New application of Chinese knotweed rhizome and aloe bowel-relaxing capsule in preparation of medicine for treating colorectal cancer

Abstract

The invention belongs to the field of medicines, and relates to a novel application of a Chinese knotweed rhizome and aloe bowel-relaxing capsule, in particular to a novel application of the Chinese knotweed rhizome and aloe bowel-relaxing capsule in a medicine for treating colorectal cancer. The colorectal cancer model mice are administered with the Chinese knotweed rhizome-aloe bowel-relaxing capsules, the difference of indexes of each group of mice is observed, and the prevention and treatment effect of the Chinese knotweed rhizome-aloe bowel-relaxing capsules on colorectal cancer is investigated. Experimental results show that the Chinese knotweed rhizome and aloe bowel-relaxing capsule not only can obviously improve the body mass of a mouse with colorectal cancer and reduce the number of tumors of the mouse with colorectal cancer, but also can reduce the tumor weight of the mouse with colorectal cancer, and is remarkable in tumor inhibition effect. The Chinese knotweed rhizome and aloe bowel-relaxing capsule is used for treating colorectal cancer, can avoid toxic and side effects of western medicines, and is higher in safety.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of medicine, and relates to a new use of Shouhui Tongbian Capsules, in particular to a new use of Shouhui Tongbian Capsules in the preparation of a drug for treating colorectal cancer. BACKGROUND

[0002] Colorectal cancer, also known as "colorectal cancer", includes colon cancer and rectal cancer, which is a cancer originating from the epithelium of the large intestine. The symptoms of colorectal cancer are changes in bowel habits and stool characteristics, hematochezia, tenesmus (frequent desire to defecate, anal distension, pain, incomplete defecation, and desire to defecate after defecation), intractable constipation, stool shape change, diarrhea / constipation alternation, abdominal pain, and abdominal or rectal mass. According to the clinical symptoms of changes in bowel habits and stool characteristics, abdominal pain, and the presence of tumors observed directly under colonoscopy, and confirmed by biopsy as cancer, colorectal cancer can be diagnosed.

[0003] The pathogenesis of colon cancer is a multi-factor and multi-step gradual development process. Colon cancer is mainly adenocarcinoma, mucous adenocarcinoma, and undifferentiated carcinoma, which is in the form of polypoid and ulcerative. Colon cancer can develop along the intestinal wall, spread along the longitudinal axis of the intestinal canal, or infiltrate the deep layer of the intestinal wall. In addition to metastasis through lymphatic vessels and blood flow, and local invasion, it can also implant into the abdominal cavity or spread along the suture line and incision surface.

[0004] At present, the clinical treatment of colorectal cancer mainly combines surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. However, due to the toxic side effects of radiotherapy and chemotherapy, drug resistance, and the high cost of targeted therapy and immunotherapy, the treatment effect and prognosis of colorectal cancer are not satisfactory. Although anti-PD-L1-based immunotherapy has been approved as a standard treatment for various cancers, its therapeutic effect in most colorectal cancers is still limited due to low response to immunotherapy.

[0005] Traditional Chinese medicine has the characteristics of multiple targets and small side effects, and has made great progress in anti-tumor research. Traditional Chinese medicine emphasizes strengthening the body and eliminating pathogens, and has unique advantages in the prevention and treatment of colorectal cancer, such as improving patients' nausea, vomiting, diarrhea, and other digestive symptoms, regulating immune function, reversing chemotherapy resistance, prolonging survival, and improving quality of life. Modern pharmacological research of traditional Chinese medicine has proved that the effective components of traditional Chinese medicine with anti-tumor effect include polysaccharides, flavonoids, saponins, alkaloids, etc.

[0006] Chinese patent CN100453105C discloses a composition and preparation method with functions of relieving constipation, detoxification, weight loss, and lipid reduction. It has now been approved for production, and the product is Shouhui Tongbian Capsules. This product is a compound traditional Chinese medicine preparation made from eight Chinese medicinal herbs: Polygonum multiflorum, Aloe vera, Cassia seed, Lycium barbarum, donkey-hide gelatin, ginseng, Atractylodes macrocephala, and Citrus aurantium, which can be used to specifically treat functional constipation.

[0007] The prescription for Shouhui Tongbian Capsules is based on the clinical experience of renowned traditional Chinese medicine practitioners. This formula, grounded in traditional Chinese medicine theory and incorporating clinical experience, combines laxatives and detoxifying agents with blood-nourishing and dryness-moistening agents, along with qi-tonifying and spleen-strengthening agents. This allows the formula to achieve a balance of tonification and purgation, using the principle of "clearing" as its primary function, with both downward movement and upward movement, and tonification within purgation. The formula employs a combination of dispersing and tonifying, a balance of urgency and gentleness, mutually restraining and complementing each other, ensuring that tonification does not lead to stagnation and purgation does not harm the body's vital energy. This formula is particularly effective in treating constipation caused by internal accumulation of toxins and deficiency of yin fluids. It comprehensively improves gastrointestinal function, with definite efficacy, rapid onset of action, and no toxic side effects. It also has detoxifying, beautifying, weight-loss, and lipid-lowering effects. Clinical application demonstrates its definite efficacy and plays an important role in the treatment of functional constipation. Summary of the Invention

[0008] The main objective of this invention is to provide the use of Shouhui Tongbian Capsules in the preparation of drugs for treating colorectal cancer, primarily targeting a new indication for the already marketed product "Shouhui Tongbian Capsules". The formulation patent for Shouhui Tongbian Capsules is CN100453105C, entitled "A Composition and Preparation Method with Functions of Relieving Constipation, Detoxification, Weight Loss, and Lipid Reduction," which has been granted. This invention's Shouhui Tongbian Capsules significantly improve weight loss caused by colorectal cancer, reduce the number of colorectal cancer tumors, inhibit colorectal cancer tumor growth, and have a significant anti-colorectal cancer effect.

[0009] The objective of this invention is mainly achieved through the following technical solutions:

[0010] The present invention, Shouhui Tongbian Capsules, is prepared according to the preparation or extraction method of each component in the composition and preparation method of a composition having the functions of relieving constipation, detoxification, weight loss and lipid reduction in patent CN100453105C.

[0011] The present invention, Shouhui Tongbian Capsules, is prepared from Polygonum multiflorum, Aloe vera, Cassia seed, Lycium barbarum, donkey-hide gelatin, ginseng, Atractylodes macrocephala, and Citrus aurantium as raw materials.

[0012] The ingredients, by weight, are as follows: Polygonum multiflorum 60-150 parts by weight, Aloe vera 100-200 parts by weight, Cassia seed 80-180 parts by weight, Lycium barbarum 30-150 parts by weight, Colla corii asini 30-150 parts by weight, Ginseng 20-100 parts by weight, Atractylodes macrocephala 20-100 parts by weight, and Citrus aurantium 50-200 parts by weight.

[0013] The preferred ingredients are: 120 parts by weight of Polygonum multiflorum, 160 parts by weight of Aloe vera, 140 parts by weight of Cassia tora, 75 parts by weight of Lycium barbarum, 75 parts by weight of donkey-hide gelatin, 50 parts by weight of ginseng, 50 parts by weight of Atractylodes macrocephala, and 120 parts by weight of Citrus aurantium.

[0014] The preparation steps for the above-mentioned Shouhui laxative capsules are as follows:

[0015] (1) Grind the donkey-hide gelatin into a fine powder, pass it through an 80-mesh sieve, and set aside;

[0016] (2) Ginseng, Polygonum multiflorum, Cassia seed and aloe were extracted twice by reflux with 60% ethanol. The first time, 10 times the amount of ethanol was added and the second time, 8 times the amount of ethanol was added. Each extraction lasted 2 hours. The extracts were filtered separately and the filtrates were combined to obtain filtrate I for later use.

[0017] (3) Add water to wolfberry, atractylodes macrocephala and immature bitter orange and decoct twice. For the first decoction, add 8 times the amount of water, soak for 1 hour, decoct for 1.5 hours and filter. For the second decoction, add 6 times the amount of water, decoct for 1.5 hours and filter. Combine the filtrates and concentrate to a clear extract with a relative density of 1.10 to 1.20 (80℃). Place at room temperature, stir and add ethanol to make the purity reach 60% (20℃), refrigerate and stand for more than 24 hours, filter and obtain filtrate II for later use.

[0018] (4) Combine the filtrate I obtained in step (2) with the filtrate II obtained in step (3), concentrate it to a thick paste with a relative density of 1.30-1.35 (70℃), dry it, pulverize it, add the fine powder of donkey-hide gelatin prepared in step (1) and an appropriate amount of dextrin, mix it evenly, granulate it by dry method, and fill it into capsules to obtain the product.

[0019] Compared with the prior art, the present invention has achieved significant technical effects:

[0020] Pharmacological studies have found that Shouhui Tongbian Capsules have a significant anti-colorectal cancer effect.

[0021] The mice with colorectal cancer were given Shouhui Tongbian capsules, and the differences in various indicators among the mice in each group were observed to investigate the preventive and therapeutic effects of Shouhui Tongbian capsules on colorectal cancer.

[0022] Shouhui Tongbian Capsules can not only significantly improve the body weight of mice with colorectal cancer and reduce the number of tumors in mice with colorectal cancer, but also reduce the tumor weight in mice with colorectal cancer, showing a significant tumor-suppressing effect.

[0023] After intervention with Shouhui Tongbian capsules in mice with colorectal cancer, the mice's weight improved, while after intervention with the positive drug oxaliplatin in mice with colorectal cancer, the mice's weight decreased significantly.

[0024] The present invention, Shouhui Tongbian Capsules, is used for the treatment of colorectal cancer, which can avoid the toxic side effects of Western medicine and has higher safety. Specific Implementation

[0025] To enable those skilled in the art to better understand the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of the present invention.

[0026] Unless otherwise specified, the instruments, reagents, and materials involved in the following embodiments are all conventional instruments, reagents, and materials that are already available in the prior art and can be obtained through legitimate commercial channels.

[0027] The following experiments further illustrate the beneficial effects of the Shouhui Tongbian Capsules of the present invention.

[0028] Pharmacological Example: Study on the effect of Shouhui Tongbian Capsules on AOM / DSS inflammation-related colorectal cancer mice

[0029] 1. Experimental Procedure

[0030] 1.1 Animal adaptation

[0031] SPF-grade C57BL / 6J mice were quarantined for 7 days after arrival. Sixty healthy male mice were selected as test animals. The main inspection items during the quarantine period included, but were not limited to: whether the number and quality indicators of animals were consistent with those required at the time of application; general condition; and weight. Animals that failed the above quarantine inspections were not included in this experiment.

[0032] 1.2 Modeling and Drug Administration

[0033] After quarantine, the mice were randomly divided into two groups: a normal group (n=10) and a model group (n=50). The normal group had free access to normal drinking water. The model group was established as follows: on day 1, the mice were injected intraperitoneally with 10 mg / kg azomethane (AOM). One week later, they were fed a (1%-3%) sodium dextran sulfate (DSS) solution for one week. After that, they were given normal drinking water for 14 days. This stage was considered one modeling cycle, and three consecutive cycles were performed.

[0034] After the modeling cycle was completed, the modeling group was randomly divided into 5 groups according to body weight: model group (10 animals), Shouhui Tongbian capsule low dose - 75mg / kg group (10 animals), Shouhui Tongbian capsule medium dose - 150mg / kg group (10 animals), Shouhui Tongbian capsule high dose - 300mg / kg group (10 animals), and oxaliplatin - 10mg / kg group (10 animals).

[0035] Intervention was carried out according to the above drug dosages (Shouhui Tongbian capsules were administered by gavage once a day; oxaliplatin was administered by intraperitoneal injection once every 4 days) for 4 consecutive weeks until the end of the trial.

[0036] 1.3 Detection Indicators

[0037] After the experiment began, the mice were weighed once a week.

[0038] After the experiment, the animals were weighed, anesthetized, and dissected; the spleen was removed, weighed, and the spleen index was calculated.

[0039] The colon and rectum were dissected, and the intestines were washed with pre-cooled PBS. The intestinal lumen was opened along the long axis, and the surface of the intestinal lumen was carefully observed and palpated for tumor formation. If tumor formation was found, the tumors were counted and the number of tumors was recorded.

[0040] Carefully remove all tumors and weigh them to obtain their weight.

[0041] The tumor inhibition rate is calculated based on the tumor weight using the following formula: Inhibition rate = (tumor weight in the model group - tumor weight in the treatment group) / tumor weight in the model group × 100%.

[0042] 2. Statistical processing

[0043] All data were statistically processed using GraphPad Prism 7.0. This indicates that one-way ANOVA is used to detect whether there are differences in the overall data. If there are differences, the t-test is used to test the significance, with p < 0.05 considered statistically significant.

[0044] 3. Experimental Results and Discussion

[0045] Table 1. Changes in body weight of mice in each group

[0046]

[0047]

[0048] Compared with the normal control group, # p<0.05, ## p<0.01, ### p<0.01.

[0049] Compared with the model group, * p<0.05.

[0050] As shown in Table 1, compared with the normal group, the body weight of mice in the model group decreased significantly, which was statistically significant.

[0051] Compared with the model group, the high-dose Shouhui laxative group significantly improved the weight loss in mice with colorectal cancer. In the positive control group (oxaliplatin), the mice experienced a significant weight loss after intervention, indicating that oxaliplatin had significant side effects.

[0052] Table 2 Comparison of tumor numbers in mice of different groups

[0053]

[0054] Compared with the normal control group, # p<0.05, ## p<0.01, ### p<0.01.

[0055] Compared with the model group, * p<0.05.

[0056] As shown in Table 2, compared with the normal group, the number of tumors in the model group mice was significantly increased, showing a statistically significant difference.

[0057] Compared with the model group, the high-dose group of Shouhuitongbian significantly reduced the number of colorectal cancer tumors in mice, with an effect comparable to that of the positive control drug oxaliplatin.

[0058] Table 3 Comparison of tumor weight in mice of different groups

[0059]

[0060]

[0061] Compared with the normal control group, # p<0.05, ## p<0.01, ### p<0.01.

[0062] Compared with the model group, * p<0.05, ** p<0.01.

[0063] As shown in Table 3, compared with the normal group, the tumor weight of the model group mice was significantly increased, showing a statistically significant difference.

[0064] Compared with the model group, the high-dose group of Shouhuitongbian significantly reduced the tumor weight of colorectal cancer mice, with an effect comparable to that of the positive control drug oxaliplatin.

[0065] Table 4 Comparison of tumor inhibition rates in mice of different groups

[0066]

[0067] As shown in Table 4, compared with the model group, the high-dose Shouhui Tongbian group showed a significant inhibitory effect on colorectal cancer.

[0068] Animal experiments of this invention show that Shouhui Tongbian Capsules significantly improve the weight loss, reduce the number of tumors, and decrease the tumor weight in colorectal cancer model mice, thus suggesting that Shouhui Tongbian Capsules can inhibit tumor growth and have a significant anti-colorectal cancer effect.

[0069] The above content is only for illustrating the technical concept of the present invention and should not be construed as limiting the scope of protection of the present invention. Any modifications made to the technical solution based on the technical concept proposed in this invention shall fall within the scope of protection of the claims of this invention.

Claims

1. The use of Shouhui Tongbian Capsules in the preparation of drugs for treating colorectal cancer.

2. The use as described in claim 1, characterized in that, The Shouhui laxative capsules are made from Polygonum multiflorum, aloe vera, cassia seed, wolfberry, donkey-hide gelatin, ginseng, Atractylodes macrocephala and Citrus aurantium.

3. The use as described in claim 2, characterized in that, The Shouhui laxative capsules are prepared from the following raw materials: 60-150 parts by weight of Polygonum multiflorum, 100-200 parts by weight of Aloe vera, 80-180 parts by weight of Cassia tora, 30-150 parts by weight of Lycium barbarum, 30-150 parts by weight of donkey-hide gelatin, 20-100 parts by weight of ginseng, 20-100 parts by weight of Atractylodes macrocephala, and 50-200 parts by weight of Citrus aurantium.

4. The use as described in claim 3, characterized in that, The Shouhui laxative capsules are made from the following raw materials: 120 parts by weight of Polygonum multiflorum, 160 parts by weight of Aloe vera, 140 parts by weight of Cassia tora, 75 parts by weight of Lycium barbarum, 75 parts by weight of donkey-hide gelatin, 50 parts by weight of ginseng, 50 parts by weight of Atractylodes macrocephala, and 120 parts by weight of Citrus aurantium.

5. The use as described in claim 1, characterized in that, The preparation steps of the Shouhui laxative capsules are as follows: (1) Grind the donkey-hide gelatin into a fine powder, pass it through an 80-mesh sieve, and set aside; (2) Ginseng, Polygonum multiflorum, Cassia seed and aloe were extracted twice by reflux with 60% ethanol. The first time, 10 times the amount of ethanol was added and the second time, 8 times the amount of ethanol was added. Each extraction lasted 2 hours. The extracts were filtered separately and the filtrates were combined to obtain filtrate I for later use. (3) Add water to wolfberry, atractylodes macrocephala and immature bitter orange and decoct twice. For the first decoction, add 8 times the amount of water, soak for 1 hour, decoct for 1.5 hours and filter. For the second decoction, add 6 times the amount of water, decoct for 1.5 hours and filter. Combine the filtrates and concentrate to a clear extract with a relative density of 1.10 to 1.20 (80℃). Place at room temperature, stir and add ethanol to make the purity reach 60% (20℃), refrigerate and stand for more than 24 hours, filter and obtain filtrate II for later use. (4) Combine the filtrate I obtained in step (2) with the filtrate II obtained in step (3), concentrate it to a thick paste with a relative density of 1.30-1.35 (70℃), dry it, pulverize it, add the fine powder of donkey-hide gelatin prepared in step (1) and an appropriate amount of dextrin, mix it evenly, granulate it by dry method, and fill it into capsules to obtain the product.

6. The use as described in claim 1, characterized in that, The Shouhui laxative capsules improve weight loss caused by colorectal cancer.

7. The use as described in claim 1, characterized in that, The Shouhui laxative capsules reduce the number of colorectal cancer tumors.

8. The use as described in claim 1, characterized in that, The Shouhui laxative capsules inhibit the growth of colorectal cancer tumors.

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