CN102309656B - Traditional Chinese medicine composition with effect of preventing and treating cancers and medicinal application of traditional Chinese medicine composition - Google Patents

Abstract

The invention discloses a composition with an effect of preventing and treating cancers. The composition is mainly prepared from the following Chinese herbal medicines in percentage by mass: 20 to 90 percent of airpotato yam rhizome and 10 to 80 percent of Chinese magnoliavine fruit. The Chinese medicinal composition has the effect of preventing and treating the cancers, can eliminate the limit that liver injury is easily induced by chemotherapeutic medicinal medicines, is suitable for treating various cancers such as liver cancer, gastric cancer, breast cancer, lung cancer, bladder cancer, ovarian cancer, prostate cancer, esophagus cancer, pancreatic cancer, colon cancer, colorectal cancer, skin cancer, thyroid cancer, cervical carcinoma, leukemia and the like, can be used for preparing anti-cancer medicaments, realizes the application of the airpotato yam rhizome and Chinese magnoliavine fruit compositions to the preparation of medicaments for treating the cancers, develops the application range and the medicinal value of the airpotato yam rhizome and the Chinese magnoliavine fruit and makes creative contribution to the development of traditional Chinese medicine.

Description

Traditional Chinese medicine composition with effect of preventing and treating cancer and its medical application

technical field

The invention relates to a traditional Chinese medicine composition capable of preventing and treating cancer. In addition, the invention also relates to the medical application of the traditional Chinese medicine composition.

Background technique

Cancer is one of the major diseases that seriously threaten human health and life. In the treatment of cancer, although the traditional radiotherapy and chemotherapy have made great progress, because it kills cancer cells, it also produces different degrees of toxic side effects on the human body, mainly bone marrow suppression and low immune function. Cause leukopenia, etc., sometimes even have to interrupt treatment, which also limits the efficacy of drugs. In order to overcome a series of ills caused by traditional radiotherapy and chemotherapy, pharmaceutical workers have been exploring continuously in recent years, and the application of herbal medicines to prevent and treat cancer has become a hot research field

Huangyaozi is the dry tuber of Dioscorea bulbifera L. in the Dioscoreaceae family. It is widely distributed in tropical and subtropical regions of Asia, and also exists in some parts of Africa. It is traditionally used as a medicine mainly in China. As early as 500-600 AD, xanthate seed powder, decoction or tincture had been used in the treatment of diseases such as goiter (tumor), gastric cancer, rectal cancer, sore throat, pharyngitis, uterine bleeding in modern medicine, and Among them, the treatment of goiter (tumor) and multiple types of cancer is the most commonly used; in modern clinical practice, xanthate is often used for esophageal cancer, gastric cancer, liver cancer, rectal cancer, breast cancer, lung cancer, cervical cancer, nasopharyngeal cancer, maxillary sinus cancer , bladder cancer and other types of cancer treatment.

Compatibility is one of the characteristics of traditional Chinese medicine, through compatibility can play a synergistic effect. After consulting related materials, the inventor found that xanthate chinensis and schisandra chinensis are often used in combination. Therefore, it is the main focus of the present invention to find a safe and effective drug for preventing and treating cancer through the compatibility of xanthophyll fruit and schisandra chinensis.

Contents of the invention

The technical problem to be solved by the present invention is to provide a traditional Chinese medicine composition capable of preventing and treating cancer. The traditional Chinese medicine composition is a broad-spectrum anticancer agent.

Another technical problem to be solved by the present invention is to propose the application of the traditional Chinese medicine composition in the preparation of medicines for preventing and treating cancer diseases.

In order to solve the above-mentioned technical problems, the traditional Chinese medicine composition with the effect of preventing and treating cancer proposed by the present invention is mainly prepared from the following raw materials in mass percentages: 20%-90% xanthate chinensis and 10%-80% schisandra chinensis.

There is nothing special about the preparation process of the traditional Chinese medicine composition with anti-cancer effect of the present invention. The Xanthium chinensis tubers and Schisandra chinensis roots are powdered separately, extracted with water, 20% to 95% ethanol, acetone, ethyl acetate, gasoline or petroleum ether, and added with common pharmaceutical excipients to make any pharmaceutical dosage form, preferably soaked Ointment, liquid extract, liquor, tincture, oral liquid, pill, powder, dropping pill, tablet or capsule.

The anti-cancer effect of the traditional Chinese medicine composition of the present invention is likely to be closely related to the synergistic effect between the following substances: diterpene lactones in Xanthophyllum chinensis, especially Xanthomonas A, Xanthomonas B, Xanthomones C, Xanthosin D, Xanthosin E, Xanthosin F, Huangdusu G, Huangdusu H, Huangdusu I, Huangdusu J, Huangdusu K, Huangdusu L, Huangdusu M, and their derivatives, as well as lignin substances in Schisandra chinensis, especially Schisandra C, Schizandrin A, Schisandrin Alcohol B, Schizandrin A, Schisandrin B, Schisandrin C, Schisandrin A, and Schisandrin B.

Subsequent drug effect experiments will prove that the Chinese medicine composition of the present invention can replace chemotherapy drugs to prevent and treat liver cancer, gastric cancer, breast cancer, lung cancer, bladder cancer, ovarian cancer, prostate cancer, esophageal cancer, pancreatic cancer, large intestine cancer, colon cancer, skin cancer , thyroid cancer, cervical cancer, leukemia and other types of cancer diseases.

The traditional Chinese medicine composition of the invention is a pure natural plant extract that can be used both as medicine and food, and can prevent and treat cancer efficiently while avoiding the side effect of liver damage induced by chemotherapeutic drugs.

Detailed ways

The present invention is further described below in conjunction with specific examples. These examples should be understood as only for illustrating the present invention but not for limiting the protection scope of the present invention. After reading the contents of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent changes and modifications also fall within the scope defined by the claims of the present invention.

Example 1 (Ethanol Extract of Fructus Xanthophyllum, Ethanol Extract of Fructus Schisandra, and Composition of Ethanol Extract of Fructus Fructus Schizandra on the S180 Solid Tumor of Mouse Sarcoma)

The present invention first investigates the effect of the composition of ET and Schisandra ethanol extract (SE) on mouse sarcoma S180 solid tumor.

1.1 Experimental materials

1.1.1 Test animals

体重18～22g，购自上海斯莱克实验动物有限责任公司，动物合格证号：SCXK(沪2007-0005)。小鼠饲养温度(22±1)℃，相对湿度(65±10)％，照明时间每天12h。ICR mice,

Weight 18-22g, purchased from Shanghai Slack Experimental Animal Co., Ltd., animal certificate number: SCXK (Shanghai 2007-0005). The mice were reared at a temperature of (22±1)°C, a relative humidity of (65±10)%, and lighting time of 12 hours per day.

1.1.2 Test drug and its preparation

Ethanol extract (ET) of Xanthogonia chinensis tuber slices coarse powder, extracted three times with 10 times the amount of 80% ethanol for 3 hours each time, the filtrates were combined and then concentrated under reduced pressure until there was no alcohol smell. The ethanol extract of Xanthophylla ET was obtained.

Schisandra Alcoholic Extract (SE): use Schisandra coarse powder, extract three times with 10 times the amount of 70% ethanol, each time for 3 hours, combine the filtrates, concentrate under reduced pressure until there is no alcohol, and the concentration is 1g/mL based on the crude drug of Schisandra to obtain Schisandra Alcoholic extract SE.

Composition of Alcoholic Extract of Chrysanthemum Fructus Schizandra: Combining the Alcoholic Extract of Champagne Fructus and Schizandra Alcohol Extract at a ratio (weight ratio) of 1/1 to 4/1 to obtain the composition ET+SE of Alcoholic Extract of Chrysanthemum Fructus Schizandra.

1.2 Experimental method

Using in vivo experiments in tumor-bearing mice, the corresponding tumor cells were extracted from the abdomen of sarcoma S180 tumor-bearing mice, stained with trypan blue, counted, diluted with sterile saline to (1.0-1.3)×10 ⁷ cells/mL, and centrifuged Put the tumor cells in the tube into the right axilla of ICR mice by subcutaneously injecting (sc) the injection volume at 0.1 mL/mouse. Randomly grouped according to body weight, respectively Control (CMC-Na), 5-Fu, Schizandra alcohol extract SE, Xanthophyllum alcohol extract ET, ET+SE groups. Each extract or monomer compound was dissolved to the required concentration with 0.5% CMC-Na, and 24 hours after inoculation, it was administered by intragastric administration (ig) according to body weight, and the CMC-Na group was given 0.5% CMC-Na of the same volume as ig, 5-Fu (dissolved in dd water to 2.5 mg/mL) group was injected intraperitoneally (ip), injected once every other day; continuous administration for 12 days, 24 hours after the last administration, the eyeball was picked and blood was collected for centrifugation to separate the serum and then measure the serum ALT and AST activity; tumor tissue was taken, weighed, and photographed. The tumor inhibition ratio (Tumor inhibition ratio) was calculated according to the formula.

Tumor inhibition ratio (%)=[(C-T)/C]×100, wherein C refers to the average tumor weight of the CMC-Na control group, and T refers to the average tumor weight of the administration group. A significant difference in tumor weight and a tumor inhibition rate > 30% are the criteria for the drug to have anti-tumor activity.

1.3 Experimental results

1.3.1 Effect of ET, SE and their composition ET+SE on mouse sarcoma S180 solid tumor

Compared with the model group, as shown in Table 1, after 12 days of continuous administration of ET (100mg/kg) in mice inoculated with sarcoma S180, the tumor weight was significantly reduced (P<0.05), indicating that ET (100mg/kg) has a significant effect on S180 entities. Tumor is effective; compared with ET (100mg/kg), after compatibility with SE (100mg/kg), the tumor weight was significantly reduced (P<0.05), and the tumor inhibition rate was significantly improved, indicating that the alcohol extract of Schizandra chinensis can enhance the alcohol extract of Xanthophyllum chinensis. antitumor activity.

Table 1 ET, SE and its composition ET+SE are on the influence of mouse sarcoma S180 solid tumor (n=10)

Compared with model group, ^* P<0.05, ^** P<0.01; compared with ET, ^## P<0.01

1.3.2 Effects on serum biochemical indicators

It can be seen from Table 2 that the positive drug 5-Fu can significantly increase the serum liver damage indexes ALT and AST of S180 tumor-bearing mice (P<0.01), indicating that 5-Fu induces liver toxicity in tumor-bearing mice, while While maintaining the curative effect, the traditional Chinese medicine composition of the present invention has no obvious influence on the liver damage index, which shows that the traditional Chinese medicine composition of the present invention has the advantage of avoiding the side effect of liver damage induced by the chemotherapeutic drug 5-Fu.

)The influence of table 2 composition ET+SE on mouse sarcoma S180 serum biochemical index (n=10;

)

Compared with the model group, ^* P<0.05, ^** P<0.01

Example 2 (composition powder suspension, water extract, 70% ethanol extract, ethyl acetate extract, acetone extract, 120# gasoline extract, artificial gastric juice extract in vivo anti-tumor effect research)

After confirming that the ethanol extract composition of Chrysanthemum schisandrae has strong anti-S180 solid tumor effect, the present invention further investigates the in vivo anti-tumor effect of the suspension of the traditional Chinese medicine composition of the present invention and various extracts thereof.

2.1 Experimental materials

2.1.1 Test animals (same as 1.1.1 of Example 1)

2.1.2 Test drug and its preparation

The whole powder suspension of the composition: 36g of Xanthium chinensis and 36g of Schisandra chinensis, pulverized, passed through a 150-mesh sieve, and suspended in 180mL of distilled water.

Water extract of the composition: 54g of xanthophyll fruit, 18g of schisandra chinensis, add 10 times the amount of water, reflux extraction 3 times, 3 hours each time, filter and combine the filtrate, recover water to make the concentration 0.4g/mL.

Composition 70% ethanol extract: 54g xanthophylla chinensis, 18g schisandra chinensis, add 10 times the amount of 70% ethanol, reflux extraction 3 times, each time 3h, filter and combine the filtrates, recover ethanol to make the concentration 0.4g/mL.

Composition Ethyl acetate extract: 54g xanthophyll fruit, 18g schisandra chinensis, add 10 times the amount of ethyl acetate, reflux extraction 3 times, each time 3h, filter and combine the filtrate, recover ethyl acetate to make the concentration 0.4g/mL.

Composition Acetone extract: 54g xanthophylla chinensis, 18g schisandra chinensis, add 10 times the amount of ethyl acetate, reflux extraction 3 times, each time 3h, filter the combined filtrate, recover acetone to make the concentration 0.4g/mL.

Composition 120# gasoline extract: 54g xanthophyll fruit, 18g schisandra chinensis, add 10 times the amount of 70% ethanol, reflux extraction 3 times, each time 3h, filter and combine the filtrate, recover 120# gasoline to make the concentration 0.4g/mL.

Composition artificial gastrointestinal juice extract: 54g of xanthophylla chinensis, 18g of schisandra chinensis, add 10 times the amount of artificial gastric juice, shake on a shaker (simulating gastrointestinal peristalsis) for 4 hours, put the filtrate and dregs into 10 times the amount of artificial intestinal juice, and shake Shake on the bed for 4 hours, collect intestinal juice, and recover to make the concentration 0.4g/mL.

2.2 Experimental method (same as 1.2 of Example 1)

2.3 Experimental results

As shown in Table 3, compared with the model group, the tumor weights of each administration group were significantly reduced, indicating that the whole powder suspension and various extracts of the composition of Xanthomonas chinensis and Schisandra chinensis have anti-tumor effects, among which 70% ethanol extract and acetic acid Ethyl extract has the strongest effect; and the antitumor effect of the composition 70% ethanol and ethyl acetate extract is significantly stronger than that of the positive drug 5-Fu, while the composition acetone extract, full powder suspension, water The anti-tumor effect of the extract, acetone and gasoline extract is equivalent to that of 5-Fu.

Table 3 The influence of composition suspension and various extracts on sarcoma S180 solid tumor (n=10)

Compared with the model group, ^* P<0.05, ^** P<0.01

Embodiment 3 (in vitro anticancer activity research of Chinese medicine composition and active ingredient thereof)

Through whole animal experiments, it was found that the Chinese medicine composition of the present invention has an anti-tumor effect, and the inventors isolated the diterpene lactone component Furanoidin B (Kawasaki T, Komori T, Setoguchi S. Furanoidnorditerpenes from Dioscoreacae plants .1. Diosbulins A, B, and C from Dioscorea bulbiferaform a spontanea.Chem Pharm Bull, 1968; 16: 2430-2435.) (purity above 98%); lignin compounds contained in Schisandra schisandra C, Schisandrin A, Schisandrin B, Schizandrin A, Schisandrin B, Schisandrin C, Schisandrin A and Schisandrin B were all purchased from Shanghai Ronghe Pharmaceutical Technology Development Co., Ltd., with a purity of more than 95%. The inventor further investigated the anticancer activity of the traditional Chinese medicine composition of the invention and its active ingredients through in vitro experiments.

In the following, Schisandra C, which has the strongest synergistic effect on the active ingredient of Xanthin B among the lignin components of Schisandra chinensis, will be introduced as an example. Wherein, the chemical structures of Diosbulbin B (Diosbulbin B) and Schizandrin C (Schizandrin C) are as follows.

3.1 Experimental materials

3.1.1 Source of cell lines

Human liver cancer Hep3B, gastric cancer SGC-7901, pancreatic cancer BXPC-3, breast cancer MCF-7, lung cancer A549, bladder cancer T24 human ovarian cancer HO8910, colon cancer LS174, colorectal cancer CCL229, prostate cancer PC-3, esophageal cancer Eca- 109. Cell lines of skin cancer A431, thyroid cancer SW-579, leukemia K562 and cervical cancer Hela were purchased from Shanghai Institute of Cell Biology, Chinese Academy of Sciences.

3.1.2 Main reagents

Type IV collagenase (Sigma Company), DEME medium (GIBCO Company), fetal bovine serum (Hangzhou Sijiqing Biological Company), dimethyl sulfoxide (DMSO) (GIBCO Company), MTT (Sigma Company), protease inhibitors (Amresco), 5-Fu (Shanghai Bangcheng), and other reagents are of domestic analytical grade.

3.1.3 Main instruments and equipment

Laminar flow ultra-clean bench; carbon dioxide incubator, purchased from Thermo Company; inverted phase contrast microscope, purchased from Olympus Company; microplate reader, purchased from Biotek Company.

3.2 Experimental method

Cell proliferation test (MTT): cells were digested with 0.25% trypsin, centrifuged at 1000rpm, and cultured in DMEM high-sugar medium containing 5% activated carbon inactivated serum without phenol red at 37°C and 95% _CO2 for 48h (to exclude endogenous Hormone interference), that is, the cells enter the logarithmic growth phase, digest the cells with 0.25% trypsin, inoculate the cells on a 96-well culture plate at 2×10 ³ /well, the volume of each well is 180 μL, and the cells adhere to the wall for 24 hours. Set up 5 duplicate wells, respectively set solvent control, 5-Fu positive control, and experimental drug group, and continue to observe and cultivate for 48 hours after adding the drug.

Color development and colorimetry: After 48 hours of drug-added culture, the culture plate was taken out, 20 μL of MTT solution (5 mg/mL) was added to each well, and the culture was continued for 4 hours at 37° C. and 5% CO ₂ to terminate the culture. Carefully aspirate and discard the culture supernatant in the wells, add 150 μL DMSO to each well and shake for 10 minutes to fully dissolve the crystals, select 490 nm to measure the absorbance (OD) of each well on an automatic microplate reader (BIO-TEK), which is proportional to the number of living cells ) to calculate the cell growth inhibition rate (IR). IR=(OD value of control well-OD value of experimental well)/OD value of control well×100%.

3.3 Experimental results

As can be seen from Table 4-8, the 70% ethanol extract of the Chinese medicine composition of the present invention and its diterpene lactone active ingredient flavin B can significantly inhibit human liver cancer cell Hep3B, gastric cancer cell SGC-7901, bladder cancer cell T24, ovarian cancer Cell HO8910, pancreatic cancer cell BXPC-3, breast cancer cell MCF-7, lung cancer cell A549, colon cancer cell LS174, colorectal cancer cell CCL229, prostate cancer cell PC-3, esophageal cancer cell Eca-109, skin cancer cell A431, The growth of thyroid cancer cells SW-579, leukemia cells K562, and cervical cancer cells Hela suggests that the traditional Chinese medicine composition and its diterpene lactone component flavin B can be used to treat liver cancer, gastric cancer, breast cancer, lung cancer, bladder cancer, and ovarian cancer , prostate cancer, esophageal cancer, pancreatic cancer, colorectal cancer, colon cancer, skin cancer, thyroid cancer, cervical cancer, leukemia and other types of cancer treatment. At the same time, the present invention also investigated the anticancer effect of the active ingredient composition, and found that among the lignin components contained in Schisandra chinensis, such as schisandra acetin, it can significantly enhance the anticancer effect of flavin B on the above various cancer cells when it is compatible with flavin B. Anticancer effect, and the anticancer activity after compatibility is stronger than that of the chemotherapeutic drug 5-Fu, suggesting that the lignin components contained in Schisandra chinensis can be compatible with the diterpene lactones contained in Xanthophyllum chinensis for the treatment of the above cancer diseases , and can be used as an alternative to the chemotherapy drug 5-Fu.

The influence of table 4 composition and its active ingredient on human cancer BXPC-3, MCF-7, A549 cell growth inhibitory rate (%)

Compared with solvent control group, ^* P<0.01; compared with 5-Fu, ^# P<0.05

The influence of table 5 composition and its active ingredient on human cancer SGC-7901, Hep3B, T24 cell growth inhibition rate (%)

Compared with solvent control group, ^* P<0.01; compared with 5-Fu, ^# P<0.05

The influence of table 6 composition and its active ingredient on human cancer HO8910, LS174, PC-3 cell growth inhibitory rate (%)

Compared with solvent control group, ^* P<0.01 Compared with 5-Fu, ^#P <0.05

The influence of table 7 composition and its active ingredient on human cancer CCL229, Eca-109, A431 cell growth inhibitory rate (%)

Compared with solvent control group, ^* P<0.01; compared with 5-Fu, ^# P<0.05

The influence of table 8 composition and active ingredient thereof on human cancer SW-579, K562, Hela cell growth inhibitory rate (%)

Compared with solvent control group, ^* P<0.01; compared with 5-Fu, ^# P<0.05

Embodiment 4 (preparation of liquid extract)

Take 600g of xanthophylla chinensis and 200g of schisandra chinensis, beat into powder, use 70% ethanol as solvent, soak for 48 hours, slowly percolate, collect 425mL of the initial percolation liquid, and store it in another container; continue percolation until the percolation liquid is nearly colorless, collect and continue liquid, concentrated at 55°C to a thick paste, added 680mL of the first decant liquid, mixed evenly, diluted to 800mL with 70% ethanol, left to stand for 3d, filtered, and obtained.

Embodiment 5 (preparation of tablet)

Take 600g of Xanthium chinensis and 200g of Schisandra chinensis, powder them, and pass through a 100-mesh sieve. Spray an appropriate amount of 70% ethanol, add 17.5% microcrystalline cellulose, add 7.5% microcrystalline cellulose and 20% starch, make granules, dry, add 10% microcrystalline cellulose and 1% magnesium stearate , mixed and pressed into tablets.

Embodiment 6 (preparation of dropping pill)

Take 600g of Fructus Xanthophyllum and 200g of Fructus Schisandra, powder them, reflux and extract them with 70% ethanol for 3 times, each time for 2 hours, recover the ethanol to obtain the extract, use PGE4000 as the base, and the ratio of the drug to the drug is 1:1.5, and simethicone is used as the condensing agent. drop system.

Embodiment 7 (preparation of capsule)

Take 600g of xanthophyll fruit and 200g of schisandra chinensis, powder, reflux and extract with ethyl acetate for 3 times, each time for 2 hours, recover ethyl acetate to obtain extract, dry, crush, pass through a 100-mesh sieve, add 5% magnesium stearate, mix and pack into hard capsules.

Claims (4)

1. a Chinese medicine composition with anti-curing cancers effect, is characterized in that, by Rhizoma Dioscoreae Bulbiferae ethanol extraction and schisandra chinensis ethyl hydrate extract, the weight ratio with 100:150 mixes for it, wherein:

Aforementioned Rhizoma Dioscoreae Bulbiferae ethanol extraction system adopts Rhizoma Dioscoreae Bulbiferae tuber decoction pieces coarse powder, and with 10 times of amount 80% ethanol extractions three times, each 3h, is evaporated to without alcohol taste after filtrate merging, and the Rhizoma Dioscoreae Bulbiferae crude drug concentration of take is 2g/mL;

Aforementioned schisandra chinensis ethyl hydrate extract system adopts Fructus Schisandrae Chinensis coarse powder, and with 10 times of amount 70% ethanol extractions three times, each 3h, is evaporated to without alcohol taste after filtrate merging, and the Fructus Schisandrae Chinensis crude drug concentration of take is 1g/mL.

2. the Chinese medicine composition with anti-curing cancers effect according to claim 1, is characterized in that, this Chinese medicine composition is extractum, fluid extract, medicated wine, tincture, oral liquid, pill, powder, tablet or capsule.

3. the Chinese medicine composition with anti-curing cancers effect according to claim 2, is characterized in that, pill is drop pill.

4. in claim 1-3, the Chinese medicine composition described in any one is prevented and treated the application in hepatocarcinoma, gastric cancer, breast carcinoma, pulmonary carcinoma, bladder cancer, ovarian cancer, carcinoma of prostate, the esophageal carcinoma, cancer of pancreas, colorectal cancer, colon cancer, skin carcinoma, thyroid carcinoma, cervical cancer or leukemic medicine in preparation.