Application of traditional Chinese medicine composition in preparation of medicine for preventing or treating colon cancer

Abstract

The invention relates to application of a traditional Chinese medicine composition in preparation of medicines for preventing or treating colon cancer. The traditional Chinese medicine composition comprises sculellaria barbata, astragalus membranaceus, angelica sinensis, nightshade, radix curcumae, red ginseng, duchesnea indica, saussurea involucrata, cyclea verticillata and salvia miltiorrhiza. The traditional Chinese medicine composition has a good prevention or treatment effect on colon cancer, specifically, proliferation of colon cancer cells is inhibited, a good prevention and treatment effect is shown in a colon cancer mouse model, and the size of mouse tumors can be remarkably reduced. The invention provides an effective strategy for prevention or treatment of colon cancer, and provides a new direction for application of the traditional Chinese medicine composition.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology and relates to the application of a traditional Chinese medicine composition in the preparation of drugs for the prevention or treatment of colon cancer. Background Technology

[0002] Colorectal cancer is a common malignant tumor of the digestive tract that occurs in the colon, most commonly at the junction of the rectum and sigmoid colon. The highest incidence is in the 40-50 age group, with a male-to-female ratio of 2-3:1, ranking third among gastrointestinal tumors. Colorectal cancer is mainly adenocarcinoma, mucinous adenocarcinoma, or undifferentiated carcinoma, and its gross morphology includes polypoid and ulcerative forms. Colorectal cancer can develop circumferentially along the intestinal wall, spread longitudinally along the intestinal tract, or infiltrate deep into the intestinal wall. Besides metastasis via lymphatic vessels, bloodstream, and local invasion, it can also implant into the abdominal cavity or spread along sutures and incision surfaces. Patients with chronic colitis, colorectal polyps, and obese men are susceptible populations.

[0003] Colorectal cancer falls under the categories of "accumulation," "visceral toxins," "intestinal accumulation," and "anal lock hemorrhoids" in Traditional Chinese Medicine (TCM). Its pathogenesis is closely related to factors such as genetics, social environment, lifestyle, and dietary habits. Colorectal cancer is characterized by insufficient vital energy (Qi) and dysfunction of the spleen and kidneys, combined with symptoms such as damp-heat and blood stasis. Therefore, treatment should focus on tonifying the spleen, nourishing Yin and generating fluids, and clearing heat. Xinlikang capsules contain flavonoids. Related reports indicate that various natural flavonoids can participate in the occurrence and progression of tumors and related diseases by influencing the activity of immune cells. The entire formula emphasizes the synergistic effect of "treatment" and "tonification."

[0004] Xinlikang capsules are a traditional Chinese medicine composed of 10 ingredients: Scutellaria barbata, Astragalus membranaceus, Angelica sinensis, Solanum nigrum, Curcuma longa, Panax ginseng, Duchesnea indica, Saussurea involucrata, Rhizoma Cyathulae, and Salvia miltiorrhiza. It has the effects of replenishing qi and blood, removing blood stasis and detoxifying. However, there are no reports in the current technology that Xinlikang capsules can be used to treat colon cancer. Summary of the Invention

[0005] In view of the shortcomings of the prior art, the purpose of this invention is to provide an application of a traditional Chinese medicine composition in the preparation of a drug for the prevention or treatment of colon cancer.

[0006] To achieve this objective, the present invention adopts the following technical solution:

[0007] In a first aspect, the present invention provides the application of a traditional Chinese medicine composition in the preparation of a drug for the prevention or treatment of colon cancer, the traditional Chinese medicine composition comprising Scutellaria barbata, Solanum nigrum, Duchesnea indica, Rhizoma Cyathulae, Astragalus membranaceus, Panax ginseng, Saussurea involucrata, Angelica sinensis, Curcuma longa, and Salvia miltiorrhiza.

[0008] This invention creatively discovers that the aforementioned traditional Chinese medicine composition has good preventive or therapeutic effects on colon cancer, specifically by inhibiting the proliferation of colon cancer cells. It demonstrates good preventive and therapeutic effects in a mouse model of colon cancer, significantly reducing tumor volume. This invention provides an effective strategy for the prevention or treatment of colon cancer and offers a new direction for the application of the aforementioned traditional Chinese medicine composition.

[0009] Colorectal cancer is a digestive tract tumor, and tumors in different locations vary greatly in etiology, pathological mechanisms, and treatment methods. For example, colon cancer can occur anywhere in the colon, while rectal cancer typically occurs within 15cm of the anus. Colon cancer surgery usually completely removes the tumor and performs intestinal anastomosis, while rectal cancer surgery, especially low rectal cancer, may require a permanent stoma. Rectal cancer patients generally require preoperative and postoperative radiotherapy and chemotherapy to improve treatment outcomes, while colon cancer usually does not require radiotherapy, and the proportion of patients receiving preoperative chemotherapy is lower.

[0010] Preferably, the traditional Chinese medicine composition comprises, by weight, 400-600 parts of Scutellaria barbata (e.g., 400, 420, 450, 500, 550, 600 parts, etc.), 300-500 parts of Solanum nigrum (e.g., 300, 320, 350, 400, 450, 500 parts, etc.), and 130-330 parts of Duchesnea indica (e.g., 130, 150, 170, etc.). 00 portions, 230 portions, 300 portions, 330 portions, etc.), 100-300 portions of *Rhizoma Cyrtomegaloides* root (e.g., 100 portions, 120 portions, 150 portions, 180 portions, 200 portions, 250 portions, 300 portions, etc.), 400-600 portions of *Radix Astragali* (e.g., 400 portions, 420 portions, 450 portions, 500 portions, 550 portions, 600 portions, etc.), 80-280 portions of red ginseng (e.g., 80 portions, 100 portions, etc.), 120, 150, 200, 250, 280 portions, etc.); Snow Lotus 400-600 portions (e.g., 400, 420, 450, 480, 510, 550, 600 portions, etc.); Angelica 60-260 portions (e.g., 60, 80, 100, 130, 150, 180, 200, 230, 260 portions, etc.); Turmeric 80 -280 portions (e.g., 80, 100, 130, 150, 180, 200, 230, 260, 280 portions, etc.) and 70-270 portions of Salvia miltiorrhiza (e.g., 70, 80, 100, 130, 150, 180, 200, 230, 270 portions, etc.). Other specific point values ​​within the above range can be selected, which will not be elaborated here.

[0011] Preferably, the traditional Chinese medicine composition comprises, by weight, 480-520 parts of Scutellaria barbata (e.g., 480, 490, 500, 510, 520 parts, etc.), 380-420 parts of Solanum nigrum (e.g., 380, 390, 400, 410, 420 parts, etc.), 210-250 parts of Duchesnea indica (e.g., 210, 220, 230, 240, 250 parts, etc.), 180-220 parts of Rhizoma Cyathulae (e.g., 180, 190, 200, 210, 220 parts, etc.), 480-520 parts of Astragalus membranaceus (e.g., 480, 490, 500, 510, 520 parts, etc.), and 1 part of Panax ginseng. 60-200 portions (e.g., 160, 170, 180, 190, 200, etc.), 480-520 portions of snow lotus (e.g., 480, 490, 500, 510, 520, etc.), 140-180 portions of angelica (e.g., 140, 150, 160, 170, 180, etc.), 160-200 portions of turmeric (e.g., 160, 170, 180, 190, 200, etc.), and 150-190 portions of salvia miltiorrhiza (e.g., 150, 160, 170, 180, 190, etc.). Other specific values ​​within the above ranges can be selected, and will not be elaborated here.

[0012] Preferably, the drug for treating colon cancer inhibits the proliferation of colon cancer cells.

[0013] Preferably, the drug further includes pharmaceutically acceptable excipients.

[0014] Preferably, the pharmaceutically acceptable excipients include any one or a combination of at least two of the following: excipients, lubricants, binders, preservatives, flavoring agents, carriers, disintegrants, emulsifiers, solubilizers, osmotic pressure regulators, surfactants, coating materials, colorants, pH adjusters, antioxidants, antibacterial agents, or buffers.

[0015] Preferably, the excipient comprises any one or a combination of at least two of starch, dextrin, or sucrose.

[0016] Preferably, the lubricant comprises any one or a combination of at least two of magnesium stearate, calcium stearate, or talc.

[0017] Preferably, the binder comprises glucose and / or maltodextrin.

[0018] Preferably, the dosage form of the drug includes capsules, tablets, granules, pills, powders, solutions, emulsions, or suspensions.

[0019] Secondly, the present invention provides an application of a traditional Chinese medicine composition in the preparation of a proliferation inhibitor for colon cancer cells, the traditional Chinese medicine composition comprising Scutellaria barbata, Solanum nigrum, Duchesnea indica, Rhizoma Cyathulae, Astragalus membranaceus, Panax ginseng, Saussurea involucrata, Angelica sinensis, Curcuma longa, and Salvia miltiorrhiza.

[0020] According to the research results of this invention, the traditional Chinese medicine composition has a significant inhibitory effect on the proliferation of colon cancer cells. Therefore, this result indicates that the traditional Chinese medicine composition can be used as an in vitro experimental reagent in scientific research, such as studying the growth and metabolic mechanisms or behavior of colon cancer cells, and screening drugs for the treatment of colon cancer. The proliferation inhibitor claimed in this invention is not intended to eliminate the cause or lesion, that is, it is an application in the preparation of a colon cancer cell proliferation inhibitor for a non-therapeutic purpose.

[0021] Preferably, the traditional Chinese medicine composition comprises, by weight, 400-600 parts of Scutellaria barbata (e.g., 400, 420, 450, 500, 550, 600 parts, etc.), 300-500 parts of Solanum nigrum (e.g., 300, 320, 350, 400, 450, 500 parts, etc.), and 130-330 parts of Duchesnea indica (e.g., 130, 150, 170, etc.). 00 portions, 230 portions, 300 portions, 330 portions, etc.), 100-300 portions of *Rhizoma Cyrtomegaloides* root (e.g., 100 portions, 120 portions, 150 portions, 180 portions, 200 portions, 250 portions, 300 portions, etc.), 400-600 portions of *Radix Astragali* (e.g., 400 portions, 420 portions, 450 portions, 500 portions, 550 portions, 600 portions, etc.), 80-280 portions of red ginseng (e.g., 80 portions, 100 portions, etc.), 120, 150, 200, 250, 280 portions, etc.); Snow Lotus 400-600 portions (e.g., 400, 420, 450, 480, 510, 550, 600 portions, etc.); Angelica 60-260 portions (e.g., 60, 80, 100, 130, 150, 180, 200, 230, 260 portions, etc.); Turmeric 80 -280 portions (e.g., 80, 100, 130, 150, 180, 200, 230, 260, 280 portions, etc.) and 70-270 portions of Salvia miltiorrhiza (e.g., 70, 80, 100, 130, 150, 180, 200, 230, 270 portions, etc.). Other specific point values ​​within the above range can be selected, which will not be elaborated here.

[0022] Preferably, the traditional Chinese medicine composition comprises, by weight, 480-520 parts of Scutellaria barbata (e.g., 480, 490, 500, 510, 520 parts, etc.), 380-420 parts of Solanum nigrum (e.g., 380, 390, 400, 410, 420 parts, etc.), 210-250 parts of Duchesnea indica (e.g., 210, 220, 230, 240, 250 parts, etc.), 180-220 parts of Rhizoma Cyathulae (e.g., 180, 190, 200, 210, 220 parts, etc.), 480-520 parts of Astragalus membranaceus (e.g., 480, 490, 500, 510, 520 parts, etc.), and 1 part of Panax ginseng. 60-200 portions (e.g., 160, 170, 180, 190, 200, etc.), 480-520 portions of snow lotus (e.g., 480, 490, 500, 510, 520, etc.), 140-180 portions of angelica (e.g., 140, 150, 160, 170, 180, etc.), 160-200 portions of turmeric (e.g., 160, 170, 180, 190, 200, etc.), and 150-190 portions of salvia miltiorrhiza (e.g., 150, 160, 170, 180, 190, etc.). Other specific values ​​within the above ranges can be selected, and will not be elaborated here.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] This invention creatively discovers that the aforementioned traditional Chinese medicine composition has good preventive or therapeutic effects on colon cancer, specifically by inhibiting the proliferation of colon cancer cells. It demonstrates good preventive and therapeutic effects in a mouse model of colon cancer, significantly reducing tumor volume. This invention provides an effective strategy for the prevention or treatment of colon cancer and offers a new direction for the application of the aforementioned traditional Chinese medicine composition. Attached Figure Description

[0025] Figure 1 This is a graph showing the effect of different concentrations of Xinlikang on the viability of MC-38 cells;

[0026] Figure 2 These are anatomical images of tumors in the model group, low-dose group, medium-dose group, high-dose group, and positive drug administration group. Detailed Implementation

[0027] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention in any way.

[0028] Unless otherwise specified, the reagents and consumables used in the following embodiments were purchased from conventional reagent manufacturers in the art; unless otherwise specified, the experimental methods and techniques used were conventional methods and techniques in the art.

[0029] The MC-38 cells used in the following examples belong to the C57BL / 6 mouse colon cancer cell line and were obtained from Nanjing Shenghang Biotechnology Co., Ltd.

[0030] Xinlikang Capsules are produced by Guiyang Xintian Pharmaceutical Co., Ltd., and contain, by weight parts, 501 parts of Scutellaria barbata, 402 parts of Solanum nigrum, 231 parts of Duchesnea indica, 200 parts of Rhizoma Cynanchi, 501 parts of Astragalus membranaceus, 181 parts of Panax ginseng, 501 parts of Saussurea involucrata, 161 parts of Angelica sinensis, 181 parts of Curcuma longa, and 171 parts of Salvia miltiorrhiza (disclosed in CN103901138B).

[0031] PD-1 inhibitors are produced by MedChemExpress, a US-based biotechnology company.

[0032] Example 1

[0033] This embodiment investigates the effects of different concentrations of Xinlikang on the proliferation of colon cancer cells:

[0034] Logarithmic growth phase colon cancer MC-38 cells were washed twice with PBS, digested with trypsin, then centrifuged, resuspended, diluted, and counted to a cell suspension concentration of 10⁻⁶. 5 Cells were cultured at a density of 0.1 mL / well to 96-well plates. Except for the control group, each well contained 0.1 mL of culture medium, and PBS buffer was added to the four sides of each well. After 24 hours of cell adhesion, 0 μg / mL of culture medium was added to each well. -1 50 μg·mL -1 100 μg·mL -1 200 μg·mL -1 400 μg·mL -1 800 μg·mL -1 The Xinlikang drug solution was prepared by serially diluting the granules from the Xinlikang capsules in high-glucose DMEM medium (serum-free). The 0% group was designated as the control group. After culturing for 24 hours, CCK-8 reagent was added to each well, and the cells were incubated for 1 hour before measurement. The OD value of each well was measured at a wavelength of 450 nm to calculate the cell viability.

[0035] Cell viability = (absorbance of drug-treated group - absorbance of blank group) / (absorbance of control group - absorbance of blank group) × 100%.

[0036] Data are expressed as mean ± standard deviation ( (n=6) represents the number of times n is used.

[0037] Table 1

[0038] Group OD value Cell viability inhibition rate (%) control group 1.099±0.028 — <![CDATA[50μg·mL -1 ]]> 1.029±0.030 6.40 <![CDATA[100μg·mL -1 ]]> <![CDATA[0.999±0.059 ** ]]> 9.11 <![CDATA[200μg·mL -1 ]]> <![CDATA[0.988±0.040 ** ]]> 10.17 <![CDATA[400μg·mL -1 ]]> <![CDATA[0.818±0.025 ** ]]> 25.64 <![CDATA[800μg·mL -1 ]]> <![CDATA[0.397±0.011 *** ]]> 63.09 Blank group 0.128±0.002 —

[0039] The results are as follows Figure 1 As shown in Table 1 (*P<0.05, **P<0.01, ***P<0.001), the traditional Chinese medicine composition of the present invention has a significant inhibitory effect on the proliferation of colon cancer MC-38 cells. Compared with the control group, Xinlikang capsules at 50-800 μg·mL -1 Within the specified dosage range, the drug inhibited MC-38 cell viability in a dose-dependent manner, with statistically significant differences, particularly at a drug concentration of 800 μg / mL. -1 The inhibition rate was 63.09%, and the calculated IC50 was... 50 It is 560.9 μg·mL -1 .

[0040] Example 2

[0041] This example investigates the effects of different doses of Xinlikang capsules on colon cancer tumors in mice:

[0042] (1) Establishment of a colon cancer mouse model: Sixty 6-week-old SPF-grade male C57BL / 6 mice were used. They were randomly divided into six groups (n=10 per group): a blank control group, a model group, a low-dose group, a medium-dose group, and a high-dose group (hereinafter referred to as the blank group, low-dose group, medium-dose group, and high-dose group), and a positive control group. Except for the blank group, the other groups were inoculated with a suspension of MC-38 colon cancer cells (concentration of 1×10⁻⁶). 7 pcs·mL -1 Mice in the control group were injected subcutaneously with an inoculation volume of 0.15 mL to prepare a colon cancer model; mice in the control group were injected subcutaneously with an equal volume of PBS solution at the same site.

[0043] (2) After the modeling was completed, mice in the blank group and tumor-bearing group were given physiological saline (0.1 mL·10 g) by gavage daily. -1 Low-dose group of tumor-bearing mice were administered 0.675 g / kg of Xinlikang capsule granules daily by gavage. -1 The medium-dose group of tumor-bearing mice was administered 1.35 g / kg of Xinlikang capsule granules daily by gavage. -1 High-dose group of tumor-bearing mice were administered 2.7 g / kg of Xinlikang capsule granules daily by gavage. -1 The positive control group of tumor-bearing mice received an intraperitoneal injection of 10 mg / kg of PD-1 inhibitor solution. -1 Twice a week.

[0044] During the experimental period, the diet and survival of mice in each group were observed. The body weight of the tumor-bearing mice in each group was measured, and the tumor size was also measured. Curves showing changes in body weight and tumor volume were plotted. After the experiment, mice in each group were euthanized and dissected to examine and record the tumor volume. The results are shown in Tables 2 and 3. Figure 2 As shown.

[0045] Tumor volume: V = 0.5 × tumor long axis × (short axis perpendicular to the long axis) 2 .

[0046] Data are expressed as mean ± standard deviation ( (n=5) indicates that ANOVA was used to perform statistical analysis on the data.

[0047] Table 2

[0048]

[0049]

[0050] Table 3

[0051] Group <![CDATA[Dose / (g·kg -1 )]]> Tumor weight / g Inhibition rate (%) Model group — 1.46±0.176 — low-dose group 0.675 <![CDATA[0.49±0.066 ** ]]> 66.58 medium dose group 1.350 <![CDATA[0.41±0.028 ** ]]> 71.92 High-dose group 2.700 <![CDATA[0.75±0.062 * ]]> 48.49 Positive drug group 0.010 <![CDATA[0.23±0.038 ** ]]> 84.11

[0052] The results showed that the traditional Chinese medicine composition of the present invention has a significant inhibitory effect on the growth of colon cancer tumors. Compared with the model group, the tumor volume and tumor quality were significantly reduced in the low, medium, and high dose groups and the positive control group, and it can be used for the treatment of colon cancer patients.

[0053] The applicant declares that the technical solution of this invention is illustrated by the above embodiments, but this invention is not limited to the above embodiments, that is, it does not mean that this invention must rely on the above embodiments to be implemented. Those skilled in the art should understand that any improvements to this invention, equivalent substitutions of raw materials for the products of this invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of this invention.

[0054] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0055] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

Claims

1. The application of a traditional Chinese medicine composition in the preparation of a drug for the prevention or treatment of colon cancer, characterized in that, The herbal composition includes Scutellaria barbata, Solanum nigrum, Duchesnea indica, Rhizoma Cyathulae, Astragalus membranaceus, Panax ginseng, Saussurea involucrata, Angelica sinensis, Curcuma longa, and Salvia miltiorrhiza.

2. The application according to claim 1, characterized in that, The traditional Chinese medicine composition comprises, by weight, 400-600 parts of Scutellaria barbata, 300-500 parts of Solanum nigrum, 130-330 parts of Duchesnea indica, 100-300 parts of Rhizoma Cyathulae, 400-600 parts of Astragalus membranaceus, 80-280 parts of Panax ginseng, 400-600 parts of Saussurea involucrata, 60-260 parts of Angelica sinensis, 80-280 parts of Curcuma longa, and 70-270 parts of Salvia miltiorrhiza. Preferably, the traditional Chinese medicine composition comprises, by weight, 480-520 parts of Scutellaria barbata, 380-420 parts of Solanum nigrum, 210-250 parts of Duchesnea indica, 180-220 parts of Rhizoma Cyathulae, 480-520 parts of Astragalus membranaceus, 160-200 parts of Panax ginseng, 480-520 parts of Saussurea involucrata, 140-180 parts of Angelica sinensis, 160-200 parts of Curcuma longa, and 150-190 parts of Salvia miltiorrhiza.

3. The application according to claim 1 or 2, characterized in that, The drugs mentioned above for the prevention or treatment of colon cancer inhibit the proliferation of colon cancer cells.

4. The application according to any one of claims 1-3, characterized in that, The drug also includes pharmaceutically acceptable excipients.

5. The application according to claim 4, characterized in that, The pharmaceutically acceptable excipients include any one or a combination of at least two of the following: excipients, lubricants, binders, preservatives, flavoring agents, carriers, disintegrants, emulsifiers, solubilizers, osmotic pressure regulators, surfactants, coating materials, colorants, pH adjusters, antioxidants, antibacterial agents, or buffers.

6. The application according to claim 5, characterized in that, The excipients include any one or a combination of at least two of starch, dextrin, or sucrose.

7. The application according to claim 5 or 6, characterized in that, The lubricant includes any one or a combination of at least two of magnesium stearate, calcium stearate, or talc.

8. The application according to any one of claims 5-7, characterized in that, The binder comprises glucose and / or maltodextrin.

9. The application according to any one of claims 1-8, characterized in that, The dosage forms of the drug include capsules, tablets, granules, pills, powders, solutions, emulsions, or suspensions.

10. The application of a traditional Chinese medicine composition in the preparation of a proliferation inhibitor for colon cancer cells, characterized in that, The herbal composition includes Scutellaria barbata, Solanum nigrum, Duchesnea indica, Rhizoma Cyathulae, Astragalus membranaceus, Panax ginseng, Saussurea involucrata, Angelica sinensis, Curcuma longa, and Salvia miltiorrhiza. Preferably, the traditional Chinese medicine composition comprises, by weight, 400-600 parts of Scutellaria barbata, 300-500 parts of Solanum nigrum, 130-330 parts of Duchesnea indica, 100-300 parts of Rhizoma Cyathulae, 400-600 parts of Astragalus membranaceus, 80-280 parts of Panax ginseng, 400-600 parts of Saussurea involucrata, 60-260 parts of Angelica sinensis, 80-280 parts of Curcuma longa, and 70-270 parts of Salvia miltiorrhiza. Preferably, the traditional Chinese medicine composition comprises, by weight, 480-520 parts of Scutellaria barbata, 380-420 parts of Solanum nigrum, 210-250 parts of Duchesnea indica, 180-220 parts of Rhizoma Cyathulae, 480-520 parts of Astragalus membranaceus, 160-200 parts of Panax ginseng, 480-520 parts of Saussurea involucrata, 140-180 parts of Angelica sinensis, 160-200 parts of Curcuma longa, and 150-190 parts of Salvia miltiorrhiza.

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