Application of Traditional Chinese Medicine Compositions and Compound Improvers

Abstract

This invention relates to the field of novel pharmaceutical applications, specifically to the application of traditional Chinese medicine (TCM) compositions and their compounding modifiers. The application of the TCM composition in the preparation of promoters that enhance the efficacy of chemotherapy drugs, wherein the active ingredients of the TCM composition, by weight, include 20-120 parts of Ganoderma lucidum, 10-90 parts of American ginseng or ginseng, 3-60 parts of fermented Cordyceps militaris powder and / or 3-90 parts of Cordyceps sinensis, and 10-60 parts of rose petals. This TCM composition can improve the efficacy of chemotherapy and, more importantly, alleviate the biochemical side effects caused by chemotherapy, further expanding the application of TCM compositions.

Description

Technical Field

[0001] This invention relates to the field of new pharmaceutical application technology, and more specifically, to the application of traditional Chinese medicine compositions and compound improvers. Background Technology

[0002] Chemotherapy, short for chemical drug therapy, is a treatment method that uses chemical drugs to inhibit the proliferation, invasion, and metastasis of cancer cells, ultimately killing them. It is a systemic treatment, and along with surgery and radiotherapy, it is considered one of the three major treatments for cancer. However, while chemotherapy kills tumor cells, it also damages normal cells, causing gastrointestinal reactions, bone marrow suppression, and immunosuppression, leading to weakened immune function. Current technologies include the use of traditional Chinese medicine formulas to improve some of the side effects of chemotherapy, such as nausea and vomiting, but improvements to biochemical side effects are less common, and even fewer efforts can simultaneously improve the efficacy of chemotherapy while addressing side effects.

[0003] In view of this, the present invention is proposed. Summary of the Invention

[0004] The purpose of this invention is to provide applications and compound improvers of traditional Chinese medicine compositions. The traditional Chinese medicine compositions provided in the embodiments of this invention can improve the efficacy of chemotherapy and, more importantly, mitigate the biochemical side effects caused by chemotherapy, further expanding the applications of traditional Chinese medicine compositions.

[0005] This invention is implemented as follows:

[0006] In a first aspect, the present invention provides the application of a traditional Chinese medicine composition in the preparation of an enhancer that improves the chemotherapy effect of chemotherapy drugs. By weight, the active ingredients of the traditional Chinese medicine composition include 20-120 parts of Ganoderma lucidum, 10-90 parts of American ginseng or ginseng, 3-60 parts of fermented Cordyceps sinensis powder and / or 3-90 parts of Cordyceps sinensis and 10-60 parts of rose.

[0007] In optional embodiments, the chemotherapeutic effects of the chemotherapy drugs include any one or at least two of the following: reducing tumor volume, reducing tumor weight, reducing the level of the blood biochemical marker AST, and reducing the level of the blood biochemical marker CREA.

[0008] In an optional embodiment, the chemotherapy drug is a chemotherapy drug targeting malignant tumors;

[0009] The preferred chemotherapy drug is one that targets non-small cell lung cancer; cisplatin is more preferred.

[0010] Secondly, the present invention provides the application of a traditional Chinese medicine composition in the preparation of an improver to improve the side effects caused by chemotherapy drugs. By weight, the active ingredients of the traditional Chinese medicine composition include 20-120 parts of Ganoderma lucidum, 10-90 parts of American ginseng or ginseng, 3-60 parts of fermented Cordyceps sinensis powder and / or 3-90 parts of Cordyceps sinensis and 10-60 parts of rose. The side effects caused by chemotherapy drugs include any one or at least two of the following: decreased RBC content, decreased PLT content, decreased Hgb content, and decreased thymus index.

[0011] In an optional embodiment, the chemotherapy drug is a chemotherapy drug targeting malignant tumors;

[0012] The preferred chemotherapy drug is one that targets non-small cell lung cancer; cisplatin is more preferred.

[0013] Thirdly, embodiments of the present invention provide the application of a pharmaceutical composition in the preparation of an improver that simultaneously improves the side effects caused by chemotherapy drugs and enhances the chemotherapy effect of chemotherapy drugs. By weight, the active ingredients of the traditional Chinese medicine composition include 20-120 parts of Ganoderma lucidum, 10-90 parts of American ginseng or ginseng, 3-60 parts of fermented Cordyceps sinensis powder and / or 3-90 parts of Cordyceps sinensis and 10-60 parts of rose. The side effects caused by chemotherapy drugs include any one or at least two of the following: decreased RBC content, decreased PLT content, decreased Hgb content, and decreased thymus index.

[0014] In optional embodiments, the chemotherapeutic effects of the chemotherapy drugs include any one or at least two of the following: reducing tumor volume, reducing tumor weight, reducing the level of the blood biochemical marker AST, and reducing the level of the blood biochemical marker CREA.

[0015] Fourthly, the present invention provides a composite improver that can enhance the chemotherapy effect of chemotherapy drugs or improve the side effects caused by chemotherapy drugs. The active ingredients of the composite improver include a traditional Chinese medicine composition and a chemotherapy drug. By weight, the active ingredients of the traditional Chinese medicine composition include 20-120 parts of Ganoderma lucidum, 10-90 parts of American ginseng or ginseng, 3-60 parts of fermented Cordyceps sinensis powder and / or 3-90 parts of Cordyceps sinensis and 10-60 parts of rose.

[0016] In an optional embodiment, each milligram of the chemotherapy drug is added to a solution formed by adding 30-40 ml of the traditional Chinese medicine composition.

[0017] In an optional embodiment, the composite improver may further include pharmaceutically acceptable additives or excipients.

[0018] The present invention has the following beneficial effects: The traditional Chinese medicine composition provided in the embodiments of the present invention can enhance the effect of chemotherapy. Specifically, it can reduce tumor volume, tumor weight, and the levels of the blood biochemical markers AST and CREA. Simultaneously, it can improve the side effects of chemotherapy, such as reducing chemotherapy-induced decreases in RBC, PLT, Hgb, and thymus index. Attached Figure Description

[0019] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0020] Figure 1 A graph showing the detection results of tumor volume provided in an embodiment of the present invention;

[0021] Figure 2-3 This is a graph showing the results of blood biochemistry analysis provided in an embodiment of the present invention.

[0022] Figure 4-5 This is a graph showing the results of organ index analysis provided in an embodiment of the present invention.

[0023] Figure 6 A weight change graph provided for an embodiment of the present invention. Detailed Implementation

[0024] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.

[0025] This invention provides a new application of a traditional Chinese medicine composition, the active ingredients of which are derived from 20-120 parts of Ganoderma lucidum, 10-90 parts of American ginseng or ginseng, 3-60 parts of fermented Cordyceps sinensis powder and / or 3-90 parts of Cordyceps sinensis, and 10-60 parts of rose.

[0026] The medicine formed by this traditional Chinese medicine composition can be purchased directly, such as purchasing Shenlingcao oral liquid; or it can be prepared in accordance with CN201210184710.5.

[0027] Specifically, new applications include one or both of the following applications;

[0028] (1) As a promoter to enhance the effect of chemotherapy drugs, specifically, it can further promote the effect of chemotherapy, thereby reducing tumor volume, reducing tumor weight, reducing the content of blood biochemical indicator AST and reducing the content of blood biochemical indicator CREA, or any one or at least two of them.

[0029] (2) As an improver to improve the side effects caused by chemotherapy drugs, it specifically improves the reduction of RBC content, PLT content, Hgb content and thymus index caused by chemotherapy.

[0030] Furthermore, the chemotherapy mentioned above is for malignant tumors, such as non-small cell lung cancer, and the chemotherapy drugs used can be alkylating agents, such as cisplatin.

[0031] Therefore, the above-mentioned traditional Chinese medicine composition can be combined with chemotherapy to form a composite improver. This composite improver can not only enhance the therapeutic effect of chemotherapy drugs but also improve the side effects caused by chemotherapy. Specifically, each milligram of the chemotherapy drug corresponds to 30-40 ml of the solution formed by the traditional Chinese medicine composition.

[0032] Furthermore, the composite improver also includes pharmaceutically acceptable additives or excipients, such as, but not limited to, lubricants, fillers, preservatives, solubilizers, disintegrants, flavoring agents, and emulsifiers.

[0033] The features and performance of the present invention will be further described in detail below with reference to embodiments.

[0034] experiment

[0035] 1. Materials and Methods

[0036] 1.1 Animals, Cells, Reagents and Major Instruments

[0037] Forty male C57BL / 6J mice, weighing 15–18g and 4–5 weeks old, were purchased from Spifort (Beijing) Biotechnology Co., Ltd. They were housed in a barrier environment at the Jiangzhong Pharmaceutical Animal Experiment Center, with a temperature of 20–26℃, relative humidity of 40%–70%, and alternating 12h / 12h lighting daily. Mice had free access to food and water. Mouse Lewis lung cancer cells were purchased from the Cell Bank of the Chinese Academy of Sciences and cultured in DMEM medium with 10% newborn calf serum at 37℃ in a 5% CO2 cell culture incubator. The herbal composition included: Shenlingcao (200mL / bottle, Jiangzhong Pharmaceutical Co., Ltd.); cisplatin (25mg / bottle, Sigma); PBS (Solepro); and 0.9% physiological saline (Jiangxi Kelun Pharmaceutical Co., Ltd.). A digital caliper (Deli Group Co., Ltd.); an animal biochemical analyzer (Shenzhen Mindray Bio-Medical Electronics Co., Ltd.); and an animal hematology analyzer (Shenzhen Mindray Bio-Medical Electronics Co., Ltd.) were also used.

[0038] 1.2 Preparation, treatment and grouping of tumor-bearing mice

[0039] Log-phase LLC non-small cell lung cancer cells were harvested and inoculated into the backs of male C57 mice, with each mouse receiving 0.2 mL (approximately 5 × 10⁻⁶ cells). 6 (cells / mL), tumor volume reaches 50-100 mm² 5-7 days after inoculation. 3 When no ulceration occurred, the tumor-bearing mouse model was successfully established. At this point, the mice were divided into four groups based on both tumor volume and body weight: the tumor-bearing model group, the traditional Chinese medicine combination group (hereinafter referred to as the Shenlingcao group), the chemotherapy group, and the Shenlingcao + chemotherapy group. The Shenlingcao group was administered at a dose of 150 mL / kg. -1 Administered via ig (daily, 14 times); chemotherapy group received 4 mg / kg. -1 Mice were administered the medication intraperitoneally (IP) once every two days for a total of 7 times. After 19 days, blood samples, tumor samples, thymus samples, and spleen samples were collected from each group of mice for relevant indicator testing.

[0040] 1.3 Measurement of tumor volume and weight

[0041] The longest diameter (a) and shortest diameter (b) of the tumor tissue were measured every 3 days using vernier calipers. The tumor volume (V) = 1 / 2ab 2 After the last administration, tumor tissue was dissected and weighed (g). Tumor inhibition rate (%) = (tumor weight of tumor-bearing model group - tumor weight of drug-treated group) / tumor weight of tumor-bearing model group × 100%.

[0042] 1.4 Animal blood cell analyzer for routine blood tests

[0043] Blood was collected after the last administration, and the levels of neutrophils (Neu), red blood cells (RBC), platelets (PLT), and hemoglobin (HGB) were measured using an animal blood cell analyzer.

[0044] 1.5 Animal biochemical analyzer for detecting biochemical indicators

[0045] Blood samples were collected after the last administration, and the levels of liver aspartate aminotransferase (AST) and renal creatinine (CREA) were measured using an animal biochemical analyzer.

[0046] 1.6 Organ Index Calculation

[0047] After the last administration, the thymus and spleen were dissected and weighed, and the organ index was calculated (organ index = organ weight / animal body weight × 100, unit is g·100g). -1 ).

[0048] 1.7 Statistical Analysis

[0049] Quantitative data are expressed as mean ± standard deviation (x±s). Statistical analysis was performed using SPSS 16.0. One-way ANOVA was used for comparisons among multiple groups. A p-value < 0.05 was considered statistically significant.

[0050] 2. Results

[0051] 2.1 Tumor growth in each group of tumor-bearing mice

[0052] See results Figure 1 ,in Figure 1 In the middle, A represents the gross tumor size in LLC tumor-bearing mice; Figure 1 The figure shows that B represents the change in tumor volume. According to the tumor volume results in mice, compared with the tumor-bearing model group, the tumor volume in the treatment groups decreased from day 10 to 20, and the tumor volume decreased significantly from day 16 to 20 (P<0.0001). Compared with the chemotherapy group, the tumor volume in the *Shenlingcao* + chemotherapy group was significantly reduced (P<0.05), indicating that the traditional Chinese medicine combination can enhance the effect of chemotherapy and significantly reduce tumor volume.

[0053] 2.2 Tumor weight in each group of tumor-bearing mice

[0054] The results are shown in Table 1.

[0055] Table 1 Changes in tumor weight

[0056]

[0057] Table 1 shows that the tumor weight in the mice treated with the drug was significantly lower than that in the tumor-bearing model group (P<0.01). The tumor weight in the *Shenlingcao* + chemotherapy group was significantly lower than that in the chemotherapy group (P<0.05). The tumor inhibition rate in the *Shenlingcao* + chemotherapy group was 86.83%, which was 27.95% higher than that in the chemotherapy group, suggesting that combining *Shenlingcao* with chemotherapy is more effective in inhibiting tumor growth.

[0058] 2.3 Blood biochemical properties of mice in each group

[0059] See results Figure 2 and Figure 3 ,like Figure 2 As shown, in the liver marker AST, tumor-bearing mice showed increased AST expression compared to the normal group. However, the AST expression in the *Smilax glabra* + chemotherapy group was significantly lower than that in the model group and the chemotherapy group (P<0.05). In the kidney marker CREA, the CREA expression in the *Smilax glabra* + chemotherapy group was significantly lower than that in the chemotherapy group (P<0.05), indicating that *Smilax glabra* can reduce the levels of the blood biochemical markers AST and CREA, thereby enhancing the efficacy of chemotherapy.

[0060] Figure 3 The left side of the image shows the ALT content expression chart, and the right side shows the CK content expression chart. According to... Figure 4 It can be seen that the ALT expressions in the chemotherapy group and the Shenlingcao + chemotherapy group were higher than those in the Shenlingcao group and the model group (P<0.05), and the combination of Shenlingcao did not improve the abnormal ALT expression caused by chemotherapy drugs in tumor-bearing mice. The CK expressions in the Shenlingcao group and the chemotherapy group were higher than those in the normal group, and the expression in the combined group was higher than that in the chemotherapy group alone, indicating that Shenlingcao could not improve the abnormal CK expression in tumor-bearing mice caused by chemotherapy. * P<0.05, **** P<0.0001, compared with the model group. aaa P<0.001, compared with the Shenlingcao group.

[0061] 2.4 Blood routine of mice in each group

[0062] The results are shown in Table 2 and Table 3.

[0063] Table 2 Blood routine results

[0064]

[0065] As can be seen from Table 2, compared with the normal group, the red blood cells, hemoglobin and platelets in each group of tumor-bearing mice decreased. However, the cell expression in the Shenlingcao group showed an obvious increasing trend compared with the chemotherapy group and the Shenlingcao + chemotherapy group (a<0.05, a<0.0001), and the combination of Shenlingcao and chemotherapy showed better results than chemotherapy alone (##<0.01, #<0.0001), indicating that Shenlingcao could reduce the side effects of chemotherapy.

[0066] Table 3 Detection results of blood routine in peripheral blood of mice

[0067]

[0068] As can be seen from Table 3, the white blood cell count, lymphocyte count, eosinophil count and basophil count in the chemotherapy group were lower than those in the normal group (P<0.0001). After the combination of Shenlingcao, the expressions of the above indexes showed an upward trend, but there was no significant difference. Therefore, Shenlingcao did not improve the decrease in white blood cell expression in tumor-bearing mice caused by chemotherapy drugs. Δ P<0.05, ΔΔ P<0.01, ΔΔΔΔ P<0.0001, compared with the normal group. a P<0.05, aaaa P<0.0001, compared with the Shenlingcao group.

[0069] 2.5 Organ index of mice in each group

[0070] The results are shown in Figure 4 and Figure 5 According to Figure 4It was found that the thymus index in the chemotherapy group and the *Shenlingcao* + chemotherapy group was significantly lower than that in the normal group and the model group (p<0.001). Compared with the chemotherapy group, the thymus index in the *Shenlingcao* + chemotherapy group was increased (p<0.01). Regarding the spleen index, compared with the normal group, the spleen index in the model group was significantly increased (p<0.05). Compared with the model group, the spleen index in the chemotherapy group and the *Shenlingcao* + chemotherapy group was significantly lower (p<0.01), indicating that the *Shenlingcao*, i.e., the traditional Chinese medicine composition provided in this embodiment of the invention, can reduce the side effects of chemotherapy.

[0071] according to Figure 5 It was found that the expression of indices in the heart, liver, kidney, and lungs varied among the different groups of mice, especially in the liver, although the differences were not statistically significant. The cardiac index was lowest in the combined treatment group compared to the other groups, consistent with the blood biochemistry results showing the highest CK expression in the combined treatment group, indicating cardiac function impairment. This suggests that the combined use of the two drugs may have some negative effects on the mouse heart. The liver index was lowest in the chemotherapy group, but showed an upward trend after the combined use of Shenlingcao (a type of herb), suggesting that Shenlingcao has a certain protective effect on the mouse liver.

[0072] 2.6 Changes in body weight of mice in each group

[0073] Depend on Figure 6 It was observed that, 14 days after tumor inoculation, the body weight of mice in the chemotherapy group and the group receiving ginseng and ginseng combined with chemotherapy was significantly lower than that in the non-chemotherapy group (P<0.01), and the body weight of mice in the chemotherapy group continued to decrease after 14 days of modeling. The body weight of mice in the combined treatment group gradually improved after 14 days, showing an increase compared to the chemotherapy group, but the upward trend was not significant, suggesting that ginseng and ginseng did not improve the body weight reduction in tumor-bearing mice induced by chemotherapy drugs. ΔΔ P<0.01, ΔΔΔΔ P<0.0001, compared with the normal group. aa P<0.01, aaaa P<0.0001, compared with the Ginseng and Licorice group.

[0074] In summary, the oral liquid of Shenlingcao, a traditional Chinese medicine composition, administered concurrently with chemotherapy in the experiments provided in this invention significantly reduced tumor volume on day 20 (P<0.0001), and was significantly lower than that in the chemotherapy group (P<0.05); significantly reduced tumor weight in mice; and significantly reduced AST and CREA levels. This indicates that the traditional Chinese medicine composition provided in this invention can enhance the effect of chemotherapy and can be used as a chemotherapy promoter for tumor treatment. Simultaneously, the oral liquid of Shenlingcao, a traditional Chinese medicine composition, administered concurrently with chemotherapy significantly increased the number of RBCs, PLTs, and Hgb levels in mice; and significantly increased the thymus index in mice, indicating that the traditional Chinese medicine composition can reduce the side effects caused by chemotherapy.

[0075] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. The application of Shenlingcao oral liquid in the preparation of drugs that simultaneously enhance the efficacy of chemotherapy drugs and alleviate the side effects caused by chemotherapy drugs, characterized in that, The improvement of the chemotherapy effect and the reduction of the side effects caused by the chemotherapy drug are as follows: reducing tumor volume, reducing tumor weight, reducing the content of blood biochemical markers AST and CREA, improving the reduction of RBC content, improving the reduction of PLT content, improving the reduction of Hgb content, and improving the reduction of thymus index; the chemotherapy drug is cisplatin, and the chemotherapy is for non-small cell lung cancer.

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