Traditional Chinese medicine enema for treating radiation enteritis

Abstract

The invention provides a traditional Chinese medicine enema for treating radiation enteritis, and belongs to the technical field of biological medicines. According to the technical scheme, a simplified formula and a complete formula are included, the complete formula comprises 12 components including radix scutellariae, rhizoma coptidis, the root of Chinese pulsatilla, the bark of ash, raw radix sanguisorbae, herba patriniae, vinegar-processed rhizoma corydalis, radix puerariae thomsonii, cortex phellodendri, oldenlandia diffusa, dandelion and the root of three-nerved spicebush, and according to the simplified formula, the cortex phellodendri, the oldenlandia diffusa, the dandelion and the root of three-nerved spicebush are removed on the basis of the complete formula. Compared with a complete formula, the simple formula provided by the invention has the advantages that the medicine flavor is reduced from 12 to 8, and potential medicine interaction and intestinal irritation are reduced. The Chinese pulsatilla root decoction is based on Chinese pulsatilla root decoction, the raw sanguisorba root and the patrinia herb are supplemented to enhance mucous membrane repair, the corydalis tuber relieves pain, the pachyrhizua angulatus improves diarrhea, and effective improvement of a classic formula is achieved. The traditional Chinese medicine composition has the effects of clearing heat, drying dampness, cooling blood, detoxifying, promoting qi circulation, relieving pain, raising yang and stopping diarrhea, has the effects of clearing heat, cooling blood, stopping bleeding, relieving pain and the like, and has an exact and remarkable treatment effect on radiation enteritis.

Description

Technical Field

[0001] The invention relates to the technical field of biomedicine, in particular to a traditional Chinese medicine enema for treating radiation enteritis. Background Art

[0002] Cervical cancer and endometrial cancer are common malignancies of the female reproductive system. External pelvic radiotherapy is an important treatment option for these cancers. Pelvic radiotherapy inevitably causes damage to pelvic organs, particularly the rectum. Almost all patients who undergo pelvic radiotherapy experience rectal injury. Radiation enteritis (RE) can be acute or chronic. Acute RE refers to the onset of increased intestinal motility and cramping one to two weeks after the start of radiotherapy, manifesting as abdominal pain, nausea, vomiting, and diarrhea. Chronic RE refers to the onset of abdominal pain, bloody stools, anal pain, tenesmus, and dyspnea several months to years after the completion of radiotherapy. According to statistics, each year in the United States, 1.5 to 2 million cancer patients who survive radiotherapy develop intestinal disturbances. Mild RE symptoms are tolerable and resolve spontaneously. Severe RE symptoms can persist for a long time and may be accompanied by bleeding, strictures, or fistulas. In the most severe cases, it can lead to death.

[0003] The incidence of RE is correlated with radiation dose. At a radiation dose of 45 Gy, approximately 5% of patients experience RR symptoms, while at a dose of 65 Gy, the incidence rises to 50%. The radiation doses used to treat different malignancies are very close to those that cause RE. For example, the average doses for cervical or endometrial cancer, ovarian cancer, and bladder cancer are 40-80 Gy, 40-50 Gy, and 40-60 Gy, respectively. Reports indicate that even with doses less than 45 Gy for external pelvic radiotherapy, the incidence of severe late small bowel complications remains as high as 5%-15%. Patients with cervical and endometrial cancer who receive postoperative adjuvant radiotherapy have a relatively good prognosis and long survival due to their earlier stage. Therefore, in addition to achieving effective treatment outcomes, the goal of external pelvic radiotherapy should focus on mitigating acute and chronic radiation damage and improving patients' quality of life.

[0004] In clinical practice, RE lacks ideal prevention and treatment options other than symptomatic and supportive care. Current clinical treatments include: endoscopic laser coagulation or formaldehyde spraying for intestinal bleeding; the use of cytoprotectants such as amifostine before chemoradiotherapy to mitigate chemoradiotoxic reactions in the gastrointestinal tract and prevent RE; and the use of hyperbaric oxygen, oral antioxidants / probiotics, or parenteral nutrition for patients with persistent abdominal symptoms to accelerate intestinal mucosal regeneration and recovery of intestinal function. Traditional Chinese medicine has also made some attempts to treat RE, such as using Gegenqinlian Decoction for oral administration, Compound Danshen Injection for intravenous administration, and retention enemas with Chinese herbal decoctions, which have shown some efficacy. However, these treatments are generally symptomatic and supportive, and their efficacy is less than ideal. Under these circumstances, the development of effective drugs and therapies remains a technical challenge in this field. Summary of the Invention

[0005] The present invention aims to provide a Chinese medicine enema for treating radiation enteritis in response to the technical defects of the prior art, so as to solve the technical problem in the prior art of lacking effective therapeutic drugs and treatment plans for radiation enteritis.

[0006] In order to achieve the above technical objectives, the present invention adopts the following technical solutions: A traditional Chinese medicine enema for treating radiation enteritis comprises the following ingredients in parts by weight: 8-12 parts of scutellaria baicalensis, 8-12 parts of coptis chinensis, 12-18 parts of pulsatilla scabra, 8-12 parts of qinpi cortex, 12-18 parts of sanguisorba officinalis, 12-18 parts of patrinia herba, 8-12 parts of vinegar-processed corydalis yanhusuo, and 15-25 parts of kudzu vine.

[0007] Preferably, the Chinese medicine enema comprises the following ingredients in parts by weight: 10 parts of Scutellaria baicalensis, 10 parts of Coptis chinensis, 15 parts of Pulsatilla scabra, 10 parts of Fraxinus qin, 15 parts of Sanguisorba officinalis, 15 parts of Patrinia chinensis, 10 parts of vinegar-processed Corydalis yanhusuo, and 20 parts of Pueraria lobata.

[0008] Preferably, the Chinese medicine enema is composed of the following ingredients in parts by weight: 10 parts of Scutellaria baicalensis, 10 parts of Coptis chinensis, 15 parts of Pulsatilla scabra, 10 parts of Fraxinus qin, 15 parts of Sanguisorba officinalis, 15 parts of Patrinia chinensis, 10 parts of vinegar-processed Corydalis yanhusuo, and 20 parts of Pueraria lobata.

[0009] Preferably, the Chinese medicine enema further comprises the following ingredients in parts by weight: 10 parts of Phellodendron chinense.

[0010] Preferably, the Chinese medicine enema further comprises the following ingredients in parts by weight: 30 parts of Hedyotis diffusa.

[0011] Preferably, the Chinese medicine enema further comprises the following ingredients in parts by weight: 15 parts of dandelion.

[0012] Preferably, the Chinese medicine enema further comprises the following ingredients in parts by weight: 10 parts of Linderae serrata.

[0013] Preferably, the Chinese medicine enema is composed of the following ingredients in parts by weight: 10 parts of scutellaria baicalensis, 10 parts of coptis chinensis, 15 parts of pulsatilla scabra, 10 parts of qinpi cortex, 15 parts of sanguisorba officinalis, 15 parts of patrinia herba, 10 parts of vinegar-processed corydalis yanhusuo, 20 parts of kudzu vine, 10 parts of phellodendron amurense, 30 parts of oldenlandia diffusa, 15 parts of dandelion, and 10 parts of lindera striata.

[0014] The present invention provides a traditional Chinese medicine enema for treating radiation enteritis. The technical solution includes a simplified formula and a complete formula. The complete formula includes 12 ingredients: scutellaria baicalensis, coptis chinensis, pulsatilla scabra, qinpi cortex, sanguisorba officinalis, patrinia chinensis, vinegar-processed yanhusuo, kudzu vine, phellodendron amurense, hedyotis diffusa, dandelion, and lindera serrata. The simplified formula is based on the complete formula but excludes phellodendron amurense, hedyotis diffusa, dandelion, and lindera serrata.

[0015] The present invention is simplified as follows: 1. Retain the core heat-clearing and dampness-drying drugs Scutellaria baicalensis and Coptis chinensis: Both are important medicines for clearing heat and drying dampness. They are good at clearing damp heat in the middle and upper parts of the body, and can also purge fire and detoxify. They are effective for intestinal mucosal inflammation and internal damp heat caused by radiation enteritis.

[0016] Remove Huangbai: Although it clears heat and dries dampness, it tends to go to the lower burner (such as damp heat in the urinary system). After streamlining, Huangqin and Coptis chinensis are used to take care of damp heat in the middle burner and intestines.

[0017] 2. Highlight the classic combination of detoxification and anti-dysentery Bai Tou Weng + Qin Pi: Derived from Bai Tou Weng Decoction in Treatise on Febrile Diseases, it is specially used to treat bloody dysentery caused by heat toxins. It can clear damp heat from the intestines, cool blood and stop dysentery. It is also effective for the bloody stools and tenesmus caused by radiation enteritis.

[0018] 3. Strengthen cooling blood, stopping bleeding and draining pus Raw Sanguisorba officinalis: cools blood and stops bleeding, detoxifies and heals sores, and directly repairs bleeding and ulcers in the intestinal mucosa caused by radiation damage.

[0019] Patrinia scabra: clears away heat and detoxifies, removes blood stasis and discharges pus, improves local intestinal stasis and heat stagnation and ulcer exudation.

[0020] 4. Keep key symptomatic drugs Corydalis yanhusuo (prepared with vinegar): promotes blood circulation, qi circulation and relieves pain, relieves abdominal pain caused by radiation enteritis, and vinegar preparation enhances the analgesic effect.

[0021] Pueraria lobata: promotes the development of clear yang, produces body fluid and stops diarrhea, improves diarrhea and loss of intestinal fluid.

[0022] 5. Streamlining drugs with duplicate effects Remove Houttuynia cordata and Taraxacum mongolicum: Although both can clear away heat and detoxify, their effects overlap with those of Pulsatilla scabra and Patrinia lappa. After streamlining, the classic combination is mainly used.

[0023] Remove Wu Yao: Its function of warming the middle, promoting qi and relieving pain can be replaced by Corydalis yanhusuo to avoid the warm and dry nature of the medicine that promotes heat.

[0024] The following is the relevant basis for the components of the present invention in classical Chinese medicine theory, modern pharmacology and clinical research: 1. Heat-clearing and dampness-drying drugs (Scutellaria baicalensis, Coptis chinensis) Chinese Pharmacopoeia 2020 Edition Scutellaria baicalensis: bitter and cold in nature, enters the lung, gallbladder, spleen, and large intestine meridians, clears heat and dampness, purges fire and detoxifies, and is used for diarrhea caused by damp heat; Coptis chinensis: clears heat and dampness, purges fire and detoxifies, and is especially good at clearing damp heat in the middle burner (National Pharmacopoeia Committee, 2020).

[0025] Modern research support Baicalin and berberine can alleviate intestinal inflammation by inhibiting the NF-κB pathway.

[0026] 2. Baitouweng Decoction (Bulrushi, Qinpi) Classical Literature "Treatise on Febrile Diseases: Differentiation of Jueyin Disease Pulse and Symptoms and Treatment" states: "For patients with fever and heavy diarrhea, Bai Tou Weng Decoction is the main treatment," clearly stating its classic status in treating toxic heat and bloody diarrhea (Zhang Zhongjing, Eastern Han Dynasty).

[0027] Clinical Research Enema of Baitouweng decoction can reduce the levels of IL-6 and TNF-α and improve mucosal damage in patients with radiation enteritis.

[0028] 3. Cooling blood, stopping bleeding, and repairing mucosa (Sanguisorba officinalis, Patrinia scabra) Compendium of Materia Medica Sanguisorba officinalis “stops pus and blood, and treats intestinal wind”; Patrinia paniculata “breaks up long-standing blood clots, discharges pus and relieves pain” (Li Shizhen, Ming Dynasty).

[0029] Pharmacological evidence Tannins from raw Sanguisorba officinalis can astringe and stop bleeding, and promote the healing of intestinal mucosal ulcers; total flavonoids from Patrinia salsa can reduce inflammation by regulating intestinal flora.

[0030] 4. Promotes Qi flow, relieves pain, and stops diarrhea (Yinghusuo, Puerariae) Leigong Paozhi Lun Vinegar-processed Corydalis yanhusuo “specifically enters the blood, promotes qi circulation and relieves pain” (Lei Zhu, Northern and Southern Dynasties).

[0031] Modern Research Tetrahydropalmatine relieves visceral pain by inhibiting COX-2 expression; puerarin can regulate intestinal water metabolism and reduce diarrhea.

[0032] 5. Streamlining drug evidence Huang Bai and Damp-Heat in the Lower Burner The "Yaoyao Huayi" points out that Huangbai "specializes in relieving the fire of the kidney and bladder" and has a weak association with middle-jiao intestinal lesions (Jia Suoxue, Ming Dynasty).

[0033] Disadvantages of Linderae Root’s Warming and Drying Properties Modern research suggests that warming and drying drugs should be used with caution in radiation enteritis to prevent aggravation of intestinal mucosal congestion.

[0034] Compared to the complete formula, the streamlined formula of the present invention reduces the number of medicinal ingredients from 12 to 8, reducing potential drug interactions and intestinal irritation. Furthermore, this streamlined formula balances heat-clearing and dampness-drying, cooling blood and detoxifying, promoting qi and relieving pain, and promoting yang and stopping diarrhea. It targets the core "damp-heat-blood stasis-qi stagnation" of radiation enteritis, thus more closely adhering to the pathogenesis. Furthermore, this streamlined formula, based on the structure of Baitouweng Decoction, is supplemented with raw Sanguisorba officinalis and Patrinia chinensis to enhance mucosal repair, Corydalis yanhusuo to relieve pain, and Pueraria lobata to improve diarrhea, achieving an effective improvement on the classic formula. The present invention has the effects of clearing heat, cooling blood, stopping bleeding, and relieving pain, and has a clear and significant therapeutic effect on radiation enteritis. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 This is a graph showing the experimental results of the survival rate of mice 15 days after irradiation in a specific embodiment of the present invention.

[0036] Figure 2 This is a graph showing the statistical results of the number of small intestinal crypt cells in each group of mice (x±s) in a specific embodiment of the present invention.

[0037] Figure 3 1 is a diagram showing the HE staining results of the small intestine of each group of mice in a specific embodiment of the present invention.

[0038] Figure 4 This is a graph showing the immunohistochemical staining results of Villin in mouse small intestinal villi in a specific embodiment of the present invention (×10).

[0039] Figure 5 This is a graph showing the statistical results of mouse small intestinal villus length (x±s) in a specific embodiment of the present invention. DETAILED DESCRIPTION

[0040] The following is a detailed description of specific embodiments of the present invention. To avoid excessive unnecessary detail, well-known structures or functions will not be described in detail in the following examples. Approximate language used in the following examples can be used for quantitative expression to indicate that a certain amount of variation is allowed without changing the basic function. Unless otherwise defined, technical and scientific terms used in the following examples have the same meanings as those commonly understood by those skilled in the art to which the present invention belongs.

[0041] 1. A Traditional Chinese Medicine Enema for Treating Radiation Enteritis Includes simplified formula and complete formula.

[0042] The simplified formula is as follows: Scutellaria baicalensis 10g, Coptis chinensis 10g, Pulsatilla scabra 15g, Qinpi 10g, Sanguisorba officinalis 15g, Patrinia 15g, Corydalis yanhusuo (vinegar) 10g, Pueraria lobata 20g.

[0043] The complete formula is as follows: Scutellaria baicalensis slices 10g, Coptis chinensis 10g, Phellodendron amurense 10g, Hedyotis diffusa 30g, Pulsatilla scabra 15g, Taraxacum mongolicum 15g, Pueraria lobata 20g, Qinpi 10g, Sanguisorba officinalis 15g, Patrinia scabra 15g, Linderae scabra 10g, Corydalis yanhusuo (vinegar) 10g.

[0044] 2. Enema decoction method: Seven sets of medicine are decocted at a time. The method is as follows: 1. Place each Chinese herbal medicine slice in a decoction container, add 17 bottles of mineral water to cover the Chinese herbal medicine, and soak for 2 hours; decoct for 2 hours for the first time (start timing after boiling and decoct on low heat for 2 hours), and collect the decoction in a container; add 13 bottles of mineral water for the second time and decoct for 1.5 hours (start timing after boiling and decoct on low heat for 1.5 hours), and collect the decoction in a container.

[0045] 2. Concentrate the decoctions collected twice (evaporate the water using a wide-mouthed container) to approximately 700 ml and place in three 250 ml infusion bottles. Seal the three 250 ml infusion bottles and steam them in a steamer for 30 minutes. Let cool and set aside.

[0046] 3. Usage and precautions of enema: 1. Usage: Use the 250ml infusion bottle in 5 doses. Use twice a day, 50ml each time for enema.

[0047] 2. The preheated temperature of the medicine solution should be 36-38℃, close to body temperature (the purpose is to reduce intestinal irritation).

[0048] 3. Before taking the medication, empty your bowels and bladder (constipation is sufficient). Lie on your left side, using a small pillow to elevate your buttocks by about 10 cm, keeping them elevated 30 degrees. Apply a small amount of suppository to the tip of the syringe and inject 50 ml (one bag) of the medication into the rectum. Leave it in the enema for at least 30 minutes, twice daily. After the enema, turn over several times to ensure that the medication fully contacts the entire intestinal mucosa. The patient should lie flat for 1-2 hours and minimize activity.

[0049] 4. Keep unused enema solution in the refrigerator.

[0050] 5. Usage of Yunnan Baiyao: For patients with bloody stools, add 1.5-2g of Yunnan Baiyao to each enema and mix well with the enema solution (powder instructions: 0.25-0.5g each time, 4 times a day. Capsule instructions: Take 1-2 capsules (specification 0.25g / capsule) orally at a time, 4 times a day.

[0051] 6. Enema: The enema tube should be soft and of appropriate length (8 to 15 cm) and can be purchased at a pharmacy or online.

[0052] IV. Clinical Use Patients were given self-prepared Chinese herbal enemas, and their safety and effectiveness were evaluated based on indicators such as abdominal pain, anal pain, increased anal secretions, frequency of diarrhea, frequency of bloody stools, and bloody stools.

[0053] Exclusion criteria: Potential subjects who meet any of the following criteria will be excluded from the trial: (1) Those who cannot tolerate enema administration; (2) Patients with intestinal stenosis or intestinal obstruction; (3) Those with a history of intestinal diseases (such as gastrointestinal dysfunction); (4) Those who are allergic to any ingredient in the enema prescription; (5) Patients with severe cardiovascular disease; (6) Patients with acute abdomen; (7) Gastrointestinal bleeding; (8) Use antibiotics, intestinal mucosal protective agents, and enemas 7 days before administration.

[0054] (9) Patients who are considered unsuitable to participate in this study by other researchers.

[0055] According to Traditional Chinese Medicine (TCM), radiation is an exogenous pathogenic heat and toxic heat, capable of directly attacking the internal organs, leading to internal accumulation of heat and toxicity, and damaging the body's vital energy. The resulting radiation reaction reflects the symptoms of heat and toxicity. Heat damages the intestines, accumulating heat within them. Combined with dampness within the intestines, damp heat accumulates in the lower intestines, disrupting digestion and causing diarrhea and abdominal pain. Damp heat stagnates in the intestines, stagnates Qi and blood, and damages the lipid membranes and blood vessels, resulting in bloody stools. Dampness is sticky, and the combination of dampness and heat results in mucus in the stool or unpleasant diarrhea. Therefore, this disease is caused by stagnant damp heat, stagnant toxicity in the rectum, and burns to the blood vessels.

[0056] This study formulated an enema based on Traditional Chinese Medicine (TCM) theory to relieve and treat varying degrees of abdominal pain, diarrhea, and bloody stools caused by intestinal heat accumulation, qi and blood stagnation, and dampness stagnation after radiation exposure. The enema formula includes Scutellaria baicalensis, Coptis chinensis, Phellodendron chinense, Hedyotis diffusa, Pulsatilla scutellariae, Taraxacum mongolicum, Pueraria lobata, Fraxinus qinpi, Sanguisorba officinalis, Patrinia chinensis, Linderae scutellariae, and Corydalis yanhusuo. Scutellaria baicalensis, Coptis chinensis, and Phellodendron chinense clear heat and dampness, purge fire and detoxify; Hedyotis diffusa promotes dampness and relieves stranguria; Pulsatilla scutellariae, Pueraria lobata, and Fraxinus qinpi cool blood and arrest diarrhea, promote yang and relieve diarrhea, and astringe dysentery; Taraxacum mongolicum reduces swelling and resolves stagnation; Sanguisorba officinalis cools blood and arrests bleeding; Patrinia chinensis, Linderae scutellariae, and Corydalis yanhusuo activate blood circulation, remove blood stasis, promote qi circulation, and relieve pain. The formula's efficacy is heat-clearing, blood-cooling, hemostatic, and analgesic.

[0057] Traditional Chinese medicine enema solutions are liquid preparations made from decocted or concentrated Chinese medicinal materials. Enemas can be injected directly into the rectum, where they are absorbed directly from the intestinal mucosa, resulting in high local concentrations and rapid onset of action. Furthermore, the drug, mixed with the rectal fluid, enters the systemic circulation directly through the rectal veins, avoiding the first-pass effect in the liver. This allows for both local and systemic therapeutic effects. Therefore, while exerting its local effects, traditional Chinese medicine enemas can also regulate exogenous heat in RE patients, effectively dispelling pathogenic factors and strengthening the body's righteousness.

[0058] Based on Traditional Chinese Medicine theory, this study has developed a customized enema formula for some RE patients who visit our hospital. This formula utilizes a retention enema method and provides guidance on enema administration. Post-treatment follow-up visits have shown improvement or improvement in RE patients' symptoms, with a preliminary statistically significant efficacy rate of 61.3%. Based on this clinical experience, this study will evaluate the efficacy and safety of this enema formula using a replicated mouse model of intestinal damage after abdominal gamma-ray irradiation to clarify its therapeutic efficacy and dose-response relationship. The enema formula will then undergo clinical trials to further evaluate its efficacy and safety, verify its dose-response relationship, and determine a reasonable dosing regimen.

[0059] The efficacy of the present invention was evaluated by the following test methods.

[0060] Study 1: The protective effect of a self-prepared enema on the survival of irradiated mice 1.1 Research Materials and Methods 1.1.1 Research Materials (1) Experimental animals C57BL / 6J mice, 40, ♀, SPF grade, were provided by Beijing Huafukang Biotechnology Co., Ltd. The experimental animals were 8–12 weeks old and weighed 20.0–22.0 g; Animals were housed in the Radiation Medicine Research Animal Room of the Institute of Radiation Medicine, Chinese Academy of Medical Sciences. All animals were maintained under the same conditions and had free access to water and food.

[0061] (2) Experimental drugs Preparation of a self-prepared radiation enteritis enema: Soak the twelve ingredients in the recipe in water for 2 hours. Decoction is then performed twice: once with 8 times the amount of water and decocted for 2 hours. The second time, with 6 times the amount of water, is decocted for 1.5 hours. The combined decoctions are filtered. After evaporation to a desired volume, the solution is allowed to cool to room temperature. The relative density is then measured to obtain the test drug.

[0062] Low-dose solution: When the volume of test 1 is evaporated to 150 ml, stop evaporation and let the solution stand at room temperature. The relative density is measured to be 1.12.

[0063] Medium-dose solution: When the volume of test sample 2 is reduced to 100 ml, stop evaporation and allow the solution to stand at room temperature. The relative density is 1.17. This dose is the dose used in the author's previous clinical practice.

[0064] High-dose solution: When the volume of test sample 3 is evaporated to 75 ml, stop evaporation and let the solution stand at room temperature. The relative density is measured to be 1.19.

[0065] (3) Irradiation conditions The 137Cs γ-ray radiation source was purchased from Atomic Energy of Canada Ltd., with a dose rate of 0.99 Gy·min -1 The mice in the irradiation group, prevention group, and treatment group received a single dose of 12 Gy of abdominal irradiation.

[0066] 1.1.2 Research Methods (1) Method of administration All mice were administered the drug by enema. The enema technique involved grasping the mouse's tail and slowly inserting a glycerin-coated tube approximately 4 cm through the anus. The drug solution was then slowly injected, 0.3 ml per enema (the dosage was based on the author's previous clinical experience, converted to human-mouse equivalents). The enema was left in place for 20 seconds, then the tube was removed and the mouse was inverted for 30 seconds. Anesthesia was not required. The enema device consisted of a modified blood collection tube connected to an external syringe, effectively preventing intestinal irritation and drug leakage.

[0067] (2) Observation of mouse survival rate Mice were randomly divided into six groups based on body weight: control, irradiation, prevention, low-dose treatment, medium-dose treatment, and high-dose treatment, with 10 mice in each group. The control group was not irradiated, while the other five groups received a single dose of 12 Gy of abdominal irradiation. The prevention group received daily enema for three days before irradiation and continued to receive medication for four days after irradiation, for a total of seven doses. The treatment group received daily enema after irradiation for a total of four doses. Both the control and irradiation groups received normal saline enema. The survival rate of the mice was observed for 15 days.

[0068] 1.2 Research Results Depend on Figure 1 As shown, 15 days after irradiation, the survival rate of the preventive group was the highest, surpassing that of the high-, medium-, and low-dose treatment groups: 50% for the preventive group, 40% for the medium-dose group, and 30% for the irradiated group. All mice in the low-dose group died by day 8, while mice in the high-dose group developed neurological abnormalities by day 10.

[0069] 1.3 Summary Enema administration can reduce the acute mortality rate of mice after abdominal irradiation. The survival rate of mice in the prevention group is higher than that in the irradiation group and the treatment group. That is, enema administration to mice before radiation can prolong the survival rate of mice, suggesting that this Chinese medicine enema may have a certain preventive and protective effect on abdominal irradiated mice.

[0070] Study 2: Protective Effects of Self-prepared Enemas on Radiation-Injured Small Intestine in Irradiated Mice 2.1 Research Materials and Methods 2.1.1 Research Materials (1) Experimental animals C57BL / 6J mice, 40, ♀, SPF grade, were provided by Beijing Huafukang Biotechnology Co., Ltd. The experimental animals were 8–12 weeks old and weighed 20.0–22.0 g; Animals were housed in the Radiation Medicine Research Animal Room of the Institute of Radiation Medicine, Chinese Academy of Medical Sciences. All animals were maintained under the same conditions and had free access to water and food.

[0071] (2) Experimental drugs Preparation of a self-prepared radiation enteritis enema: Soak the twelve ingredients in the prescription in water for 2 hours, decoct twice, and filter the combined decoctions. After evaporation stops, allow the solution to cool to room temperature. Measure the relative density to obtain the test drug. This dosage represents the dosage used in the author's previous clinical practice.

[0072] (3) Irradiation conditions 137Cs γ-ray radiation source, purchased from Atomic Energy of Canada Ltd., with a dose rate of 0.99 Gy·min -1 The mice in the irradiation group, prevention group, and treatment group received a single dose of 12 Gy of abdominal irradiation.

[0073] (4) Statistical analysis SPSS 17.0 statistical software was used for data analysis. Quantitative data were expressed as mean ± S (x ± s). One-way analysis of variance was used for comparisons among multiple groups, and t-test was used for pairwise comparisons between groups. The test level was α = 0.05, and P < 0.05 was considered statistically significant.

[0074] 2.1.2 Research Methods (1) Method of administration All mice were administered the drug by enema. The enema technique involved grasping the mouse's tail and slowly inserting a glycerin-coated tube approximately 4 cm through the anus. The drug solution was then slowly injected, 0.3 ml per enema (the dosage was based on the author's previous clinical experience, converted to human-mouse equivalents). The enema was left in place for 20 seconds, then the tube was removed and the mouse was inverted for 30 seconds. Anesthesia was not required. The enema device consisted of a modified blood collection tube connected to an external syringe, effectively preventing intestinal irritation and drug leakage.

[0075] (2) Test method Mice were randomly divided into four groups based on body weight: control, irradiation, prevention, and treatment groups, with six mice in each group. The control group was not irradiated, while the other three groups received a single dose of 12 Gy of local abdominal irradiation. The prevention group received daily enema for three days before irradiation and continued to receive medication for four days after irradiation, for a total of seven doses. The treatment group received daily enema after irradiation for a total of four doses. Both the control and irradiation groups received normal saline enema.

[0076] Three days after irradiation, mice were sacrificed by cervical dislocation, and small intestinal tissue was collected for paraffin blocks. Hematoxylin and eosin staining was performed using the hematoxylin-eosin method. Immunohistochemical staining of small intestinal tissue was performed, followed by microwave repair and mounting. Image J 1.37 analysis software was used to observe intestinal villus morphology and measure villus length.

[0077] (3) Hematoxylin-eosin staining method Xylene I: 15 minutes; Xylene II: 15 minutes; Anhydrous ethanol I: 5 minutes; Anhydrous ethanol II: 5 minutes; 95% alcohol: 5 minutes; 80% alcohol: 5 minutes; Rinse with tap water: 5 minutes; Distilled water: rinse once; Hematoxylin: 6 minutes; Rinse with water; 1% hydrochloric acid alcohol: color separation (a few seconds); Rinse with water; Ammonia blueing: 10-30 seconds; Rinse with water; Rinse once with distilled water; Eosin (15-30 seconds); Rinse with water (rinse lightly); 75% (dip once quickly); 95% (dip once quickly); Anhydrous ethanol I (observe the eosin staining effect under a microscope); Anhydrous ethanol II (5 minutes); Xylene I transparent (5 minutes); Xylene II transparent (5 minutes); Seal the slide.

[0078] (4) Immunohistochemical staining method Specimen preparation: Dewaxing in xylene I: 15 minutes; dewaxing in xylene II: 15 minutes; anhydrous ethanol I: 5 minutes; anhydrous ethanol II: 5 minutes; blocking endogenous peroxidase in 3% H2O2: 30 minutes; 95% alcohol: 5 minutes; 80% alcohol: 5 minutes; rinsing with tap water: 5 minutes.

[0079] Antigen retrieval: Place the slides in a square jar from the staining rack, wash 3-5 times with distilled water, and microwave-repair with repair solution: boil for 10 minutes, then maintain the temperature at 97-100℃ for 10 minutes; let them air dry; wash with water - wash with distilled water - soak in PBS for 5 minutes; block with goat serum for 15-30 minutes; shake off the serum, wipe dry with gauze, add primary antibody, and incubate at room temperature for 40 minutes; incubate at 4℃ overnight; return to room temperature for 1 hour; wash three times with PBS, 3 minutes each time; add secondary antibody to the slide and let it stand at room temperature for 1 hour; wash three times with PBS, 5 minutes each time; develop with DAB; rinse with water for 5 minutes; wash with distilled water; stain the nuclei with hematoxylin for 3 minutes; rinse with water for 5 minutes; stain with 80% alcohol for 2 minutes; stain with 95% alcohol for 2 minutes; ethanol I: 5 minutes; ethanol II: 5 minutes; let dry; clear with xylene I: 5 minutes; clear with xylene II: 5 minutes; and seal the slides.

[0080] 2.2 Research Results 2.2.1 Small intestinal crypt cell count Table 1 The number of small intestinal crypt cells in each group of mice (x ± s cells·cm -1 , n=10)

[0081] Note: Compared with the control group, 1) P < 0.05; compared with the irradiation group, 2) P < 0.01 Figure 3 The results showed that the crypts in the control group were deep, but the arrangement of crypts changed after irradiation, and the depth of crypts decreased. The number of crypt cells in the small intestine of mice decreased significantly after irradiation, and the number of crypts (cm -1 ) were: 16.9±5.55 in the control group, 6.9±3.51 in the irradiation group, 10.3±2.21 in the prevention group, and 3.40±2.91 in the treatment group, with significant differences among the groups (P<0.05). Compared with the irradiation group, the number of crypt cells in the prevention group increased significantly, while the number in the treatment group was lower than that in the irradiation group. This suggests that administering Chinese herbal enema before irradiation has a preventive and protective effect on the intestinal mucosa, while enema after the intestinal mucosal barrier has been severely damaged is less effective.

[0082] 2.2.2 Small intestinal villus length Table 2 Villus length of mouse small intestine (x±s μm, n=6)

[0083] Note: Compared with the control group, 1) P < 0.05; compared with the irradiation group, 2) P < 0.01 Figure 4Microscopic examination revealed that the intestinal villi of the control group were neatly arranged, with normal morphology and abundant glandular cells. After irradiation, the villi length was significantly reduced compared to the control group. The villus lengths (μm) were: 585.32±21.39 in the control group, 227.22±44.36 in the irradiation group, 386.43±56.48 in the prevention group, and 189.42±39.90 in the treatment group. There was no significant difference between the irradiation and treatment groups, but significant differences were observed among the remaining groups (P<0.05).

[0084] 2.3 Summary The above experimental research results all show that when mice were given enema fluid before the intestinal mucosal barrier was severely damaged, the number of small intestinal crypt cells and intestinal villus length of the mice were higher than those in the irradiation group and the treatment group, which was statistically significant.

[0085] Study 3: Clinical efficacy and safety evaluation of a self-prepared Chinese herbal enema in the treatment of radiation-induced intestinal mucosal barrier damage in gynecological tumors The purpose of this study was to evaluate the effectiveness and safety of self-prepared enemas and to provide an effective treatment for the prevention and treatment of clinical radiation enteritis.

[0086] 3.1 Research Materials and Methods 3.1.1 General Information Patients who visited Tianjin Central Obstetrics and Gynecology Hospital and were diagnosed with radiation enteritis or intestinal reactions after radiotherapy were selected and included in the treatment group. A total of 64 subjects were expected to be included.

[0087] 3.1.2 Admission criteria (1) Inclusion criteria: Patients must meet all of the following criteria to be eligible: 1) Female patients aged ≥18 years; 2) All are gynecological malignancies, including cervical cancer, endometrial cancer, vaginal cancer, etc.; 3) receiving pelvic radiotherapy (intracavitary irradiation and / or external irradiation); 4) diagnosed with radiation enteritis or intestinal reactions after radiotherapy; 5) Sign the informed consent form.

[0088] (2) Exclusion criteria: Those who have any of the following conditions are not allowed to participate in this trial: 1) Those who cannot tolerate enema administration; 2) Patients with intestinal stenosis or intestinal obstruction; 3) Patients with a history of intestinal diseases (such as gastrointestinal dysfunction); 4) Those who are allergic to any ingredient in the enema prescription; 5) Patients with severe cardiovascular disease; 6) Patients with acute abdomen; 7) Gastrointestinal bleeding; 8) Use antibacterial drugs, intestinal mucosal protective agents, and enema before administration; 9) Patients who are considered unsuitable to participate in this study by other researchers.

[0089] 3.1.3 Investigational Drugs A custom enema formula for radiation enteritis is available. The formula consists of: Scutellaria baicalensis 10g, Coptis chinensis 10g, Phellodendron amurense 10g, Hedyotis diffusa 30g, Pulsatilla scabra 15g, Taraxacum mongolicum 15g, Pueraria lobata 20g, Fragrant Cortex qinpi 10g, Sanguisorba officinalis 15g, Patrinia scabra 15g, Linderae scutellariae 10g, and Corydalis yanhusuo 10g. One dose of these herbs is decocted and concentrated to 100ml. Patients are instructed to follow a standardized decoction method for both decoction and medication administration.

[0090] 3.1.4 How to use the drug Prepare a self-prepared enema twice daily, 50ml per enema. Precautions: Preheat the solution to 36-38°C, close to body temperature, to minimize intestinal irritation. Empty all bowels and bladder before administration (emptying the bladder is sufficient for constipation). Lie flat on your left side, using a small pillow to elevate your hips by approximately 10cm, keeping them elevated at a 30-degree angle. Apply a small amount of suppository to the tip of the syringe. Place 50ml of the solution into the enema device and inject it into the rectum at once. Hold the syringe for at least 30 minutes. After the enema, turn the patient several times to ensure the solution fully contacts the entire intestinal mucosa. The patient should lie flat for 1-2 hours, minimizing activity.

[0091] Combined with previous clinical experience, the intubation length is shortened to 8-15 cm, and the patient's drug retention position is alternating between semi-prone and semi-sitting positions, so that the drug can stay in the lesion-prone area for as long as possible and exert its therapeutic effect more fully.

[0092] The treatment group took the medicine for 7 days, and patients could choose whether to continue taking the medicine for 14 days. Patients were visited before, on and after the 7th and 14th days of taking the medicine.

[0093] 3.1.5 Concomitant medication and treatment During the trial, other Chinese and Western medicines for treating gastroenteritis should not be used, including antibiotics, montmorillonite powder, etc. If necessary, medications or other treatments must be taken, and the name, usage, dosage, and time of administration should be recorded.

[0094] 3.1.6 Trial Steps and Visit Process (1) Informed consent This is done before the subject undergoes the screening examination. At this time, the trial details are fully explained verbally and in writing. The subject is given ample time to consider whether to participate and to raise any concerns. If they agree to participate, they must sign an informed consent form before any study-related procedures are performed.

[0095] (2) Screening period / baseline period: The following needs to be done from day -14 to day 0: verify the inclusion and exclusion criteria; collect general information, including demographics (age, height, weight), past medical history, current medical history, etc.; divide the patients into trial groups and provide medication guidance; and fill in the "Patient Questionnaire".

[0096] (3) Treatment period: The treatment group started taking the medication as soon as intestinal reactions occurred; patients were informed to fill out the "Patient Follow-up Form" and observe efficacy indicators; adverse events and concomitant medications were recorded, and compliance was judged.

[0097] 3.1.7 Efficacy evaluation criteria 3.1.7.1 Efficacy indicators (1) Traditional Chinese Medicine Symptom Score: This method, developed with reference to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines," observes patients for major symptoms such as abdominal pain, diarrhea, bloody stools, and tenesmus. Score scores of 0, 1, 2, and 3 are assigned based on absence, mild, moderate, and severe severity, respectively. Evaluations are conducted once before and after treatment. TCM syndrome efficacy evaluation is categorized into four levels: clinical remission, marked effect, effectiveness, and ineffectiveness. Effectiveness is assessed by changes in TCM syndrome scores, with scores for each syndrome compared before and after treatment. Nimodipine efficacy assessment: Syndrome efficacy (%) = (pre-treatment syndrome score - post-treatment syndrome score) / pre-treatment syndrome score × 100%. Specific grading standards are established for reference and are shown in the table below.

[0098] Cured: Symptoms and signs disappear or essentially disappear, with a symptom score reduction of ≥95%; Markedly effective: Symptoms and signs significantly improve, with a symptom score reduction of ≥70% but <95%; Effective: Symptoms and signs improve, with a symptom score reduction of ≥30% but <70%; Ineffective: No improvement or worsening of symptoms and signs, with a symptom score reduction of <30% or an increase. Clinical efficacy = (cured + markedly effective + effective) / n × 100%.

[0099] Table 3. TCM syndrome scoring criteria

[0100] (3) Grading of acute radiation injury: According to the RTOH / EORTC acute radiation injury grading standard, attending physicians and above will evaluate the patients before and after treatment to assess the treatment effect before and after medication.

[0101] Table 4 RTOH / EORTC acute radiation injury grading criteria

[0102] (4) Quality of life evaluation: In accordance with the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines," patients were examined before and after treatment, and changes in quality of life were assessed using the Karnofsky score (a self-assessment of health status) as an indicator. Improvement: Patients experienced an increase of 10 points or more in their score after treatment compared to before treatment. Stability: Patients experienced an increase or decrease of less than 10 points in their score after treatment. Reduction: Patients experienced a decrease of 10 points or more in their score after treatment compared to before treatment.

[0103] Table 5 Karnofsky functional status scoring criteria

[0104] 3.1.7.2 Safety indicators Safety assessments will include monitoring and recording of all adverse events (AEs) and serious adverse events (SAEs).

[0105] 3.2 Research Results 3.2.1 General Information Sixty-four patients were enrolled, of whom two withdrew (one due to death from primary disease progression and one due to surgical treatment for progressive enteritis), three were excluded (one due to medication errors and two due to medication duration violations), and eight were lost to follow-up. A total of 51 patients completed all follow-up at the end of the trial. Fifty of them had a clinical diagnosis of cervical cancer and one had endometrial cancer, all receiving concurrent chemoradiotherapy. Patient ages ranged from 25 to 73 years (52.69 ± 10.66). FIGO stage was stage I in two patients, stage II in 31, and stage III in 18. Two patients developed intestinal symptoms within three weeks of radiotherapy, while the remaining patients experienced symptoms for six months to one and a half years. The radiotherapy regimen consisted of intensity-modulated radiation (IMRT) with a 95% PTV of 48.6 Gy / 27 fractions and intracavitary irradiation with 600 cGy / week of Ir192, five to six fractions. The prescription EQD2 is 90Gy, the rectal EQD2, and the cumulative absorbed dose in the rectum is 40-60Gy.

[0106] 3.2.2 TCM syndrome scores before and after treatment Compared with pre-treatment, the patients' abdominal pain, bloody stools, diarrhea, tenesmus, and total symptom scores all decreased after receiving the Chinese herbal enema. The symptom summary score was 176 before treatment and 78 after treatment. The total effective rate after treatment was 74.51% (see Table 6).

[0107] 25 patients took the drug for 7 days, with a total effective rate of 63.64%. 26 patients chose to continue taking the drug for 14 days, with a total effective rate of 81.82% at the 14-day follow-up.

[0108]

[0109] Table 7 Total effective rate

[0110] 3.2.3 RTOH / EORTC acute radiation injury grading before and after treatment Compared with before treatment, the acute radiation injury grade of patients after treatment with Chinese medicine enema was lower than that before treatment, see Table 8.

[0111] Table 8 RTOH / EORTC acute radiation injury grades before and after treatment

[0112] 3.2.4 Comparison of quality of life before and after treatment Comparison of changes in KPS scores before and after treatment is shown in Table 9. The results show that 72.54% of patients had improved scores after treatment, indicating that the use of self-prepared enemas can improve the quality of life of patients with radiation enteritis.

[0113] Table 9 Evaluation of quality of life after treatment

[0114] 3.2.5 Adverse reactions A total of 2 patients experienced adverse reactions, one of whom experienced anal distension and pain on the 6th day of medication, which was probably related to the drug; the other experienced discomfort around the umbilicus on the 2nd day of medication, which was probably related to the drug.

[0115] All patients had no systemic adverse reactions during follow-up, and no serious adverse reactions were found.

[0116] 3.3 Summary Self-prepared Chinese medicine enemas can effectively alleviate mucosal reactions, thereby reducing patients' pain and improving their quality of life. The total effective rate is greater than 70%, with reliable efficacy and few adverse reactions.

[0117] These experimental results demonstrate that the present invention's formula primarily provides astringency, antispasmodics, anti-inflammatory properties, intestinal mucosal protection, and the promotion of damage repair and hemostasis, aiming to achieve overall improvement in the disease, as well as long-term efficacy (preventing recurrence). Animal experiments and clinical trials have confirmed that the present invention has preventive and therapeutic effects on intestinal mucosal barrier damage in mice with acute radiation enteritis, fully embodying Traditional Chinese Medicine's approach to preventing radiation enteritis before it develops.

[0118] The embodiments of the present invention are described in detail above, but the contents are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, and improvements made within the scope of the present invention shall be included in the scope of protection of the present invention.

Claims

1. A Chinese medicine enema for treating radiation enteritis, characterized in that: The traditional Chinese medicine enema comprises the following ingredients in parts by weight: 8-12 parts of scutellaria baicalensis, 8-12 parts of coptis chinensis, 12-18 parts of pulsatilla scabra, 8-12 parts of qinpi cortex, 12-18 parts of sanguisorba officinalis, 12-18 parts of patrinia herba, 8-12 parts of vinegar-processed corydalis yanhusuo and 15-25 parts of kudzu vine.

2. A Chinese medicine enema for treating radiation enteritis according to claim 1, characterized in that: The traditional Chinese medicine enema comprises the following ingredients in parts by weight: 10 parts of scutellaria baicalensis, 10 parts of coptis chinensis, 15 parts of pulsatilla scabra, 10 parts of qinpi cortex, 15 parts of sanguisorba officinalis, 15 parts of patrinia herba, 10 parts of vinegar-processed corydalis yanhusuo and 20 parts of kudzu vine.

3. A Chinese medicine enema for treating radiation enteritis according to claim 2, characterized in that: The traditional Chinese medicine enema is composed of the following ingredients in parts by weight: 10 parts of scutellaria baicalensis, 10 parts of coptis chinensis, 15 parts of pulsatilla scabra, 10 parts of qinpi cortex, 15 parts of sanguisorba officinalis, 15 parts of patrinia herba, 10 parts of vinegar-processed corydalis yanhusuo and 20 parts of kudzu vine.

4. A Chinese medicine enema for treating radiation enteritis according to claim 2, characterized in that: The traditional Chinese medicine enema further comprises the following ingredients in parts by weight: 10 parts of Phellodendron chinense.

5. A Chinese medicine enema for treating radiation enteritis according to claim 2, characterized in that: The traditional Chinese medicine enema further comprises the following ingredients in parts by weight: 30 parts of oldenlandia diffusa herb.

6. A Chinese medicine enema for treating radiation enteritis according to claim 2, characterized in that: The traditional Chinese medicine enema further comprises the following ingredients in parts by weight: 15 parts of dandelions.

7. A Chinese medicine enema for treating radiation enteritis according to claim 2, characterized in that: The traditional Chinese medicine enema further comprises the following ingredients in parts by weight: 10 parts of Linderae striata.

8. The Chinese medicine enema for treating radiation enteritis according to claim 2, characterized in that: The traditional Chinese medicine enema is composed of the following ingredients in parts by weight: 10 parts of scutellaria baicalensis, 10 parts of coptis chinensis, 15 parts of pulsatilla scabra, 10 parts of qinpi cortex, 15 parts of sanguisorba officinalis, 15 parts of patrinia herba, 10 parts of vinegar-processed corydalis yanhusuo, 20 parts of kudzu vine, 10 parts of phellodendron amurense, 30 parts of oldenlandia diffusa, 15 parts of dandelion, and 10 parts of lindera atractylodes.

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