A traditional Chinese medicine composition for treating acute lower gastrointestinal hemorrhage combined with intestinal flora disorder and application thereof

Abstract

The application discloses a traditional Chinese medicine composition for treating acute lower gastrointestinal hemorrhage combined with intestinal flora disorder and application thereof. The traditional Chinese medicine composition comprises the following components by weight: Huanglian 1 part, fried Huaihua 1-30 parts, Jingjie Sui 1-50 parts, bran-fried Chizhi 1-50 parts, raw Puhuang 1-30 parts and Shiliupi 1-30 parts. The traditional Chinese medicine composition is reasonable in compatibility, and can effectively shorten the fecal occult blood negative conversion time and clinical symptoms of patients with acute lower gastrointestinal hemorrhage in early clinical application. Animal experiments have proved that the composition can reduce intestinal mucosal injury of lower gastrointestinal hemorrhage mice, effectively improve intestinal flora disorder, and reduce the occurrence probability of adverse events such as digestive tract perforation and acute peritonitis. The composition can effectively improve the life quality of patients in the idea of combination of prevention and treatment, and is low in cost and can be well applied to clinical treatment.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparation technology, specifically relating to a traditional Chinese medicine composition and its application for treating acute lower gastrointestinal bleeding complicated with intestinal flora imbalance. Background Technology

[0002] Lower gastrointestinal bleeding is defined as bleeding in the intestines distal to the ligament of Treitz, with a reported incidence of 50 cases per 100,000 [1. Oakland K, Chadwick G, East JE, et al. Diagnosis and management of acute lower gastrointestinal bleeding: guidelines from the British society of gastroenterology[J]. Gut, 2019, 68(5): 776-789 2]. Acute lower gastrointestinal bleeding (ALGIB) occurs within 72 hours and accounts for 20%-30% of all gastrointestinal bleeding cases. [2. ASGE Standards of Practice Committee, Pasha SF, Shergill A, et al. The role of endoscopy in the patient with lower GI bleeding[J]. Gastrointest Endosc, 2014, 79(6): 875-885; 3. Strate LL, Gralnek IM. ACG Clinical Guideline: management of patients with acute lower gastrointestinal bleeding[J]. Am J Gastroenterol, 2016, 111(4): 459-474; 4. Colorectal Group of Chinese Society of Gastroenterology Endoscopy, Chinese Medical Doctor Association, Colorectal Group of Gastroenterology Physician Branch, National Clinical Research Center for Digestive Diseases. Guidelines for the Diagnosis and Treatment of Lower Gastrointestinal Bleeding (2020) [J]. Chinese Journal of Gastroenterology Endoscopy, 2020, 37(10): 685-695.

[0003] Many patients with ALGIB can be relieved by conservative treatment, with a generally good prognosis. The in-hospital mortality rate is 3.4%-8.8%, and death is mainly due to unstable complications [5. Oakland K, Guy R, Uberoi R, et al. Acute lower GI bleeding in the UK: patient characteristics, interventions and outcomes in the first nationwide audit[J]. Gut, 2018, 67(4): 654-662 6. Lanas A, García-Rodríguez LA, Polo-Tomás M, et al. Time trends and impact of upper and lower gastrointestinal bleeding and perforation in clinical practice[J]. Am J Gastroenterol, 2009, 104(7): 1633-1641]. However, a considerable number of patients will experience severe persistent bleeding or rebleeding, and their condition will be critical, requiring emergency hospitalization and hemostatic interventions such as endoscopy, interventional radiology, and surgery, with a poor prognosis. In addition, studies have confirmed that patients with acute lower gastrointestinal bleeding complicated by severe intestinal flora imbalance have a significantly higher rate of rebleeding and mortality.

[0004] In clinical practice, patients with acute lower gastrointestinal bleeding in the small intestine have a significantly higher risk of developing the large intestine bleeding than those with the small intestine bleeding. Therefore, this invention focuses on the small intestine bleeding, but it also has therapeutic effects on the large intestine bleeding. Due to the high cost and poor patient acceptance of emergency enteroscopy, its clinical adoption rate is not high. Although proton pump inhibitors (PPIs) are widely used to treat gastrointestinal bleeding, increasing evidence suggests that PPIs do not reduce the risk of small bowel mucosal damage and lower gastrointestinal bleeding. To some extent, they exacerbate the damage to the barrier function of the small bowel mucosa and the alteration of the microbial barrier. (7. Yamada A, Niikura R, Maki K, et al. Proton pump inhibitor therapy did not increase the prevalence of small-bowel injury: apropensity-matched analysis. PLoSOne, 2017, 12(8): e0182586; 8. Washio E, Esaki M, Maehata Y, et al. Proton pump inhibitors increase incidence of nonsteroidal anti-inflammatory drug-induced small bowel injury: a randomized, placebo-controlled Trial. Clin Gastroenterol Hepatol, 2016, 14(6):809-815.). Large-scale clinical trials and animal studies have not yet found drugs with proven efficacy, so how to provide a safe and effective treatment has become an urgent problem to be solved in clinical practice. Summary of the Invention

[0005] The purpose of this invention is to provide a traditional Chinese medicine composition, preparation method and formulation for treating acute lower gastrointestinal bleeding complicated with intestinal flora imbalance, so as to solve the problems existing in the prior art and achieve effective treatment for acute lower gastrointestinal bleeding complicated with intestinal flora imbalance.

[0006] To achieve the above objectives, the present invention provides the following technical solution:

[0007] In a first aspect, the present invention provides a traditional Chinese medicine composition comprising the following components: 1 part by weight of Coptis chinensis, 1-30 parts by weight of stir-fried Sophora japonica flowers, 1-50 parts by weight of Schizonepeta tenuifolia spike, 1-50 parts by weight of stir-fried Citrus aurantium peel, 1-30 parts by weight of raw Typha pollen, and 1-30 parts by weight of pomegranate peel.

[0008] In this invention, the Coptis chinensis, stir-fried Sophora japonica flowers, Schizonepeta tenuifolia spikes, stir-fried Citrus aurantium with wheat bran, raw Typha pollen, and pomegranate peel are all processed traditional Chinese medicine products made from the corresponding raw materials.

[0009] Preferably, the traditional Chinese medicine composition comprises the following components: 1 part by weight of Coptis chinensis, 6-15 parts by weight of stir-fried Sophora japonica flowers, 6-20 parts by weight of Schizonepeta tenuifolia spike, 3-30 parts by weight of stir-fried Citrus aurantium, 3-15 parts by weight of raw Typha pollen, and 6-30 parts by weight of pomegranate peel.

[0010] Secondly, the present invention further provides a traditional Chinese medicine composition prepared from medicinal materials including the following:

[0011] The medicinal materials include: 1 part by weight of Coptis chinensis, 1-30 parts by weight of stir-fried Sophora japonica flowers, 1-50 parts by weight of Schizonepeta tenuifolia spikes, 1-50 parts by weight of stir-fried Citrus aurantium peel, 1-30 parts by weight of raw Typha pollen, and 1-30 parts by weight of pomegranate peel.

[0012] Preferably, the medicinal materials include: 1 part by weight of Coptis chinensis, 6-15 parts by weight of stir-fried Sophora japonica flowers, 6-20 parts by weight of Schizonepeta tenuifolia spikes, 3-30 parts by weight of stir-fried Citrus aurantium peel, 3-15 parts by weight of raw Typha pollen, and 6-30 parts by weight of pomegranate peel.

[0013] The preparation is carried out as follows: the medicinal materials are boiled in water, and the filtrate is collected to obtain the final product.

[0014] The preparation method also includes the process of boiling the filter residue and combining the filtrate.

[0015] Thirdly, the present invention further provides a traditional Chinese medicine preparation comprising the above-mentioned traditional Chinese medicine composition.

[0016] The preparations include decoctions, granules, powders, capsules, tablets, mixtures, and oral liquids.

[0017] Fourthly, the present invention further provides the use of the aforementioned traditional Chinese medicine composition or preparation in the preparation of a drug for treating acute lower gastrointestinal bleeding complicated with intestinal flora imbalance.

[0018] The drug treats acute lower gastrointestinal bleeding complicated by intestinal flora dysbiosis by promoting the restoration and strengthening of the small intestinal mechanical barrier, improving intestinal oxidative stress and immune microenvironment, reducing cell apoptosis, and increasing the richness of beneficial intestinal flora.

[0019] Explanation of the formula of the traditional Chinese medicine composition of this invention:

[0020] This invention modifies and adapts the classic formula Huaihua San, applying the external method of removing blood stasis and stopping bleeding to lower gastrointestinal bleeding in internal medicine. The formula uses Huaihua (Sophora japonica) and pomegranate peel as the principal herbs, and Typha pollen as the assistant herb, supplemented by Schizonepeta tenuifolia, Citrus aurantium, and Coptis chinensis, to achieve the effects of clearing the intestines, detoxifying, calming the stomach, and regulating blood.

[0021] Sophora japonica flowers clear the intestines, stop bleeding, cool the blood, and purge heat; pomegranate peel astringes the intestines, dries dampness, and stops bleeding. The combination of these two herbs cools the blood and stops bleeding; one is cold, the other warm, clearing away toxins and heat without compromising the drying and turbidity-resolving effects. The clearing and astringent properties prevent the intestinal cleansing effect from being excessive while allowing it to remain at the site of the lesion for a longer period, achieving both dispersing and astringing effects. When taken internally as a powder, the combination of pomegranate peel and Sophora japonica flowers can treat chronic bleeding. Therefore, the bitter and astringent properties of Sophora japonica flowers can enhance the drying, astringent, and hemostatic effects of pomegranate peel.

[0022] Cattail pollen is the main ingredient in the ancient blood-regulating formula Shixiao Powder. It has a mild medicinal property, promotes blood circulation and removes blood stasis, and has the effect of promoting metabolism. It is also highly effective in eliminating carbuncles, dispersing nodules and relieving pain.

[0023] Schizonepeta tenuifolia disperses heat in the blood and, when stir-fried until black, enters the blood to stop bleeding. Citrus aurantium promotes qi circulation and widens the intestines, aiming to achieve the effect of "regulating qi and regulating blood". Coptis chinensis clears heat, dries dampness, drains fire, and detoxifies.

[0024] This invention imposes strict limitations on the key drug processing methods. Raw Sophora japonica flowers excel at clearing heat and cooling the blood, and are often used for blood heat causing reckless bleeding, liver heat causing red eyes, headaches, and dizziness. Roasted Sophora japonica flowers can mitigate their bitter and cold nature, preventing damage to the middle jiao (spleen and stomach) and facilitating the preservation of active ingredients; their hemostatic effect is stronger than the raw product. Charred Sophora japonica flowers have very weak heat-clearing and blood-cooling effects, possess astringent properties, and excel in hemostasis; however, charred Sophora japonica flowers require higher processing standards, and excessive carbonization can easily affect product quality. Modern pharmacology also confirms that the percentage content of rutin, from highest to lowest, is: roasted Sophora japonica flowers > raw Sophora japonica flowers > charred Sophora japonica flowers. Processing temperature has a significant impact on rutin content in Sophora japonica flowers; the higher the processing temperature, the higher the percentage content of rutin; however, excessively long processing times will gradually decrease the percentage content of rutin. The percentage content of quercetin, from highest to lowest, is: charred Sophora japonica flowers > roasted Sophora japonica flowers > raw Sophora japonica flowers. The percentage content of quercetin gradually increases with increasing temperature, but at excessively high temperatures, quercetin content shows a decreasing trend. The changes in tannins also reflect the mechanism by which the hemostatic effect of processed Sophora japonica flowers is enhanced. The quality of tannins, from highest to lowest, is: stir-fried Sophora japonica flowers > raw Sophora japonica flowers > charred Sophora japonica flowers. In this formula, stir-fried Sophora japonica flowers, which have stable quality and strong hemostatic effect, are selected.

[0025] Fried Bitter Orange Peel (Zhi Ke) possesses the effects of regulating qi, relieving chest congestion, and eliminating bloating. The effective components of Zhi Ke mainly fall into three categories: alkaloids, flavonoids, and volatile oils. The main volatile oil component is α-limonene, which is the material basis for Zhi Ke's qi-regulating, stagnation-relieving, cough-suppressing, phlegm-reducing, and antibacterial effects. However, due to its "drying" nature, it traditionally needs to be processed before being used in traditional Chinese medicine. Fried with wheat bran weakens its efficacy, primarily focusing on regulating qi, relieving chest congestion, and eliminating bloating, thus mitigating its pungent nature. This formula uses fried Bitter Orange Peel.

[0026] Typha pollen contains various bioactive components and has a long history of medicinal use, recorded in classic texts such as *Rihuazi Materia Medica* and *Shennong's Classic of Materia Medica*. It possesses properties of promoting blood circulation, stopping bleeding, and promoting diuresis. The charred form of Typha pollen is unique to Chinese medicine and can be effectively used to treat various bleeding disorders and other diseases. Both raw and charred Typha pollen have hemostatic effects. The raw form has a higher content of flavonoid glycosides and polysaccharides, primarily exhibiting a blood-activating effect. After charring, a large amount of these components are decomposed and destroyed due to the increased temperature, resulting in a significant decrease in the content of flavonoid glycosides and polysaccharides, while the aglycone content remains relatively unchanged. Simultaneously, some decomposition products may condense into tannins, increasing the tannin content. Therefore, the content of blood-activating components decreases, while the content of hemostatic components relatively increases, resulting in a predominantly hemostatic effect. This formula focuses on the blood-activating and hemostatic properties of Typha pollen, emphasizing its blood-activating and hemostatic effects, which differs from simply increasing the dosage of hemostatic drugs. Meanwhile, since cattail pollen is a type of medicinal material and is in powder form, the traditional method of charring it not only easily leads to uneven heating, affecting the quality of the finished product, but also poses a serious safety hazard as the flammable powder can cause combustion during charring. Therefore, raw cattail pollen is still the main material used in clinical practice.

[0027] This invention addresses the underlying cause of qi and blood stagnation in this disease by employing a large number of blood-regulating and qi-invigorating herbs. It also considers the function of the intestines and stomach as relying on unobstructed flow, and the promotion of qi and blood as a form of tonification. Furthermore, warming herbs such as pomegranate peel and schizonepeta are added to the formula among the many cold-natured herbs to promote circulation, ensuring hemostasis without causing blood stasis while simultaneously protecting the middle jiao from damage by the coldness. The entire formula, consisting of six herbs, utilizes the three principles of "eliminating, supporting, and tonifying"—clearing heat and reducing swelling, dispelling wind and detoxifying, and regulating blood and qi—to treat acute lower gastrointestinal bleeding. By adjusting the dosage and adding or subtracting medications, the heat of Taiyin and Yangming meridians is cleared in the early stage to relieve stagnation of Qi and blood, which is conducive to the recovery of visceral toxins in the early stage and prevents their further development. During the development stage of visceral toxins, the purging method is used to expel the pathogenic factors that have been retained in the body, taking into account both pathogenic factors and healthy Qi, and stimulating Qi and blood to completely expel the pathogenic factors, which is conducive to clearing the pathogenic factors before they penetrate into the blood and damage the body's foundation. In the middle and late stages, when the remaining pathogenic factors have not been cleared and the healthy Qi needs to be restored, the tonifying method is used to consolidate the therapeutic effect, promote the recovery of Qi, blood, Yin and Yang in the body, and prevent the recurrence of visceral toxins.

[0028] In modern pharmacology, Sophora japonica flowers mainly contain flavonoids and monoterpenes, both of which have antioxidant and anti-inflammatory effects and can prevent bacterial translocation caused by damage to the intestinal mucosal barrier. Typha pollen's main active component is also flavonoids, possessing antithrombotic and anti-inflammatory activities. It can reduce and repair bleeding after small intestinal mucosal damage by promoting intrinsic and extrinsic coagulation systems and inhibiting fibrinolysis, without affecting platelet function. The flavonoids and tannins in pomegranate peel have strong bactericidal and antiviral effects and can stop bleeding by increasing the activity of coagulation factors. Coptis chinensis can exert anti-inflammatory effects by regulating inflammatory factors, modulating the leakage of gastrointestinal flora and intestinal lipopolysaccharides, and controlling the levels of inflammatory and oxidative stress responses in gastrointestinal tissues.

[0029] While the individual pharmacological effects of the active ingredients in the aforementioned Chinese medicinal herbs are well-known, the combined formulation can maintain tight junctions and adhesions between intestinal epithelial cells through anti-inflammatory and antioxidant effects in the early stages of disease. This maintains epithelial cell polarity and regulates intestinal barrier permeability, thereby inhibiting intestinal mucosal epithelial cell apoptosis and repairing damaged tight junction structures, thus protecting the intestinal mucosal barrier. By regulating the intestinal flora, it reduces the inflammatory response of intestinal epithelial cells, alleviates damage to the mucosal barrier, and simultaneously increases the number of probiotics, promoting the development and maturation of the body's immune system, enhancing humoral and cellular immunity, improving macrophage phagocytic activity and complement function, and promoting sIgA secretion and intestinal epithelial cell mucin synthesis. This technical effect, achieved through a specific formulation, is difficult for those skilled in the art to foresee.

[0030] The beneficial effects achieved by this invention are as follows:

[0031] This invention combines Coptis chinensis, Sophora japonica, Schizonepeta tenuifolia, Citrus aurantium, Typha pollen, and pomegranate peel in a specific ratio to obtain a composition that can effectively treat acute lower gastrointestinal bleeding complicated with intestinal flora imbalance. Attached Figure Description

[0032] Figure 1 The graph shows the comparison of changes in body weight of rats in each group before and after weight loss; in the graph: *p<0.05, **p<0.01, ****p<0.0001, n=8.

[0033] Figure 2 Comparative images of the pathological morphology of small intestinal tissue in each group of rats (HE×100); In the images: scale bar = 100μm; arrows indicate goblet cells infiltrated by inflammatory cells.

[0034] Figure 3 A schematic diagram illustrating how a traditional Chinese medicine composition can increase the level of sIgA in the small intestinal mucosa; in the figure: *p<0.05, **p<0.01, n=8.

[0035] Figure 4 A schematic diagram illustrating the reduction of DAO levels in rat plasma by a traditional Chinese medicine composition; in the figure: *p<0.05, **p<0.01, ***p<0.001, n=8.

[0036] Figure 5 A graph showing the reduction of intestinal ROS levels in rats by a traditional Chinese medicine composition; in the graph: *p<0.05, **p<0.01, ***p<0.001, n=8.

[0037] Figure 6 This is a diagram showing the expression of SOD in the rat small intestine; the scale bar in the diagram is 100 μm.

[0038] Figure 7This figure shows the expression of CAT in the rat small intestine; the scale bar in the figure is 100 μm.

[0039] Figure 8 Venn diagrams and abundance grading curves of OTU distribution in the gut microbiota of rats in each group.

[0040] Figure 9 Histograms of phylum abundance among gut microbiota groups in each group of rats.

[0041] Figure 10 The graph shows the α-diversity index of gut microbiota in each group of rats; in the graph: *p<0.05, **p<0.01, ***p<0.001. n = 8).

[0042] Figure 11 The graph shows the sparse intestinal flora curves of rats in each group.

[0043] Figure 12 The diagram shows the PCoA analysis of the gut microbiota of rats in each group.

[0044] Figure 13 This is a graph showing the differences in gut microbiota among the rat groups; in the graph, R 2 =0.443093, P=0.001.

[0045] Figure 14 The diagram shows the LEFSe analysis of the gut microbiota of rats in each group.

[0046] Figure 15 This is a random forest analysis diagram of the gut microbiota of rats in each group.

[0047] Figure 16 The graph shows the statistical results of the metabolic pathways of the gut microbiota in each group of rats. Detailed Implementation

[0048] The present invention will be further described below with reference to specific embodiments, but the present invention is not limited to the following embodiments.

[0049] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0050] Unless otherwise specified, all reagents, materials, instruments, etc. used in the following examples are commercially available.

[0051] The stir-fried Sophora japonica flowers, Nepeta cataria spikes, pomegranate peel, stir-fried Citrus aurantium peel, raw Typha pollen, and Coptis chinensis used in the following examples were all purchased from Bozhou Qiji Trading Co., Ltd.

[0052] Example 1

[0053] A traditional Chinese medicine composition for treating acute lower gastrointestinal bleeding complicated with intestinal flora imbalance, comprising the following components in parts by weight:

[0054] Coptis chinensis 1 part, stir-fried Sophora japonica flowers 15 parts, Schizonepeta tenuifolia spikes 6 parts, stir-fried Citrus aurantium 15 parts, raw Typha pollen 15 parts, pomegranate peel 10 parts.

[0055] The preparation method is as follows:

[0056] (1) Take each medicinal material according to the above proportions, add water and decoct. After boiling, simmer for 1 hour. Filter to obtain filtrate one and residue respectively. Bottle filtrate one for later use.

[0057] (2) Take the above-obtained dregs, add water and decoct. After boiling, simmer for 1 hour, filter to obtain filtrate two, and bottle for later use.

[0058] (3) Combine filtrate one and filtrate two to obtain the traditional Chinese medicine decoction.

[0059] Example 2

[0060] A traditional Chinese medicine composition for treating acute lower gastrointestinal bleeding complicated with intestinal flora imbalance, comprising the following components in parts by weight:

[0061] Coptis chinensis 1 part, stir-fried Sophora japonica flowers 9 parts, Schizonepeta tenuifolia spikes 20 parts, stir-fried Citrus aurantium 30 parts, raw Typha pollen 9 parts, pomegranate peel 30 parts.

[0062] The preparation method is as follows:

[0063] (1) Take each medicinal material according to the above proportions, add water and decoct. After boiling, simmer for 1 hour. Filter to obtain filtrate one and residue respectively. Bottle filtrate one for later use.

[0064] (2) Take the above-obtained dregs, add water and decoct. After boiling, simmer for 1 hour, filter to obtain filtrate two, and bottle for later use.

[0065] (3) Combine filtrate one and filtrate two to obtain the traditional Chinese medicine decoction.

[0066] Example 3

[0067] A traditional Chinese medicine composition for treating acute lower gastrointestinal bleeding complicated with intestinal flora imbalance, comprising the following components in parts by weight:

[0068] Coptis chinensis 1 part, stir-fried Sophora japonica flowers 6 parts, Schizonepeta tenuifolia spikes 6 parts, stir-fried Citrus aurantium 3 parts, raw Typha pollen 3 parts, pomegranate peel 6 parts.

[0069] The preparation method is as follows:

[0070] (1) Take each medicinal material according to the above proportions, add water and decoct. After boiling, simmer for 1 hour. Filter to obtain filtrate one and residue respectively. Bottle filtrate one for later use.

[0071] (2) Take the above-obtained dregs, add water and decoct. After boiling, simmer for 1 hour, filter to obtain filtrate two, and bottle for later use.

[0072] (3) Combine filtrate one and filtrate two to obtain the traditional Chinese medicine decoction.

[0073] clinical trials

[0074] Forty-five patients with acute lower gastrointestinal bleeding admitted to the outpatient department of Dongzhimen Hospital from January 2021 to December 2023 were randomly divided into group A (n=15), group B (n=13), and group C (n=17). There were 24 males and 23 females; their ages ranged from 50 to 90 years, with a mean age of 68 years; and their body mass index ranged from 17 to 33 kg / m². 2 Average 22kg / m 2 ;

[0075] Inclusion criteria: Diagnostic criteria for acute lower gastrointestinal bleeding, with no obvious upper gastrointestinal bleeding observed on gastroscopy; 24-hour blood loss of less than 500 mL, without dizziness, palpitations, or other significant decreases in circulating blood volume; age > 50 years; good medication adherence.

[0076] Exclusion criteria: allergy to the drugs used in this study; no use of acid-suppressing drugs in the 7 days prior to enrollment; gastrointestinal bleeding due to varicose veins; comorbid immune system diseases, hematological diseases, malignant tumors, and severe organ dysfunction; or need for surgical hemostasis.

[0077] Treatment methods: In addition to basic treatment, Group A received 200ml of the decoction of traditional Chinese medicine from Example 1, orally twice daily; Group B received 200ml of the decoction of traditional Chinese medicine from Example 2, orally twice daily; and Group C received 200ml of the decoction of traditional Chinese medicine from Example 3, orally twice daily. All three groups received continuous treatment for 3 days.

[0078] Observation indicators:

[0079] ① Clinical efficacy. Efficacy was judged according to the following criteria: Marked effect: Symptoms such as melena or dark red bloody stools and abdominal pain disappeared within 24 hours after treatment, the occult blood test was negative, vital signs were stable, and hemostasis was successful; Effective: Symptoms such as melena or dark red bloody stools and abdominal pain disappeared within 24–48 hours after treatment, the occult blood test was negative, vital signs were stable, and hemostasis was successful; Ineffective: Symptoms such as melena or dark red bloody stools and abdominal pain persisted beyond 48 hours after treatment, and hemostasis failed. Total effective rate = Marked effect rate + Effective rate.

[0080] ② Medication safety. Record the occurrence of adverse reactions such as diarrhea, rash, and nausea.

[0081] result:

[0082] 1. Clinical efficacy: The total effective rate of treatment in group A was 93.33%, which was significantly higher than that in group B (76.92%) and group C (88.23%), and the difference was statistically significant (P<0.05).

[0083] Table 1 Comparison of clinical efficacy

[0084] Group n Effectiveness % efficient% invalid% Total effective percentage Group A 15 11(73.33) 3(20.00) 1(6.67) 14(93.33) Group B 13 9(69.23) 1(7.69) 3(23.07) 10(76.92) Group C 17 10(58.82) 5(29.41) 2(11.76) 15(88.23) χ2 24.200 P 0.00

[0085] 2. Drug safety: The total incidence of adverse reactions in group A (13.33%), group B (15.38%), and group C (5.88%) was statistically significant (P<0.05).

[0086] Table 2. Occurrence of Adverse Reactions

[0087] Group n diarrhea% nausea% rash% total% Group A 15 0(0.00) 2(13.33) 0(0.00) 2(13.33) Group B 13 1(7.69) 0(0.00) 1(7.69) 2(15.38) Group C 17 0(0.00) 1(5.88) 0(0.00) 1(5.88) χ2 27.222 P 0.00

[0088] Comparing the clinical efficacy of Examples 1, 2, and 3, no adverse events such as sudden death occurred in any of the patients. Although Example 1 showed better efficacy, it had a higher incidence of adverse reactions. Example 3 showed definite efficacy and a lower incidence of side effects, therefore Example 3 was selected as the animal experiment proportion. All enrolled patients experienced varying degrees of improvement in their stool, changing from bloody and black stools to soft, yellow stools, but the average time for symptom improvement was 6 days.

[0089] Animal experiments and lower gastrointestinal bleeding caused by acute small intestinal mucosal injury

[0090] 1. Materials and Methods

[0091] 1.1 Traditional Chinese Medicine Composition Reagents

[0092] The traditional Chinese medicine decoction prepared in Example 3 is referred to as PHQPY.

[0093] 1.2 Animals

[0094] SD rats: SPF grade, healthy, male, 8 weeks old, 40 rats, weighing (200±20)g, purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.

[0095] Animals were acclimatized for one week before the experiment began. They were housed in individually ventilated cages, eight animals per cage, in a clean environment (temperature 22-26℃, humidity 50%-60%), with ethical approval number 22-43.

[0096] 1.3 Establishment and grouping of an acute small intestinal mucosal injury-induced lower gastrointestinal bleeding model

[0097] The subjects were randomly divided into 5 groups using a random number table method (blank group K, model group M, low-dose PD and high-dose PG groups of traditional Chinese medicine composition, and rebamipide group R, n=8).

[0098] Except for the control group rats which were given saline by gavage, the other four groups of rats were given a small intestinal mucosal injury model by gavage with diclofenac sodium (trade name: diclofenac, purchased from Novartis) 5 mg / kg for 3 consecutive days.

[0099] After modeling, the Chinese medicine composition group and the model group were administered physiological saline by gavage for 3 days. The dosage of the Chinese medicine composition was calculated based on an adult body weight of 60kg (125g / d). The dosage of the rats was converted according to the "Equivalent Dose Ratio Table of Human and Animal Body Surface Area Conversion", with a high dose of 26.25g / kg and a low dose of 6.5625g / kg administered by gavage for 3 days. The rebamipide group was administered rebamipide tablets (trade name: Membusida, purchased from Zhejiang Dajia Pharmaceutical Co., Ltd.) at 31.5mg / kg by gavage for 3 days.

[0100] Fecal samples were collected to assess gut microbiota abundance. Within 24 hours after the last gavage, rats were intraperitoneally injected with 2% sodium pentobarbital (40 mg / kg), and blood was collected from the abdominal aorta and left to stand for 60 minutes. The serum was then centrifuged at 2000 x g for 15 min and stored at -80°C. The small intestine was removed and macroscopically examined; approximately 2 cm of the most severely damaged small intestine was fixed with 4% paraformaldehyde. The remaining small intestine samples were rapidly frozen in liquid nitrogen and stored at -80°C for subsequent data analysis.

[0101] 1.4 Hematoxylin and eosin (H&E) staining

[0102] Small intestinal tissues from rats in each group were fixed with 4% paraformaldehyde for 24 h, then routinely dehydrated, embedded in paraffin, cut into 4 μm sections, and mounted on microscope slides. The sections were stained with hematoxylin for 3 min, dehydrated, stained with eosin for 3 min, sealed, and then images were acquired by scanning.

[0103] 1.5 Immunohistochemistry and immunofluorescence assay for protein expression in small intestinal tissue

[0104] Tissue sections were heated at 60℃ for 1 hour, followed by routine dewaxing and hydration. They were then placed in 0.01 mol / L citrate buffer (pH 6.0) and microwaved to repair antigens. The microwave was heated on medium-high for 9 minutes, allowed to cool naturally for 15 minutes, then on high for 5 minutes, and allowed to cool naturally for 1 hour. Endogenous peroxidase was blocked using the SP method for 10 minutes. The sections were then washed twice with phosphate-buffered saline (PBS) for 5 minutes each time. The sections were blocked with 5% BSA blocking solution for 1 hour and washed three times with PBS for 5 minutes each time.

[0105] Immunohistochemistry was performed by incubating with primary antibody (SOD 1:600, catalog number: Servicebio10269-1-AP; CAT 1:500, catalog number: Servicebio 21260-1-AP) at 4°C overnight, followed by warming at 37°C for 45 min. The primary antibody was discarded, the cells were rinsed, and secondary antibody was added. The cells were incubated at room temperature for 15 min, rinsed, and horseradish enzyme-labeled streptavidin working solution was added. The cells were incubated at room temperature for 15 min, rinsed, dried, and developed with DAB at room temperature for 10 min. The staining intensity was controlled under a microscope (brown cytoplasm indicated positive expression cells). The reaction was stopped by rinsing with tap water for 5 min. Hematoxylin was used for counterstaining, followed by rinsing with tap water for 2 min. The cells were then dehydrated routinely, mounted with neutral resin, and examined under a microscope.

[0106] 1.6 ELISA method for detection

[0107] According to the kit instructions, the plasma DAO level and intestinal sIgA level of rats in each group were detected by ELISA.

[0108] 1.7 Flow Cytometry

[0109] Collect intestinal tissue into a culture dish, cut the intestinal segment laterally with scissors, and wash away as much of the intestinal contents as possible in PBS. Add 5 ml of PBS and grind the intestinal tissue through a 200-mesh filter until sufficient cells are exudated. Rinse the filter screen repeatedly with the cell suspension, and transfer the filtered cell suspension to a flow cytometry tube. Centrifuge at 500 g for 5 min and discard the supernatant. Add ROS probe (probe dilution ratio 1:1000) and incubate at 37°C for 20 min (no reagent added to blank tubes, 1 μL of rebamipide added to rebamipide group tubes). After the reaction, centrifuge at 500 g for 5 min and discard the supernatant. Resuspend the cells in 300 μL of PBS and analyze the FITC channel.

[0110] 1.8 Sequencing and Bioinformatics Analysis of 16S rRNA Genes in Mouse Feces

[0111] For gut microbiota analysis, fecal samples were collected. Total DNA was extracted using the QIAamp-DNA Stool Mini kit and subjected to electrophoresis. ABI Gene was used. The V3-V4 region of the bacterial 16S rRNA gene was amplified using a PCR system (Applied Biosystems, Foster City, CA, USA). PCR products were quantified using a Quanti Fluor™-ST handheld fluorometer with UV / blue channel (Promega Corporation, Madison, WI, USA). The 16S rRNA gene sequencing data were classified into operational taxonomic units (OTUs) with over 100% similarity using Shanghai Majorbio Bio-Pharm Technology Co., Ltd., generating a representative set of sequences, which were then taxonomically assigned using the Greengenes database (DeSantis et al., 2006). Sparse curves were analyzed using QIIME2 (2019.4), and richness estimates and diversity indices were calculated. Statistical analyses were performed on the five groups using OTU-level α-diversity, β-diversity, principal coordinate analysis (PCoA), taxonomic analysis, intragroup linear discriminant analysis (LDA), and effect size (LEfSe). Biological function analysis of the samples was performed using the KEGG database. Visualize the analysis results using R language (Version 2.15.3).

[0112] 1.9 Statistical Methods

[0113] Experimental data were statistically analyzed using SPSS 26.0 software, and continuous data were expressed as mean ± standard deviation (x±s). If the data followed a normal distribution, one-way ANOVA was used for comparisons among multiple groups, and LSD test was used for multiple comparisons. If the data did not follow a normal distribution, nonparametric tests were used, specifically two-tailed tests, with a significance level of α = 0.05. P < 0.05 was considered statistically significant.

[0114] 1.10 Results

[0115] 1.10.1 The traditional Chinese medicine composition can improve symptoms of small intestinal mucosal damage.

[0116] The therapeutic effect of diclofenac sodium in a rat model of small intestinal mucosal injury was evaluated using in vivo experiments. The results showed that:

[0117] (1) Weight: such as Figure 1 As shown, the weight loss in rats was alleviated after treatment with the traditional Chinese medicine composition.

[0118] (2) Small intestinal mucosal damage: such as Figure 2As shown, HE staining indicated a significant improvement in non-specific inflammation of the small intestinal mucosal epithelium. Compared with the model group, the small intestinal mucosal epithelium in the low-dose and high-dose groups of the traditional Chinese medicine composition showed varying degrees of repair, reduced mucosal surface exudation, significantly reduced loss of villous surface epithelium, and more regular villus arrangement and shape, with a small amount of chronic inflammatory cell infiltration visible. In the rebamipide group, there was no significant exudation in the small intestinal mucosa, no significant loss of villous surface epithelium, and a small amount of chronic inflammatory cell infiltration visible.

[0119] (3) Feces: The black stool (gastrointestinal bleeding) in rats was alleviated after treatment with the Chinese medicine composition, and the stool of some mice in the treatment group turned yellow.

[0120] 1.10.2 Traditional Chinese medicine composition restores intestinal barrier function and inhibits cell apoptosis

[0121] Experimental results show that:

[0122] like Figure 3 As shown, diclofenac sodium decreased the level of sIgA in the rat intestine. The low-dose PHQPY group and the rebamipide group could restore the level of sIgA in the intestine to normal levels, while the high-dose PHQPY group could increase the level of sIgA in the intestine.

[0123] like Figure 4 As shown, both the high-dose PHQPY group and the rebamipide group can reduce DAO in rat plasma to normal levels, with the high-dose PHQPY group showing a more significant reduction trend.

[0124] The results above show that the traditional Chinese medicine composition provided by the present invention can repair small intestinal mucosal damage, strengthen its barrier function, and reduce cell apoptosis, thereby playing a therapeutic role.

[0125] 1.10.3 Traditional Chinese medicine compositions can reduce intestinal damage caused by oxidative stress.

[0126] like Figure 5 As shown, both the high-dose PHQPY group and the rebamipide group could alleviate the increase in intestinal ROS in rats induced by diclofenac sodium, and the high-dose PHQPY group had a more significant benefit in reducing intestinal ROS levels.

[0127] like Figure 6 , Figure 7 Immunohistochemistry showed that the distribution of SOD and CAT, protective enzymes, in the small intestine was significantly reduced in the model group. The PHQPY and rebamipide groups showed increased distribution of SOD and CAT in the intestine, with the high-dose PHQPY group showing a particularly significant increase, as evidenced by a significant increase in SOD and CAT staining in the immunohistochemical sections. Figure 6 The image shown is a representative image from 8 biologically independent animals (n=8). Figure 7The images shown are representative images of eight biologically independent animals with n=8 biological characteristics.

[0128] 1.10.4 Traditional Chinese medicine compositions improve gut microbiota imbalance

[0129] To investigate the effects of PHQPY on gut microbiota dysbiosis, fecal 16S rRNA gene amplicon sequencing was analyzed to provide an overview of the gut microbiota composition.

[0130] like Figure 8 As shown, the OTUs in the control group, model group, low-dose PHQPY, high-dose PHQPY, and rebamipide group were 3706, 3557, 5665, 7832, and 5168, respectively, and the number of unique OTUs were 2732, 2583, 4691, 6858, and 4194, respectively.

[0131] like Figure 9 As shown, the histogram of the gut microbiota structure reveals the types and relative abundance of microorganisms. Firmicutes, Bacteroidetes, and Actinobacteria are the main species in each group, with a relative abundance ratio of over 95%. The proportion of Firmicutes in the model group is significantly increased, while the high-dose PHQPY group can reduce the percentage of Firmicutes and increase the percentage of Bacteroidetes. The proportions of Firmicutes and Bacteroidetes in the low-dose PHQPY group and the rebamipide group are similar to those in the blank control group, indicating that all three can improve the gut microbiota imbalance caused by diclofenac sodium, and the high-dose traditional Chinese medicine group shows excellent performance.

[0132] α-diversity analysis was then performed.

[0133] like Figure 10 , Figure 11 As shown, the Chao1 index results and sparse curves indicate the differences in gut microbiota richness among the rat groups. It is evident that the mean richness of the gut microbiota in the model group was significantly lower than that in the other groups. Meanwhile, the high-dose PHQPY group significantly increased the richness of the gut microbiota. The Shannon and Simpson indices in the figure demonstrate the gut microbiota diversity among the rat groups. The model group exhibits lower gut microbiota diversity, which was partially improved by the rebamipide group, while the traditional Chinese medicine group restored its diversity to normal levels.

[0134] The Bray-Curtis distance index (PCoA) was used to analyze the β-diversity of rats in each group. PCoA is a visualization method for studying the similarity or difference of data.

[0135] The results are as follows Figure 12As shown, the model group and the rebamipide group are significantly different from the other three groups, and the ellipses of the model group, the blank control group, and the traditional Chinese medicine group do not intersect. This indicates a significant difference in the gut microbiota distribution within the model group, reflecting that the traditional Chinese medicine group can significantly improve the gut microbiota after diclofenac sodium-induced small intestinal mucosal damage. Further validation was performed using Adonis intergroup difference analysis to accurately determine the magnitude and significance of the differences between groups. The results are as follows: Figure 13 As shown.

[0136] In the LEfSe clustering tree, each circle, from the inside out, represents a different species at the phylum, class, order, family, and genus level, and provides a visual representation of the microbial community within each group responsible for essential functions between groups. Colored circles represent biomarkers, and microorganisms performing key functions are represented by nodes with the same color as the group. Larger nodes correspond to a greater number of microorganisms.

[0137] like Figure 14 As shown, species with LDA absolute values ​​≥3 are significantly different in family and genus. Four microbial taxa were enriched in the blank control group (Eubacterium, Ruminococcaceae, Alistipes, and Rikenellaceae); seven microbial taxa were enriched in the model group (Lactobacillaceae, Lactobacillus, Lactobacillales, etc.); 30 microbial taxa were enriched in the low-dose PHQPY group (Clostridiales, Clostridia, Peptostreptococcaceae, etc.); 32 microbial taxa were enriched in the high-dose PHQPY group (Actinobacteria, Corynebacteriales, Corynebacteriaceae, etc.); and eight microbial taxa were enriched in the rebamipide group (Parabacteroides, Selenomonadales, Negativicutes, etc.).

[0138] Subsequently, the Random Forests (Breiman, 2001) algorithm, a classic and efficient machine learning algorithm based on decision trees, was used to effectively, robustly, and accurately classify the microbial community samples to identify marker species. Classification was performed at the species level, and the top 20 most important species were selected. The results are as follows: Figure 15 As shown.

[0139] Finally, the metabolic pathways of the gut microbiota in each group of rats were analyzed using KEGG, such as... Figure 16As shown, the abundance values ​​of gut microbiota metabolic pathways are mainly concentrated in the biosynthesis process, especially in the three pathways of Nucleoside and Nucleotide Biosynthesis, Amino Acid Biosynthesis, and Cofactor, Prosthetic Group, Electron Carrier, and Vitamin Biosynthesis.

[0140] Within the intestinal lumen, sIgA is the most abundant antibody secreted by the mucosal immune system, playing a role in restricting the entry of intestinal antigens into the bloodstream and controlling the intestinal microbiota. sIgA prevents antigens and pathogens from entering epithelial cells and clears pathogens through peristalsis and mucociliary activity. Differences in the binding mode of sIgA to microorganisms affect the physiological functions of the intestinal microbiota, promoting the colonization of beneficial bacteria and inhibiting the infectivity of pathogenic bacteria. Under normal circumstances, sIgA secretion is relatively stable. The main reason for the decreased sIgA level in the model group is likely due to the resulting intestinal microbiota dysbiosis, where bacterial proteases produced by certain pathogenic bacteria can cleave sIgA, inactivating it and leading to infection. Traditional Chinese medicine compound formulas increase sIgA secretion, thereby enhancing the recognition and presentation functions of intestinal immune cells and promoting the resolution of inflammation; furthermore, they can enhance the regulatory effect on the intestinal microbiota to maintain intestinal microbiota homeostasis.

[0141] Superoxide dismutase (SOD) and catalase (CAT) are important protective enzymes in the body. SOD catalyzes the conversion of superoxide into H2O2, while CAT specifically removes excess H2O2 from the body, preventing the accumulation of lipid peroxides, reducing ROS production, significantly improving lipid accumulation, and decreasing the degree of oxidative stress damage and regulatory cell death. Excessive ROS production amplifies inflammatory responses and exacerbates inflammatory symptoms, especially in the gastrointestinal tract, leading to damage to the intestinal mucosa and pathogen invasion, subsequently stimulating the immune response, and ultimately leading to the development of inflammatory bowel disease. Excessive ROS can also induce dysbiosis of the gut microbiota.

[0142] This experiment selected rat feces for collection before the last gavage. Although the gut microbiota at this time had not yet reached the rat's homeostatic state, it could better reflect the changing trends of the gut microbiota under the influence of inflammation and drugs. The above-mentioned effects, as well as the direct effects of NSAIDs, led to gut microbiota dysbiosis in the model group. OTUs indicated that the five groups had similar homogeneity, but the model group had the lowest relative abundance. In addition to changes in gut microbiota abundance, the composition of the microbiota also changed. The study showed that at the phylum level, Bacteroidetes and Firmicutes had the highest abundance. The Firmicutes / Bacteroidetes (F / B) ratio plays a central role in maintaining normal intestinal homeostasis; increases or decreases in the F / B ratio affect the gut ecology. Compared with the blank group, the proportion in the model group increased to 157.18%, while the proportions in the low-dose, high-dose, and rebamipide groups decreased to 99.50%, 76.24%, and 86.14%, respectively. The differences between the treatment groups and the blank group were all smaller than those in the model group, with the low-dose group showing the smallest difference from the blank group. We analyzed that this might be related to the fact that the stool sampling time had not yet reached a relatively stable period, but it still showed that both the traditional Chinese medicine group and the positive control group tended to maintain the F / B ratio.

[0143] The genera *Lactobacillus* and *Helicobacter* show significant differences, as shown in Table 3.

[0144] Table 3 Content of *Lactobacillus* and *Helicobacter* genera

[0145]

[0146] Lactobacillus is a classic probiotic family. Lactobacillus intestinalis promotes intestinal barrier integrity by increasing the mRNA levels of tight junction-related markers. Undissociated lactic acid, a metabolite of Lactobacillus intestinalis, plays a major inhibitory role against specific intestinal pathogens. Other metabolites produced by Lactobacillus intestinalis, such as organic acids, bacteriocins, and antimicrobial peptides, also have inhibitory effects on Gram-negative bacteria. Lactobacillus reuteri can reduce the abundance of opportunistic pathogens by regulating gut microbiota, affecting the levels of SCFAs in the gut, reducing serum LPS levels, decreasing oxidative stress, restoring the expression levels of intestinal mucosal barrier proteins, and reducing inflammatory cytokine levels. Lactobacillus reuteri can promote butyrate formation, upregulate the transcription of antimicrobial peptide encoding genes, and prevent hyperimmune responses in the peri-intestinal tract and within the gut. Furthermore, it can increase the abundance of other probiotics, thereby limiting the relative abundance of harmful bacteria. Helicobacter rodentium is a harmful bacterium that promotes the production of reactive oxygen species (ROS) metabolites. Under enzymatic action, these ROS generate oxygen free radicals, ultimately causing oxidative damage to host cell membranes, activating neutrophils and inflammatory cytokines, leading to inflammatory responses and systemic damage. Therefore, PHQPY likely plays a role in correcting gut microbiota dysbiosis and its subsequent effects by exhibiting significant differences from the model group in the *Lactobacillus* and *Helicobacter* genera.

[0147] PCoA showed that the samples from each group were relatively concentrated, indicating strong reproducibility of gut bacteria within each group, reliable and stable data, and significant research value. The model group was significantly different from the control group and the two traditional Chinese medicine groups, with virtually no overlap. This indicates a difference in sample distance between the model group and these three groups, suggesting strong heterogeneity and substantial differences in gut microbiota composition among the groups. The gut microbiota of the rebamipide group was relatively similar to that of the model group, suggesting that the main pathway by which rebamipide improves diclofenac sodium-induced small intestinal mucosal damage is not primarily through gut microbiota, but rather through scavenging oxygen free radicals, inhibiting oxidative stress and inflammatory responses, and reducing the destruction of tight junction proteins, thus protecting the intestinal mucosa. However, as research continues, it has been found that gut microbiota plays a crucial role in related intestinal diseases, and compound traditional Chinese medicine may surpass the efficacy of rebamipide through existing pathways, providing further assistance to the body at the gut microbiota level.

[0148] LDA scores showed that Rikenellaceae was enriched in the blank control group. Rikenellaceae bacteria have the ability to ferment and produce short-chain fatty acids in the human gut. The content of Rikenellaceae was significantly reduced in patients with enteritis. Furthermore, experiments have confirmed that Rikenellaceae helps create a healthier metabolic environment. Clostridiales were enriched in the low-dose PHQPY group. Clostridiales can reduce inflammation and improve intestinal damage and intestinal immunity by increasing arginine levels. Actinobacteria were enriched in the high-dose PHQPY group. Actinobacteria can inhibit the expression of pro-inflammatory factors and has antibacterial efficacy against various harmful bacteria, and is considered a promising antibacterial compound in biotechnology. Interestingly, in this experiment, the top two enriched bacteria in the model group were Lactobacillaceae and Lactobacillaceles. The number of Lactobacillaceae units in the model group was 2.84 times that of the blank group. Both are considered probiotic species in the gut, which can affect host mucosal immune cells and intestinal cells by promoting butyrate production, thereby restoring intestinal homeostasis. This result may be due to the fact that the experimental model was established by acute intervention with diclofenac sodium for 3 days. After the pathogenic factors of the acute intervention disappeared in the following 3 days, the rat intestine underwent self-repair. The unit values ​​of Lactobacillaceae and Lactobacilles in the Chinese medicine group were similar to those in the blank control group, suggesting that the flora relied on for intestinal self-repair is different from the flora relied on when small intestinal mucosal damage is improved by Chinese medicine.

[0149] Experimental results show that the traditional Chinese medicine composition can restore and strengthen the small intestinal mechanical barrier, improve intestinal oxidative stress and immune microenvironment. This interacts and promotes the repair of intestinal flora imbalance caused by diclofenac sodium, thus aiding in the recovery of intestinal mucosal damage. Although the above experiment used diclofenac sodium as the research drug, the traditional Chinese medicine composition and treatment approach provided by this invention can be extended to all cases of acute lower gastrointestinal bleeding complicated by intestinal flora imbalance.

[0150] Although the present invention has been described in detail above with general descriptions and specific embodiments, modifications or improvements can be made to it, which will be obvious to those skilled in the art. Therefore, all such modifications or improvements made without departing from the spirit of the present invention fall within the scope of protection claimed by the present invention.

Claims

1. A traditional Chinese medicine composition for treating acute lower gastrointestinal bleeding complicated with intestinal flora imbalance, comprising the following components: Coptis chinensis 1 part by weight, stir-fried Sophora japonica flowers 6-15 parts by weight, Schizonepeta tenuifolia spikes 6-20 parts by weight, stir-fried Citrus aurantium 3-30 parts by weight, raw Typha pollen 3-15 parts by weight, and pomegranate peel 6-30 parts by weight.

2. The traditional Chinese medicine composition according to claim 1, characterized in that: The preparation of the traditional Chinese medicine composition is carried out according to the following operation: the medicinal materials are decocted with water, and the filtrate is collected to obtain the composition.

3. The traditional Chinese medicine composition according to claim 2, characterized in that: The preparation method also includes the process of boiling the filter residue and combining the filtrate.

4. A traditional Chinese medicine preparation for treating acute lower gastrointestinal bleeding complicated with intestinal flora imbalance, comprising the traditional Chinese medicine composition according to claim 1.

5. The traditional Chinese medicine preparation according to claim 4, characterized in that: The preparations include decoctions, granules, powders, capsules, tablets, mixtures, and oral liquids.

6. The use of the traditional Chinese medicine composition of claim 1 or the traditional Chinese medicine preparation of claim 4 or 5 in the preparation of a drug for treating acute lower gastrointestinal bleeding complicated with intestinal flora imbalance.

7. The use according to claim 6, characterized in that: The drug treats acute lower gastrointestinal bleeding complicated with intestinal flora disorder by promoting the restoration and strengthening of the small intestinal mechanical barrier, improving intestinal oxidative stress and immune microenvironment, reducing cell apoptosis, and increasing the richness of the beneficial intestinal flora.

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