A Chinese medicine composition for treating and / or preventing low anterior rectal resection syndrome and its use

Abstract

The present invention relates to a Chinese medicine composition for treating and / or preventing low anterior rectal resection syndrome and its use, and belongs to the field of Chinese medicine. The Chinese medicine composition of the present invention is a preparation prepared from the following raw materials in weight ratio: 10-25 parts of Evodia rutaecarpa, 10-25 parts of Ginseng, 10-45 parts of Astragalus, 10-25 parts of Atractylodes macrocephala, 8-25 parts of Paojiang, 10-25 parts of Cimicifuga, 10-25 parts of Bupleurum, 8-25 parts of Terminalia chebula, and 10-25 parts of Prunus mume. The present invention also provides a preparation method and use of the Chinese medicine composition. The pharmaceutical composition of the present invention treats low anterior rectal resection syndrome, has the effects of descending Yangming, ascending Taiyin, astringing intestines and stopping diarrhea, and has a significant effect on improving diarrhea and anal swelling in LARS patients.

Description

Technical Field

[0001] The invention relates to a traditional Chinese medicine composition for preventing and / or treating low anterior rectal resection syndrome, a preparation method and application thereof, and belongs to the field of traditional Chinese medicine. Background Art

[0002] According to statistics from the National Cancer Center, the incidence of colorectal cancer in China ranks second among all malignant tumors, and the mortality rate ranks fourth, and the incidence rate continues to rise. In clinical cases, rectal cancer is more common than colon cancer, and about 70%-80% of cases are mainly middle and low rectal cancer. At present, anal preservation surgeries such as low anterior resection (LAR) and total mesorectal excision have gradually replaced abdominoperineal resection as the preferred surgical procedure for radical treatment of low rectal cancer, which can prevent patients from carrying a stoma for life. However, about 70%-90% of patients will experience varying degrees of anorectal dysfunction after anal preservation surgery, such as increased bowel movements, incomplete bowel movements, difficulty in defecation, and even fecal incontinence, which is clinically called low anterior resection syndrome (LARS).

[0003] The LARS International Collaborative Group proposed in 2020 that LARS refers to the occurrence of at least one of the following symptoms after LAR surgery (frequent bowel movements, urgency, incontinence, fecal matter, difficulty emptying, changes in stool consistency, recurrent anal pain, and unpredictable changes in bowel function), and leads to at least one of the following consequences (toilet dependence, excessive attention to bowel function, dissatisfaction with bowel function, seeking countermeasures and compromises, affecting mental and emotional, affecting social daily activities, affecting intimate relationships, and affecting image commitment and responsibility). The latest research shows that the average follow-up time of patients with rectal cancer after anal preservation surgery is more than 6 years, and LARS can still persist, and even accompany a small number of patients for life. LARS patients in the group after anal preservation surgery rarely have the opportunity to obtain a good quality of life, and the higher the severity of LARS, the lower the patient's quality of life, which can further affect the patient's social life and mental state. Modern medicine believes that surgical damage to the anal sphincter and the anorectal nerve plexus and other factors lead to a significant decrease in the sphincter contraction function, hindering the normal defecation function of the anorectum. At present, clinical western medicine treatment plans mostly use oral intestinal probiotic preparations, 5-hydroxytryptamine agonists and antagonists, sacral nerve and transcutaneous tibial nerve stimulation therapy, pelvic floor rehabilitation training, etc.

[0004] The basis of rectal cancer is spleen and stomach weakness. From the perspective of traditional Chinese medicine theory, the spleen and stomach transport qi, blood and body fluids. If the spleen and stomach are weak, the transport is inadequate and the transportation and transformation are impaired, resulting in the accumulation of dampness, phlegm and blood stasis in the large intestine and anus, evolving into cancer toxins and eventually forming tumors. After rectal cancer surgery, the body fluids are further damaged, qi is weak and sinks, and the clear yang does not rise, which leads to the dysfunction of the large intestine in descending and draining turbidity, and then a series of symptoms of abnormal defecation function such as loose stools, frequent bowel movements, and heavy anus are manifested. Spleen and stomach deficiency and insufficient vital energy are the main causes of rectal cancer surgery. At present, the traditional Chinese medicine classification of LARS includes: spleen and kidney deficiency type (spleen and kidney yang deficiency type and spleen and kidney qi deficiency type), spleen deficiency and dampness syndrome, and spleen deficiency and qi collapse syndrome. According to the above etiology and pathogenesis, traditional Chinese medicine adopts three major treatment principles: purgation of excess, tonification of deficiency, and tonification and purgation at the same time. At present, the methods of TCM for treating LARS include: internal treatment, such as taking Chinese medicine orally; external treatment, such as Chinese medicine enema, acupuncture and foot bath, etc.; and internal and external treatment, such as taking Chinese medicine prescriptions orally combined with acupuncture treatment, etc. (Tian Yuan, et al., Research Progress on TCM Treatment of Low Anterior Resection Syndrome of Rectal Cancer, Chinese Journal of Integrated Traditional Chinese and Western Medicine Surgery, Vol. 27, No. 2, April 2021). Shi Qi Chong, et al., Treating Low Anterior Resection Syndrome from the Perspective of Spleen and Stomach, Chinese Folk Therapy, 2020-03-14, disclosed that the pathogenesis of low anterior resection syndrome LARS is spleen and stomach weakness, failure of clear yang to rise, and dysfunction of qi movement, resulting in excessive diarrhea, and the main treatment is to regulate the spleen and stomach.

[0005] Regarding the main symptoms of LARS patients, diarrhea and anal distension, the literature reports are as follows: Zhong Fuqiang et al. (China Medical Guide, 2020, Vol. 18, No. 2, pp. 166-167) used the method of clearing heat, promoting dampness and stopping diarrhea, and used the national famous traditional Chinese medicine practitioner Bai Changchuan's experience prescription, Gegenqinlian Decoction, to treat diarrhea in LARS patients, with significant results. Xu Qiqi (Master's thesis, Clinical observation of Buzhong Yiqi Decoction in the treatment of low anterior resection syndrome (spleen deficiency and qi collapse syndrome) after rectal cancer surgery, Chengdu University of Traditional Chinese Medicine, 2021) classified LARS as spleen deficiency and qi collapse syndrome, and used Buzhong Yiqi Decoction combined with defecation function training for treatment, which improved the patient's bowel movement frequency and anal distension symptoms. Zhu Guolong (Master's thesis, Clinical efficacy of Buzhong Yiqi Decoction plus acupuncture in the treatment of diarrhea caused by qi deficiency and instability after rectal cancer surgery, Fujian University of Traditional Chinese Medicine, 2023) used Buzhong Yiqi Decoction plus acupuncture to improve diarrhea caused by qi deficiency and instability after rectal cancer surgery, with significant efficacy. Feng Shuo et al. (A double-blind randomized controlled clinical study on the treatment of low anterior resection syndrome of rectal cancer with Shenling Baizhu granules, Journal of Beijing University of Chinese Medicine, 2024) conducted a randomized double-blind controlled clinical study on the treatment of low anterior resection syndrome of rectal cancer with Shenling Baizhu granules. The results showed that Shenling Baizhu granules can improve the symptoms of LARS patients in the short term, including appetite, stool texture, abdominal distension, abdominal pain, and belching. In the literature report, Shengyang Chushi Decoction, Ehuang Decoction, Xianjue Decoction with added ingredients, etc. are used to treat LARS. Most of the prescriptions reported so far only have an improvement effect on one of the main symptoms of LARS, such as diarrhea and anal distension, while the only prescription that has an improvement effect on both diarrhea and anal distension is reported in the treatment of Buzhong Yiqi Decoction, which limits its clinical use. Summary of the invention

[0006] The present invention provides a traditional Chinese medicine composition for preventing and / or treating low anterior rectal resection syndrome, and also provides a preparation method and application of the traditional Chinese medicine composition.

[0007] The present invention provides a traditional Chinese medicine composition for preventing and / or treating low anterior rectal resection syndrome, which is a preparation prepared from raw materials in the following weight ratio:

[0008] 10-25 parts of Evodia rutaecarpa, 10-25 parts of Ginseng, 10-45 parts of Astragalus, 10-25 parts of Atractylodes macrocephala, 8-25 parts of Paojiang, 10-25 parts of Cimicifuga heracleifolia, 10-25 parts of Bupleurum, 8-25 parts of Terminalia chebula, and 10-25 parts of Prunus mume.

[0009] More preferably, it is a preparation prepared from raw materials in the following weight ratio:

[0010] 18 parts of Evodia rutaecarpa, 15 parts of ginseng, 10 parts of astragalus, 12 parts of atractylodes, 10 parts of roasted ginger, 10 parts of cimicifuga, 10 parts of bupleurum, 10 parts of terminalia chebula, and 10 parts of ebony.

[0011] The Chinese medicine composition of the present invention is an oral preparation prepared by using the powder of the raw material medicine, the water extract of the raw material medicine or the organic solvent extract of the raw material medicine as active ingredients and adding auxiliary materials commonly used in pharmacy.

[0012] Wherein, the oral preparation is decoction, oral liquid, granule, capsule, powder, pill or tablet.

[0013] The present invention provides use of the traditional Chinese medicine composition in preparing a medicine for preventing and / or treating low anterior rectal resection syndrome.

[0014] Wherein, the medicine is used to treat low anterior rectal resection syndrome for treating Yangming deficiency-cold syndrome.

[0015] The low anterior rectal resection syndrome refers to the anorectal dysfunction of varying degrees experienced by patients with rectal cancer after undergoing anal-preserving surgeries such as low anterior rectal resection and total mesorectal excision, such as increased bowel movement frequency, incomplete bowel movements, and even fecal incontinence and anal distension, especially for the treatment of diarrhea or anal distension. Common diseases include rectal cancer, rectal tumors, rectal ulcers, etc., and patients who have undergone rectal resection.

[0016] The Chinese medicine composition of the present invention is an in-hospital empirical prescription, which is modified from the Wuzhuyu Decoction in "Treatise on Febrile Diseases" by Zhang Zhongjing in the Han Dynasty. It has been repeatedly verified in clinical practice and has a significant effect on improving the symptoms of diarrhea and anal swelling in LARS patients.

[0017] LARS is a syndrome of abnormal defecation caused by the loss of normal rectal or colonic function after the occurrence of rectal or colon tumors and the subsequent artificial removal of rectal or colon tumors. According to traditional Chinese medicine, the stomach, small intestine, and large intestine all belong to Yangming, and Yangming dries gold and transforms dregs to transport body fluids. LARS is caused by acquired factors that cause the loss of Yangming function. From the perspective of the six meridians, the LARS disease is located in Yangming. Yangming is divided into meridian syndrome and visceral syndrome, and visceral syndrome is divided into heat syndrome and cold syndrome. After surgery, rectal cancer patients suffer from spleen and stomach deficiency and insufficient vital energy. The inventors differentiated LARS into Yangming deficiency and cold syndrome in traditional Chinese medicine based on the clinical manifestations of LARS patients. At present, the traditional Chinese medicine classification of LARS includes: spleen and kidney deficiency type (spleen and kidney yang deficiency type and spleen and kidney qi deficiency type), spleen deficiency and dampness syndrome, and spleen deficiency and qi collapse syndrome. There is no literature report on the differentiation of LARS into Yangming deficiency and cold syndrome in traditional Chinese medicine.

[0018] Yangming deficiency and cold syndrome is a syndrome type of six meridian differentiation of cold. The original text of Treatise on Cold Damage is in Article 243 of Treatise on Cold Damage: Differentiation of Yangming Disease Pulse and Symptoms and Treatment. "Wanting to vomit after eating belongs to Yangming. Wuzhuyu Decoction is the main treatment. If the decoction makes the condition worse, it belongs to the upper Jiao." Article 190: "If a patient with Yangming disease can eat, it is called stroke; if he cannot eat, it is called cold." Article 191: "If a patient with Yangming disease suffers from cold, he cannot eat, has difficulty urinating, and sweats profusely on his hands and feet. This is the onset of solid masses. The stool must be hard at first and then loose. The reason for this is that the stomach is empty and cold, and water and food cannot be separated." According to the above three original texts, the pathogenesis of Yangming deficiency and cold is fear of cold and inability to receive water and food, resulting in inability to eat and symptoms of hard stool at first and then loose stool. Doctors of all dynasties have been particularly insightful in explaining the Yangming deficiency and cold syndrome. Huang Yuanyu, a master of qi transformation in the Qing Dynasty, discussed in "Shanghan Xuanjie" that Yangming transforms qi from dry metal, which is dry earth; Taiyin is dominated by wet earth, which is wet earth. In fact, it is always in Yangming, so-called Yangming middle earth, no further transmission, which is the syndrome of Qi; if it is weak, the disease is in Yangming and the yang is weak and the qi is retreating, and the Taiyin spleen will rise and take over its power. The foot Yangming stomach uses the hand Yangming large intestine to transform dryness. If the hand Yangming large intestine cannot transform dryness, the water is cold and the earth is wet, the yin qi condenses, the masses are hard, and many diseases are loose and diarrhea, which is the so-called large mass diarrhea in the fifty-seventh difficult chapter of the Difficult Classic. The late old Chinese medicine doctor Mr. Li Chengdao also discussed the Yangming deficiency cold syndrome in his "Experiences in Clinical Validation of Treatise on Febrile and Miscellaneous Diseases". "I read through the 83 articles on Yangming disease pulse and treatment in Treatise on Febrile Diseases repeatedly, and then I realized that the symptoms of Yangming disease should be divided into two: one is internal heat, and the other is internal deficiency cold syndrome."

[0019] Wuzhuyu Decoction comes from Zhang Zhongjing's Treatise on Febrile Diseases in the Han Dynasty. "Eating food and wanting to vomit belongs to Yangming, and Wuzhuyu Decoction is the main treatment." It is mainly used to treat deficiency and cold syndromes of Yangming, Shaoyin and Jueyin meridians. The pathogenesis of the diseases it treats is mostly attributed to deficiency and cold of the liver and stomach and turbid yin rising. Zheng Qin'an mentioned in the True Transmission of Medical Principles that "Wuzhuyu Decoction is a medicine for reducing adverse reactions, nourishing the liver and warming the middle." Therefore, Wuzhuyu Decoction plus or minus is the main prescription for LARS treatment. The drug formula of the present invention takes Wuzhuyu, ginseng and roasted ginger from "Wuzhuyu Decoction" to nourish the middle and reduce adverse reactions.

[0020] Evodia rutaecarpa is bitter and pungent in taste, and enters the liver, spleen, stomach, and kidney meridians. It enters the foot yangming and foot taiyin meridians, and can descend yangming and raise taiyin meridians. Ginseng is sweet in taste to replenish yang, slightly bitter in taste to replenish yin, benefit the five internal organs' vital energy, raise stomach qi, and treat spleen and stomach yang deficiency. It can warm and replenish the spleen and stomach, restore yang and rescue adverse conditions. The two are used together as the main medicine to warm and replenish the spleen and stomach, raise yang and stop diarrhea, and descend adverse conditions and stop vomiting. Astragalus enters the hand and foot taiyin meridians, is sweet, warm and pure yang, can harmonize yang, benefit yin, purge heat, help stomach qi, and benefit the triple burner's vital yang. Atractylodes macrocephala has a thick taste and a thin qi, enters the foot yangming meridian, can strengthen stomach yang to transform spleen yin, and roasted ginger can warm the spleen and stomach, treat internal cold, and help Evodia rutaecarpa regulate the spleen and stomach. Astragalus and Atractylodes macrocephala are added to the formula and used together with roasted ginger to assist ginseng and Evodia rutaecarpa in warming and nourishing the spleen and stomach, and enhancing the effect of nourishing the spleen and replenishing qi. The three medicines are the ministerial medicines. Cimicifuga has the effect of raising yang qi, can directly enter the yangming and taiyin primordial qi, lead the clear qi upward, level the qi of the five internal organs and six bowels, and go up with the stomach qi. Bupleurum has the effect of raising yang qi, and the two are adjuvants, leading qi upward and lifting the sinking qi. Terminalia chebula belongs to the spleen and large intestine meridians, astringes Taiyin to stop diarrhea, and Prunus mume astringes the lungs, astringes the intestines, produces body fluids, greatly replenishes the primordial yin, uses yin to replenish qi, and collects the primordial yin in the lower burner to transform yang. The two are the guiding medicines to enhance the effect of astringing the intestines and stop diarrhea. The whole formula has the effect of descending yangming, ascending Taiyin, astringing the intestines and stopping diarrhea.

[0021] The beneficial effects of the present invention are:

[0022] The pharmaceutical composition of the present invention treats low anterior rectal resection syndrome, has the effects of lowering Yangming, raising Taiyin, astringing the intestine and stopping diarrhea, and is particularly effective in improving diarrhea and anal swelling in LARS patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 This is the statistical chart of the average number of bowel movements per day of LARS;

[0024] Figure 2 This is a statistical chart of VAS scores for anal distension of the medicinal mixture of the present invention. DETAILED DESCRIPTION

[0025] The raw materials and equipment used in the present invention are all known products, which are obtained by purchasing commercial products. In order to make the purpose, technical solution and advantages of the present application clearer, the technical solution of the present application will be described in detail in conjunction with the embodiments below, but the protection scope of the present invention is not limited thereto.

[0026] Example 1 Preparation of the pharmaceutical composition of the present invention

[0027] Take the following raw materials: 18g of Evodia rutaecarpa, 15g of Ginseng, 10g of Astragalus, 12g of Atractylodes macrocephala, 10g of Paojiang, 10g of Cimicifuga, 10g of Bupleurum, 10g of Terminalia chebula, and 10g of Prunus mume. Add 10 times the amount of water, heat and reflux to extract twice, each time for 1 hour, combine the extracts, and make a mixture to obtain the product.

[0028] Example 2 Preparation of the pharmaceutical capsule of the present invention

[0029] Weigh the raw materials: 25g of Evodia rutaecarpa, 25g of ginseng, 45g of Astragalus, 25g of Atractylodes macrocephala, 25g of Zingiber officinale, 25g of Cimicifuga heracleifolia, 25g of Bupleurum chinense, 25g of Terminalia chebula, and 25g of Prunus mume, add water and boil, filter, concentrate the filtrate to an extract, add starch, granulate, reconstitute the grains, and put into capsules.

[0030] Example 3 Preparation of the pharmaceutical tablets of the present invention

[0031] Weigh the raw materials: 10 parts of Evodia rutaecarpa, 10 parts of ginseng, 10 parts of astragalus, 10 parts of Atractylodes macrocephala, 8 parts of roasted ginger, 10 parts of Cimicifuga heracleifolia, 10 parts of Bupleurum chinense, 8 parts of Terminalia chebula, and 10 parts of Prunus mume, grind into powder, and directly press into tablets to obtain the product.

[0032] The beneficial effects of the present invention are demonstrated by clinical trials as follows.

[0033] Test Example 1 Clinical Trial of the Chinese Medicine of the Present Invention

[0034] 1. General Information

[0035] Eighteen patients who met the criteria were enrolled in the outpatient department of West China Hospital of Sichuan University and were divided into two groups according to the random number table method. The two groups were comparable in age, gender, and disease course.

[0036] 2. Diagnostic criteria

[0037] Western medicine diagnostic criteria: Refer to the international consensus definition of LARS proposed by the LARS International Collaborative Group in 2020: The patient must have undergone anterior resection (sphincter-sparing rectal resection) and have at least one of the symptoms leading to one of the consequences:

[0038] (1) Symptoms: frequent bowel movements; urgency; fecal incontinence; fecal contamination; difficulty emptying; changes in stool consistency; recurrent anal pain; unpredictable changes in bowel function;

[0039] (2) Consequences: Toilet dependence; excessive focus on bowel function; dissatisfaction with bowel function; seeking solutions and compromises; affecting mental and emotional state; affecting daily social activities; affecting intimate relationships; affecting image commitment and responsibility.

[0040] TCM diagnostic criteria: If two of the following main and secondary symptoms are present, it is Yangming deficiency-cold syndrome:

[0041] Main symptoms: fatigue, anal distension, abdominal distension, poor appetite, frequent bowel movements, rectal prolapse, incontinence;

[0042] Secondary symptoms: sallow complexion, weak bowel movements, loose stools, dizziness, pale tongue, thin white tongue coating, and slow or weak pulse.

[0043] 3. Inclusion criteria

[0044] (1) Aged 18-75, regardless of gender;

[0045] (2) Patients with a preoperative clinical diagnosis of high-mid rectal cancer or low-mid rectal cancer and TNM stage I-III;

[0046] (3) Meet the LARS diagnostic criteria and LARS score ≥ 30 points;

[0047] (4) Defecation frequency > 5 times / day;

[0048] (5) The time since anal preservation surgery for rectal cancer (including preventive stoma reduction surgery) is ≥ 1 month;

[0049] (6) The estimated survival time is ≥ 6 months;

[0050] (7) Have basic communication and comprehension skills, and be able to cooperate with examinations, treatment, and follow-up;

[0051] (8) Voluntarily participate in this study and sign the informed consent form;

[0052] 4. Intervention measures

[0053] Experimental Group

[0054] In the present application, 9 patients who were given the Chinese medicine compound preparation of the present invention were randomly selected as the test group (the ratio was prepared according to the method in Example 1: 18g of Evodia rutaecarpa, 15g of Ginseng, 10g of Astragalus, 12g of Atractylodes macrocephala, 10g of Paojiang, 10g of Cimicifuga, 10g of Bupleurum, 10g of Terminalia chebula, and 10g of Prunus mume. The mixture of Example 1 was given three times a day after meals for a course of 8 weeks, and during the treatment period, the patients stopped using other drugs that improve the gastrointestinal dysfunction of the patients and promote the recovery of intestinal function (other drugs such as those taken daily to treat diseases such as hypertension were not stopped). The number of bowel movements and the VAS score of anal distension of the patients were recorded, and the average daily number of bowel movements and the average daily VAS score of anal distension were calculated at week 0, week 2, and week 4, respectively.

[0055] Control group

[0056] Nine patients were randomly selected and given Buzhong Yiqi Decoction as the control group (10g ginseng, 20g stir-fried Atractylodes macrocephala, 5g roasted licorice, 30g astragalus, 10g angelica, 10g bupleurum, 5g cimicifuga, 15g tangerine peel). The Buzhong Yiqi Decoction mixture was given three times a day after meals, and the rest of the treatment methods were the same as the experimental group.

[0057] 5. Efficacy results

[0058] The clinical effect evaluation of Chinese herbal compound preparations on improving LARS diarrhea symptoms is shown in Table 1 and Figure 1 As shown:

[0059] Table 1 Statistics of the average number of bowel movements per day in LARS ( , n=9)

[0060] Group 0 Weeks 2 weeks 4 weeks Buzhong Yiqi Decoction Group 9.67 ± 2.78 6.78 ± 2.10 <![CDATA[4.44 ± 1.13 ** ]]> The drug combination of the present invention 14.00 ± 6.22 <![CDATA[8.33 ± 3.35 ** ]]> <![CDATA[6.44 ± 3.17 **** ]]>

[0061] Note: Compared with the data of week 0, ** P<0.01, **** P<0.0001

[0062] The drug of the present invention improves the LARS anal swelling evaluation, which is evaluated by the anal swelling VAS score. The results are shown in Table 2 and Figure 2 As shown:

[0063] Table 2 Average anal swelling VAS score ( , n=9)

[0064] Group 0 Weeks 2 weeks 4 weeks The drug combination of the present invention 33.33 ± 31.62 21.11 ± 19.81 21.86

[0065] 6. Results Analysis

[0066] Buzhong Yiqi Decoction comes from "Neiwaishang Bianhuo Lun" written by Li Gao (named Dongtan) in the Jin and Yuan Dynasties, and is also seen in "Spleen and Stomach Theory". It is made according to the idea of ​​"warming those who are tired" and "benefiting those who are damaged" in "Huangdi Neijing", and has the effects of tonifying the middle and replenishing qi, raising yang and lifting the sunken. Currently, it is often used in clinical studies to treat and improve postoperative defecation disorders or gastrointestinal dysfunction after rectal cancer surgery, mainly diarrhea. Therefore, the present invention designs Buzhong Yiqi Decoction as a control group to compare the efficacy of the compound preparation of the present invention in improving diarrhea symptoms in LARS patients.

[0067] As shown in Table 1 and Figure 1 As shown in the figure, the Buzhong Yiqi Decoction group was able to improve the frequency of bowel movements in patients at the second week of treatment, but there was no statistical significance. The frequency of bowel movements in patients was significantly improved at the fourth week ( P <0.01); and the drug of the present invention can significantly improve the frequency of bowel movements in patients in the second week of treatment ( P <0.01), and the frequency of bowel movements in patients was significantly improved in the 4th week ( P <0.0001), indicating that the drug of the present invention is more effective in improving diarrhea symptoms in LARS patients.

[0068] As shown in Table 2 and Figure 2 As shown, after 4 weeks of treatment with the drug of the present invention, the VAS score of anal distension in LARS patients was improved, indicating that the drug of the present invention can improve the anal distension feeling of patients while improving diarrhea symptoms, greatly improve the quality of life of patients, and has great prospects for clinical application.

[0069] The following is case information of LARS patients treated with the drug of the present invention. It can be seen that the drug of the present invention has great advantages in clinical application in improving the defecation function and anal swelling symptoms of patients.

[0070] Test Example 2 Typical clinical cases of the drug of the present invention

[0071] Case 1

[0072] Mao XX, female, 65 years old, main medical history: 3+ months after rectal cancer surgery, increased bowel movement for 1+ month. 3+ months ago, she underwent "laparoscopic transabdominal and anal resection of ultra-low rectal cancer (ISR-5), NOSE-3b one-time colon anal anastomosis liver protection" at West China Hospital, and was discharged after treatment. 1+ month, the frequency of bowel movements increased, an average of 20 times / day, yellow loose stools, and she went to a certain hospital for treatment and was diagnosed with rectal cancer anterior resection syndrome. The condition improved during the treatment, but worsened when the medication was stopped. Both Chinese and Western medicines were ineffective. Current symptoms: general fatigue, weight loss, 10-15 bowel movements per day, diarrhea, occasional abdominal pain, anal swelling, slightly red tongue tip, thin white tongue coating, stringy and thin pulse, no history of hepatitis, tuberculosis, and no history of drug allergies. Western diagnosis: rectal cancer anterior resection syndrome, Chinese medicine diagnosis: diarrhea (Yangming deficiency cold syndrome), treatment: raise yang and lift the sunken, dispel cold and stop diarrhea. After taking the Chinese medicinal compound of Example 1 of the present invention orally for 1 month, the frequency of bowel movements was 3-5 times / day, and the feeling of heaviness and distension in the anus disappeared.

[0073] Case 2

[0074] Xie XX, female, 72 years old, main medical history: rectal neoplasms were found 2+ months ago, diarrhea and anal distension for 1 month. Colonoscopy at West China Hospital 2+ months ago showed: about 3cm away from the anus, a 3cm-sized raised neoplasm was visible, the surface was congested and eroded, and the biopsy was brittle and easy to bleed. The pathological biopsy tumor stage was cT2N0M0. After excluding surgical contraindications, laparoscopic rectal cancer ultra-low resection, colon anastomosis + intestinal adhesion lysis + anoplasty were performed at West China Hospital. After surgery, she recovered well and was discharged from the hospital. One month ago, the frequency of bowel movements began to increase, about 15 times / day, with small amounts and incomplete defecation. She needed to use sanitary napkins for a long time, anal distension, and normal urination. Repeated treatment with montmorillonite powder, probiotics, etc. did not show significant improvement, so she came to the outpatient clinic of West China Hospital for further treatment. Current symptoms: general fatigue, poor appetite, 15-16 bowel movements per day, diarrhea and abdominal distension, anal distension, red tongue, thick white fur, and deep pulse. No history of hepatitis, tuberculosis, or drug allergy. 7+ years ago, he was treated with surgery at West China Hospital for "intestinal adhesion after conservative treatment of pancreatitis" and recovered well after surgery. Western diagnosis: anterior resection syndrome of rectal cancer, Chinese medicine diagnosis: diarrhea (Yangming deficiency and cold syndrome), treatment: raising yang and lifting sunken, dispersing cold and stopping diarrhea. After taking the Chinese medicine compound of Example 1 of the present invention orally for 2 months, the number of bowel movements was 10 times / day, and the feeling of anal distension disappeared. After follow-up for 1 month, the patient was in good spirits, with a bowel movement of about 5-8 times / day, which was basically formed.

[0075] Case 3

[0076] Liang XX, male, 78 years old, main medical history: 1 month after ileal surgery, fecal incontinence for 1+ week. 1 month ago, the patient was admitted to West China Hospital due to ileostomy status, and small bowel resection, intestinal anastomosis and intestinal adhesion lysis were performed under general anesthesia. After the operation, he recovered well and was discharged smoothly. 1+ week ago, after resuming normal diet, he began to have diarrhea, fecal incontinence, about 15 times a day, anal distension, no abdominal pain, no nausea and vomiting, no fever, chills and other discomforts. After taking antidiarrheal drugs (montmorillonite powder, diphenoxylate, etc.) (the specific dosage is unknown) on his own, there was no obvious improvement, so he went to the Department of Integrated Traditional Chinese and Western Medicine of West China Hospital. Current symptoms: clear mind, poor spirit, general fatigue, anemia, 12-15 bowel movements per day, diarrhea, incomplete defecation, anal distension VAS score of 20 points, red tongue, thin white fur, left pulse deep, right pulse thin. No history of hepatitis, tuberculosis, no drug allergy. Previous medical history of coronary heart disease and Alzheimer's disease. Western medicine diagnosis: rectal cancer anterior resection syndrome, Chinese medicine diagnosis: diarrhea (Yangming deficiency and cold syndrome), treatment: raising yang and lifting the sunken, dispersing cold and stopping diarrhea. After taking the Chinese medicine compound of Example 1 of the present invention orally for half a month, the number of bowel movements was 12 times / day, and the feeling of anal distension was reduced compared with before. After one month of follow-up, the patient was in good spirits, and the number of bowel movements was about 10 times / day, which was basically formed. After telephone communication, he asked to continue Chinese medicine conditioning.

[0077] Case 4

[0078] Zhao XX, male, 67 years old, medical history: diagnosed with rectal cancer 8 months ago, 3 months after neoadjuvant treatment. Endoscopic biopsy pathology 8 months ago showed upper rectal adenocarcinoma with liver and lung metastasis (cT3N2M1b IVa stage). After 3 months of neoadjuvant treatment (unknown details), there was no significant improvement, and he went to West China Hospital for treatment. After completing relevant examinations, excluding absolute contraindications, he underwent laparoscopic high anterior resection and colorectal anastomosis of rectal cancer under general anesthesia on April 17, 2024. After surgery, he was given fluid replacement, anti-infection and other treatments and was discharged from the hospital. 1+ month ago, the patient had diarrhea, about 6 times a day, intermittent abdominal pain, no abdominal distension, and no anal distension. After taking probiotics, pinaverium bromide, montmorillonite powder and other drugs, there was no significant improvement, so he went to the outpatient clinic of West China Hospital. Current symptoms: clear mind, general spirit, anxious state, 6-7 bowel movements / day, unformed, dull abdominal pain, no anal distension, no fever and chills. The tongue is pale red, the coating is thin and white, the pulse is deep, and weak when pressed hard. There is no history of hepatitis, tuberculosis, or drug allergy. There is a history of chronic obstructive pulmonary disease. The diagnosis of Western medicine is: rectal cancer anterior resection syndrome, and the diagnosis of traditional Chinese medicine is: diarrhea (Yangming deficiency and cold syndrome). Treatment: raising yang and lifting the sunken, dispersing cold and stopping diarrhea. After taking the Chinese medicine compound of Example 1 of the present invention orally for 1 month, the number of bowel movements is 2 times / day. Follow-up for 1 month, normal life has been restored.

[0079] Case 5

[0080] Du XX, male, 75 years old, main complaint history: anal secretions for 4+ years, rectal mass found for 2+ months, diarrhea for 1 month. Anal secretions for 4+ years (details unknown). Colonoscopy at West China Hospital 2+ months ago showed: mass in the middle rectum, rectal cancer (T3N1bM0) considered. Pathology showed: rectal neoplasms, adenocarcinoma with focal canceration. After excluding absolute contraindications, laparoscopic radical high rectal resection was performed under general anesthesia at West China Hospital, and the patient recovered well after surgery. One month ago, the patient had abdominal distension, anal distension, diarrhea, frequent bowel movements, about 8-10 times a day, no nausea and vomiting, no fever and chills, no black stools and bloody stools. Self-administered probiotics and other drugs did not show significant improvement, and he went to the outpatient clinic of West China Hospital. Current symptoms: clear mind, poor spirit, insomnia, 8 bowel movements / day, diarrhea, anal distension, no fever and chills, etc. Pale red tongue, thick white fur, deep and thin pulse, weak when pressed hard. Physical examination: soft abdomen, no tenderness, rebound pain and muscle tension in the abdomen. No history of hepatitis, tuberculosis, drug allergy, and blood transfusion. Western diagnosis: anterior resection syndrome of rectal cancer, Chinese medicine diagnosis: diarrhea (Yangming deficiency and cold syndrome), treatment: raising yang and lifting the sunken, dispersing cold and stopping diarrhea. After taking the Chinese medicine compound of Example 1 of the present invention orally for 1 month, the number of bowel movements was 5 times / day. Follow-up for 1 month, the number of bowel movements was basically normal, but there was still abdominal distension, and important conditioning was continued.

[0081] Case 6

[0082] Han XX, male, 71 years old, main complaint history: repeated blood in the stool for half a year, diarrhea for 2+ months. The patient had repeated blood in the stool half a year ago, and the amount of blood in the stool was unknown each time. Colonoscopy at West China Hospital showed: 0.4-0.5 cm polyps were visible in the blind tip and sigmoid colon. Rectum and anal canal: Horseshoe-shaped neoplasms can be seen occupying 3 / week of the intestinal cavity about 8-12 cm from the anus, and the new material is fragile and easy to bleed. A 0.4 cm polyp can be seen about 5 cm from the anus. Pathology: Glandular high-grade intraepithelial neoplasia / intramucosal carcinoma formation, cancer cells are MLH (+), MSH2 (+), MSH6 (+), PMS2 (+), HER2 (0). After excluding surgical contraindications, laparoscopic radical low anterior rectal resection and D3 lymph node dissection were performed under general anesthesia at West China Hospital. After surgery, antibiotics were given to prevent infection, fluid replacement and other symptomatic supportive treatments, and the patient improved and was discharged from the hospital. 2+ months ago, due to incontinence of bowel movements, the amount of each time varied, about 7-10 times / day, anal distension and discomfort, which seriously affected the quality of life, he went to West China Hospital for treatment. Current symptoms: clear consciousness, good spirit, 7 bowel movements / day, fecal incontinence, anal distension (VAS score of about 10 points), dry mouth, palpitations, no fever and chills, no nausea and vomiting, no black stools and bloody stools, etc. Pale tongue, white fur, thin and astringent pulse. Physical examination: no special. Past history: 2 hemorrhoid surgeries (specific details unknown). Western diagnosis: anterior resection syndrome of rectal cancer, Chinese medicine diagnosis: diarrhea (Yangming deficiency and cold syndrome), treatment: rising yang and lifting the sunken, warming yang and stopping diarrhea. After taking the Chinese medicine compound of Example 1 of the present invention orally for 1 month, the number of bowel movements was 5 times / day. Follow-up for 1 month, the number of bowel movements was 4 times / day, which was basically back to normal.

[0083] Case 7

[0084] Li XX, male, 69 years old, main complaint history: increased bowel movement for 6+ years, rectal tumor found 2+ months ago, aggravated for 1 week. The patient had increased bowel movement 6 years ago, about 10-15 times a day, unformed, no black stool or bloody stool, no significant improvement after treatment in other hospitals. 2+ months ago, he visited West China Hospital for colonoscopy, which showed: a nodular tumor of about 4.5 cm in size was visible 10 cm away from the anus, with lobed surface, and obvious glandular duct under NBI. Glycerol fructose + methylene blue was injected submucosally around the lesion, and the lifting was good. A Dual knife was used to perform a C-shaped incision on the anal side, peeling off part of the lesion submucosal layer, and then circumferentially incised the lesion mucosa. During the operation, it was found that the center of the lesion had invaded the muscularis propria, and the possibility of advanced Ca was considered. After excluding absolute contraindications, the patient underwent "laparoscopic ultra-low anterior resection of rectal cancer and colorectal anastomosis" under general anesthesia on April 24, 2024. After the operation, he was given treatment such as infection prevention, fluid replacement, and nutritional support, and was discharged from the hospital after improvement. One week ago, the patient had an increase in bowel movements again, about 25 times / day, with a small amount of yellow watery stools, accompanied by fatigue, a feeling of anal prolapse, occasional palpitations, poor appetite, no fever and chills, and no black stools or bloody stools. He took montmorillonite powder, compound glutamine and other drugs by himself, but there was no obvious improvement, so he went to West China Hospital for treatment. Current symptoms: clear mind, good spirit, fatigue, fear of cold, 25 bowel movements / day, fecal incontinence, anal swelling (VAS score of about 100 points), dry mouth and no desire to drink, palpitations and chest tightness, poor appetite, and no obvious edema in both lower limbs. The tongue is pale purple, the fur is white, and the pulse is deep and stringy. Physical examination: The abdominal incision healed well, without redness, swelling, pain or exudation. Past history: No special. Western diagnosis: anterior resection syndrome of rectal cancer, Chinese medicine diagnosis: diarrhea (Yangming deficiency and cold syndrome), treatment: raising yang and lifting the sunken, dispersing cold and stopping diarrhea. After taking the Chinese medicine compound of Example 1 of the present invention orally for 2 months, the number of bowel movements was 10 times / day. Follow-up for 1 month, the number of bowel movements was 10 times / day, the patient said that his mental state was better than before, and he was re-examined for medicine.

[0085] Case 8

[0086] Yue XX, male, 56 years old, complained of "fecal incontinence for half a month 2+ months after rectal cancer surgery". Colonoscopy at West China Hospital 2+ months ago showed anastomosis in the rectum near the anal canal, and obvious congestion of the mucosa on the anal side of the anastomosis, accompanied by nodular changes. Transrectal color Doppler ultrasound (perirectal) examination showed: 1 / 6 annular thickening of the anal canal wall below the anastomosis (2-4 o'clock), with an upper and lower diameter of about 24mm, a maximum thickness of about 6mm, and a lower edge reaching the white line area. The local hierarchical structure was unclear, and punctate blood flow signals were visible inside. Several lymph nodes were found around the rectum, the larger of which was about 12×7mm, with unclear cortical-medullary boundaries and not rich blood flow signals inside. After excluding absolute contraindications, the patient underwent transanal rectal tumor resection under general anesthesia at West China Hospital. During the operation, the patient was found to have a neoplasm of about 2.0×1.0cm in size at 4-6 o'clock in the rectum and anal canal, a superficial raised neoplasm, across the dentate line, with a depressed center, medium texture, and movable. The tumor was completely removed during the operation and sent for frozen examination. The frozen pathology results showed that adenocarcinoma was found. After surgery, the patient was given symptomatic treatment such as oxygen inhalation, fluid replacement, and preventive anti-infection, and improved. Half a month ago, the patient had fecal incontinence, about 15 times a day, unformed, with anal swelling (VAS score of about 70 points), abdominal pain and distension, and normal urination. Self-administration of montmorillonite powder and Jinshuangqi did not show significant improvement. For further treatment, the patient visited the Department of Integrated Traditional Chinese and Western Medicine of West China Hospital. Current symptoms: clear mind, general spirit, fatigue, fear of cold and wind, poor sleep, poor appetite, defecation 15 times / day, abdominal discomfort, anal pain, dry mouth and thirst, no panic and chest tightness, no aversion to cold and fever, no edema of both lower limbs. Pale tongue, thin white fur, slippery pulse. Physical examination: normal abdominal appearance, soft abdomen, no tenderness and rebound pain, no mass palpable in the abdomen, no liver palpable under the ribs, no kidneys palpable. Past history: no special. Western diagnosis: anterior resection syndrome of rectal cancer, gastrointestinal dysfunction. Chinese medicine diagnosis: diarrhea (Yangming deficiency and cold syndrome), treatment: rising yang and lifting sinking, dispersing cold and stopping diarrhea. After taking the Chinese medicine compound of Example 1 of the present invention orally for 2 weeks, the number of bowel movements was 6 times / day, and the anal swelling score (VAS score of about 20 points) was taken for 1 month, and the number of bowel movements was 2 times / day, which was basically back to normal.

[0087] In summary, the present invention discloses a Chinese medicine composition for treating low anterior resection syndrome, which can significantly reduce the number of bowel movements and anal distension in patients, improve the quality of life of patients, and has a significant therapeutic effect. The composition provided by the present invention has easy-to-obtain raw materials, a simple preparation method, and has good application prospects in the preparation of drugs for preventing and / or treating low anterior resection syndrome.

[0088] In summary, the medicinal flavor and dosage of the present invention have been proven through a large number of clinical practices to be superior to Buzhong Yiqi Decoction in terms of the efficacy of improving diarrhea, and can significantly improve the patient's anal swelling. The Chinese medicine composition provided by the present invention can significantly improve the symptoms of LARS patients, improve the quality of life of patients, and has a positive effect on the prognosis and recovery of patients after rectal resection. Its subsequent research and development can make up for the current state of no medicine available for such patients, and has great clinical application value and prospects.

Claims

1. A Chinese medicine composition for preventing and / or treating low anterior rectal resection syndrome, characterized in that: It is a preparation made from raw materials in the following weight ratio: 18 parts of Evodia rutaecarpa, 15 parts of ginseng, 10 parts of astragalus, 12 parts of atractylodes, 10 parts of roasted ginger, 10 parts of cimicifuga, 10 parts of bupleurum, 10 parts of terminalia chebula, and 10 parts of ebony.

2. The Chinese medicine composition for preventing and / or treating low anterior rectal resection syndrome according to claim 1, characterized in that: It is an oral preparation prepared with the powder of the raw material drug, the water extract of the raw material drug or the organic solvent extract of the raw material drug as the active ingredient, and the excipients commonly used in pharmacy.

3. The Chinese medicine composition for preventing and / or treating low anterior rectal resection syndrome according to claim 2, characterized in that: The oral preparation is a decoction, an oral liquid, a granule, a capsule, a powder, a pill or a tablet.

4. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for preventing and / or treating low anterior rectal resection syndrome.

5. The use according to claim 4, characterized in that: The medicine is a medicine for treating low anterior rectal resection syndrome of Yangming deficiency-cold syndrome.

6. The use according to claim 4 or 5, characterized in that: The medicine is a medicine for treating diarrhea or anal swelling.

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