Traditional Chinese medicine composition for tonifying spleen and detoxifying as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention provides a spleen-tonifying and detoxifying traditional Chinese medicine composition as well as a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition comprises a formula A and a formula B. The traditional Chinese medicine composition has a comprehensive conditioning effect and can relieve chemotherapy side effects, improve intestinal flora distribution, promote intestinal health, enhance the chemotherapy effect and improve the disease control rate. Wherein the formula A focuses on tonifying spleen and regulating qi, and improving nausea, vomiting and other symptoms at the initial stage of chemotherapy, and the formula B is added with medicines for clearing away heat and toxic materials and promoting blood circulation to remove blood stasis on the basis, is suitable for patients with myelosuppression with cancer toxicity residue, and strengthens the effects of clearing away heat and toxic materials and removing stasis; the composition has a multi-target action mechanism, and through the combined action of multiple ways, the treatment effect is enhanced, and the side effect is reduced.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, and in particular relates to a spleen-strengthening and detoxifying traditional Chinese medicine composition, its preparation method and application. Background Technology

[0002] Colorectal cancer, the third most common malignant tumor worldwide, exhibits significant spatial heterogeneity and a trend towards earlier onset. Despite advancements in colorectal cancer screening technologies, most patients present at middle or late stages, resulting in relatively poor prognosis. Treatment primarily relies on surgery and multidisciplinary intervention, with chemotherapy playing a crucial role. However, chemotherapy-related toxicities significantly impact treatment continuity and reduce patients' quality of life, creating a dual burden on both physical and psychological well-being. Reducing chemotherapy side effects, improving patient quality of life, enhancing chemotherapy adherence, and improving postoperative patient well-being have become key focuses of current colorectal cancer research. Summary of the Invention

[0003] In view of this, the purpose of the present invention is to provide a traditional Chinese medicine composition for strengthening the spleen and detoxifying, so as to improve its clinical efficacy as an adjuvant chemotherapy in the postoperative treatment of colon cancer.

[0004] To achieve the above objectives, the present invention provides the following technical solution: A traditional Chinese medicine composition for strengthening the spleen and detoxifying, comprising formula A and formula B; Formula A comprises the following components in parts by weight: Astragalus membranaceus: 10-15 parts, Codonopsis pilosula: 6-10 parts, Atractylodes macrocephala: 5-8 parts, Poria cocos: 6-10 parts, Citrus reticulata peel: 5-8 parts, Pinellia ternata: 4-6 parts, Aucklandia lappa: 4-6 parts, Amomum villosum: 3-5 parts, Dioscorea opposita: 8-12 parts, Massa fermentata: 6-10 parts, stir-fried chicken gizzard lining: 5-8 parts, stir-fried malt: 6-10 parts, Bupleurum chinense: 4-6 parts, Glycyrrhiza uralensis: 2-4 parts; Formula B comprises the following components in parts by weight: Astragalus membranaceus: 10-15 parts, Codonopsis pilosula: 6-10 parts, Atractylodes macrocephala: 5-6 parts, Poria cocos: 7-8 parts, Citrus reticulata peel: 5-6 parts, Dioscorea opposita: 8-10 parts, Hedyotis diffusa: 7-8 parts, Scutellaria barbata: 5-6 parts, Cinnamomum cassia: 3-5 parts, Cornus officinalis: 5-6 parts, Massa fermentata: 7-8 parts, Bupleurum chinense: 2-4 parts, Sparganium stoloniferum: 4-6 parts, Curcuma zedoaria: 5-6 parts, Coix lacryma-jobi: 8-10 parts, Glycyrrhiza uralensis: 2-3 parts.

[0005] Another object of the present invention is to provide a method for preparing a spleen-strengthening and detoxifying traditional Chinese medicine composition, comprising the following steps: (1) Raw material preparation: Weigh the raw materials of formulation A and formulation B respectively, and wash them; (2) First decoction: Add water to the raw materials of formula A and formula B respectively, then heat to boiling and keep boiling for 30-40 minutes. Filter to obtain the first decoction and residue. (3) Second decoction: Add water to the filter residue, heat to boiling again, and decoct for 20-25 minutes while maintaining boiling. Filter to obtain the second decoction. (4) Combine the first decoction and the second decoction to obtain Formula A and Formula B.

[0006] Preferably, the amount of water added in the first decoction in step (2) is 7-10 times the mass of the formula.

[0007] Preferably, the amount of water added in the second decoction in step (3) is 2-5 times the mass of the formula.

[0008] The third objective of this invention is to provide an application of a spleen-strengthening and detoxifying traditional Chinese medicine composition in chemotherapy for colorectal cancer.

[0009] This application has the following beneficial effects: (1) The spleen-strengthening and detoxifying traditional Chinese medicine composition of the present invention has a comprehensive conditioning effect. It not only targets the tumor itself, but also enhances the patient's overall health, improves immunity, and improves quality of life by regulating the spleen and stomach. Specifically, Astragalus membranaceus has the effect of invigorating qi and consolidating the exterior, and enhancing immunity; Codonopsis pilosula has the effect of invigorating the middle and replenishing qi, and improving the function of the spleen and stomach; Atractylodes macrocephala has the effect of strengthening the spleen and drying dampness, and promoting digestion.

[0010] (2) The spleen-strengthening and detoxifying traditional Chinese medicine composition of the present invention can reduce the side effects of chemotherapy, improve gastrointestinal reactions, effectively alleviate symptoms such as nausea, vomiting and loss of appetite caused by chemotherapy, and improve patient tolerance. Specifically, tangerine peel: regulates qi and strengthens the spleen, improves digestion; pinellia: has an antiemetic effect and can relieve nausea; costus root: promotes the smooth flow of qi and reduces abdominal distension and discomfort. The combination of tangerine peel, pinellia and costus root can reduce oxidative stress, thereby reducing the gastrointestinal toxicity caused by chemotherapy.

[0011] (3) The spleen-strengthening and detoxifying traditional Chinese medicine composition of the present invention can improve the distribution of intestinal flora and promote intestinal health: by regulating the intestinal microecology, it can improve the ratio of beneficial bacteria and harmful bacteria, thereby maintaining intestinal function and immune regulation.

[0012] (4) The spleen-strengthening and detoxifying traditional Chinese medicine composition of the present invention can enhance the effect of chemotherapy and improve the disease control rate. Specifically, Sparganium rhizome and Curcuma rhizome can inhibit VEGF (vascular endothelial growth factor) and MMP-9 (matrix metalloproteinase), thereby reducing the metastasis and invasion of tumor cells.

[0013] (5) The spleen-strengthening and detoxifying Chinese medicine composition of the present invention has a dynamic formulation design. In the early stage of chemotherapy, formulation A focuses on strengthening the spleen and regulating qi to improve symptoms such as nausea and vomiting. Formulation B adds heat-clearing and detoxifying and blood-activating and stasis-removing drugs on the basis of the above, which is suitable for patients with bone marrow suppression accompanied by residual cancer toxins and enhances the detoxification and nodule-dispersing effect.

[0014] (6) The spleen-strengthening and detoxifying traditional Chinese medicine composition of the present invention has a multi-target mechanism of action, which enhances the therapeutic effect and reduces side effects through multiple pathways. Specifically, Astragalus-Codonopsis-Atractylodes macrocephala: improves gastrointestinal toxicity after chemotherapy; Hedyotis diffusa and Scutellaria barbata: promote cell apoptosis and enhance anti-tumor effect. Attached Figure Description

[0015] Figure 1 A diagram illustrating the grouping of animals for experiments.

[0016] Figure 2 The results show the comparison of the anal canals of mice in the animal experimental model group and the intervention group.

[0017] Figure 3 This is a display of the colorectal morphology among different groups in the animal experiment.

[0018] Figure 4 Statistical analysis of colorectal length among different groups in animal experiments.

[0019] Figure 5 HE staining results for intestinal tissue in the Control group.

[0020] Figure 6 HE staining results of intestinal tissue from the Model group.

[0021] Figure 7 HE staining results of intestinal tissue from the JPJDF group. Detailed Implementation

[0022] Example 1 A traditional Chinese medicine composition for strengthening the spleen and detoxifying, consisting of formula A and formula B; Formula A consists of the following components by weight: Astragalus membranaceus: 12g, Codonopsis pilosula: 8g, Atractylodes macrocephala: 6g, Poria cocos: 8g, Citrus reticulata peel: 6g, Pinellia ternata: 5g, Aucklandia lappa: 5g, Amomum villosum: 4g, Dioscorea opposita: 10g, Massa fermentata: 8g, stir-fried chicken gizzard lining: 6g, stir-fried malt: 8g, Bupleurum chinense: 5g, Glycyrrhiza uralensis: 3g; Formula B consists of the following components by weight: Astragalus membranaceus: 12g, Codonopsis pilosula: 8g, Atractylodes macrocephala: 6g, Poria cocos: 8g. Dried tangerine peel: 6g, Chinese yam: 10g, Hedyotis diffusa: 8g, Scutellaria barbata: 6g, Cinnamomum cassia: 5g, Cornus officinalis: 6g, Medicated leaven: 8g, Bupleurum chinense: 4g, Sparganium stoloniferum: 6g, Curcuma zedoaria: 6g, Coix lacryma-jobi: 10g, Glycyrrhiza uralensis: 3g.

[0023] The preparation method of the spleen-strengthening and detoxifying traditional Chinese medicine composition includes the following steps: (1) Raw material preparation: Weigh the raw materials of formulation A and formulation B respectively, and wash them; (2) First decoction: Add 800g of water to the raw materials of formula A and formula B respectively, then heat to boiling and keep boiling for 30 minutes, filter to obtain the first decoction and residue; (3) Second decoction: Add 400g of water to the filter residue, heat to boiling again, and keep boiling for 20 minutes. Filter to obtain the second decoction. (4) Combine the first decoction and the second decoction to obtain Formula A and Formula B.

[0024] The following experiments were conducted using the spleen-strengthening and detoxifying traditional Chinese medicine composition from Example 1: Experiment 1: Animal Experiment Four-week-old male SPF-grade C57BL / 6 mice (Hunan Slack Jingda Experimental Animal Co., Ltd., SCXK (Xiang) 2020-0004) were selected and housed in a specific pathogen-free environment, provided with sterile food and water, and allowed free access. After two weeks of acclimatization, mice were randomly selected as the control group (Control n=20), while the remaining mice were induced with azomethane (10 mg / kg) via intraperitoneal injection. One week later, the mice were given a 2% concentration of the inflammatory agent sodium dextran sulfate in their drinking water for seven consecutive days, followed by 14 days of drinking water with distilled water, completing one cycle. This cycle was repeated twice to establish a colorectal cancer mouse model.

[0025] After the first cycle, mice that were successfully induced to develop the model were randomly divided into a model group (Model n=20) and a spleen-strengthening and detoxifying optimized formula intervention group (JP JDF n=20). Starting from the second cycle, mice in the spleen-strengthening and detoxifying optimized formula group were treated daily by gavage with the spleen-strengthening and detoxifying optimized formula (the spleen-strengthening and detoxifying traditional Chinese medicine composition prepared in Example 1, denoted as JPJDYHF) until the end of the experiment (Formula A was administered for 21 days; Formula B was administered for 21 days).

[0026] The Jianpi Jiedu formula significantly affected the proliferation, apoptosis, and drug resistance of colorectal cancer cells under multiple dosage conditions. This study applied the clinical oral dosage to a mouse model based on the clinical dosage for adult colorectal cancer patients, combined with a weight conversion relationship (assuming an average healthy adult weight of 70 kg and a conversion factor of 9.1). The gavage dose of the optimized Jianpi Jiedu formula in the intervention group was equivalent to the clinically equivalent dose (4.174 g / kg / day).

[0027] At the end of the experiment, whole blood samples were collected from the orbital rim, centrifuged, and the supernatant was stored at -80°C. Mice were euthanized, and intestinal tissue, intestinal contents, thymus, and spleen were harvested. The length, size, and number of tumors in the colorectal tissue were measured.

[0028] Figure 1 A diagram illustrating the grouping of animals for experiments.

[0029] Figure 2 This shows the comparison results of the anal canals of mice in the animal experimental model group and the intervention group. Figure 2 It can be seen that JPJDYHF intervention reduced the severity of intestinal prolapse caused by colorectal cancer.

[0030] Figure 3 This image shows the morphology of the colon and rectum in different groups during animal experiments. Figure 3 It can be seen that the spleen-strengthening and detoxifying optimized formula significantly reduced the tumor burden in a mouse model of colorectal cancer, including the number and size of tumors.

[0031] Figure 4 Statistical analysis of colorectal length among different groups in animal experiments. Figure 4 It can be seen that the intervention of the spleen-strengthening and detoxifying optimized formula significantly alleviated the intestinal shortening in a mouse model of colorectal cancer.

[0032] Figure 5 HE staining results of intestinal tissue in the Control group; Figure 6 HE staining results of intestinal tissue from the Model group; Figure 7 HE staining results of intestinal tissue from the JPJDF group. Figure 5-7 It can be seen that the spleen-strengthening and detoxifying optimized formula significantly reduced the severity of intestinal gland dysplasia and carcinogenesis in a mouse model of colorectal cancer.

[0033] In conclusion, the optimized formula for strengthening the spleen and detoxifying significantly alleviated anal prolapse, tumor burden, and intestinal shortening in a mouse model of colorectal cancer. Pathological staining showed that the optimized formula reduced the severity of dysplasia and carcinogenesis in the intestinal tissue.

[0034] Trial 2: Clinical Trial Subjects: Patients with advanced primary CRC who underwent postoperative chemotherapy were selected as the study subjects, including 30 patients in the treatment group and 30 patients in the control group.

[0035] In the treatment group, there were 30 patients, including 16 males and 14 females; their ages ranged from 34 to 74 years, with a mean age of (58.03±11.11) years; 1 patient was classified as stage II on the TNM scale, 8 as stage III, and 21 as stage IV. In the control group, there were 30 patients, including 20 males and 10 females; their ages ranged from 29 to 74 years, with a mean age of (58.78±10.15) years; 2 patients were classified as stage II on the TNM scale, 7 as stage III, and 21 as stage IV.

[0036] Treatment methods: Control group: Treatment of CRC was based on the first-line recommended regimens in the CSCO guidelines, such as Xelox / FOLFOX / FOLFIRI. Patients with indications for targeted therapy could receive combined targeted therapy.

[0037] Treatment group: The spleen-strengthening and detoxifying traditional Chinese medicine composition of the present invention was combined with the above-mentioned Western medicine treatment. Formula A decoction was started on the 4th day of chemotherapy and taken orally for five consecutive days, 200mL per day. Formula B decoction was started on the 9th day of chemotherapy and taken orally for four consecutive days, 200mL per day.

[0038] The comparison results of general information of the two groups of patients are shown in Table 1.

[0039] Table 1

[0040] The comparison of TCM syndrome scores between the two groups of patients at enrollment is shown in Table 2. P=0.525>0.05, indicating that there was no statistically significant difference in TCM syndrome scores between the two groups of patients at enrollment, and they were comparable.

[0041] Table 2

[0042] (1) Chemotherapy success rate The evaluation will be based on whether the patient can proceed to the second chemotherapy cycle as required.

[0043] Good success rate: Patients who can enter the second cycle of chemotherapy within 22-28 days after the start of the first cycle of chemotherapy.

[0044] Poor pass rate: Patients who can enter the second cycle of chemotherapy within 28-35 days after the start of the first cycle of chemotherapy.

[0045] Failed: Patients who entered the second cycle of chemotherapy more than 35 days after the start of the first cycle.

[0046] The results are shown in Table 3: Table 3

[0047] (2) In the control group, 5 patients achieved partial remission (PR), 17 had stable disease (SD), and 8 had progressive disease (PD), with an objective response rate (OR) of 16.70% and a disease control rate (DCR) of 73.30%. In the treatment group, 14 patients achieved partial remission (PR), 13 had stable disease (SD), and 3 had progressive disease (PD), with an objective response rate (OR) of 46.70% and a disease control rate (DCR) of 90.00%. Specific results are shown in Table 4.

[0048] Table 4

[0049] (3) Analysis of the incidence of neurotoxicity after chemotherapy showed that the combination of traditional Chinese medicine and chemotherapy could significantly reduce the incidence and severity of neurotoxicity. The total incidence of neurotoxicity in the control group was 53%, of which 3.3% were grade III toxicity; the total incidence in the treatment group decreased to 36.7%, and no grade III-IV severe toxicity occurred. The data indicate that the intervention of traditional Chinese medicine reduced the overall risk of neurotoxicity by 17.7% and completely suppressed the occurrence of severe toxicity. The results are shown in Table 5.

[0050] Table 5

[0051] (4) The diversity of gut microbiota was assessed using two indicators: species richness and evenness. The Shannon and Simpson indices primarily reflect the diversity and evenness of species distribution within the sample. The Shannon index considers both richness and evenness; a higher value indicates greater diversity. Conversely, a higher Simpson index indicates lower community diversity. The Chaol index primarily provides information on community species richness; a higher value means a greater total number of species. Furthermore, the Good's Coverage index was used to assess the OTU coverage of the sample. All groups had Good's Coverage values ​​exceeding 99.9%, indicating that the obtained OTUs essentially covered all sequences present in the sample. The results are shown in Table 6.

[0052] Table 6

[0053] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition for strengthening the spleen and detoxifying, characterized in that, Including formulation A and formulation B; Formula A comprises the following components in parts by weight: Astragalus membranaceus: 10-15 parts, Codonopsis pilosula: 6-10 parts, Atractylodes macrocephala: 5-8 parts, Poria cocos: 6-10 parts, Citrus reticulata peel: 5-8 parts, Pinellia ternata: 4-6 parts, Aucklandia lappa: 4-6 parts, Amomum villosum: 3-5 parts, Dioscorea opposita: 8-12 parts, Massa fermentata: 6-10 parts, stir-fried chicken gizzard lining: 5-8 parts, stir-fried malt: 6-10 parts, Bupleurum chinense: 4-6 parts, Glycyrrhiza uralensis: 2-4 parts; Formula B comprises the following components in parts by weight: Astragalus membranaceus: 10-15 parts, Codonopsis pilosula: 6-10 parts, Atractylodes macrocephala: 5-6 parts, Poria cocos: 7-8 parts, Citrus reticulata peel: 5-6 parts, Dioscorea opposita: 8-10 parts, Hedyotis diffusa: 7-8 parts, Scutellaria barbata: 5-6 parts, Cinnamomum cassia: 3-5 parts, Cornus officinalis: 5-6 parts, Massa fermentata: 7-8 parts, Bupleurum chinense: 2-4 parts, Sparganium stoloniferum: 4-6 parts, Curcuma zedoaria: 5-6 parts, Coix lacryma-jobi: 8-10 parts, Glycyrrhiza uralensis: 2-3 parts.

2. The preparation method of the spleen-strengthening and detoxifying traditional Chinese medicine composition according to claim 1, characterized in that, Includes the following steps: (1) Raw material preparation: Weigh the raw materials of formulation A and formulation B respectively, and wash them; (2) First decoction: Add water to the raw materials of formula A and formula B respectively, then heat to boiling and keep boiling for 30-40 minutes. Filter to obtain the first decoction and residue. (3) Second decoction: Add water to the filter residue, heat to boiling again, and decoct for 20-25 minutes while maintaining boiling. Filter to obtain the second decoction. (4) Combine the first decoction and the second decoction to obtain Formula A and Formula B.

3. The method for preparing the spleen-strengthening and detoxifying traditional Chinese medicine composition according to claim 2, characterized in that, The amount of water added during the first decoction in step (2) is 7-10 times the mass of the formula.

4. The preparation method of the spleen-strengthening and detoxifying traditional Chinese medicine composition according to claim 2, characterized in that, The amount of water added during the second decoction in step (3) is 2-5 times the mass of the formula.

5. The application of the spleen-strengthening and detoxifying traditional Chinese medicine composition according to claim 1 in the chemotherapy of colorectal cancer.

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