Pharmaceutical compositions containing Shouhui laxative capsules for the treatment of colorectal cancer and their applications.

Abstract

This invention belongs to the field of pharmaceutical technology and relates to a pharmaceutical composition containing Shouhui Tongbian capsules for the treatment of colorectal cancer and its application. The combination of Shouhui Tongbian capsules and oxaliplatin significantly improves weight loss, reduces tumor number and weight in colorectal cancer model mice, demonstrating a significant synergistic effect in the treatment of colorectal cancer. In this invention, the combination of Shouhui Tongbian capsules and oxaliplatin, while treating colorectal cancer, allows the two drugs to exert a synergistic effect, reducing drug dosage, decreasing drug toxicity and side effects, and improving medication safety.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology and relates to a pharmaceutical composition containing Shouhui Tongbian capsules for the treatment of colorectal cancer and its application. Background Technology

[0002] Colorectal cancer is a malignant epithelial tumor that originates from the intestinal mucosa, penetrates the muscularis mucosa, and infiltrates the submucosa or deeper structures. Early symptoms of colorectal cancer are often subtle; some patients may experience occult blood in stool or indigestion. As the tumor gradually infiltrates adjacent tissues, various symptoms may appear, including abdominal pain, changes in bowel habits, rectal bleeding, abdominal masses, and intestinal obstruction. By the time obvious signs or symptoms appear, the cancer has often progressed to an advanced stage, seriously threatening the patient's life.

[0003] Despite advancements in surgical techniques, chemotherapy, and radiation therapy, surgery remains the first-line treatment for colorectal cancer. Key characteristics of colorectal cancer treatment in recent years include: a gradual increase in early-stage lesions and a rise in the proportion of endoscopic treatment; definite efficacy of traditional surgery and a steadily decreasing surgical scope; diversified neoadjuvant therapy modalities for locally advanced patients, requiring individualized selection; and a clear trend towards refined diagnosis and treatment of advanced disease, with steadily improving efficacy but breakthroughs remaining challenging.

[0004] The three traditional treatments for cancer include chemotherapy, radiotherapy, and surgery. Chemotherapy is the primary treatment for advanced malignant tumors, playing a role that radiotherapy and surgery cannot replace. Classic chemotherapy drugs such as cisplatin, carboplatin, and oxaliplatin, all divalent platinum-based antitumor drugs, are widely used in the treatment of solid tumors such as lung cancer, nasopharyngeal carcinoma, ovarian cancer, breast cancer, and colorectal cancer. Oxaliplatin, a platinum-based antitumor drug, is primarily used in chemotherapy for patients with gastric cancer, colorectal cancer, and hepatobiliary and pancreatic cancer.

[0005] Among platinum-based antitumor drugs, divalent platinum-based chemotherapy drugs have serious side effects in clinical treatment, including gastrointestinal reactions, weight loss, ototoxicity, nephrotoxicity, neurotoxicity, and myelosuppression. They also suffer from low bioavailability and are not suitable for oral administration. Furthermore, drug resistance resulting from reduced drug uptake and inactivation, DNA damage repair, cell cycle arrest, and disruption of apoptosis during treatment severely limits the clinical use of platinum-based chemotherapy drugs. Summary of the Invention

[0006] One object of the present invention is to provide the use of Shouhui Tongbian capsules in combination with oxaliplatin in the preparation of a medicament for treating colorectal cancer.

[0007] A second objective of this invention is to provide a pharmaceutical composition containing Shouhui Tongbian capsules and oxaliplatin.

[0008] A third objective of this invention is to provide the use of Shouhui Tongbian Capsules in the preparation of a remedy for or treatment of weight loss caused by platinum-based chemotherapy drugs.

[0009] A fourth object of the present invention is to provide a medicament kit for treating colorectal cancer.

[0010] According to one aspect of the present invention, the present invention provides the use of Shouhui Tongbian capsules in combination with platinum-based chemotherapy agents in the preparation of a drug for treating cancer, wherein the cancer is colorectal cancer.

[0011] In a preferred embodiment of the present invention, the platinum-based chemotherapeutic agent is cisplatin, carboplatin, nedaplatin, lobaplatin, or oxaliplatin.

[0012] In a preferred embodiment of the present invention, the platinum-based chemotherapeutic agent is oxaliplatin.

[0013] Regarding the administration method and dosage, the dosage of Shouhui Tongbian Capsules is 10 mg / kg, taken orally three times a day, with each dosing cycle lasting four weeks. Oxaliplatin is administered by injection or infusion at a dose of 1 mg / kg, once every four days, with each dosing cycle lasting four weeks.

[0014] Furthermore, the oxaliplatin is administered intravenously or intraperitoneally.

[0015] Furthermore, the oxaliplatin is administered intravenously.

[0016] This invention utilizes Shouhui Tongbian Capsules in combination with platinum-based chemotherapy agents to reduce tumor weight in colorectal cancer patients.

[0017] In a preferred embodiment of the present invention, the platinum-based chemotherapeutic agent is oxaliplatin.

[0018] According to a second aspect of the present invention, the present invention provides a pharmaceutical composition for treating colorectal cancer, characterized in that the pharmaceutical composition comprises Shouhui Tongbian capsules and oxaliplatin.

[0019] According to a third aspect of the present invention, the present invention provides the use of Shouhui Tongbian Capsules in the preparation of a medicament for relieving or treating weight loss caused by platinum-based chemotherapy drugs, characterized in that the platinum-based chemotherapy drug is oxaliplatin.

[0020] According to a fourth aspect of the present invention, the combined treatment regimen of the present invention can administer each drug to the patient separately according to the above-described regimen, or it can be prepared in the form of a medicine pack or medicine box for convenient administration. The present invention provides a medicine box for treating colorectal cancer, comprising the following components: Shouhui Tongbian capsules and a platinum-based chemotherapy agent.

[0021] In a preferred embodiment of the present invention, the platinum-based chemotherapeutic agent is oxaliplatin.

[0022] As used in this article, “cancer” refers to a physiological disorder in mammals characterized by uncontrolled excessive proliferation of cells.

[0023] As used herein, the term "treatment" and other similar synonyms include relieving, reducing, or improving symptoms of a disease or condition; inhibiting a disease or condition, such as preventing its progression; alleviating a disease or condition; improving a disease or condition; relieving symptoms caused by a disease or condition; or stopping symptoms of a disease or condition; preventing other symptoms; improving or preventing the underlying metabolic causes of symptoms; and, moreover, the term includes preventative purposes. The term also includes achieving therapeutic and / or preventative effects. A therapeutic effect refers to the cure or improvement of the underlying disease being treated. Furthermore, the cure or improvement of one or more physiological symptoms associated with the underlying disease is also a therapeutic effect; for example, an improvement is observed in a patient even though they may still be affected by the underlying disease. In terms of preventative effects, the composition may be administered to patients at risk of developing a specific disease, or to patients exhibiting one or more physiological symptoms of a disease, even if no disease diagnosis has been made.

[0024] As used herein, the term "chemotherapeutic agent" refers to a chemical compound that can be used to treat cancer. The chemotherapeutic agents used in this invention relate to platinum-based chemotherapeutic agents, specifically cisplatin, carboplatin, nedaplatin, lobaplatin, or oxaliplatin.

[0025] As used in this article, the terms “combination,” “aggregation,” or “conjunctive use” refer to the application of two or more drug components together, as a mixture, simultaneously, or sequentially as single formulations to a patient or subject in any order.

[0026] The term "synergistic effect" as used in this article refers to the simple additive effect of two or more drug components that is greater than the effect of the components administered alone.

[0027] Animal studies have shown that when Shouhui Tongbian Capsules are used in combination with oxaliplatin to treat colorectal cancer, Shouhui Tongbian Capsules significantly alleviate oxaliplatin-induced weight loss and improve quality of life.

[0028] The combination of Shouhui Tongbian Capsules and oxaliplatin showed a significantly better effect in reducing the number of colorectal cancer tumors in mice than either the Shouhui Tongbian Capsules group or the oxaliplatin group alone. This indicates that Shouhui Tongbian Capsules and oxaliplatin have a significant synergistic effect in reducing the number of colorectal cancer tumors in mice.

[0029] The combination of Shouhui Tongbian Capsules and oxaliplatin showed a significantly better effect in reducing tumor weight in colorectal cancer mice than either the Shouhui Tongbian Capsules group or the oxaliplatin group alone. This indicates that Shouhui Tongbian Capsules and oxaliplatin have a significant synergistic effect in reducing tumor weight in colorectal cancer mice.

[0030] Compared with the prior art, the present invention has the following advantages:

[0031] The combined use of Shouhui Tongbian capsules and oxaliplatin significantly improved the weight loss, reduced the number of tumors, and decreased the tumor weight in mice with colorectal cancer, suggesting that Shouhui Tongbian capsules can inhibit tumor growth and have a significant synergistic effect in the treatment of colorectal cancer.

[0032] This invention combines Shouhui Tongbian Capsules and oxaliplatin to treat colorectal cancer, with the two drugs working synergistically to reduce drug dosage, decrease drug toxicity and side effects, and improve medication safety. Detailed Implementation

[0033] The technical solution of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0034] Pharmacological Examples: Effects of the combination of the present invention's Shouhui Tongbian Capsules and oxaliplatin on a mouse model of colorectal cancer.

[0035] 1. Experimental Procedure

[0036] 1.1 Animal adaptation

[0037] SPF-grade C57BL / 6J mice were quarantined for 7 days after arrival, and 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; weight; animals that failed the above quarantine were not included in this experiment.

[0038] 1.2 Modeling and Drug Administration

[0039] After quarantine, the mice were randomly divided into two groups: a normal group (n=10) and a model group (n=40). The normal group had free access to normal drinking water. The model group was established as follows: on day 1, mice were injected intraperitoneally with 10 mg / kg azomethane (AOM), followed by feeding them (1%-3%) sodium dextran sulfate (DSS) solution for one week, and then they were fed normal drinking water for 14 days. This stage was considered one modeling cycle, and three consecutive cycles were performed.

[0040] After the modeling cycle was completed, the model group 1 was randomly divided into 3 groups according to body weight: the model group (n=10), the Shouhui Tongbian Capsule - 300mg / kg group (n=10), the Oxaliplatin - 10mg / kg group (n=10), and the Shouhui Tongbian Capsule - 300mg / kg + Oxaliplatin - 10mg / kg combination group (n=10). Then, the intervention was started according to the above drug dosages (Shouhui Tongbian Capsule was 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.

[0041] 1.3 Detection Indicators

[0042] After the experiment began, the mice were weighed once a week.

[0043] After the experiment, the animals were weighed, anesthetized, and dissected; the spleen was removed, weighed, and the spleen index was calculated.

[0044] 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 tumors were formed, the tumors were counted and the number of tumors was recorded. All tumors were carefully removed and weighed to obtain the tumor weight.

[0045] The tumor inhibition rate is calculated based on the tumor weight using the following formula: Tumor inhibition rate = (Tumor weight in the model group - Tumor weight in the treatment group) / Tumor weight in the model group × 100%.

[0046] 2. Data Statistics

[0047] Experimental data are expressed as mean ± standard deviation. Statistical analysis was performed using GraphPad Prism 8.0.2 software. One-way ANOVA was used for comparisons between groups, and multi-way ANOVA was used for repeated measures data. A p-value < 0.05 was considered statistically significant.

[0048] 3. Experimental Results

[0049] 3.1 Mouse body weight

[0050] Table 1. Changes in body weight of mice in each group

[0051] Group Body weight (g) normal group 27.90±1.45 Model group <![CDATA[23.88±2.41 ### ]]> Shouhui Laxative Capsule Group <![CDATA[27.05±1.30 ** ]]> O'Sullivan Group 22.88±2.02 Joint Group <![CDATA[26.69±1.15 ** ]]>

[0052] Compared with the normal control group, ### p<0.01.

[0053] Compared with the model group, ** p<0.01.

[0054] 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.

[0055] Compared with the model group, there was no significant difference in body weight among mice in the oxaliplatin group. After oxaliplatin chemotherapy, the mice did not gain body weight, and oxaliplatin could not improve the weight loss in mice with colorectal cancer.

[0056] Compared with the model group, the Shouhui Tongbian capsule group and the combined group significantly improved the weight loss of colorectal cancer mice.

[0057] When Shouhui Tongbian Capsules and oxaliplatin are used in combination to treat colorectal cancer, Shouhui Tongbian Capsules significantly alleviate oxaliplatin-induced weight loss and improve quality of life.

[0058] Table 2 Comparison of tumor numbers in mice of different groups

[0059]

[0060]

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

[0062] Compared with the model group, ** p<0.01, *** p<0.001.

[0063] 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.

[0064] Compared with the model group, the Shouhui Tongbian Capsule group and the Oxaliplatin group significantly reduced the number of colorectal cancer tumors in mice.

[0065] The combined group showed a better effect in reducing the number of colorectal cancer tumors in mice, significantly superior to the Shouhui Tongbian capsule group and the oxaliplatin group. This indicates that Shouhui Tongbian capsule and oxaliplatin have a significant synergistic effect in reducing the number of colorectal cancer tumors in mice.

[0066] Table 3 Comparison of tumor weight in mice of different groups

[0067] Group Tumor weight (mg) normal group 0.00±0.00 Model group <![CDATA[111.30±14.66 ### ]]> Shouhui Laxative Capsule Group <![CDATA[78.30±28.97 ** ]]> O'Sullivan Group <![CDATA[73.60±19.86 *** ]]> Joint Group <![CDATA[41.10±18.98 *** ]]>

[0068] Compared with the normal control group, ### p<0.01.

[0069] Compared with the model group, *** p<0.001.

[0070] 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.

[0071] Compared with the model group, the Shouhui Tongbian capsule group and the oxaliplatin group significantly reduced the tumor weight of colorectal cancer mice.

[0072] The combined group showed a better effect in reducing tumor weight in colorectal cancer mice, significantly superior to the Shouhui Tongbian capsule group and the oxaliplatin group. This indicates that Shouhui Tongbian capsule and oxaliplatin have a significant synergistic effect in reducing tumor weight in colorectal cancer mice.

[0073] Table 4 Comparison of tumor inhibition rates in mice of different groups

[0074] Group Tumor inhibition rate % normal group - Model group - Shouhui Laxative Capsule Group 29.65％ O'Sullivan Group 33.87％ Joint Group 63.07％

[0075] As shown in Table 4, compared with the model group, the combined group showed a significant inhibitory effect on colorectal cancer.

[0076] The combined group showed a better effect in improving mouse body weight, significantly superior to the Shouhui Tongbian Capsule group and the oxaliplatin group. This indicates that Shouhui Tongbian Capsule and oxaliplatin have a significant synergistic effect in improving the body weight of mice with colorectal cancer.

[0077] In summary, the combined use of Shouhui Tongbian Capsules and oxaliplatin significantly improved the weight loss, reduced the number of tumors, and decreased the tumor weight in colorectal cancer model mice, suggesting that Shouhui Tongbian Capsules can inhibit tumor growth and have a significant synergistic effect in the treatment of colorectal cancer.

[0078] The above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description, and any obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

[0079] Although the invention has been described in conjunction with its specific aspects, it should be understood that the invention is capable of further modifications and this application is intended to cover any changes, uses or alterations that generally follow the principles of this disclosure and include deviations from this disclosure that are within the scope of known or conventional practices in the field to which this invention pertains and that can be applied to the essential features set forth above and claimed below.

Claims

1. The use of Shuohuotongchuan Capsules in combination with oxaliplatin for the preparation of a drug for treating cancer, characterized in that, The cancer is colorectal cancer.

2. Use according to claim 1, characterized in that, The dosage of the Shouhao laxative capsule is 10 mg / kg, taken orally 3 times a day, and each 4 weeks is a dosing cycle.

3. Use according to claim 1, characterized in that, The dosage of the oxaliplatin is 1 mg / kg, injected or infused, once every 4 days, and each 4 weeks is a dosing cycle.

4. Use according to claim 1, characterized in that, The Shouhao laxative capsule and oxaliplatin are combined to reduce the tumor weight of a colorectal cancer patient.

5. Use according to claim 1, characterized in that, The Shouhao laxative capsule can relieve the weight loss caused by oxaliplatin chemotherapy.

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