Traditional Chinese medicine composition for treating malignant tumor complicated with pleural effusion

Abstract

The invention relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition for treating malignant tumor complicated with pleural effusion, which is prepared from the following raw material medicines in parts by weight: 8-16 parts of mirabilite, 2-4 parts of rheum officinale, 2 parts of euphorbia kansui, 1 part of cassia twig and 1 part of pericarpium zanthoxyli. Aiming at the symptoms and pathogenesis of malignant tumor complicated with pleural effusion, the traditional Chinese medicine composition adopts the treatment principles of purging heat, expelling water and warming yang, has the advantages of cheap raw materials, simplicity and convenience in preparation, convenience in use and small side effect, can be externally applied for a long time, and has obvious curative effect through years of clinical application and observation and analysis. The composition has a good clinical curative effect on malignant tumor complicated with pleural effusion.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition for treating malignant tumors combined with pleural effusion. Background Art

[0002] Pleural effusion (MPE) is the accumulation of excessive fluid in the pleural cavity due to any cause. Its causes vary, with neoplastic disease being a major contributing factor. Malignant pleural effusion (MPE) refers to the accumulation of fluid in the pleural cavity caused by a primary malignant tumor originating in the pleura or in other locations that invades the pleura. It is a key indicator of tumor dissemination or advanced tumor progression. Lung cancer is the most common cancer, followed by breast cancer. MPE presents with dyspnea, fatigue, and weight loss, and in the late stages, cachexia may develop, severely impacting patients' quality of life and survival, with a median survival of only 3 to 12 months. Western medical treatment primarily focuses on palliative care, including thoracentesis, intercostal tube drainage, intrathoracic sclerosant perfusion, thoracoscopy, pleurodesis, or placement of an indwelling catheter in the pleural cavity. However, nearly all Western medical treatments for MPE have varying degrees of limitations, such as infection, pneumothorax, and empyema. The treatment of pleural effusion in non-MPE patients is mainly based on etiological treatment combined with symptomatic treatment. For cancer patients, these treatment options increase the complexity of existing treatments, limit the use of certain chemotherapy regimens, and increase the risk of infection.

[0003] Based on the characteristics of pleural effusion, modern physicians generally consider it to fall under the category of "suspended fluid" in Traditional Chinese Medicine. The "Suwen: Treatise on the Meridians" describes normal fluid metabolism as follows: "Fluid enters the stomach, circulates, and transports essence upward to the spleen. The spleen disperses the essence, which then returns to the lungs, regulating the water channels and transporting it downward to the bladder. The essence of water is distributed to the four directions, running parallel to the five meridians." The normal metabolism and distribution of fluid are closely related to the coordinated function of the lungs, spleen, and kidneys. Based on a deficiency of Zhongyang, exposure to wind and cold, or infiltration of cold and dampness, improper diet, or fatigue can disrupt the qi transformation of the triple energizer, impair lung regulation, weaken the spleen's function, and weaken the kidney's ability to transform fluids. This leads to the accumulation of body fluids, internal generation of pathogenic fluids, and their flow to the hypochondria, resulting in suspended fluid.

[0004] External application of Chinese medicine is one of the major characteristics of traditional Chinese medicine and an important means of external treatment. It has unique advantages in the treatment of pleural effusion. It is easy to operate, economical and practical, has significant clinical efficacy, and has few toxic and side effects.

[0005] However, there is no report on a traditional Chinese medicine composition for treating malignant tumors combined with pleural effusion, which has few side effects, good efficacy and can be applied externally for a long time. Summary of the Invention

[0006] The purpose of the present invention is to address the deficiencies in the prior art and provide a traditional Chinese medicine composition (hereinafter referred to as Jiao Sui Xiao Shui Tie) for treating malignant tumors combined with pleural effusion, which has few side effects, good efficacy, and can be applied externally for a long time.

[0007] The first aspect of the present invention provides a traditional Chinese medicine composition for treating malignant tumors combined with pleural effusion, which is composed of the following raw materials in parts by weight: 8-16 parts of Glauber's salt, 2-4 parts of rhubarb, 2 parts of kansui, 1 part of cassia twig, and 1 part of Sichuan pepper.

[0008] Furthermore, the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 8 parts of Glauber's salt, 2 parts of rhubarb, 2 parts of kansui, 1 part of cassia twig, and 1 part of Sichuan pepper.

[0009] The second aspect of the present invention provides a traditional Chinese medicine compound preparation for external use with the traditional Chinese medicine composition as the active ingredient. The traditional Chinese medicine compound preparation for external use is prepared into a common dosage form in pharmacy using conventional preparation methods in the art.

[0010] Furthermore, the external Chinese medicine compound preparation is an external application powder.

[0011] Crush the medicinal pieces to a fineness of 100 to 500 mesh. Mix thoroughly before use, place in a 30 cm x 30 cm gauze bag, and secure to the back of the chest on the side with the pleural effusion. Apply once daily for 4 to 6 hours. Remove if both the inner and outer layers are soaked and dripping. Continue treatment for 2 weeks.

[0012] Furthermore, the external-use Chinese herbal compound preparation also includes pharmaceutically acceptable excipients.

[0013] The third aspect of the present invention provides a use of the above-mentioned traditional Chinese medicine composition in the preparation of a medicament for treating malignant tumors combined with pleural effusion.

[0014] A fourth aspect of the present invention provides a use of the above-mentioned external-use Chinese herbal compound preparation in the preparation of a medicament for treating malignant tumors combined with pleural effusion.

[0015] Furthermore, the malignant tumor is a solid malignant tumor, including lung cancer, breast cancer, digestive tract malignant tumors (such as esophageal cancer, gastric cancer, liver cancer, colorectal cancer), cervical malignant tumors, ovarian malignant tumors, kidney malignant tumors, prostate malignant tumors, scrotal malignant tumors, etc.

[0016] The traditional Chinese medicine compound preparation (Jiao Sui Xiao Shui Tie Fang) presented herein is composed of five herbs: Glauber's Salt, Rhubarb, Ginseng, Cinnamon Twig, and Sichuan Zanthoxylum bungeanum. This formula is carefully selected and formulated based on years of clinical practice and guided by traditional Chinese medicine theory. Ginseng, a potent purgative, diuretic agent, directly targets the phlegm-drenching site, serving as the main ingredient. Rhubarb and Glauber's Salt purge heat, unblock the bowels, and moisten dryness and soften hard masses, serving as the auxiliary ingredients. Cinnamon Twig warms and unblocks the meridians, boosts yang and transforms qi, while Sichuan Zanthoxylum bungeanum warms yang, promotes diuresis, and reduces swelling. These two herbs counteract the cooling properties of Glauber's Salt, Rhubarb, and Ginseng, serving as adjuvants. Overall, the formula simultaneously clears heat, expels diuresis, and warms yang, while the dosage is simple and large, resulting in a potent and effective treatment. Because this prescription is for external use, a large dosage is recommended. Therefore, a large amount of Glauber's Salt is used to soften and dissipate hard masses, expel diuresis, and promote purgation, supplemented by Rhubarb and Ginseng to dispel the phlegm-drenching site. Despite the high dosage, the strong properties of the herbs are somewhat mitigated by transdermal administration. The five medicines are used together, with strong drugs acting slowly to eliminate evil without harming the body.

[0017] The advantages of the present invention are:

[0018] The present invention addresses the symptoms and pathogenesis of malignant tumors combined with pleural effusions, adopting the therapeutic principles of purging heat, expelling water, and warming yang. The Chinese medicinal composition uses inexpensive raw materials, is simple to prepare, convenient to use, has minimal side effects, and can be applied externally for a long time. Years of clinical application and observational analysis have shown that the composition has good clinical efficacy in treating malignant tumors combined with pleural effusions. Given that malignant tumors combined with pleural effusions significantly impact patients' quality of life, and current guidelines recommend improving patient symptoms as the primary treatment modality, the topical Chinese medicinal compound preparation provided by the present invention has promising application prospects. DETAILED DESCRIPTION

[0019] The specific implementation methods provided by the present invention are described in detail below with reference to the examples.

[0020] Example 1: Chinese medicine composition of the present invention

[0021] The drug is composed of the following raw materials in parts by weight: 8 parts of Glauber's salt, 2 parts of rhubarb, 2 parts of kansui, 1 part of cassia twig and 1 part of Sichuan pepper.

[0022] Example 2: Chinese medicine composition of the present invention

[0023] The drug is composed of the following raw materials in parts by weight: 10 parts of Glauber's salt, 3 parts of rhubarb, 2 parts of kansui, 1 part of cassia twig, and 1 part of Sichuan pepper.

[0024] Example 3: Chinese medicine composition of the present invention

[0025] The drug is composed of the following raw materials in parts by weight: 12 parts of Glauber's salt, 4 parts of rhubarb, 2 parts of kansui, 1 part of cassia twig, and 1 part of Sichuan pepper.

[0026] Example 4: Chinese medicine composition of the present invention

[0027] The drug is composed of the following raw materials in parts by weight: 14 parts of Glauber's salt, 3 parts of rhubarb, 2 parts of kansui, 1 part of cassia twig, and 1 part of Sichuan pepper.

[0028] Example 5: Chinese medicine composition of the present invention

[0029] The drug is composed of the following raw materials in parts by weight: 16 parts of Glauber's salt, 2 parts of rhubarb, 2 parts of kansui, 1 part of cassia twig, and 1 part of Sichuan pepper.

[0030] Example 6: Preparation of the Chinese medicine compound preparation of the present invention

[0031] Weigh the raw materials according to any ratio of Examples 1-5, crush the medicinal pieces into powder with a fineness of 100 to 500 mesh, mix well and put into a 30 cm × 30 cm gauze bag before use.

[0032] Example 7: Clinical Trial

[0033] (1) Case source: Cases were collected from patients with solid malignant tumors (including lung cancer, breast cancer, gastrointestinal malignancies (such as esophageal cancer, gastric cancer, liver cancer, colorectal cancer), cervical malignancies, ovarian malignancies, kidney malignancies, prostate malignancies, and scrotal malignancies) combined with pleural effusion who visited the outpatient clinics and wards of the First Oncology Department of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine from June 2024 to February 2025 and met the inclusion and exclusion criteria.

[0034] (II) Inclusion criteria: (1) Patients diagnosed with solid malignant tumors by cytological or histopathological examination; (2) Maximum depth of pleural effusion ≥30 mm under sitting ultrasound; (3) Karnofsky score ≥60 points; (4) Age ≥18 years and ≤74 years, regardless of gender; (5) Able to understand the content of this study and voluntarily sign the informed consent.

[0035] (III) Exclusion criteria: (1) Patients with a history of difficult-to-control mental illness; (2) Patients who are pregnant or breastfeeding; (3) Patients with skin damage that is not suitable for topical application or allergies to traditional Chinese medicine, etc.; (4) Patients who have received other related treatments or clinical trials.

[0036] (IV) Research methods: A prospective, randomized controlled research method was used to design the experimental plan.

[0037] The treatment group was treated with the external application of the Jiao Sui Xiao Shui Tie prescription of the present invention combined with conventional anti-tumor treatment, while the control group was treated with conventional anti-tumor treatment alone for a total of 14 days.

[0038] Preparation of Jiaosui Xiaoshui Patch: Prepare Glauber's Salt, Rhubarb, Kansui, Cinnamon Twig, and Sichuan Zanthoxylum bungeanum in a ratio of 8:2:2:1:1. Crush the medicinal pieces to a powder with a fineness of 100-500 mesh in our hospital's pharmacy. Mix thoroughly and place in a 30cm x 30cm gauze bag.

[0039] Each Jiaosui Xiaoshui patch contains five bags of traditional Chinese medicine: processed gansui powder, rhubarb powder, Sichuan pepper powder, cinnamon twig powder, and Glauber's salt powder. To use, separate the five bags of powder into a 30 cm x 30 cm gauze bag and mix thoroughly. Apply the patch to the back of the chest on the side with the pleural effusion. Apply once daily for four to six hours. Remove the patch if both the inner and outer layers are soaked and dripping. Continue treatment for two weeks.

[0040] (V) Observation indicators and efficacy evaluation:

[0041] (1) Changes in pleural effusion volume: Pleural effusion measurement method and quantitative basis: Before treatment and 14 days after treatment, the patient sat upright with his back slightly arched and his hands on his head. Coupling agent was applied to the chest cavity. Ultrasound examination was used to measure the maximum depth of the pleural effusion and the formula: y = 47.6x - 837 (x > 20 mm), or y = 20x, or y = 284.75 (x - 32) was used to estimate the pleural effusion volume. y (mL) is the pleural effusion volume, and x (mm) is the maximum depth of the anechoic zone. Since there is a positive correlation between y and x, in order to simplify the calculation, the pleural effusion volume in subsequent studies was based on the maximum depth of the anechoic zone. A pleural effusion volume of 500-1000 mL was defined as a moderate pleural effusion, and a pleural effusion volume exceeding 1000 mL was defined as a large pleural effusion. According to the inclusion criteria (maximum depth of effusion ≥30mm under sitting ultrasound), the effusion volume of all enrolled patients exceeded 500mL. Therefore, the patients with malignant tumors and pleural effusion selected for this study all had moderate or large effusions. The efficacy of pleural effusion changes was evaluated according to the clinical efficacy evaluation criteria for pleural effusion established by the World Health Organization (WHO):

[0042] ① Complete remission (CR): disappearance of effusion;

[0043] ② Partial remission (PR): effusion reduced by more than 50%;

[0044] ③Stable (SD): The effusion decreases by less than 50%, or increases by less than 25%;

[0045] ④ Ineffective (PD): The increase in effusion exceeds 25%.

[0046] (CR+PR+SD) / total number of cases is the total effective rate of pleural effusion, and (CR+PR) / total number of cases is the remission rate of pleural effusion.

[0047] (2) MDASI-TCM scale evaluation

[0048] Assessments are performed using the MDASI-TCM scale. This scale, derived from the MD Anderson Symptom Inventory (MDASI), developed in 2000 at the University of Texas MD Anderson Cancer Center, is a multi-symptom self-assessment tool that has been widely used to monitor symptoms in various cancer patients and during their treatment. Assessments are performed on the day of treatment and again between days 14 and 28 of treatment. In 2017, Professor Li Pingping and colleagues from the Beijing Cancer Hospital affiliated with Peking University validated the MD Anderson Symptom Inventory-TCM Module (MDASI-TCM), which adds seven Traditional Chinese Medicine (TCM)-specific symptom items (sweating, chills, constipation, bitter taste in the mouth, cough, palpitations, and hot palms and soles) to the 13 core MDASI symptom items (pain, fatigue, nausea, disturbed sleep, irritability, shortness of breath, forgetfulness, loss of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness / tingling). The results demonstrated that this scale was validated for assessing Chinese cancer patients receiving Traditional Chinese Medicine (TCM) treatment and is now widely used in clinical research on TCM-based cancer interventions. The version used in this study contains 20 symptom items and six items related to symptom interference, including general activities, work, mood, walking, relationships with others, and enjoyment of life. Each item in this scale uses a numerical rating scale to quantify the symptom, ranging from 0 to 10. A score of 0 indicates the absence or unaffected nature of the symptom, while a score of 10 indicates the symptom and its impact are at their most severe.

[0049] (3) Cough VAS score

[0050] The Visual Analogue Scale (VAS) is an internationally recognized cough assessment tool widely used in clinical practice. Participants are asked to mark a scale from 0 to 10 cm based on their subjective experience. A score of 0 indicates no cough, while a score of 10 indicates an extremely severe cough. The score is proportional to cough severity and is assigned by the participant based on their perceived cough intensity. Assessments are performed on the day of treatment and again between days 14 and 28 of treatment.

[0051] (4) Dyspnea VAS score

[0052] The VAS score for dyspnea is an internationally recognized clinical assessment tool widely used for the subjective evaluation of dyspnea. Participants are asked to mark a scale from 0 to 10 cm based on their perceived dyspnea. A score of 0 indicates no dyspnea, while a score of 10 indicates extremely severe dyspnea. The score is proportional to the severity of dyspnea, and participants rate their dyspnea based on their perceived intensity. Assessments are performed on the day of treatment and again between days 14 and 28 of treatment.

[0053] (5) Safety evaluation

[0054] This study conducted a statistical analysis of safety-related indicators such as blood routine, liver function, and kidney function before and after treatment, and graded them according to the NCI-CTC 5.0 adverse drug reaction grading standard of the National Cancer Institute of the United States to evaluate the safety of the drug.

[0055] (6) Results:

[0056] Between June 2024 and February 2025, 74 patients with malignant tumors and pleural effusion who met the inclusion and exclusion criteria were enrolled. Enrolled patients were randomly assigned using a website-generated random number method. Of these, 37 patients in the treatment group completed the study, and 37 were ultimately included in the statistics. Of the 37 patients in the control group, 1 was lost to follow-up during the study, and 36 were ultimately included in the statistics. A total of 73 patients were enrolled in this study, including 36 in the treatment group and 37 in the control group. There were no statistically significant differences between the two groups in terms of gender, age, previous thoracic surgery, albumin levels, maximum depth of pleural effusion on sitting ultrasound before treatment, cancer type, or stage (p>0.05), indicating comparability between the two groups.

[0057] (1) Comparison of pleural effusion depth

[0058] Before treatment, a comparison of the maximum depth of the pleural effusion under sitting ultrasound between the two groups showed a p-value of 0.085 > 0.05, indicating that the difference between the two groups was not statistically significant and therefore comparable. Intragroup comparisons showed that the maximum depth of the pleural effusion in the control group increased from 64.19 ± 30.111 mm before treatment to 69.33 ± 35.500 mm, with a statistically significant difference before and after treatment (Z = -2.397, p = 0.017 < 0.05). In contrast, the maximum depth of the pleural effusion in the treatment group decreased from 75.78 ± 32.685 mm before treatment to 50.70 ± 35.070 mm, with a statistically significant difference before and after treatment (Z = -4.930, p < 0.001). After 14 days of treatment, intergroup comparisons showed a statistically significant difference in the maximum depth of pleural effusion between the treatment and control groups under sitting ultrasound (p = 0.024 < 0.05). A comparison of pleural effusion depth between the two groups is shown in Table 1.

[0059] Table 1 Comparison of pleural effusion depth between the two groups , mm]

[0060]

[0061] Note: *p <0.05 compared with the group before treatment; #p <0.05 compared with the control group after treatment.

[0062] (2) Comparison of therapeutic effects on changes in pleural effusion

[0063] After treatment, 3 patients in the treatment group achieved complete clinical remission, 8 achieved partial remission, 25 achieved stable disease, and 1 had no effect. In the control group, 1 patient achieved complete remission, 2 achieved partial remission, 25 achieved stable disease, and 8 had no effect. A comparison of the overall efficacy between the two groups showed a statistically significant difference (χ²=9.854, p=0.013<0.05).

[0064] The pleural effusion remission rate in the treatment group was 29.73%, significantly higher than the 8.33% in the control group (χ²=5.389, p=0.020<0.05). Furthermore, the overall effective rate in the treatment group was 97.3%, significantly higher than the 77.78% in the control group (χ²=6.432, p=0.014<0.05). A comparison of the therapeutic effects on pleural effusion between the two groups is shown in Table 2.

[0065] Table 2 Comparison of therapeutic effects on changes in pleural effusion between the two groups [cases (%)]

[0066]

[0067] Note: Compared with the control group, *P <0.05, △ was tested by chi-square test, △△ was tested by Fisher's exact test.

[0068] (3) Comparison of MDASI-TCM scale scores

[0069] Before treatment, the two groups showed a statistically insignificant difference in each item of the MDASI-TCM scale (p value 0.408 > 0.05), indicating that the two groups were comparable. Comparison of the results showed that the treatment group achieved superior efficacy in improving mood, fatigue, shortness of breath, cough, appetite, and intolerance to cold (p < 0.05). Analysis of pre- and post-treatment data revealed that the treatment group achieved modest efficacy in improving cough, shortness of breath, fatigue, appetite, intolerance to cold, mood, irritability, general activity, work, walking, and enjoyment of life (p < 0.05). The control group achieved modest efficacy in improving irritability, cough, general activity, and mood (p < 0.05). See Table 3.

[0070] Table 3 Comparison of MDASI-TCM items between the two groups ( ,point)

[0071]

[0072]

[0073] Note: *p <0.05 compared with the group before treatment; #p <0.05 compared with the control group after treatment.

[0074] (4) Cough VAS score

[0075] Before treatment, the comparison of cough VAS scores of the two groups of patients showed that the p value was 0.752>0.05, indicating that the difference between the two groups was not statistically significant and therefore comparable.

[0076] After treatment, the cough VAS score in the treatment group significantly decreased from 2.70±1.175 before treatment to 1.57±1.094 (Z=-4.584, p<0.001). For the control group, the cough VAS score significantly decreased from 2.58±1.360 before treatment to 2.44±1.362 (Z=-2.236, p=0.025<0.05). A statistically significant difference was also observed between the treatment and control groups (Z=-2.925, p=0.003<0.001). See Table 4.

[0077] Table 4 Comparison of cough VAS between the two groups ,point]

[0078]

[0079] Note: *p <0.05 compared with the group before treatment; #p <0.05 compared with the control group after treatment.

[0080] (5) Dyspnea VAS score

[0081] Before treatment, the comparison of dyspnea VAS scores between the two groups of patients showed that the p value was 0.737>0.05, indicating that the difference between the two groups was not statistically significant and therefore comparable.

[0082] After treatment, the VAS score for dyspnea in the treatment group significantly decreased from 2.81±1.126 before treatment to 1.41±1.117 (Z=-4.499, p<0.001). For the control group, the VAS score for dyspnea significantly increased from 3.00±1.724 before treatment to 3.42±2.170 (Z=-2.056, p=0.040<0.05). A statistically significant difference was also observed between the treatment and control groups (Z=-4.066, p<0.001). See Table 5.

[0083] Table 5 Comparison of VAS of dyspnea between the two groups ,point]

[0084]

[0085] Note: *p <0.05 compared with the group before treatment; #p <0.05 compared with the control group after treatment.

[0086] (6) Safety evaluation

[0087] One week after treatment, only one patient in the treatment group experienced a mild erythema reaction, which resolved on its own within a day without any special treatment and was assessed as a Grade 1 adverse reaction. The patient reported having an allergic constitution.

[0088] Before treatment and 14 days after treatment, the blood routine indicators and liver and kidney function indicators of the treatment group and the control group showed no significant abnormalities (p > 0.05), indicating that the two treatment regimens had no significant effect on routine serum indicators and had good safety.

[0089] The preferred embodiments of the present invention have been specifically described above, but the present invention is not limited to the described embodiments. Those skilled in the art may make various equivalent modifications or substitutions without departing from the spirit of the present invention. These equivalent modifications or substitutions are all included in the scope defined by the claims of this application.

Claims

1. A Chinese medicine composition for treating malignant tumors combined with pleural effusion, characterized in that: The invention is composed of the following raw materials in parts by weight: 8-16 parts of Glauber's salt, 2-4 parts of rhubarb, 2 parts of kansui, 1 part of cassia twig and 1 part of Sichuan pepper.

2. The Chinese medicine composition according to claim 1, characterized in that The traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 8 parts of Glauber's salt, 2 parts of rhubarb, 2 parts of kansui, 1 part of cassia twig and 1 part of Sichuan pepper.

3. A Chinese medicine compound preparation for external use with the Chinese medicine composition according to claim 1 or 2 as an active ingredient, characterized in that: The external Chinese medicine compound preparation is prepared into a common external dosage form in pharmacy by conventional preparation methods in the art.

4. The external-use Chinese medicinal compound preparation according to claim 3, characterized in that: The external Chinese medicinal compound preparation is an external application powder.

5. The external-use Chinese medicinal compound preparation according to claim 4, characterized in that: The external Chinese medicine compound preparation also includes pharmaceutically acceptable excipients.

6. Use of the traditional Chinese medicine composition according to claim 1 or 2 in the preparation of a medicament for treating malignant tumors combined with pleural effusion.

7. Use of the external-use Chinese medicinal compound preparation according to any one of claims 3 to 5 in the preparation of a medicament for treating malignant tumors combined with pleural effusion.

8. The use according to claim 6, characterized in that The malignant tumor is a solid malignant tumor, including lung cancer, breast cancer, digestive tract malignant tumor, cervical malignant tumor, ovarian malignant tumor, kidney malignant tumor, prostate malignant tumor, and scrotal malignant tumor.

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