Traditional Chinese medicine composition for treating chemotherapy-related nausea and vomiting, acupoint patch and preparation method

Abstract

The invention discloses a traditional Chinese medicine composition for treating chemotherapy-related nausea and vomiting, an acupoint patch and a preparation method, and belongs to the technical field of traditional Chinese medicine research. According to a fine-tuning external application formula, acupoint external application is achieved, medicine transdermal absorption is matched with acupoints to stimulate channel and qi combination, and the effect is special and strong; the medication route is changed, oral administration is avoided, and the gastrointestinal burden is relieved. Aromatic traditional Chinese medicines are used for guiding channels, promoting qi circulation, dredging collaterals and promoting transdermal absorption; and the aromatic traditional Chinese medicines enter spleen and stomach channels, enlivene spleen and please stomach, and are helpful for improving gastrointestinal reactions such as nausea and vomiting. The acupoint patch is simple and easy to operate and learn, has a high degree of recognition by the masses, and is easy to popularize in western medicine hospitals and primary hospitals.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine research technology, specifically to a traditional Chinese medicine composition, acupoint patch, and preparation method for treating chemotherapy-related nausea and vomiting. Background Technology

[0002] Chemotherapy-induced nausea and vomiting (CINV) is one of the most common adverse reactions in cancer chemotherapy patients, severely impacting their quality of life and the course of chemotherapy. CINV can be classified into acute, delayed, anticipated, fulminant, and refractory types based on its onset time and treatment efficacy. Delayed CINV occurs 24 hours after chemotherapy and commonly occurs in patients receiving cisplatin, cyclophosphamide, and anthracyclines. For example, cisplatin-induced vomiting often peaks 48–72 hours after chemotherapy and can last for 6–7 days. The mechanism of gastrointestinal reactions induced by chemotherapy drugs is not yet fully understood. It is generally believed that their cytotoxic effects damage and stimulate intestinal chromaffin cells, causing them to release 5-HT, which acts on 5-HT3 receptors in the small intestine, exciting the vagus nerve and stimulating receptors in the medullary vomiting center, thus causing nausea and vomiting.

[0003] Currently, the mainstream treatment for CINV (congenital intravascular coagulation) is a combination of 5-hydroxytryptamine (5-HT) 3-receptor antagonists and dexamethasone. However, nausea and vomiting are still not satisfactorily controlled in 30% of cases, remaining a significant factor affecting patients' quality of life. This is especially true for delayed CINV, which often occurs more than 24 hours after chemotherapy, and is frequently overlooked by patients who have already been discharged, resulting in ineffective control. Nausea and vomiting related to cancer drug treatment significantly impact patients' quality of life, reduce adherence to anti-tumor therapy, and thus affect treatment efficacy. In addition, commonly used antiemetics are broadly categorized by their mechanism of action into 5-HT3 receptor antagonists, NK-1 receptor antagonists, glucocorticoids, atypical antipsychotics, benzodiazepines, phenothiazines, and other types of antiemetics. These medications require repeated use and can cause constipation, diarrhea, headache, liver and kidney damage, and even allergic reactions in some patients. Summary of the Invention

[0004] This invention provides a traditional Chinese medicine composition, acupoint patch, and preparation method for treating chemotherapy-related nausea and vomiting. It effectively solves the technical problems of poor treatment effects of existing chemotherapy-related nausea and vomiting treatments, the need for repeated use of existing antiemetic drugs, and the potential for adverse reactions such as constipation, diarrhea, headache, liver and kidney damage, and even allergic reactions in some patients. At the same time, it provides a traditional Chinese medicine composition for treating chemotherapy-related nausea and vomiting that addresses gastrointestinal reactions through local treatment, allowing the drug to directly reach the affected area, with specific and powerful effects, and has significant characteristics of traditional Chinese medicine.

[0005] The first objective of this invention is to provide a traditional Chinese medicine composition for treating chemotherapy-related nausea and vomiting, comprising the following raw materials in parts by weight: 10-30 parts of Codonopsis pilosula, 10-30 parts of stir-fried Atractylodes macrocephala, 10-30 parts of Poria cocos, 10-30 parts of Poria cocos sclerotium, 10-30 parts of Polyporus umbellatus, 10-30 parts of Citrus reticulata peel, 10-30 parts of ginger-processed Pinellia ternata, 10-30 parts of Dioscorea opposita, 30-90 parts of raw Coix lacryma-jobi, 15-45 parts of roasted malt, 15-45 parts of roasted germinated barley, 10-30 parts of Eriobotrya japonica leaf, and 15-45 parts of clove.

[0006] As a preferred embodiment, the ingredients are composed of the following parts by weight: 10 parts Codonopsis pilosula, 10 parts stir-fried Atractylodes macrocephala, 10 parts Poria cocos, 10 parts Poria cocos sclerotium, 10 parts Polyporus umbellatus, 10 parts Citrus reticulata peel, 10 parts ginger-processed Pinellia ternata, 10 parts Dioscorea opposita, 30 parts raw Coix lacryma-jobi, 15 parts roasted malt, 15 parts roasted germinated barley, 10 parts loquat leaf, and 15 parts clove.

[0007] A second objective of this invention is to provide the application of the above-mentioned traditional Chinese medicine composition in the preparation of a medicament for treating chemotherapy-related nausea and vomiting.

[0008] In a preferred embodiment, the chemotherapy-related nausea and vomiting is caused by platinum-based drugs.

[0009] A third objective of this invention is to provide an acupoint patch prepared from the aforementioned traditional Chinese medicine composition for treating chemotherapy-related nausea and vomiting.

[0010] The fourth objective of this invention is to provide a method for preparing the above-mentioned acupoint patch, comprising the following steps: Weigh each raw material according to the above-mentioned weight proportions, dry, pulverize and sieve, mix evenly to obtain a mixed powder, add water to the mixed powder to soak, heat and decoct to obtain a mixed medicinal liquid, concentrate to obtain a mixed medicinal ointment.

[0011] The matrix material is obtained by heating 5-8 parts by weight of glyceryl monostearate, 10-15 parts by weight of liquid paraffin, 10-15 parts by weight of vegetable oil, 10-15 parts by weight of polyethylene glycol, 3-5 parts by weight of beeswax, and 3-5 parts by weight of petrolatum to 60-70°C.

[0012] Add 10-20 parts by weight of glycerin and 2-5 parts by weight of potassium sorbate to the mixed ointment, then add the matrix material, stir to solidify, then add hyaluronic acid, and apply to form a film to obtain an acupoint patch.

[0013] In a preferred embodiment, the weight ratio of the mixed powder to water is 1:3~5.

[0014] In a preferred embodiment, the soaking time is 0.3h to 0.6h, and the heating and simmering time is 1h to 2h.

[0015] In a preferred embodiment, the volume of the mixed ointment is 1 / 4 to 1 / 3 of the volume of the mixed liquid.

[0016] In one preferred embodiment, the acupoint patch has a diameter of 3cm to 5cm and a thickness of 3mm to 9mm.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows: Based on the principle of the Four Gentlemen Decoction, this invention gently tonifies the spleen and stomach. The externally applied formula for gentle adjustment is based on the Four Gentlemen Decoction, in which ginseng and atractylodes enhance qi and strengthen the spleen, serving as the basic formula for tonifying the spleen qi. The Six Gentlemen Decoction is composed of the Four Gentlemen Decoction plus pinellia ternata with ginger and poria cocos, with the function of tonifying while drying dampness and resolving phlegm. The Shenling Baizhu Powder further adds platycodon grandiflorum, dolichos lablab, Chinese yam, coix lacryma-jobi, lotus seeds, etc., strengthening its ability to tonify the spleen and benefit the lungs and regulate qi movement. Using the Four Gentlemen Decoction to gently tonify the qi of the spleen and stomach, combined with the Erchen Decoction, it tonifies while promoting qi movement, regulating qi and strengthening the spleen, and protecting the spleen and stomach. With the Erchen Decoction and similar formulas, regulating qi and harmonizing the middle, in the formula, dried tangerine peel, poria cocos, and pinellia ternata with ginger regulate qi and resolve phlegm to remove the phlegm turbidity obstructing the stomach, assisted by coix lacryma-jobi for promoting diuresis and dampness elimination and strengthening the spleen and stomach, poria cocos for strengthening the spleen and calming the mind, polyporus umbellatus for nourishing yin, promoting diuresis, and enhancing immunity, and coix seeds and malt for promoting digestion and nourishing the stomach. Additionally, eriobotrya japonica leaf clears heat and resolves phlegm, its bitter and neutral nature can lower qi, combined with cloves for warming the middle and descending adverse qi, and echoing the ascending function of platycodon grandiflorum, the qi movement is smooth, the ascending and descending are in order, jointly achieving the effects of strengthening the spleen, regulating qi, resolving phlegm, and descending adverse qi and stopping vomiting. The whole formula focuses on gently adjusting the middle jiao of the spleen and stomach, not entirely using tonifying drugs for strengthening healthy qi, nor using a large amount of heavy drugs for descending adverse qi, and avoiding using pungent, fragrant, and dispersing drugs violently. Instead, it regulates qi to eliminate stagnation, strengthens the spleen to transform dampness, regulates qi to support healthy qi, and supports healthy qi to expel pathogenic factors, focusing on gentle adjustment and control. By making yin and yang harmonious, qi and blood balanced, and qi movement smooth, it achieves the effect of harmonizing the stomach, descending adverse qi, and stopping vomiting. With fragrant herbs to promote transdermal absorption, choosing cloves with pungent and warm nature for descending adverse qi. In "Yuqiu Yaojie", it is recorded that "clove has a pungent taste and a warm nature, warming and drying the spleen and stomach, expelling distension, and most effective in stopping vomiting and hiccups", which is the key herb for treating unsmooth qi in the stomach and stomach cold with hiccups, mainly entering the spleen meridian of foot taiyin and the stomach meridian of foot yangming. While promoting qi movement with pungent opening and bitter descending, it guides all the herbs into the meridian, enabling the herbs for tonifying qi, regulating qi, and removing dampness to penetrate the skin and directly reach the spleen and stomach meridians, conducting along the meridian, regulating qi and blood of the spleen and stomach, and descending adverse qi and stopping vomiting. Pharmacological research shows that the main chemical component of cloves, clove volatile oil, can have a transdermal absorption effect on three active ingredients with different physicochemical properties. Different from the strong stimulation of borneol with pungent, fragrant, and dispersing properties on the skin, the fragrant property of cloves is more gentle. While promoting the transdermal absorption of drugs, it enables the drugs to take effect gradually, penetrate slowly, achieving the effect of gentle regulation and long-term efficacy.

[0018] For the externally applied formula for gentle adjustment, when applied externally at acupoints, the transdermal absorption of drugs is combined with stimulating the meridian qi at acupoints, with specific and powerful effects; it changes the route of drug administration, avoids oral administration, and reduces the burden on the gastrointestinal tract. Guided by fragrant traditional Chinese herbs to conduct qi and dredge collaterals, it promotes transdermal absorption; and fragrant traditional Chinese herbs are good at entering the spleen and stomach meridians, awakening the spleen and pleasing the stomach, helping to improve gastrointestinal reactions such as nausea and vomiting. Description of the Drawings

[0019] Figure 1 It is a trend chart of the change in the incidence of nausea within 24 hours to 10 days after chemotherapy for the experimental group and the control group of this invention.

[0020] Figure 2 It is a trend chart of the change in the incidence of vomiting within 24 hours to 10 days after chemotherapy for the experimental group and the control group of this invention.

[0021] Figure 3Image of the acupoint patch prepared according to the present invention. Detailed Implementation

[0022] To enable those skilled in the art to better understand and implement the technical solutions of this invention, the invention will be further described below with reference to specific embodiments and accompanying drawings. However, the embodiments described are not intended to limit the invention. Unless otherwise specified, the following test methods and detection methods are conventional methods; unless otherwise specified, the reagents and raw materials are commercially available.

[0023] To address the technical problems of unsatisfactory treatment effects of existing chemotherapy-related nausea and vomiting medications, which require repeated use of existing antiemetic drugs and can cause adverse reactions such as constipation, diarrhea, headache, liver and kidney damage, and even allergic reactions in some patients, this invention provides a traditional Chinese medicine composition for treating chemotherapy-related nausea and vomiting. This composition addresses gastrointestinal reactions through local treatment, allowing the medication to directly reach the affected area, resulting in a highly effective and specific treatment with significant traditional Chinese medicine characteristics.

[0024] The technical solution and research plan of the present invention will be described in detail below.

[0025] I. Research Methods 1. Study subjects: Patients receiving platinum-based chemotherapy at Wuxi Municipal Hospital of Traditional Chinese Medicine. 1.1.1 Diagnostic Criteria: Industry-recognized diagnostic criteria are adopted: Patients who meet the diagnostic criteria for malignant tumors and are diagnosed with malignant tumors by pathology and / or cytology, or by imaging combined with specific tumor markers.

[0026] 1.1.2 Nausea and Vomiting Grading Criteria The adverse reaction grading standard CTCAE version 5.0 is adopted: Nausea: A condition characterized by nausea and / or an urgent need to vomit.

[0027] Level 1: Decreased appetite, without changes in eating habits Grade 2: Reduced oral food intake without significant weight loss, dehydration or malnutrition Grade 3: Insufficient oral energy and water intake; requires nasogastric feeding, total parenteral nutrition, or hospitalization. Vomiting: A reflex action in which stomach contents are expelled through the mouth.

[0028] Level 1: No intervention required Level 2: Outpatient intravenous fluid replacement; medical intervention required. Level 3: Nasogastric feeding required Level 4: Life-threatening Level 5: Death 1.1.3 Other adverse reaction records: Refer to the "Skin Reaction" section of the CTCAE 5.0 Adverse Reaction Grading Standard.

[0029] 1.1.4 Inclusion Criteria ① Age > 18 years old; ② Patients with a confirmed diagnosis of malignant tumor; ③ Patients receiving platinum-based chemotherapy regimens; ④ The patient had received ≥1 cycle of chemotherapy before enrollment and was scheduled to receive ≥2 cycles of chemotherapy; ⑤ Individuals with normal language expression abilities and the capacity to assess their own situation; ⑥ Good compliance, and signed informed consent form.

[0030] 1.1.5 Exclusion Criteria ① Those whose mechanical obstruction is confirmed by gastroscopy or gastrointestinal contrast radiography; ② Other diseases that may cause nausea and vomiting, such as brain metastasis, hypothyroidism, etc.; ③ Cases where the treatment efficacy cannot be determined due to incomplete data; ④ Patients with intellectual or mental disabilities.

[0031] 1.1.6 Termination Criteria and Procedures ① Those who cannot adhere to treatment; ②The patient used treatments that were not permitted under the study protocol; ③ If a serious adverse event occurs, the researcher must be suspended and the adverse event must be recorded in detail; ④ Those who experience severe allergic reactions and / or other serious complications from applying traditional Chinese medicine patches; ⑤ Those whose condition worsened during the research process; ⑥ Those who voluntarily or through their family members request to withdraw from this clinical trial during the research process. Those exhibiting the above conditions will not be included in the clinical efficacy analysis.

[0032] 1.1.7 Research Institutions and Data Collection Sources ①Research Unit: Wuxi Municipal Hospital of Traditional Chinese Medicine ②Data collection source: Clinical research data of patients with malignant tumors receiving platinum-based chemotherapy included by the research unit.

[0033] 1.2 Scheme Design This study employs a prospective, randomized, double-blind, controlled clinical trial protocol to objectively evaluate the clinical efficacy of acupoint application in treating chemotherapy-induced nausea and vomiting.

[0034] 1.2.1 Acupoint patches, such as Figure 3 As shown.

[0035] Example 1 A traditional Chinese medicine composition for treating chemotherapy-related nausea and vomiting, comprising the following ingredients: Codonopsis pilosula 10g, stir-fried Atractylodes macrocephala 10g, Poria cocos 10g, Poria cocos sclerotium 10g, Polyporus umbellatus 10g, Citrus reticulata peel 10g, Pinellia ternata 10g, Dioscorea opposita 10g, raw Coix lacryma-jobi 30g, roasted malt 15g, roasted germinated barley 15g, Eriobotrya japonica leaf 10g, and clove 15g.

[0036] A method for preparing an acupoint patch includes the following steps: S1. Weigh each raw material according to the above mass, dry, pulverize and sieve, mix evenly to obtain a mixed powder, add 660g of water to the mixed powder and soak for 30min, heat and decoct for 1h to obtain a mixed medicinal liquid, concentrate to 1 / 4 of the volume of the mixed medicinal liquid to obtain a mixed ointment.

[0037] S2, 5g of glyceryl monostearate, 10g of liquid paraffin, 10g of vegetable oil, 10g of polyethylene glycol, 3g of beeswax, and 3g of petrolatum are heated to 65°C to obtain the matrix material.

[0038] S3, add 10g of glycerin and 2g of potassium sorbate to the mixed ointment, then add the matrix material, stir and solidify, then add hyaluronic acid, spread it into a film, and obtain an acupoint patch with a diameter of 4cm and a thickness of 6mm.

[0039] Example 2 A traditional Chinese medicine composition for treating chemotherapy-related nausea and vomiting, comprising the following ingredients: Codonopsis pilosula 20g, stir-fried Atractylodes macrocephala 30g, Poria cocos 20g, Poria cocos sclerotium 10g, Polyporus umbellatus 20g, Citrus reticulata peel 30g, Pinellia ternata 10g, Dioscorea opposita 10g, raw Coix lacryma-jobi 60g, roasted malt 20g, roasted germinated barley 45g, Eriobotrya japonica leaf 15g, and clove 20g.

[0040] A method for preparing an acupoint patch includes the following steps: S1. Weigh each raw material according to the above mass, dry, pulverize and sieve, mix evenly to obtain a mixed powder, add 1240g of water to the mixed powder and soak for 30 minutes, heat and decoct for 2 hours to obtain a mixed medicinal liquid, concentrate to 1 / 3 of the volume of the mixed medicinal liquid to obtain a mixed ointment.

[0041] S2, 8g of glyceryl monostearate, 15g of liquid paraffin, 15g of vegetable oil, 15g of polyethylene glycol, 5g of beeswax, and 5g of petrolatum are heated to 70°C to obtain the matrix material.

[0042] S3, add 20g of glycerin and 5g of potassium sorbate to the mixed ointment, then add the matrix material, stir and solidify, then add hyaluronic acid, spread it into a film, and obtain an acupoint patch with a diameter of 4cm and a thickness of 6mm.

[0043] The acupoint patches are prepared uniformly by the Pharmacy Department of Wuxi Municipal Hospital of Traditional Chinese Medicine.

[0044] 1.2.2 How to use acupoint patches: ① Remove the prepared drug patch (approximately 10cm in diameter and 5mm thick, in a disc shape) and set aside; ② Expose the application site: a. Zhongwan acupoint: the midpoint of the line connecting the lower end of the sternum and the navel; b. Shenque acupoint: the navel; c. Zusanli acupoint: about four finger widths below the depression on the outer side of the kneecap.

[0045] ③ Apply the medication to the designated acupoints; ④ Each application should last for 6 hours, once a day.

[0046] 1.2.3 Conventional treatment: According to the NCCN guidelines, 0.25 mg of palonosetron hydrochloride should be administered intravenously 30 minutes before chemotherapy, with the injection time being more than 30 seconds. 1.2.4 Treatment Plan ① All patients received optimal supportive care during the observation period before the medication was applied; ② If an acute attack of nausea and vomiting occurs and is difficult to tolerate, metoclopramide hydrochloride injection 10mg may be temporarily administered intramuscularly if necessary (except for breast cancer patients). ③ Management of adverse reactions to topical medications: Adverse reactions to topical medications are mainly local skin allergic reactions. If severe allergic reactions such as rashes or blisters occur, the medication should be discontinued immediately, and symptomatic treatment should be given. This case will be recorded as a serious adverse reaction event and will not be included in the efficacy analysis. Other local skin adverse reactions will be included in the adverse reaction statistics.

[0047] 1.2.5 Treatment course: Treatment lasts for 7 days starting from the first day of chemotherapy. Observational data are recorded on days 1-7. Patients are followed up on days 8 and 10, and before the next chemotherapy session.

[0048] 1.2.6 Grouping Method: ① Control group: Placebo applied topically + standard treatment ② Treatment group: Micro-adjusted external application to acupoints + routine treatment 1.2.7 Evaluate the ending Prepare a Case Report Form (CRF) to collect clinical data. 1) General condition indicators: patient demographic characteristics, cancer incidence and treatment history, and basic vital signs.

[0049] 2) Efficacy evaluation indicators: ① Primary outcome measure: nausea and vomiting.

[0050] ②Metoclopramide usage.

[0051] ③ Quality of life: The Karnofsky Performance Status Scale (KPS) and ECOG score were used to assess the patients' quality of life in terms of physical condition. The KPS and ECOG scores of the two groups of patients were recorded before treatment, 24 hours after treatment, 10 days after treatment, and before the next chemotherapy.

[0052] 3) Safety indicators: Based on CTCAE 5.0, establish an adverse reaction observation form to record the severity of adverse events and determine their correlation with the investigational drug. Record in detail serious adverse reactions and their manifestations, correlation with the investigational drug, start time, termination time, and reason for relief. Conduct a safety assessment.

[0053] ①Before treatment and 8 days after treatment, basic vital signs and laboratory tests were performed on both groups, including complete blood count, liver and kidney function tests, and electrocardiogram. ② Record the main adverse reactions (including constipation, diarrhea, drowsiness, and local skin allergic reactions to topical medications) and adverse events during the treatment process.

[0054] 4) Satisfaction evaluation: Patient satisfaction with the nausea and vomiting response and overall treatment efficacy. Use a 5-point rating system: Level 1: Very satisfied; Level 2: Satisfied; Level 3: Average; Level 4: Dissatisfied; Level 5: Extremely dissatisfied.

[0055] 1.3 Sample size The sample size of the two groups was estimated based on the efficacy of conventional antiemetic drugs as the basis of treatment in domestic studies and the recent efficacy of acupoint application therapy in our department.

[0056] According to the calculation formula: The calculated sample size was 32 cases per group. Considering a dropout rate of 10%, a total of 72 cases were included.

[0057] 1.4 Research Methods Prospective, randomized, controlled, double-blind clinical trial.

[0058] 1.5 Statistical Methods ① Report the planned number of participants, the number of participants screened and enrolled, the number of participants actually completing the study, the number of participants excluded, and the number of participants who dropped out for each group; based on the reasons for exclusion and dropout, report the number of excluded and dropout participants and their proportions for each group. Report the number of cases treated (taking medication), the number of cases with compliance and the compliance rate for each group, and the comparability analysis, etc.

[0059] ② Use the chi-square test for count data; use the t-test for continuous data; use Ridit analysis for ordinal data; when considering multicenter effects, use the CMH chi-square test for comparing count data or ordinal data.

[0060] ③ All statistical calculations were performed using a statistical analysis system, with guidance from statistical experts. Clinical research results were analyzed using SPSS software.

[0061] 1.6 Researching Ethical Issues: This trial was conducted in accordance with the Declaration of Helsinki and relevant Chinese clinical trial research guidelines and regulations, and ethics committee approval was obtained before the project commenced. Patients who entered the next cycle of chemotherapy after enrollment received free external application of the traditional Chinese medicine "micro-adjustment external application formula" for 7 days. Before each participant was enrolled in this study, the principal investigator fully explained the purpose, procedures, and potential risks of the study to them or their designated representative, and provided each patient with a written informed consent form. Clinical trials could only proceed after the patient, their representative, or family member signed the informed consent form.

[0062] II. Research Results 2.2.1 Incidence of nausea, see Table 1 for details. Table 1. Incidence of nausea (%) As shown in Table 1, there was no statistically significant difference in the incidence of nausea between the two groups within 24 hours after chemotherapy (P>0.05). However, at days 1 (1 day), 4 (4 days), 7 (7 days), and 10 (10 days) after chemotherapy, the incidence of nausea in the treatment group was significantly lower than that in the control group (P<0.05). Figure 1 It can be seen that the incidence of nausea decreased in both groups of patients over time, but the incidence of nausea in the treatment group was consistently lower than that in the control group.

[0063] 2.2.2 Severity of nausea, see Table 2 for details. Table 2 Comparison of nausea severity (%) As shown in Table 2, there were significant differences in the severity of nausea between the treatment group and the control group within 24 hours after chemotherapy and on days 1, 4, 7, and 10. All differences were statistically significant (P<0.05).

[0064] 2.2.3 The incidence of vomiting is shown in Table 3. Table 3. Incidence of vomiting (%) As shown in Table 3, there was no statistically significant difference in the incidence of vomiting between the treatment group and the control group within 24 hours after chemotherapy (P>0.05). However, at days 1, 4, 7, and 10 after chemotherapy, the incidence of vomiting in the treatment group was significantly lower than that in the control group (P<0.05). Figure 2It can be seen that the incidence of vomiting decreased in both groups of patients over time, but the incidence of vomiting in the treatment group was consistently lower than that in the control group.

[0065] 2.2.4 Severity of vomiting, see Table 4 for details. Table 4 Comparison of the severity of vomiting (%) As shown in Table 4, there were significant differences in the severity of vomiting between the treatment group and the control group within 24 hours after chemotherapy and on days 1, 4, 7, and 10. All differences were statistically significant (P<0.05).

[0066] 2.2.5 The TCM syndrome scores of the two groups before and after treatment are shown in Table 5. Table 5. TCM syndrome scores (±s) of the two groups of patients before and after treatment. Note: Z and P represent the intra-group comparison results before and after treatment in the treatment group and the control group, respectively, using the paired rank-sum test. Z* and P* represent the inter-group comparison results between the treatment group and the control group after treatment, respectively, using the rank-sum test.

[0067] Intra-group comparison: In the treatment group, the scores for appetite and taste in the TCM syndrome indicators improved significantly after treatment (p<0.05), but there were no significant changes in bowel movements, mental state, and sleep (p>0.05). This indicates that the modified external application combined with conventional antiemetic treatment can effectively improve symptoms such as appetite and taste in patients with delayed CINV, but its efficacy on bowel movements, mental state, and sleep is not significant. In the control group, the scores for each TCM syndrome indicator did not change significantly after treatment, and the differences were not statistically significant (p>0.05).

[0068] Intergroup comparison: After treatment, the scores of appetite and taste in the treatment group were significantly improved compared with those in the control group, but there were no significant differences in the scores of defecation, mental state and sleep in the TCM syndromes of the treatment group compared with the control group. The differences were not statistically significant (p>0.05).

[0069] 4.2.6 Comparison of KPS between the two groups before and after treatment, see Table 6 for details. Table 6. KPS scores (±s) before and after treatment As shown in Table 6, the average KPS in the treatment group was 87.50±5.68, and the average KPS in the control group was 84.41±7.05. The differences within and between groups were not statistically significant (P>0.05), indicating that the modified external application formula combined with conventional antiemetic treatment had no significant effect on improving the functional status of patients with delayed CINV.

[0070] 2.3 Safety Evaluation 2.3.1 Blood biochemical indicators, see Table 7 for details. Table 7. Blood biochemical indicators (±s) before and after treatment in the two groups of patients. Note: Z and P represent the intra-group comparison results before and after treatment in the treatment group and the control group, respectively, using the paired rank-sum test, with P > 0.05 for both. Z* and P* represent the inter-group comparison results between the treatment group and the control group after treatment, using the rank-sum test, with P > 0.05 for both.

[0071] As shown in Table 7, there were no statistically significant differences in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-GGT, blood urea nitrogen, and creatinine between the two groups before and after treatment (P > 0.05). This indicates that the micro-adjusted external application of the acupoint patch did not cause liver or kidney damage.

[0072] 2.3.2 Adverse Reactions During the entire study observation process, two patients in the two groups developed symptoms such as skin redness and itching after the acupoint patch treatment. It was considered to be related to an allergic reaction to the acupoint patch material. The acupoint patch treatment was stopped in time, and anti-allergy symptomatic treatment was given. An adverse event form was filled out. Since the acupoint patch treatment could not be continued, these cases were regarded as discontinued cases.

[0073] 2.4 Patient-reported outcome evaluation 2.4.1 MAT score, see Table 8 for details. Table 8. Patient MAT scores (±s points) As shown in Table 7, the mean MAT score in the treatment group was (13.13±2.28), while the mean score in the control group was (16.26±3.45). The difference in MAT scores was statistically significant (P<0.05). This indicates that the treatment group experienced better relief from nausea and vomiting than the control group.

[0074] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. A traditional Chinese medicine composition for treating chemotherapy-related nausea and vomiting, characterized in that, It is composed of the following ingredients in parts by weight: Codonopsis pilosula 10-30 parts, stir-fried Atractylodes macrocephala 10-30 parts, Poria cocos 10-30 parts, Poria cocos sclerotium 10-30 parts, Polyporus umbellatus 10-30 parts, Citrus reticulata peel 10-30 parts, Pinellia ternata 10-30 parts, Dioscorea opposita 10-30 parts, raw Coix lacryma-jobi 30-90 parts, roasted malt 15-45 parts, roasted germinated barley 15-45 parts, Eriobotrya japonica leaf 10-30 parts, and clove 15-45 parts.

2. The traditional Chinese medicine composition for treating chemotherapy-related nausea and vomiting according to claim 1, characterized in that, It is composed of the following ingredients in parts by weight: 10 parts Codonopsis pilosula, 10 parts stir-fried Atractylodes macrocephala, 10 parts Poria cocos, 10 parts Poria cocos sclerotium, 10 parts Polyporus umbellatus, 10 parts dried tangerine peel, 10 parts ginger-processed Pinellia ternata, 10 parts Dioscorea opposita, 30 parts raw Coix lacryma-jobi, 15 parts roasted malt, 15 parts roasted germinated barley, 10 parts loquat leaf, and 15 parts clove.

3. The use of the traditional Chinese medicine composition according to claim 1 or 2 in the preparation of a medicament for treating chemotherapy-related nausea and vomiting.

4. The application according to claim 3, characterized in that, The chemotherapy-related nausea and vomiting were caused by platinum-based drugs.

5. An acupoint patch, characterized in that, It is prepared from the traditional Chinese medicine composition for treating chemotherapy-related nausea and vomiting as described in claim 1 or 2.

6. A method for preparing the acupoint patch according to claim 5, comprising the following steps: Weigh each raw material according to the weight proportions in claim 1, dry, pulverize and sieve, mix evenly to obtain a mixed powder, add water to the mixed powder to soak, heat and decoct to obtain a mixed medicinal liquid, concentrate to obtain a mixed medicinal paste; The matrix material is obtained by heating 5-8 parts by weight of glyceryl monostearate, 10-15 parts of liquid paraffin, 10-15 parts of vegetable oil, 10-15 parts of polyethylene glycol, 3-5 parts of beeswax, and 3-5 parts of petrolatum to 60-70°C. Add 10-20 parts by weight of glycerin and 2-5 parts by weight of potassium sorbate to the mixed ointment, then add the matrix material, stir to solidify, then add hyaluronic acid, and apply to form a film to obtain an acupoint patch.

7. The preparation method according to claim 6, characterized in that, The weight ratio of the mixed powder to water is 1:3~5.

8. The preparation method according to claim 6, characterized in that, The soaking time is 0.3h to 0.6h, and the heating and simmering time is 1h to 2h.

9. The preparation method according to claim 6, characterized in that, The volume of the mixed ointment is 1 / 4 to 1 / 3 of the volume of the mixed liquid.

10. The preparation method according to claim 6, characterized in that, The acupoint patch has a diameter of 3cm to 5cm and a thickness of 3mm to 9mm.

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