CN106728019B

CN106728019B - Traditional Chinese medicine composition for treating colorectal cancer and application thereof

Info

Publication number: CN106728019B
Application number: CN201710010967.1A
Authority: CN
Inventors: 孙学刚; 刘亚飞; 代宇
Original assignee: Southern Medical University
Current assignee: Southern Medical University
Priority date: 2017-01-06
Filing date: 2017-01-06
Publication date: 2020-06-30
Anticipated expiration: 2037-01-06
Also published as: CN106728019A

Abstract

The invention discloses a traditional Chinese medicine composition for treating colorectal cancer and application thereof, wherein the traditional Chinese medicine composition is prepared from the following traditional Chinese medicinal materials in parts by weight: the Chinese ash plant (15-25): 20-30) is the mother material of hard charcoal. The application of the traditional Chinese medicine composition in preparing the medicine for treating the rectal cancer has the efficacy of treating CRC, the treatment effect is good, the safety and the reliability are realized, and the traditional Chinese medicine is adopted, so that the raw materials are easy to obtain.

Description

Traditional Chinese medicine composition for treating colorectal cancer and application thereof

Technical Field

The invention relates to the field of medicines, in particular to a traditional Chinese medicine composition for treating colorectal cancer and application thereof.

Background

Colorectal cancer (CRC) is one of the common digestive tract tumors. The predicted data of the cancer in the U.S. in 2013 shows that the number of new cases and deaths of CRC are 142820 cases and 50830 cases respectively, and the new cases and deaths of the cancer are 3 rd of all types of cancer, and account for about 9 percent of the cases respectively. In recent 10 years, the incidence and mortality of colorectal cancer worldwide have been substantially stabilized, but the incidence and mortality of malignant tumors worldwide have increased. The regional distribution difference of colorectal cancer is large, and the incidence rate of colorectal cancer in developed areas is high. China is a low incidence area of colorectal cancer, but the incidence rate is on the trend of rising year by year. By 2010, the number of new cases of colorectal cancer in China is over 27 ten thousand, and more than 13 ten thousand of death cases.

CRC belongs to the categories of Fulian, intestinal and ovarian cyst in traditional Chinese medicine. There is a long history of diagnosis and treatment of CRC with traditional Chinese medicine. Su Wen (plain questions) recorded that the disease names such as bent over roof beam, pus and blood in the lower intestine , cold qi staying outside the intestine, struggling with the defensive qi, qi failing to nourish, and pathogenic factors attacking the interior, bad qi attacking the interior, and polyp growing, which indicates that the disease is related to improper diet, invasion of exogenous pathogenic factors, disharmony of nutrient and defensive factors, and injury of the five internal organs. Spleen deficiency is the root of tumor formation, and Zhang Yuan element (the main cause of the exercise) is recorded as: "strong without accumulation, deficient people with deficiency of spleen and stomach, qi and blood deficiency, and feeling in four seasons, all can become accumulation", Jingyue quan Shu (Jingyue quan Shu) has: the patients with spleen-kidney deficiency and weakness disorder have accumulated diseases; many famous old Chinese medicine have suggested that spleen strengthening should be the basis for preventing and treating tumor.

Therefore, the traditional Chinese medicine is combined with the modern preparation technology, and the traditional Chinese medicine compound preparation for treating CRC is researched and developed, so that the preparation has important significance and also has huge market development potential.

Disclosure of Invention

The invention aims to provide a traditional Chinese medicine composition for treating colorectal cancer, which has a remarkable curative effect.

The invention also aims to apply the traditional Chinese medicine composition to the preparation of medicines for treating colorectal cancer.

In order to achieve the purpose, the invention adopts the following technical scheme: a traditional Chinese medicine composition for treating colorectal cancer is prepared from the following traditional Chinese medicinal materials in parts by weight: the Chinese ash plant (15-25): 20-30) is the mother material of hard charcoal.

Preferably, the traditional Chinese medicine composition is prepared from the following traditional Chinese medicinal materials in parts by weight: the Chinese ash plant (17-22) and (22-28) are used as the Chinese ash plant mother material.

More preferably, the traditional Chinese medicine composition is prepared from traditional Chinese medicine extracts and traditional Chinese medicinal materials in the following weight ratio: the Chinese ash wood is 19: 25.

The application of the traditional Chinese medicine composition in preparing a medicine for treating colorectal cancer.

The dosage form of the medicine is decoction, tablets, capsules or granules.

The medicine is prepared by decocting the Chinese medicinal materials in the formula of the Chinese medicinal composition with water.

The medicine, tablets, capsules and granules are prepared by taking extracts of components in the formula of the traditional Chinese medicine composition as effective components and adding pharmaceutic adjuvants.

The extract is an aqueous extract.

The traditional Chinese medicine composition provided by the invention has the efficacy of treating CRC, has a good treatment effect, is safe and reliable, and adopts traditional Chinese medicines, so that the raw materials are easy to obtain.

Drawings

FIG. 1 is a graph showing the effect on body weight of a mouse in an experimental example of the present invention;

FIG. 2 is a visual chart of colon tumors of each group of mice in the experimental example of the present invention, wherein A is a visual chart of ex vivo tumors, and B is a visual chart of in vivo tumors;

FIG. 3 is a graph showing the size and weight of colon tumors in mice in an experimental example of the present invention, wherein A is a graph showing the size of tumors and B is a graph showing the weight of tumors;

FIG. 4 shows the WB assay to determine the effect of the present invention on apoptosis-related protein expression;

FIG. 5 is an IHC assay to examine the effect of the present invention on apoptosis-related protein expression;

FIG. 6 shows the ratio of MDSCs cells in the spleen of each group of mice in the experimental example of the present invention;

in the above figures, C is the control group, L is the low dose group, M is the medium dose group, H is the high dose group, and S is the cisplatin group (i.e., positive drug control group).

Detailed Description

The invention relates to a traditional Chinese medicine composition for treating CRC, which is prepared from the following traditional Chinese medicinal materials in parts by weight: the Chinese ash plant (15-25): 20-30) is the mother material of hard charcoal. Preferably, the traditional Chinese medicine composition is prepared from the following traditional Chinese medicinal materials in parts by weight: the Chinese ash plant (17-22) and (22-28) are used as the Chinese ash plant mother material. More preferably, the traditional Chinese medicine composition is prepared from the following traditional Chinese medicinal materials in parts by weight: the Chinese ash wood is 19: 25.

The prescription takes the hard-bristle Chinese knotweed herb as the monarch drug, and has the effects of clearing heat, promoting diuresis, cooling blood and detoxifying; kalopanax pictus nakai is used for assisting the monarch drug to cool blood, remove stasis, expel wind and remove dampness. Simple and effective, and has the effect of eliminating tumor.

The traditional Chinese medicine used by the invention comprises the following components:

the Polygonum cuspidatum is a variant of Polygonum cuspidatum chinensis Linn, belonging to the genus Polygonum of the family polygonaceae, the rhizome of the Polygonum cuspidatum is used as a medicine, has sour, sweet and cold properties, has the effects of clearing heat, promoting diuresis, cooling blood and detoxifying, and is used for damp-heat diarrhea, dysentery, jaundice and sore throat.

The Kalopanax Septemlobate is Root or bark Root of Kalopanax Septemlobate of Araliaceae. Bitter taste, cold nature and no toxicity. It enters spleen and stomach meridians. Has effects in cooling blood, removing blood stasis, dispelling pathogenic wind, and removing dampness. It is indicated for hemorrhoid, traumatic injury, and rheumatic osteodynia. The root contains polysaccharide, and is hydrolyzed to obtain galacturonic acid, glucose, arabinose, galactose, rhamnose, and xylose. The water-soluble polysaccharides include dextran and pectin. Has antitumor and immunity enhancing effects.

The application of the traditional Chinese medicine composition in preparing a medicine for treating colorectal cancer. The dosage form of the medicine can be oral dosage forms such as decoction, tablets, capsules or granules. The decoction is prepared by decocting the Chinese medicinal materials in the formula of the Chinese medicinal composition with water. The tablet, capsule and granule are prepared by taking the extract of the components in the formula of the traditional Chinese medicine composition as an effective component and adding pharmaceutic adjuvants, preferably, the extract is an aqueous extract and is prepared by a conventional aqueous extraction process.

The present invention will be further described with reference to the following examples, but the present invention is not limited to these specific examples.

Example 1

Putting 19g of Chinese knotweed herb and 25g of kalopanax septemlobus into a medicine pot, adding cold drinking water, soaking for 20-30 minutes, adding water to submerge the medicines, putting the medicine pot on a furnace fire, and decocting with medium fire. After the first decoction, pouring out the liquid medicine (about 150-200 ml), adding a proper amount of warm water (if the medicine residue is cooled and decocted again, cold water should be added), carrying out the second decoction, pouring out the liquid medicine (about 150-200 ml), and mixing the liquid medicines for two times for taking for 2 times.

Example 2

Soaking 190g of Chinese knotweed herb and 250g of kalopanax septemlobus in 10 times of water for 45min, extracting for 2 times for 90min each time, filtering, combining filtrates, concentrating to obtain paste (1.05-1.10, 70 ℃), drying by belt type, sieving with a 14-mesh sieve, granulating, adding an appropriate amount of magnesium stearate, mixing uniformly, and pressing into 66 tablets to obtain the tablet. Each tablet weighs 0.45 g.

Example 3

Soaking 190g of Chinese scholar tree herb and 250g of kalopanax septemlobus in 10 times of water for 45min, extracting for 2 times, each time for 90min, filtering, combining filtrates, concentrating to paste (1.05-1.10, 70 ℃), drying in a belt type manner, crushing, adding 2% of magnesium stearate, filling into capsules, and preparing into 66 capsules to obtain the hard capsules. Each granule contains 0.45g of content.

Example 4

Soaking 190g of Chinese knotweed and 250g of kalopanax septemlobus in 10 times of water for 45min, extracting for 2 times, each time for 90min, filtering, combining filtrates, concentrating to obtain paste (1.05-1.10, 70 ℃), drying by belt type, grinding into fine powder, adding an appropriate amount of dextrin and lactose, mixing uniformly, granulating, drying at 65 ℃, sieving by a 14-mesh sieve, grading, subpackaging, and preparing 66 bags to obtain the granules. Each bag weighs 5 g.

Example 5

185g of Chalcanthitum and 255g of Kalopanax pictus nakai were used to prepare tablets by the method of example 2.

Example 6

175g of Chalcanthitum and 265g of Kalopanax pictus nakai were taken and tablets were prepared by the preparation method of example 2.

Example 7

184g of Chalcanthitum and 256g of Kalopanax pictus nakai were taken and tablets were prepared by the method of example 2.

Example 8

173g of Chinese knotweed herb and 267g of Kalopanax pictus nakai were used to prepare tablets by the method of example 2.

Example 9

187g of Chinese knotweed herb and 253g of Kalopanax pictus nakai were taken, and tablets were prepared by the method of example 2.

Experimental example (study of therapeutic Effect on CRC)

1. Material

1.1 animals: athymic Nude mice (Nude Mouse for short) were purchased from the animal center of university of Zhongshan and bred in the SPF animal house of Jiu building, laboratory building of southern medical university. Mouse body weights and numbers were recorded before the experiment began.

1.2 reagent: 19g of Chinese knotweed and 25g of Kalopanax pictus nakai were purchased from southern Hospital attached to southern medical university according to example 1. Decocting twice by conventional water decoction method. Putting the medicine into a medicine pot, adding cold drinking water, soaking for 20-30 minutes, adding water to submerge the medicine, and putting the medicine pot on an electric furnace for decocting. After the first decoction, pouring out the liquid medicine (about 150-200 ml), adding a proper amount of warm water (cooling water should be added when the medicine residue is cooled and decocted again), carrying out the second decoction, pouring out the liquid medicine (about 150-200 ml), uniformly mixing the liquid medicine obtained in the two times, and subpackaging at-20 ℃ for later use.

2. Method of producing a composite material

2.1 grouping and dosing: the experimental animals were divided into 5 groups, 9 control groups, 9 high dose groups (1.1g/ml), 9 medium dose groups (0.55g/ml), 9 low dose groups (0.275g/ml), and 9 cis-platinum groups (1mg/ml), and each group of nude mice was administered the prepared liquid medicine by gavage according to the 0.2ml/d standard.

2.2 sampling:

the experimental nude mice are normally bred for 3 days after the orthotopic transplantation of the intestinal cancer tumor to adapt to the environment, free food and water are supplied, and the administration is started on the 4 th day. The weight and feed intake changes of the mice were monitored every 3 days during the experiment, the general conditions of the mice such as hair, activity, hematochezia, morchella removal and the like were observed, and the death of the mice was recorded.

And finishing the experiment after 3 weeks of administration, weighing and recording the weight, taking blood by using eyeballs, standing the blood for 2 hours, centrifuging for 15min at 3000r/min, taking supernatant, and subpackaging in an EP (ethylene propylene) tube at-80 ℃ for subsequent detection of the cell factors. Then, the mice were sacrificed by cervical dislocation, the abdominal cavity and the thoracic cavity of the mice were cut off, tissues such as liver, lung, spleen, and tumor were taken, and the taken-out materials were washed with pre-cooled physiological saline. Sucking the residual physiological saline on each tissue by using clean filter paper, equally dividing each tissue into a plurality of equal parts, wherein the tissue for pathological study is immediately put into a 4% neutral formalin solution for fixation, and the rest tissues are separately stored in a freezing tube at-80 ℃ for subsequent experimental study.

2.3 statistical treatment: all data are in mean ± sd

Showing that statistical processing is analyzed by using the sps 22.0 software when P is<There was a statistical difference at 0.05.

3 results

3.1 Effect on CRC mouse body weight:

after each group of mice was treated for 3 weeks according to the dosing schedule, the control group had 9, the high dose group had 7, the medium dose group had 9, the low dose group had 7, and the positive drug control group had 7. The high, medium and low dose groups have no significant difference with the control group, and have significant difference with the positive drug control group, and the result is shown in figure 1.

3.2 effects on CRC mouse tumors:

at the end of the experiment, each group of tumors was removed, weighed and photographed. The tumor reduction was more evident in the high dose group than in the other groups, see FIG. 2. Tumor weights were significantly lower in the high dose groups compared to each group. Tumor size was significantly smaller in the high dose group than in each group. See fig. 3. Thus, the invention can obviously inhibit the development of colon tumor.

3.3 promoting expression of apoptosis-related protein in CRC mice

PARP, Bax and Caspase9 are all related proteins for detecting tumor cell apoptosis. Western Blot (WB) results show: PARP, Bax, Caspase9 expression in the tumor tissues of the mice in the high dose and medium dose groups was significantly increased (P <0.01) compared to the control group, while PARP, Bax, Caspase9 expression in the tumor tissues of the mice in the low dose group was similar to the control group (P <0.01), and the results are shown in fig. 4. Immunohistochemistry (IHC) results were similar to Western Blot (WB) results, which are shown in fig. 5. Therefore, the invention can promote the expression of the apoptosis-related protein of the CRC mouse.

3.4 anti-cancer action by immunomodulation

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells derived from bone marrow, are precursors of Dendritic Cells (DCs), macrophages and/or granulocytes, and have the ability to significantly suppress immune cell responses. The phenotype of mouse MDSCs is CD11b + Gr-1-, divided into two subtypes, granulocyte-like MDSCs (CD11b + Ly6C-Ly6G +) and monocyte-like MDSCs (CD11b + Ly6C + Ly 6G-). MDSCs are defined in human as Lin-HLA-DR-CD33+ or CD11b + CD14-CD33 +. MDSCs exert immunosuppressive functions primarily through the production of Arg-1, iNOS (NOS2) and ROS. Under normal physiological conditions, CD11b + Gr-1+ cells account for 20% -30% of normal mouse bone marrow, and only a small amount (2% -4%) of cells exist in spleen, but are not distributed in lymph nodes and do not have immunosuppressive ability. In pathological conditions, particularly in the case of tumorigenesis, a large number of immature cells accumulate in various organs, and the normal immune function of T cells of the body is inhibited through direct cell-to-cell contact or secretion of factors.

MDSCs from spleen of mice were tested and found to have significantly increased proportion of MDSCs cells in spleen of mice in high dose group (P <0.01) compared to normal group mice, and significantly decreased proportion of MDSCs cells in spleen of mice in high dose group (P <0.01) compared to the rest of the groups, and the results are shown in FIG. 6. The invention proves that the invention plays a role in resisting cancer by influencing immune regulation.

4. Conclusion

The invention can influence the immune regulation by promoting the expression of apoptosis-related protein of CRC mice, thereby playing the role of anticancer.

Claims

1. The application of a traditional Chinese medicine composition in preparing a medicine for treating colorectal cancer is disclosed, wherein the traditional Chinese medicine composition is prepared from the following traditional Chinese medicinal materials in parts by weight: the Chinese ash wood is 19: 25; the dosage form of the medicine is decoction, which is obtained by decocting the traditional Chinese medicines in the formula of the traditional Chinese medicine composition with water, or the dosage form of the medicine is tablets, capsules or granules, which is prepared by taking water extracts of the components in the formula of the traditional Chinese medicine composition as effective components and adding pharmaceutic adjuvants.