CN111419931A

CN111419931A - Application of compound cortex phellodendri composition in preparation of medicine for preventing and treating colorectal cancer

Info

Publication number: CN111419931A
Application number: CN202010330315.8A
Authority: CN
Inventors: 王小云; 秦承雪; 霍卫国; 徐凤霞; 樊苗
Original assignee: SHANDONG HANFANG PHARMACEUTICAL CO Ltd
Current assignee: SHANDONG HANFANG PHARMACEUTICAL CO Ltd
Priority date: 2020-04-24
Filing date: 2020-04-24
Publication date: 2020-07-17

Abstract

The invention relates to the technical field of medicine and pharmacology, in particular to application of a compound phellodendron composition in preparing a medicine for preventing and treating colorectal cancer; can inhibit the growth of intestinal cancer cells, reduce the cancer rate and has obvious effect of preventing and treating colorectal cancer.

Description

Application of compound cortex phellodendri composition in preparation of medicine for preventing and treating colorectal cancer

Technical Field

The invention relates to the technical field of medicine and pharmacology, and particularly relates to application of a compound cortex phellodendri composition in preparation of a medicine for preventing and treating colorectal cancer.

Background

Colorectal cancer includes colon cancer and rectal cancer, which are common malignancies. In recent years, the incidence of this disease has been increasing, and colorectal cancer has been associated with many factors, such as high-fat low-cellulose eating habits, chronic inflammation of the large intestine, adenoma of the large intestine, genetic factors, and the like. Colorectal cancer is asymptomatic or unobvious in early stage, and only feels discomfort, dyspepsia, stool occult blood and the like. With the development of cancer, symptoms gradually appear, which are manifested as stool habit change, abdominal pain, hematochezia, abdominal mass, intestinal obstruction, etc., with or without anemia, fever, emaciation, etc. The tumor may cause the change of affected organs due to metastasis and infiltration. Colorectal cancer presents different clinical symptoms and signs due to different sites of onset.

The method for treating colorectal cancer comprises operation treatment, comprehensive treatment and radiotherapy. The existing colorectal cancer treatment is a comprehensive treatment scheme mainly based on surgical resection treatment and postoperative adjuvant radiotherapy and chemotherapy. The chemotherapy medicine comprises 5-fluorouracil, capecitabine, oxaliplatin, irinotecan, bevacizumab, cetuximab, panitumumab and other medicines, but the treatment method of operation and radiotherapy and chemotherapy can generate inevitable traumatic impact on the organism of a patient, and the chemotherapy can cause gastrointestinal tract reaction, bone marrow suppression, peripheral neuropathy and other adverse reactions of the patient.

With the development of traditional Chinese medicine, the combination of traditional Chinese medicine and western medicine becomes a hot point, and the colorectal cancer is treated by clinically using Chinese patent medicine preparations such as compound lightyellow sophora root injection, Shenmai injection and the like in combination with chemoradiotherapy; the auxiliary hospital of Nanjing Chinese medicine university gives the early colorectal cancer patients a spleen-invigorating and blood stasis-removing decoction after operation, performs early endoscopic treatment, and performs traditional Chinese medicine intervention after operation to reduce the recurrence rate of the early colorectal cancer; the Guizhou province anorectal disease hospital adopts a compound Miao medicine to improve the adverse reaction of patients after chemotherapy; in addition, documents report that the life quality of patients with advanced intestinal cancer is improved and the economic burden is reduced by decocting and taking traditional Chinese medicine compositions such as bitter apricot seeds, Chinese magnoliavine fruit, evodia rutaecarpa, ternate buttercup root, astragalus mongholicus, bighead atractylodes rhizome, dogwood, garlic, American ginseng, sophora flavescens, dried orange peel and burdock and the like. At the present stage, no direct and effective treatment method is available for eradicating colorectal cancer on the basis of not causing trauma to the organism of a patient, so that the search for a safe and effective medicament with small toxic and side effects and remarkable efficacy is a problem to be solved urgently in clinic.

The compound phellodendron amurense liquid liniment has the quality standard recorded in 'Chinese pharmacopoeia' 2015 edition, has the effects of resisting gram-positive bacteria, diminishing inflammation and promoting wound healing, and also has the effects of enhancing the phagocytic function of mononuclear macrophages and improving nonspecific immunity. The medicine is composed of five medicines of fructus forsythiae, golden cypress, honeysuckle, dandelion, centipede and the like, and has strict composition, precise monarch, minister, assistant and guide and precise and appropriate compatibility. Fructus forsythiae is a sore house holy drug, cortex Phellodendri can eliminate dampness and swelling of lower jiao, and the two drugs are monarch drugs; the ministerial drug honeysuckle is the essential drug for treating 'swelling due to overstaffed, furuncle and sore yang syndrome'; the adjuvant drug dandelion is a good product for clearing heat and removing toxicity, eliminating carbuncle and furuncle; so Wu Gong is an emotional herb for blood and meat, and can eliminate all sores and ulcers by counteracting toxic pathogen and dissipating nodulation. The medicines are combined to play the efficacies of clearing away heat and toxic material, and eliminating swelling and removing putrefaction. The compound phellodendron bark liquid liniment is currently applied to departments comprising dermatology, surgery, obstetrics and gynecology, pediatrics, wound repair center, radiation center and the like. The Chinese patent medicine clinical application guide, the anorectal disease booklet, the Chinese and western medicine combined diagnosis and treatment public opinion for ulcerative colitis and the like indicate that the compound phellodendron bark liquid liniment has obvious effect on treating perianal and perirectal abscess and ulcerative colitis in anorectal department. The compound phellodendron bark liquid liniment for treating perianal abscess and ulcerative colitis plays a role in treatment by inhibiting bacteria, diminishing inflammation, promoting granulation tissue growth and promoting wound healing. At present, the mechanism of treating colorectal cancer by traditional Chinese medicine is to induce apoptosis, inhibit cell proliferation, block cell cycle, influence invasion and metastasis of cancer cells, inhibit tumor neovascularization and regulate the immune function of organisms. Therefore, the traditional Chinese medicine for treating the inflammation can not be used for treating the cancer, and the effect can not be known definitely, and in addition, the traditional Chinese medicine for treating the colorectal cancer has the problems of limited inhibition effect and difficult control of cancer rate, and the effect is not ideal. Through the research of the prescription, no report that the compound phellodendron bark liquid liniment can be directly used for preventing and treating the colorectal cancer exists at present.

Disclosure of Invention

The invention provides an application of a compound phellodendron composition in preparing a medicine for preventing and treating colorectal cancer, which can inhibit the growth of intestinal cancer cells, reduce the cancer rate and has obvious effects of preventing and treating colorectal cancer, and solves the problems in the prior art.

The technical scheme adopted by the invention is as follows:

application of a compound cortex Phellodendri composition in preparing medicine for preventing and treating colorectal cancer is provided.

Application of a compound cortex Phellodendri composition in preparing medicine for promoting colorectal cancer induced inflammatory cytokine expression inhibition is provided.

Preferably, the compound phellodendron composition is a tablet, a capsule, a granule, a suppository, a gel, enema or a flushing agent; preferably enema.

Preferably, the compound phellodendron composition is an enema prepared by adding conventional auxiliary materials.

Preferably, the compound phellodendron composition is prepared by the following steps: decocting fructus forsythiae, cortex Phellodendri, flos Lonicerae, herba Taraxaci and Scolopendra with water for three times, mixing decoctions, filtering, concentrating the filtrate to obtain fluid extract, adding ethanol, standing, filtering, concentrating the filtrate under reduced pressure until no ethanol smell exists, adding water to 1000ml, stirring, standing, refrigerating, filtering, and sterilizing.

Preferably, the specific operation of adding water and decocting for three times is as follows: the first time is 1h, the second time is 45min, the third time is 30min, and the decoction is merged and filtered; the clear paste is clear paste with the relative density of 1.10-1.15(50 ℃); the ethanol is added in an amount to achieve an ethanol content of 70%.

Preferably, the compound phellodendron composition comprises the following active ingredients in parts by weight: 80 parts of fructus forsythiae, 40 parts of golden cypress, 40 parts of honeysuckle, 40 parts of dandelion and 2.4 parts of centipede.

Further, the colorectal cancer is inflammatory bowel disease induced colorectal cancer.

Further, the colorectal cancer is colorectal cancer induced by carcinogenic factor Azoxymethane (AOM) in the presence of Dextran Sulfate Sodium (DSS).

The invention has the beneficial effects that:

the invention provides a new application of a compound phellodendron composition in a medicine for preventing and treating colorectal cancer, which can overcome the defects of drug resistance, easy transfer, easy relapse, high toxicity, difficult tolerance, poor quality of life of patients, high cost and the like after the existing colorectal cancer operation treatment and radiotherapy and chemotherapy treatment. Can improve the survival rate and the life quality of the patients without operations. Through specific experimental study, the compound phellodendron composition has obvious effects on preventing and treating colorectal cancer, can well inhibit the growth of colorectal cancer cells and reduce the cancer rate, and provides a new medication idea for the treatment of colorectal cancer at present.

Drawings

FIG. 1 is the model establishment of AOM/DSS-induced colorectal cancer of the present invention;

FIG. 2 is a graph showing the flow data of mouse spleen CD4+ T cells in AOM/DSS-induced colorectal cancer model of the present invention;

FIG. 3 is a flow data result of mouse spleen regulatory T cells in AOM/DSS-induced colorectal cancer model of the present invention;

FIG. 4 is the flow data of mouse mesenteric lymph node CD4+ T cell in AOM/DSS-induced colorectal cancer model of the present invention;

FIG. 5 shows the flow data of mouse mesenteric lymph node regulatory T cells in AOM/DSS-induced colorectal cancer model of the present invention;

FIG. 6 shows the data of the number of intestinal tumors in mice in the AOM/DSS-induced colorectal cancer model group according to the present invention;

FIG. 7 is a picture of intestinal staining of mice in AOM/DSS-induced colorectal cancer phellodendron bark liquid group according to the present invention;

FIG. 8 is a photograph of intestinal staining of mice in the AOM/DSS-induced colorectal cancer model group according to the present invention;

FIG. 9 is a graph showing the body weight change trend of mice in the white control group, the phellodendron bark liquid stock solution group and the phellodendron bark liquid 10 times concentrated solution group in the toxicity test of the present invention;

FIG. 10 shows the morphological changes of the blank control group, the original liquid of Phellodendri cortex solution, and the 10-fold concentrated liquid of Phellodendri cortex solution in the toxicity test of the present invention.

Detailed Description

In order to clearly explain the technical features of the present invention, the following detailed description of the present invention is provided with reference to the accompanying drawings.

EXAMPLE 1 preparation of Compound cortex Phellodendri composition

The raw material medicine comprises the following components: 80g of fructus forsythiae, 40g of golden cypress, 40g of honeysuckle, 40g of dandelion and 2.4g of centipede;

the preparation method comprises the following steps: decocting the five medicines in water for three times, the first time is 1 hour, the second time is 45 minutes, the third time is 30 minutes, combining the decoction, filtering, concentrating the filtrate to obtain clear paste with the relative density of 1.10-1.15(50 ℃), adding ethanol to ensure that the ethanol content reaches 70%, standing for 24 hours, filtering, concentrating the filtrate under reduced pressure until no ethanol smell exists, adding water to 1000ml, stirring uniformly, standing, refrigerating for 24 hours, filtering, filling, and sterilizing to obtain the traditional Chinese medicine.

Example 2 application of Compound cortex Phellodendri composition in the treatment of early stage colon cancer

1. Influence of compound cortex phellodendri composition on mouse weight and immunocyte

The experimental animal is an SPF grade C57B L/6 mouse, the weight is 17-19g, the license number is SCXK (Jing) 2016-.

Model establishment As shown in FIG. 1, 6-8 week-old C57B L/6 mice were intraperitoneally injected with Azoxymethane (AOM) solution 10mg/kg on the first day, and allowed to drink freely on days 7-14, and 2% Dextran Sulfate Sodium (DSS) was prepared instead of distilled water, and allowed to drink freely on days 15-28, and 2% DSS was replaced with distilled water, 2% DSS was allowed to drink freely on

days

7 and 14 days distilled water were circulated, and 2 cycles were repeated, and the mice were treated after the experiment on day 70.

Administration treatment: the normal group is not molded; the model group was given Phosphate Buffered Saline (PBS) enema, 0.3 ml/tube/day; the cortex Phellodendri liquid group is subjected to enema with ten times of neutral concentrated compound cortex Phellodendri liquid, and the dosage is 0.3 ml/day.

The administration time is as follows: the administration is started on the first day and is continued every other day until the end of the molding.

The experimental results are as follows: compared with the normal group, the model group and the phellodendron bark liquid group have lower weight growth tendency, and the phellodendron bark liquid group is superior to the model group in the later molding period.

Spleen red blood cells of a model group mouse are taken for lysis, and immune cell change is detected in a flow mode, and the result shows that (as shown in figure 2) helper T lymphocytes (Th) are reduced compared with normal group mice; a significant increase in the proportion of Th1 helper cells, suggesting a significant increase in pro-inflammatory factors in colorectal cancer; the increased proportion of Th22 helper cells suggests an increase in immune cells in the body, which are monitored and coordinated, and that the tissues are in an inflammatory and infectious state.

As can be seen from fig. 3, Regulatory T cells (Tregs) were significantly enhanced; the significance of the negative CD4+ T cells is reduced, and the significance of the effector CD4+ T cells is increased, which indicates that the body of the mouse with colorectal cancer is seriously invaded.

Taking the intestinal lymph nodes of the mice in the model group, and carrying out flow detection on immune cell change, wherein the result shows that T lymphocytes and helper T lymphocytes are obviously reduced compared with the mice in the normal group (as shown in figure 4); inhibits the expression of helper T lymphocytes in colorectal cancer; the Th2 subtype cells were significantly reduced, suggesting that the expression of anti-inflammatory cytokines was suppressed in colorectal cancer mice. As can be seen in fig. 5, the immune cells in the intestinal lymph nodes did not change as significantly as the immune cells in the spleen.

The spleen and the intestinal lymph nodes of the mice treated by the compound cortex phellodendri composition are taken, and immune cells are detected by flow detection (figure 2-figure 5), so that the content of helper T cells in the spleen of the model group and the compound cortex phellodendri liquid group is increased compared with that of the normal group, and the compound cortex phellodendri liquid group is higher than that of the model group. The regulatory T cell phellodendron liquid group is higher than the model group. In the intestinal lymph nodes, the helper T cell compound phellodendron bark liquid group is slightly lower than the model group, and the regulatory T cell is higher than the model group. Specific data are shown in tables 1 and 2.

Table 1 statistical table of mouse spleen flow data results in AOM/DSS induced colorectal cancer model

Table 2 statistical table of flow data results of mouse intestinal lymph nodes in AOM/DSS induced colorectal cancer model

The results show that the compound phellodendron composition can better relieve colorectal cancer to a certain extent and improve the survival quality of mice.

2. The prevention and treatment effects of the compound phellodendron composition enema on AOM/DSS induced colorectal cancer model mice are as follows:

Model establishment Using 6-8 week old C57B L/6 mice, the first week was intraperitoneally injected with Azoxymethane (AOM) solution 10mg/kg and made 2% Dextran Sulfate Sodium (DSS) for free drinking for one week, the second and third weeks were made free drinking by replacing 2% DSS with distilled water, the fourth week was given 2% DSS again for one week, the fifth and sixth weeks were made free drinking by replacing 2% DSS with distilled water, the seventh week was given 2% DSS for one week, and the eighth to twelfth weeks were made free drinking by replacing 2% DSS with distilled water.

The statistics of the pre-colorectal cancer atypical hyperplasia and the cancer rate are shown in the following table 1:

TABLE 3 statistical table of in vivo pre-colorectal cancer atypical hyperplasia occurrence and cancer Rate (in percent)

As can be seen from the statistical table, the compound cortex phellodendri composition can obviously inhibit severe atypical hyperplasia and tumor incidence of a model group.

The intestinal tract of the mouse is taken and stained with methylene blue, the intestinal tumor is observed, the result of the model group is shown in figure 6, the average number of the tumors in the small intestine of each mouse is 6, and the tumors in the small intestine of each mouse are about 5-8, which are better to be emitted to the middle of the far-end rectum and the colorectal, grow regionally and are accompanied by a plurality of fine tumor particles. Compared with the model group (fig. 8), the phellodendron amurense liquid group (fig. 7) has a smaller degree of intestinal damage and has a better significance on the number and size of tumors than the model group.

The results show that the compound phellodendron composition has good prevention and treatment effects on colorectal cancer induced by inflammatory bowel diseases.

Example 3 test of toxicity of Compound cortex Phellodendri composition on mice

The experimental animal is SPF grade C57B L/6 mouse, the weight is 17-19g (8-10weeks), the license number is SCXK (Beijing) 2016-.

The experimental steps are as follows: mice were divided into three groups: blank control group, cortex Phellodendri original solution group (pH4.4), and 10 times concentrated solution group (pH7) of cortex Phellodendri solution, each group has 5 pieces, cortex Phellodendri solution group is treated by enema with 0.3 ml/piece/day to 7 days, blank control group is not treated, and weight is measured and recorded every day for 10 days.

Observation indexes are as follows: 1. body weight change index.

2. Physiological and biochemical indexes of the mouse.

3. Morphological changes of organs.

The experimental results are as follows: 1. the trend of weight change: as shown in fig. 9, in the experiment, there was no abnormal change in water drinking, food intake, excretion, mental status, etc. in each group of mice, and there was no significant difference (p <0.05) in the phellodendron amurense liquid group compared with the blank control group.

2. Influence of physiological and biochemical indexes of mice:

as shown in table 4, no significant difference was observed between the mice in blood, such as glutamic-pyruvic transaminase, albumin, serum urea nitrogen, total protein, and creatinine, and the compound cortex Phellodendri liquid group compared with the blank control group (p > 0.05).

TABLE 4 Effect of the Compound Phellodendri cortex composition on the Biochemical index of blood of mice

As shown in Table 5, there was no significant difference in the blood erythrocytes, leukocytes, platelets, lymphocytes, etc. of the mice, and the compound phellodendron amurense extract group compared with the blank control group (p > 0.05).

TABLE 5 Effect of the Compound cortex Phellodendri composition on the physiological indices of mice

3. Morphological changes of mouse organs:

after the mice are killed after dislocation, the liver, spleen, kidney and heart of the mice are quickly weighed, and the weighing data of the mice are recorded. As shown in fig. 10: compared with the blank control group, the cortex phellodendri liquid group has no significant difference in the organs of the mice (p > 0.05).

And (4) conclusion: through the detection of the weight change of the mouse, the physiological and biochemical indexes of the blood of the mouse and the weighing of the visceral organs of the mouse,

the results give: the compound cortex Phellodendri composition has no toxic effect on mice.

The above-described embodiments should not be construed as limiting the scope of the invention, and any alternative modifications or alterations to the embodiments of the present invention will be apparent to those skilled in the art.

The present invention is not described in detail, but is known to those skilled in the art.

Claims

1. Application of a compound cortex Phellodendri composition in preparing medicine for preventing and treating colorectal cancer is provided.

2. Application of a compound cortex Phellodendri composition in preparing medicine for promoting the expression of inflammatory cytokine induced by colorectal cancer is provided.

3. The use of claim 1 or 2, wherein the compound cortex Phellodendri composition is in the form of tablet, capsule, granule, suppository, gel, enema, or rinse; preferably enema.

4. The use of claim 1 or 2, wherein the compound cortex phellodendri composition is prepared by the following steps: decocting fructus forsythiae, cortex Phellodendri, flos Lonicerae, herba Taraxaci and Scolopendra with water for three times, mixing decoctions, filtering, concentrating the filtrate to obtain fluid extract, adding ethanol, standing, filtering, concentrating the filtrate under reduced pressure until no ethanol smell exists, adding water to 1000ml, stirring, standing, refrigerating, filtering, and sterilizing.

5. The use as claimed in claim 4, wherein the three times of decoction with water comprises the following specific operations: the first time is 1h, the second time is 45min, the third time is 30min, and the decoction is merged and filtered; the clear paste is clear paste with the relative density of 1.10-1.15(50 ℃); the ethanol is added in an amount to achieve an ethanol content of 70%.

6. The use of claim 1 or 2, wherein the compound cortex phellodendri composition comprises the following effective components in parts by weight: 80 parts of fructus forsythiae, 40 parts of golden cypress, 40 parts of honeysuckle, 40 parts of dandelion and 2.4 parts of centipede.

7. Use according to claim 1 or 2, wherein the colorectal cancer is inflammatory bowel disease induced colorectal cancer.

8. The use according to claim 7, wherein the colorectal cancer is colorectal cancer induced by Azoxymethane (AOM), a carcinogen, in the presence of Dextran Sulfate Sodium Salt (DSS), an inflammatory factor.