A traditional Chinese medicine composition for treating oral mucositis in patients caused by radiotherapy and chemotherapy

Abstract

The present application relates to a kind of traditional Chinese medicine composition for treating oral mucositis caused by radiotherapy and chemotherapy, the traditional Chinese medicine composition is composed of effective component and medically acceptable auxiliary materials, characterized in that, the effective component is made of the following weight percentage of raw medicinal materials: Shihuchu 33-41%, Shengdi 20-24%, Maidong 20-24%, Shengancao 17-20%.The traditional Chinese medicine composition described in the present application has the effect of benefiting stomach, generating fluid, nourishing yin and clearing heat, and the effect of treating oral mucositis caused by radiotherapy and chemotherapy is remarkable.

Description

TECHNICAL FIELD

[0001] The present application relates to medical formulations, in particular to a pharmaceutical preparation containing an undefined structure from a plant, which is suitable for treating oral mucositis caused by radiotherapy and chemotherapy. BACKGROUND

[0002] Radiotherapy-induced oral mucositis and chemotherapy-induced oral mucositis refer to the inflammatory reaction of oral mucosa caused by oral mucosa damage secondary to tumor radiotherapy and chemotherapy, and is one of the common adverse reactions of tumor radiotherapy and chemotherapy. Among patients with head and neck cancer receiving radiotherapy or chemotherapy, 59.4% to 100% of patients have oral mucositis (OM, Oral mucositis), and about 65% of patients are affected by severe oral mucositis. In conventional chemotherapy, the incidence and severity of oral mucositis vary depending on the treatment regimen, and the incidence of oral mucositis induced by chemotherapy regimens for different site tumors ranges from 6.6% to 65%. The main symptoms of ordinary oral mucositis are ulceration, superficial wound around the redness, and mild pain, which generally do not require intervention and heal in about two weeks. Unlike ordinary oral mucositis, oral mucositis caused by radiotherapy and chemotherapy is more difficult to treat clinically, often showing severe inflammatory reactions in the oral cavity, difficulty swallowing, severe reduction in food intake, secondary oral infection and even systemic infection, and repeated episodes, prolonged and difficult to heal. Long-term reduced intake of patients leads to weight loss, malnutrition, and seriously affects the quality of life of patients and even leads to the termination of tumor treatment regimens.

[0003] There is currently a lack of ideal drug treatment for oral mucositis caused by radiotherapy and chemotherapy, and clinical Western medicine often uses local anesthetics combined with antibiotics, hormone analgesics, and anti-infectives, such as "normal saline + lidocaine + gentamicin + dexamethasone", oral mucosa protectants to protect the mucosa, commonly used oral mucosa protectants include oral gels, calcium phosphate, amino acids, oral ulcer protectants, sucralfate, etc. The above treatments are prone to recurrence and have poor long-term efficacy.

[0004] Traditional Chinese medicine (TCM) is widely used in clinical practice as a multi-target treatment method, with proprietary Chinese medicines being particularly prevalent. Drugs like Kangfuxin Liquid are often used for clearing heat and detoxifying, promoting tissue regeneration, and relieving sore throat. Kouyanqing Granules, on the other hand, nourish yin, clear heat, detoxify, and reduce swelling; multiple clinical studies have confirmed their therapeutic effects. Kangfuxin Liquid is an ethanol extract of dried American cockroach bodies, possessing the functions of clearing heat and detoxifying, promoting tissue regeneration, and relieving sore throat. Previous studies have shown that Kangfuxin Liquid can also have a positive therapeutic effect on oral ulcers caused by radiotherapy and chemotherapy. The aforementioned Kouyanqing Granules formula consists of 250g of Asparagus cochinchinensis, 250g of Scrophularia ningpoensis, 250g of Ophiopogon japonicus, 300g of Lonicera japonica, and 125g of Glycyrrhiza uralensis. Asparagus cochinchinensis is the principal herb, and Ophiopogon japonicus is the assistant herb, achieving the effects of nourishing yin and moistening the lungs, benefiting the stomach and promoting fluid production. Scrophularia ningpoensis and Lonicera japonica are added to treat pathogenic heat entering the blood level, clearing heat and detoxifying, nourishing yin and cooling the blood, and relieving sore throat and reducing swelling. Glycyrrhiza uralensis is used as the guiding herb to harmonize the medicinal properties. Kouyanqing granules have been shown to reduce inflammatory factors in stomatitis caused by radiotherapy and chemotherapy, improve oral microecological indicators, enhance oral prognosis, and alleviate oral pain without increasing adverse reactions. However, the efficacy of this drug in treating oral mucositis caused by radiotherapy and chemotherapy is still not ideal. Summary of the Invention:

[0005] The technical problem to be solved by the present invention is to provide a traditional Chinese medicine composition for treating oral mucositis caused by radiotherapy and chemotherapy, which has a significant effect on treating oral mucositis caused by radiotherapy and chemotherapy.

[0006] The technical solution of the present invention to solve the above problems is as follows:

[0007] A traditional Chinese medicine composition for treating oral mucositis caused by radiotherapy and chemotherapy, the composition comprising an active ingredient and pharmaceutically acceptable excipients, characterized in that the active ingredient is made from the following raw materials in weight percentage: Dendrobium 33-41%, Rehmannia glutinosa 20-24%, Ophiopogon japonicus 20-24%, and Glycyrrhiza uralensis 17-20%.

[0008] In the above scheme, the optimal weight percentage of the raw materials is 37.1% Dendrobium, 22.2% Rehmannia glutinosa, 22.2% Ophiopogon japonicus, and 18.5% Glycyrrhiza uralensis.

[0009] The traditional Chinese medicine composition of the present invention preferably contains Dendrobium huoshanense.

[0010] The active ingredient described in the above technical solution is prepared by the following method:

[0011] Take the prescribed amount of Rehmannia glutinosa, Ophiopogon japonicus, and Glycyrrhiza uralensis, soak them in 8 times the amount of water, decoct for 1 hour, filter, and obtain decoction A; add 8 times the amount of water to the dregs and decoct for 1 hour, filter, and obtain decoction B; then combine decoction A and decoction B, concentrate, and dry to obtain water extract; then take the prescribed amount of Dendrobium officinale, pulverize, and pass through a 100-mesh sieve to obtain Dendrobium officinale fine powder; the obtained water extract and Dendrobium officinale fine powder are the effective components mentioned above.

[0012] The traditional Chinese medicine composition is prepared by the following method:

[0013] The prepared water extract, Dendrobium nobile Lindl powder and medically acceptable adjuvant are mixed uniformly, and then a granule, a capsule or a tablet is prepared by a conventional method to obtain the traditional Chinese medicine composition.

[0014] The traditional Chinese medicine composition comprises Dendrobium nobile Lindl, Rehmannia glutinosa, Ophiopogon japonicus and Glycyrrhiza uralensis Fisch. Dendrobium nobile Lindl is used as the monarch drug, which is cold in nature and sweet in taste, and enters the stomach and kidney channels, and has the effects of benefiting the stomach, generating fluid, nourishing yin and clearing heat. Ophiopogon japonicus and Rehmannia glutinosa are both sweet and cold, and are used as the ministerial drugs to assist the monarch drug in increasing fluid and moistening dryness. Glycyrrhiza uralensis Fisch. has the effects of clearing heat and detoxifying, relieving pain and regulating other drugs. The combination of the above drugs has the effects of clearing heat and detoxifying, nourishing yin and increasing fluid, and can increase water to move the boat, moisten dryness and promote defecation.

[0015] The traditional Chinese medicine composition is improved from Kouyanqing granules, that is, three drugs of Radix Asparagi, Radix Scrophulariae and Flos Lonicerae are omitted, and two drugs of Dendrobium nobile Lindl and Rehmannia glutinosa are added. Dendrobium nobile Lindl is used as the monarch drug, and Rehmannia glutinosa is used as the ministerial drug together with Ophiopogon japonicus in the original prescription. The above improvement has the following beneficial effects: 1. Dendrobium nobile Lindl enters the stomach and kidney channels, benefits the stomach, generates fluid, nourishes yin and clears heat, and is more suitable for tumor patients, and can support the healthy and eliminate the evil. The treatment principle of the original prescription is changed from nourishing yin and clearing heat, eliminating swelling and detoxifying to nourishing yin, generating fluid, supporting the healthy and supplementing deficiency. 2. Rehmannia glutinosa is sweet and cold, enters the heart, liver and kidney channels, clears heat and cools blood, nourishes yin and generates fluid. Ophiopogon japonicus is sweet, bitter and cold, enters the heart, lung and stomach channels, nourishes yin, moistens the lung and clears the heart. The combination of the two drugs enhances the effects of nourishing yin and generating fluid, and has the effects of clearing heat and cooling blood, and assisting the monarch drug in increasing fluid and moistening dryness. From the above analysis, it can be seen that the traditional Chinese medicine composition greatly enhances the effect of supplementing deficiency, and is convenient for long-term use, and can improve the state of five-organ deficiency and weight loss of tumor patients.

[0016] The traditional Chinese medicine composition is verified by 50 patients, and has definite curative effect and no adverse reaction.

[0017] The traditional Chinese medicine composition can effectively treat oral mucositis caused by radiotherapy and chemotherapy, relieve the pain of patients with mucositis, improve the life quality of tumor patients, and has no obvious toxic and side effects.

[0018] The treatment effect of the traditional Chinese medicine composition on oral mucositis caused by radiotherapy and chemotherapy can be further verified by the following research.

[0019] I. Clinical research

[0020] 1. Patient source: all cases come from inpatients and outpatients of Department of Oncology, the First Affiliated Hospital of Anhui University of Chinese Medicine.

[0021] 2. Case selection criteria:

[0022] Patients diagnosed by clinic as oral mucositis caused by radiotherapy and chemotherapy;

[0023] Oral mucositis: clinical manifestations include erythema, patchy or confluent ulcers with overlying pseudomembrane, inflammatory reaction, dysphagia, severe reduction of food intake, secondary oral infection, and even systemic infection, etc. The diagnostic criteria (referring to the Common Toxicity Criteria (CTC) proposed by the National Cancer Institute (NCI)) are as follows:

[0024]

[0025] Patients with stage III and IV malignant tumors with ECOG performance status grading standard of 0-1 and expected survival period > 6 months (referring to the 8th edition of TNM staging standard formulated by the American Joint Committee on Cancer (AJCC)). The ECOG performance status grading standard is as follows:

[0026]

[0027]

[0028] TCM diagnostic criteria: referring to the diagnostic criteria of "Guidelines for Clinical Practice of Oral Ulcer in Traditional Chinese Medicine (2018)". Oral ulcer is a mucosal disease characterized by single or multiple yellowish or whitish ulcerative spots on the lips, tongue, buccal mucosa, and upper palate, accompanied by spontaneous pain or irritation pain. It can occur at any age, but is more common in young adults. The course is self-limiting, lasting for 7-10 days, and periodically recurring.

[0029] 3. Inclusion criteria

[0030] (1) Age 18-80 years old, gender unrestricted;

[0031] (2) Patients diagnosed by clinic as oral mucositis caused by radiotherapy and chemotherapy;

[0032] (3) Patients confirmed by cytology or histopathology as having advanced malignant tumors (tumor types include lung cancer, gastric cancer, ovarian cancer, breast cancer, cervical cancer, head and neck tumors, etc.). Patients with TNM stage III-IV and ECOG grade 0-1; expected survival period > 6 months;

[0033] (4) Patients who have received radiotherapy or chemotherapy or concurrent radiotherapy and chemotherapy (chemotherapy regimen contains at least one or more of the following drugs: cyclophosphamide, methotrexate, nitrogen mustard, cisplatin, gemcitabine, cytarabine, vinca alkaloids, podophyllotoxins, taxols, etc. The radiotherapy regimen varies according to the different standards of different cancers. For lung cancer: the standard radiation dose of clinical tumor is 60 Gy, the subclinical dose is 45-50 Gy, and the palliative radiation dose is about 40 Gy. For cervical cancer: the radiation dose at point A is 85-90 Gy, and the dose at point B is 55-60 Gy (point A is located at the intersection of the uterine artery and the ureter, 2 cm above the lateral fornix and 2 cm away from the uterine axis, and point B is located at the same level as point A, 3 cm outside the A point, i.e. the obturator lymph node region. For nasopharyngeal carcinoma: GTVnx: 68-70 Gy / 30-32 f / 6-7 W; CTV1: 60-66 Gy / 30-32 f / 6-7 W; CTV2: 50-54 Gy / 30-32 f / 6-7 W; GTVnd: 60-68 Gy / 30 f / 6-7 W, etc.

[0034] (5) Patients with clear consciousness, language expression ability or reading ability, normal communication, and the ability to cooperate with the evaluation;

[0035] (6) Voluntarily join this study, patients with good compliance, can understand the situation of this study and sign the informed consent form.

[0036] 4. Exclusion criteria

[0037] (1) Known to be allergic to the components of the drug;

[0038] (2) Not in line with the diagnosis or diagnosis is not clear;

[0039] (3) Patients with primary immunodeficiency diseases and other serious infectious diseases, patients treated with immunomodulators;

[0040] (4) Patients with abnormal blood routine, liver function and kidney function;

[0041] (5) Pregnant or lactating women, and patients with mental disorders;

[0042] (6) Poor compliance;

[0043] (7) Other reasons for the researchers to consider unsuitable for participating in this study;

[0044] (8) Patients who have used other trial drugs or are in other clinical trials within the past month cannot be selected.

[0045] 5, Research content: basic information including name, gender, age, time of visit, etc.; medical history characteristics (disease duration, history of allergy, drug history, history of existing diseases, etc.); TCM clinical characteristics (main symptoms, accompanying symptoms, tongue and pulse conditions, etc.); Oral mucositis (mucosal injury, pain, discomfort, etc.).

[0046] 6, Treatment method:

[0047] (1) Group data: 142 cases meeting the requirements were selected according to the inclusion and exclusion criteria, and were randomly divided into the following two groups:

[0048] Treatment group: 50 people, 20 men and 30 women, of which 19 patients underwent simple radiotherapy, 20 patients underwent simple chemotherapy, and 11 patients underwent concurrent chemoradiotherapy, with an average age of 60.40±11.51 years;

[0049] Control group A: 50 people, 22 men and 28 women, of which 18 patients underwent simple radiotherapy, 19 patients underwent simple chemotherapy, and 13 patients underwent concurrent chemoradiotherapy, with an average age of 60.16±10.87 years;

[0050] Control group B: 42 people, 18 men and 24 women, of which 15 patients underwent simple radiotherapy, 15 patients underwent simple chemotherapy, and 12 patients underwent concurrent chemoradiotherapy, with an average age of 61.40±12.56 years.

[0051] (2) Treatment plan:

[0052] Treatment group: the granules of Example 1 below, taken with warm water, one bag at a time, twice a day (30 minutes after breakfast and dinner).

[0053] Control group A: Kouyanning granules (Guangzhou Baiyunshan Huaiyuan Pharmaceutical Co., Ltd., National Drug Standard Code: Z44021730, 10g per bag), taken with warm water, two bags at a time, twice a day, (30 minutes after breakfast and dinner).

[0054] Control group B: Kangfuxin liquid (Inner Mongolia Jingxin Pharmaceutical Co., Ltd., specifications: 100ml per bottle, batch number: Z15020805), oral, 10ml each time, 3 times a day (30 minutes after breakfast, lunch and dinner).

[0055] The treatment course is 2 weeks, and the above administration methods meet the requirements of clinical traditional Chinese medicine decoction pieces and granules and drug instructions.

[0056] 7, Efficacy evaluation criteria:

[0057] Reference to "oral mucositis" in the clinical efficacy evaluation standard of "Guiding Principles for New Drugs of Traditional Chinese Medicine", the reduction of mucosal injury area, pain relief as the main index. Comprehensive curative effect index = (treatment before the main symptom score - after treatment main symptom score) ÷ treatment before the main symptom score.

[0058] 1. Clinical cure: within 2 weeks of medication, symptoms are relieved, and symptoms and signs disappear within 2 weeks. The total score of main symptoms and signs is 0.

[0059] 2. Marked effect: within 2 weeks of medication, the comprehensive curative effect index of main symptoms and signs is reduced by more than 2 / 3.

[0060] 3. Progress: within 2 weeks of medication, the comprehensive curative effect index of main symptoms and signs is reduced by more than 1 / 3.

[0061] 4. Ineffective: within 2 weeks of medication, the comprehensive curative effect index of main symptoms and signs is reduced by less than 1 / 3 or the disease is aggravated.

[0062] 8. Observation index: at the time of visit and after 2 weeks of treatment, record the changes of patient pain score, patient discomfort score, mucositis classification and quality of life core scale.

[0063] 1. Pain rating scale

[0064] The patient is scored using the numerical rating scale, which uses the numbers 0-10 instead of words to represent the degree of pain. "What number can represent the most severe pain in the past 24 hours?" The range is from 0 (indicating no pain) to 10 (indicating pain to the extreme).

[0065]

[0066] 2. Discomfort rating scale

[0067] The patient's discomfort is scored using a three-level scoring method, 0 points: no discomfort; 1 point: mild discomfort; 2 points: moderate discomfort; 3 points: severe discomfort.

[0068] 3. Symptom classification

[0069] WHO oral mucositis grading criteria are used to grade oral mucositis symptoms before and after treatment, 0-4 points are assigned to 0-IV grades respectively; the grading and scoring criteria are as follows:

[0070] WHO oral mucositis grading

[0071] Grade Score Clinical presentation Grade 0 0 points No abnormalities of the oral mucosa. Grade I 1 point Mucosal hyperemia, edema, mild pain. Grade II 2 points Mucosal hyperemia, edema, punctate ulcers, but without affecting eating. Grade III 3 points Mucosal hyperemia, edema, patchy ulcers, covered with a white membrane, increased pain and affecting eating. Grade IV 4 points Large area of mucosal ulceration, severe pain, difficulty opening the mouth, unable to eat, requiring parenteral or enteral nutritional support.

[0072] 4. Serum inflammatory markers IL-6, TNF-α levels

[0073] Extracted fasting venous blood solution 8 mL, static 30 minutes, 2800 r / min centrifugal 15 minutes, get the upper clear liquid, and then placed in -80℃ refrigerator for preservation and standby. The absorbance was read by enzyme-linked immunosorbent assay, and the serum IL-6, TNF-α concentration values were measured. The kit comes from Shanghai Fusheng Industry Co., Ltd., and the operation is strictly in accordance with the instruction manual.

[0074] 9. Quality control and assurance of the test:

[0075] (1) Laboratory quality control measures

[0076] Establish standard operating procedures and quality control procedures for experimental observation indicators. Laboratory test results must be printed by computer. Data should be traceable.

[0077] (2) Standard operating procedures for main observation indicators

[0078] Before the start of the project, the researchers were trained on the test plan, and the consistency of the symptom and sign quantification standard was tested. Sign the researcher's statement.

[0079] 10. Statistical methods:

[0080] According to the nature of the clinical trial data (measurement data, classification data and rank data), choose the appropriate statistical analysis method. Measurement data is expressed by mean ± standard deviation, comparison between two groups uses two independent sample t test, count data uses χ 2 test; rank data uses two-sample comparison Wilcoxon rank sum test (correction).

[0081] 11. Results:

[0082] From the outpatients and inpatients, 142 patients with oral mucositis and tumors who met the conditions were selected and randomly divided into two groups, 50 patients in the treatment group, 50 patients in the control group A, and 42 patients in the control group B. The main indicators were the reduction of pain and discomfort degree. The treatment efficiency of the treatment group (94.00%) was higher than that of the control group A (84.00%) and the control group B (66.67%), and the difference was statistically significant.

[0083] (1) Statistical analysis of baseline data: There was no statistically significant difference in gender, age, pain score and discomfort score between the three groups (P>0.05), and the specific results are shown in Table 1.

[0084] Table 1. Statistical analysis of baseline data

[0085]

[0086] (2) The pain score and discomfort score of the three groups of patients before and after treatment had statistical significance (P<0.05), and the specific results are shown in Table 2 and Table 3.

[0087] Table 2. Statistical analysis of pain scores of the three groups of patients before and after treatment

[0088]

[0089] Table 3. Statistical analysis of discomfort scores of the three groups of patients before and after treatment

[0090]

[0091] (3) Statistical analysis of pain scores and discomfort scores of the three groups after treatment: the pain scores and discomfort scores of the three groups after treatment were compared pairwise, and the treatment group was better than the control group A and the control group B, the control group A was better than the control group B, and the differences were statistically significant (P<0.05), and the specific results are shown in Table 4 and Table 5.

[0092] Table 4. Statistical analysis of pain scores of the three groups of patients after treatment

[0093]

[0094] Table 5. Statistical analysis of discomfort scores of the three groups of patients after treatment

[0095]

[0096] (4) Comparison of serum inflammatory markers IL-6 levels: the difference in serum IL-6 levels of the three groups before treatment was not statistically significant (P=0.814), the differences before and after treatment of the three groups were statistically significant and the differences between groups after treatment were statistically significant (P=0.001), and the post-hoc test multiple comparison showed that the differences between each group were statistically significant (treatment group vs control group A: P=0.047, treatment group vs control group B: P<0.001, control group A vs control group B: P=0.039), and the specific results are shown in Table 6.

[0097] Table 6. Statistical analysis of IL-6 levels of the three groups before and after treatment

[0098]

[0099] (5) Comparison of serum inflammatory marker TNF-α levels: The difference in serum TNF-α levels before treatment was not statistically significant (P=0.773) among the three groups, and the difference before and after treatment was statistically significant in each group, and the difference between groups after treatment was statistically significant (P<0.001). The post-hoc test multiple comparison showed that the difference between each pair of groups was statistically significant (treatment group vs. control group A: P=0.039, treatment group vs. control group B: P<0.001, control group A vs. control group B: P=0.009). See Table 7 for details.

[0100] Table 7. Statistical analysis of TNF-α levels before and after treatment in the three groups

[0101]

[0102] (6) Statistical analysis of efficacy: In the treatment group, 12 cases were cured, 22 cases were markedly effective, 13 cases were effective, and 3 cases were ineffective, with a total effective rate of 94.00% (50 cases); in the control group A, 5 cases were cured, 18 cases were markedly effective, 19 cases were effective, and 8 cases were ineffective, with a total effective rate of 84.00% (50 cases); in the control group B, 2 cases were cured, 7 cases were markedly effective, 19 cases were effective, and 14 cases were ineffective, with a total effective rate of 66.670% (42 cases). The difference in efficacy and effective rate between the three groups was statistically significant. See Table 8 for details.

[0103] Table 8. Comparison of efficacy in different groups

[0104]

[0105] In the cases included in this study, no adverse reactions were reported in any of the three groups, indicating that the drug has high safety.

[0106] II. Animal experiments

[0107] 1. Drugs and reagents:

[0108] Treatment group: Take the granules of Example 1 and dissolve in ultrapure water to 66.67 mg / ml;

[0109] Control group A: Take Kouyankeling granules and dissolve in ultrapure water to 66.67 mg / ml;

[0110] Control group B: Kangfuxin liquid;

[0111] Reagents: 5-fluorouracil was purchased from Tianjin Jinyao Pharmaceutical Co., Ltd.; acetic acid was purchased from Tianjin Kaition Chemical Reagent Co., Ltd.; chloral hydrate was purchased from Tianjin Kaition Chemical Reagent Co., Ltd.

[0112] Experimental animals: Male Wistar rats were purchased from Liaoning Changsheng Biological Technology Co., Ltd.

[0113] Experimental instruments: decoction pot, beaker, gauze, glass rod, freeze dryer, rotary evaporator.

[0114] 2. Experimental method

[0115] Comparison of the treatment effects of the treatment group and control group A and control group B on the 5-fluorouracil-induced oral mucositis model of Wistar rats:

[0116] 2.1 Experimental process

[0117] According to the modeling method introduced in the relevant literature, male Wistar rats were randomly divided into 5 groups, namely the normal group, the model group, the treatment group, the control group A, and the control group B, 6 rats in each group. Except for the normal group, the remaining rats were intraperitoneally injected with 5-fluorouracil at a concentration of 60 mg / kg and 40 mg / kg on the 1st day and the 3rd day, and acetic acid treatment was performed 2 days after the last administration of 5-fluorouracil. On the 6th day, intervention was started in each group, and each group was intervened for 2 weeks.

[0118] 2.2 Dose of administration

[0119] Normal group: physiological saline gavage, 15 ml / kg, once a day;

[0120] Model group: physiological saline gavage, 15 ml / kg, once a day;

[0121] Treatment group: the granules prepared in Example 1 were prepared into a liquid for gavage, and the dose of administration was 15 ml / kg, once a day; Control group A: Kouqinyinqian granules were prepared into a liquid for gavage, and the dose of administration was 15 ml / kg, once a day;

[0122] Control group B: Kangfuxin liquid was gavaged, and the dose of administration was 10 ml / kg, once a day.

[0123] 2.3 Observation index

[0124] 2.3.1 Average body weight and food intake of each group

[0125] The body weight of rats in each group was recorded at 8:30 every morning, and the average body weight of each group was calculated. The food of each group was collected and weighed to calculate the food intake.

[0126] 2.3.2 OM score

[0127] Each group respectively on the 8th, 10th, 12th, 14th day, 2 rats were anesthetized with 10% chloral hydrate (3.5 ml / 1 kg, intraperitoneal injection), and the tongue and mucosa tissue were photographed with a camera for visual assessment and scoring. (Visual assessment was performed by three people in real time.)

[0128] 0: normal cheek pouch, no erythema congestion or not obvious; no bleeding area, ulcer or abscess.

[0129] 1: moderate erythema congestion, no bleeding area, ulcer or abscess.

[0130] 2: severe erythema congestion, with bleeding area, small ulcer or scar tissue, but no abscess.

[0131] 3: severe erythema, congestion, with bleeding area, large area of ulcer and abscess.

[0132] 2.3.3 Serum inflammatory markers

[0133] Enzyme-linked immunosorbent assay (ELISA) was used to detect cytokines in buccal mucosa tissue. On the 24th day, the buccal mucosa tissue of the rats was soaked in normal saline, washed clean, and then added twice the amount of normal saline. The tissue was then homogenized in a homogenizer. After centrifugation, the supernatant was used for detection of cytokines IL-6 and TNF-α.

[0134] 2.4 Statistical methods:

[0135] All data were analyzed using SPSS 26.0 software. Numerical variable data were expressed as mean ± standard deviation; for numerical variable data, data that conformed to normal distribution were analyzed by t-test, and data that did not conform to normal distribution were analyzed by rank sum test; comparison of means between multiple samples was analyzed by one-way ANOVA, and if the variances were equal, LSD method was used, and if the variances were not equal, rank sum test was used; for ordinal categorical variable data with two levels, chi-square test was used, and for ordinal categorical data with more than two levels, rank sum test was used. P<0.05 was considered statistically significant.

[0136] 3 Results:

[0137] 3.1 Comparison of oral mucosa tissue efficacy in oral mucositis model rats between treatment group and control group A, control group B:

[0138] The experimental results are shown in Figure 1 The oral mucositis score was performed on the 8th, 12th, 16th, and 20th days. The normal control group maintained a score of 0, the model group maintained the highest overall OM score, and the treatment group had a lower overall OM score than the model group, control group A, and control group B, with a statistically significant difference (P<0.05).

[0139] 3.2 Comparison of IL-6 and TNF-α levels in buccal mucosa tissue after treatment in the treatment group and control group:

[0140] The test results are as follows Figure 2 As shown, the level of cytokine IL-6 in the treatment group was significantly lower than that in control group A, control group B, and model group, and the difference was statistically significant (P < 0.001).

[0141] The test results are as follows Figure 3 As shown, the level of cytokine TNF-α in the treatment group was significantly lower than that in control group A, control group B, and model group, and the difference was statistically significant (P < 0.001).

[0142] 3.3 Comparison of body weight in rats with oral mucositis model in treatment group A and control group B:

[0143] Experimental results are as follows Figure 4 As shown, rats were weighed daily at the start of the experiment, and weight changes were compared pairwise between the two groups. The average weight loss in the treatment group was lower than that in the model group, control group A, and control group B, and the differences were statistically significant (P < 0.01, P < 0.01, P = 0.046). The difference between control group A and the model group and control group B was statistically significant (P < 0.01, P = 0.029), while the difference between control group B and the model group was not statistically significant (P = 0.124).

[0144] 4. Conclusion

[0145] This study used a 5-fluorouracil + acetic acid-induced oral mucositis model to evaluate the protective effects of the experimental drug, Kouyanqing granules, and Kangfuxin liquid. The results showed that the experimental drug, Kouyanqing granules, and Kangfuxin liquid could significantly alleviate the induced oral mucositis symptoms and reduce the level of inflammatory factors in the buccal mucosa. In pairwise comparisons between the two groups, the experimental drug was significantly superior to Kouyanqing granules and Kangfuxin liquid. Attached Figure Description

[0146] Figure 1 Bar chart showing the effects of different drugs on oral mucositis scores in rats with a 5-fluorouracil + acetic acid-induced oral mucositis model.

[0147] Figure 2 A bar chart showing the effects of different drugs on the level of the cytokine IL-6 in the buccal mucosa tissue of rats with a 5-fluorouracil + acetic acid-induced oral mucositis model.

[0148] Figure 3 A bar chart showing the effects of different drugs on the level of the cytokine TNF-α in the buccal mucosa tissue of rats with a 5-fluorouracil + acetic acid-induced oral mucositis model.

[0149] Figure 4Bar graph of the effect of different drugs on the body weight of 5-fluorouracil + acetic acid-induced oral mucositis model rats. DETAILED DESCRIPTION

[0150] Example 1 (granules)

[0151] [Prescription] Dendrobium huoshanense 1350g, Rehmannia 810g, Ophiopogon 810g, and Radix Glycyrrhizae 675g.

[0152] [Preparation method]

[0153] (1) Take Rehmannia, Ophiopogon, and Radix Glycyrrhizae according to the prescription amount, add 18L of water, soak, and then decoct for 1h, filter to obtain decoction liquid A; add 18L of water to the residue and decoct for 1h, filter to obtain decoction liquid B; then combine the decoction liquid A and the decoction liquid B, concentrate, dry, and obtain the water extract;

[0154] (2) Take Dendrobium huoshanense according to the prescription amount, crush, and pass through a 100-mesh sieve to obtain Dendrobium huoshanense fine powder;

[0155] (3) Mix the water extract obtained in step (1) and the Dendrobium huoshanense fine powder obtained in step (2) uniformly, add an appropriate amount of dextrin, mix uniformly, granulate, dry, and prepare granules 2250g, and pack into 12g / bag.

[0156] Example 2 (capsules)

[0157] [Prescription] Dendrobium huoshanense 1440g, Rehmannia 806g, Ophiopogon 770g, and Radix Glycyrrhizae 629g.

[0158] [Preparation method]

[0159] Steps (1)-(2) are the same as in Example 1;

[0160] (3) Add an appropriate amount of starch, mix uniformly, granulate, dry, and pack into capsules to prepare 1000 capsules.

[0161] Example 3 (tablets)

[0162] [Prescription] Dendrobium huoshanense 1262g, Rehmannia 867g, Ophiopogon 830g, and Radix Glycyrrhizae 686g.

[0163] [Preparation method]

[0164] Steps (1)-(2) are the same as in Example 1;

[0165] (3) Add an appropriate amount of starch, mix uniformly, granulate, and press into tablets 1000 tablets.

Claims

1. A traditional Chinese medicine composition for treating oral mucositis in patients caused by radiotherapy and chemotherapy, the traditional Chinese medicine composition being composed of an effective component and a medically acceptable auxiliary material, characterized in that, The effective component is made of raw medicinal materials with the following weight percentage: Dendrobium 33-41%, Rehmanniae Radix 20-24%, Ophiopogonis Radix 20-24%, and Radix Glycyrrhizae 17-20%.

2. The traditional Chinese medicine composition for treating oral mucositis in patients caused by radiotherapy and chemotherapy according to claim 1, characterized in that, The effective component is made of raw medicinal materials with the following weight percentage: Dendrobium 37.1%, Rehmanniae Radix 22.2%, Ophiopogonis Radix 22.2%, and Radix Glycyrrhizae 18.5%.

3. The traditional Chinese medicine composition for treating oral mucositis in patients caused by radiotherapy and chemotherapy according to claim 1 or 2, characterized in that, The effective component is made of the following method: According to the prescription amount, Rehmanniae Radix, Ophiopogonis Radix, and Radix Glycyrrhizae are added with 8 times amount of water for soaking and decocting for 1 hour, and then filtered to obtain decocting liquid A; the residue is added with 8 times amount of water for decocting for 1 hour, and then filtered to obtain decocting liquid B; then, decocting liquid A and decocting liquid B are combined, concentrated, and dried to obtain the water extract; according to the prescription amount, Dendrobium is taken, crushed, and sieved through a 100-mesh screen to obtain Dendrobium fine powder; the obtained water extract and Dendrobium fine powder are the effective component.

4. The Chinese medicine composition for treating oral mucositis in patients caused by radiotherapy and chemotherapy according to claim 3, characterized in that, The traditional Chinese medicine composition is in the form of granules, capsules, or tablets.

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