group and the control group. These results indicate that this formula can specifically regulate the species-level composition of the gut microbiota in IBS-D model mice, promoting the proliferation of some beneficial bacteria and inhibiting the growth of some opportunistic pathogens.

[0072] 3) Differential microbiota analysis To screen the key bacterial species for achieving therapeutic effects in this invention, differential bacterial populations at the species level in the mouse gut were analyzed, and the results are as follows: Figure 9 At each level, a Kruskal-Wallis rank-sum test was performed between groups, where... Lactobacillus_ johnsoniiThe abundance of beneficial bacteria, particularly *Bacillus subtilis*, was significantly lower in the model group than in the normal group, while it was significantly higher in the traditional Chinese medicine group than in the model group (P < 0.05). LEfSe differential discriminant species analysis used linear discriminant analysis (LDA) to estimate the impact of each component (species) abundance on the differential effect; a higher LDA value indicates a greater contribution. Specifically, the abundance of beneficial bacteria in the traditional Chinese medicine group was significantly higher. Lactobacillus_johnsonii The LDA contribution value of the bacteria is greater than 4 at the order, family, genus and species levels, indicating that it is very likely to be a key bacterial species that influences this formula.

[0073] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A traditional Chinese medicine composition, characterized in that, The herbal composition comprises 4-16g of Codonopsis pilosula, 4-16g of stir-fried Atractylodes macrocephala, 3-12g of Psoralea corylifolia, 2-8g of Alpinia officinarum, 3-12g of Poria cocos, 4-16g of Dolichos lablab, 2-8g of Aucklandia lappa, 3-12g of Corydalis yanhusuo, and 2-8g of prepared Glycyrrhiza uralensis.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition consists of 4-16g of Codonopsis pilosula, 4-16g of stir-fried Atractylodes macrocephala, 3-12g of Psoralea corylifolia, 2-8g of Alpinia officinarum, 3-12g of Poria cocos, 4-16g of Dolichos lablab, 2-8g of Aucklandia lappa, 3-12g of Corydalis yanhusuo, and 2-8g of prepared Glycyrrhiza uralensis.

3. The traditional Chinese medicine composition according to claim 1 or 2, characterized in that, In the formulation of the traditional Chinese medicine composition, the mass ratio of Codonopsis pilosula and stir-fried Atractylodes macrocephala is 1:

1.

4. The traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, The composition of the traditional Chinese medicine includes 8g of Codonopsis pilosula, 8g of stir-fried Atractylodes macrocephala, 6g of Psoralea corylifolia, 4g of Alpinia officinarum, 6g of Poria cocos, 8g of Dolichos lablab, 4g of Aucklandia lappa, 6g of Corydalis yanhusuo, and 4g of prepared Glycyrrhiza uralensis.

5. The traditional Chinese medicine composition according to any one of claims 1-4, characterized in that, The herbal composition consists of 8g of Codonopsis pilosula, 8g of stir-fried Atractylodes macrocephala, 6g of Psoralea corylifolia, 4g of Alpinia officinarum, 6g of Poria cocos, 8g of Dolichos lablab, 4g of Aucklandia lappa, 6g of Corydalis yanhusuo, and 4g of prepared Glycyrrhiza uralensis.

6. The traditional Chinese medicine composition according to any one of claims 1-5, characterized in that, The dosage forms of the traditional Chinese medicine composition include tablets, capsules, powders, pills, granules, oral liquids, syrups, or decoctions.

7. The traditional Chinese medicine composition according to any one of claims 1-6, characterized in that, The dosage of the traditional Chinese medicine composition is 4.10-9.40 g / kg / day.

8. The use of the traditional Chinese medicine composition according to any one of claims 1-7 in the preparation of a medicament for treating diarrhea-predominant irritable bowel syndrome.

9. A traditional Chinese medicine preparation, characterized in that, The ingredients of the traditional Chinese medicine preparation include the traditional Chinese medicine composition according to any one of claims 1-8 and optionally one or more pharmaceutically acceptable excipients.

10. The traditional Chinese medicine preparation according to claim 9, characterized in that, The pharmaceutically acceptable excipients are selected from at least one of the following pharmaceutically acceptable solvents, solubilizers, co-solvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, flow aids, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesives, binding agents, penetration enhancers, pH adjusters, buffers, plasticizers, surfactants, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and anti-flocculation agents, filter aids, release inhibitors, polymeric framework materials, and film-forming materials.

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