CN111729056A

CN111729056A - Anticancer medicine composition and its prepn

Info

Publication number: CN111729056A
Application number: CN201910212622.3A
Authority: CN
Inventors: 石小和
Original assignee: Individual
Current assignee: Individual
Priority date: 2019-03-20
Filing date: 2019-03-20
Publication date: 2020-10-02

Abstract

The invention belongs to the technical field of medicines, and particularly relates to an anticancer pharmaceutical composition which comprises the following raw materials in parts by weight: 20-80 parts of fermented grains, 50-300 parts of fermented vinegar, 5-30 parts of vinegar paste and 49-121 parts of traditional Chinese medicines. The fermented grains, vinegar and vinegar paste not only contain various active substances with tumor inhibiting and treating effects such as polypeptide and flavone, but also contain various microorganisms such as lactococcus, enterococcus, xanthomonas, gluconacetobacter, bacillus, lactobacillus, acetic acid bacteria, aspergillus, mucor and alternaria, and can ferment and process Chinese medicinal materials to generate microorganism metabolism active substances and enhance medicinal properties. The anticancer pharmaceutical composition provided by the invention can reach the tumor focus and directly act on the cancerated tissue, change the growth microenvironment of the tumor focus, regulate the tumor immune metabolism, and inhibit the proliferation and metastasis of tumor cells, thereby effectively inhibiting the growth of the cancer cells and inducing the apoptosis of the cancer cells.

Description

Anticancer medicine composition and its prepn

Technical Field

The invention belongs to the technical field of medicines, and particularly relates to an anticancer pharmaceutical composition and a preparation method thereof.

Background

According to the reports of the world health organization, tumors are the second leading cause of death in the world after cardiovascular diseases. In China, the incidence of tumors is continuously increased for years, the incidence of cancers is close to the world level, but the mortality rate is higher than the world level. Tumors become a public health problem and even a social problem which must be highly regarded in China, and China urgently needs to fight against the tumors. The first malignant tumor is lung cancer, and the second is gastric cancer, colorectal cancer, liver cancer and esophageal cancer; the first death was lung cancer, followed by liver cancer, gastric cancer, esophageal cancer, and colorectal cancer. The tumor autonomous standardization of China is less, the diagnosis and treatment levels of primary hospitals are uneven, and the diagnosis and treatment homogenization degree is low, so that the tumor prevention and control research of China is difficult. The current tumor status can be summarized as follows: the prevention of tumors in China is difficult due to the complex pathogenesis of the tumors, the difficult control of high-risk factors and the like; the factors such as few effective screening technologies and low early diagnosis technology level generally cause late tumor discovery; the tumor treatment difficulty is high due to poor tumor treatment effect, high recurrence and metastasis rate, large side effect of tumor treatment, poor accuracy and the like.

At present, the main treatment methods of tumors mainly comprise surgical resection, radiotherapy and chemotherapy treatment. The surgical resection treatment and the radiotherapy are both local treatments, only resection is performed on the cancerated part, the tumor cells in the body cannot be completely eliminated, the recurrence rate after treatment is high, severe trauma is caused to the body of a patient, and the toxic and side effects are severe. The tumor is generally treated by the cooperation of the surgical resection and chemotherapy, but the chemotherapy is easy to generate multi-drug resistance, has great damage to normal cells of a human body and great toxic and side effects, the drugs cause irreversible damage to healthy cells of a patient, the patient is difficult to be treated safely and effectively, and the body is extremely exhausted to accelerate death. In addition, the tumor will recur again some time after the patient has stopped receiving chemotherapy. In addition, biological antibody drugs are expensive to treat, vary in therapeutic effect from person to person, and require regular long-term maintenance therapy.

At present, chemical drugs for treating tumors often have the defects of complex synthesis and preparation process, insignificant treatment effect, great toxic and side effects, lack of targeting property, easy generation of drug resistance and the like. The traditional Chinese medicine is the most important means for replacing, supplementing and assisting in treating malignant tumors, but has poor effects on enhancing the chemotherapy treatment effect, reducing adverse reactions and tumor treatment toxicity, and cannot effectively achieve the purposes of improving the life quality of patients and prolonging the life cycle of the patients.

Disclosure of Invention

The embodiment of the invention aims to provide an anticancer pharmaceutical composition, and aims to solve the technical problems of insignificant treatment effect, large toxic and side effect, easy generation of drug resistance and the like of the existing chemical drugs for treating tumors.

Another object of the embodiments of the present invention is to provide a method for preparing an anticancer pharmaceutical composition.

In order to achieve the purpose of the invention, the technical scheme adopted by the invention is as follows:

an anticancer pharmaceutical composition comprises an anticancer extracting solution and an anticancer traditional Chinese medicinal material composition, and the anticancer pharmaceutical composition comprises the following raw materials in parts by weight: 20-80 parts of fermented grains, 50-300 parts of fermented vinegar, 5-30 parts of vinegar paste and 49-121 parts of traditional Chinese medicines;

wherein, the Chinese-medicinal material includes: 3-8 parts of turtle shell, 1-2 parts of frankincense, 1-2 parts of myrrh, 2-3 parts of rhizoma sparganii, 2-3 parts of curcuma zedoary, 1-3 parts of endothelium corneum gigeriae galli, 2-4 parts of rhizoma cyperi, 1-2 parts of radix euphorbiae lantu, 1-3 parts of pokeberry root, 1-3 parts of monkshood, 3-10 parts of astragalus membranaceus, 3-10 parts of codonopsis pilosula, 1-3 parts of ginseng, 1-3 parts of pseudo-ginseng, 5-20 parts of poria cocos, 1-3 parts of cyrtomium rhizome, 2-3 parts of patrinia scabiosaefolia, 8-15 parts of rabdosia rubescens, 0.5-3 parts of gamboge, 2-4 parts of kelp, 2-4 parts of bighead atractylodes rhizome, 2-3 parts of lumbricus.

Further, the preparation of the fermented grains at least comprises the following steps:

obtaining a grain raw material, adding water into the grain raw material for soaking, steaming, adding water accounting for 140-260% of the weight of the grain raw material, and stewing to obtain a stewing material;

obtaining famous wine fungus series yeast, adding the famous wine fungus series yeast accounting for 20-70% of the weight of the grain raw material into the stewing material, mixing, adding water accounting for 40-70% of the weight of the grain raw material, and sequentially performing fermentation treatment and aging treatment to obtain a primary fermented product;

and adding a cereal skin material accounting for 100-300% of the weight of the cereal raw material into the primary fermented product, mixing, and sequentially performing fermentation treatment and aging treatment to obtain fermented grains.

Further, the preparation of the fermented vinegar at least comprises the steps of:

obtaining fermented grains, frying 30-50% of the fermented grains with slow fire, mixing with the rest fermented grains, performing water extraction treatment on the mixture of the fermented grains at 35-85 ℃, and collecting water extract to obtain a water extraction product;

and (3) freezing and concentrating the water extract product to obtain the fermented vinegar.

Further, the preparation of the vinegar paste at least comprises the following steps: and (3) sealing and ageing the fermented vinegar for 6-48 months to obtain semi-solid paste, namely vinegar paste.

Further, the anti-cancer pharmaceutical composition further comprises auxiliary materials allowed in a pharmaceutical scope, wherein the auxiliary materials allowed in the pharmaceutical scope comprise: at least one of a solvent, a solubilizer, an emulsifier, an adhesive, a disintegrant, a filler, a lubricant, a stabilizer, a glidant, a flavoring agent, a preservative, a suspending agent, a coating material, an anti-adhesive, a penetration enhancer, a pH regulator, a buffer, a surfactant, a thickener, a humectant, an absorbent, a diluent, a flocculant, and a deflocculant.

Further, at least the treatment of: leukemia, lymphoma, gastric cancer, colon cancer, and oral cancer.

Accordingly, the preparation method of the anti-cancer pharmaceutical composition comprises the following steps:

obtaining traditional Chinese medicinal materials with a formula amount, and crushing to obtain traditional Chinese medicinal material powder;

adding the fermented vinegar with the formula amount into the Chinese medicinal material powder for soaking treatment, and stir-frying with slow fire to obtain a stir-fried product with slow fire;

obtaining fermented grains and vinegar paste with a formula amount, adding the fermented grains and the vinegar paste into the product stir-fried with slow fire, mixing, and performing fermentation treatment to obtain a fermentation product;

adding water with the weight ratio of 3-9 times of that of the raw materials into the fermentation product, and extracting to obtain an anticancer pharmaceutical composition, wherein the anticancer pharmaceutical composition comprises: anticancer extractive solution and anticancer Chinese medicinal composition.

Further, the particle size of the traditional Chinese medicine powder is not more than 180 micrometers; and/or the presence of a gas in the gas,

the soaking time is 1-15 days; and/or the presence of a gas in the gas,

the water content of the product fried by slow fire is 15 to 25 percent; and/or the presence of a gas in the gas,

the conditions of the fermentation treatment include: fermenting for 15-120 days in an environment with the temperature of 15-40 ℃ and the humidity of 60% -80%; and/or the presence of a gas in the gas,

the step of extracting processing includes: decocting the mixture for 15-60 minutes by slow fire, and filtering to obtain filtrate as the anticancer extracting solution and filter residues as the anticancer Chinese medicinal material composition.

Further, still include: concentrating the anticancer extracting solution to obtain a thick anticancer extracting solution, drying the thick anticancer extracting solution, and crushing to obtain a powdery anticancer extract; and/or the presence of a gas in the gas,

drying the anticancer traditional Chinese medicine composition, and then crushing to obtain a powdery anticancer traditional Chinese medicine composition.

Further, still include: in the anticancer pharmaceutical composition, auxiliary materials allowed in a pharmaceutical range are added to prepare a pharmaceutically acceptable dosage form, wherein the pharmaceutically acceptable dosage form comprises: at least one of oral liquid, capsule, tablet, unguent, powder, granule, pill, suppository and extract injection.

The anti-cancer pharmaceutical composition provided by the invention takes fermented grains, fermented vinegar, vinegar paste and traditional Chinese medicinal materials as raw materials, the raw materials are natural food materials, the raw materials are easy to obtain and harmless to human bodies, the toxic and side effects are extremely small, the curative effect is good, and the raw materials are easily accepted by patients, wherein the fermented grains contain various microorganisms such as lactococcus, enterococcus, xanthomonas, acetobacter gluconicum, bacillus, lactobacillus, acetic acid bacteria, aspergillus, mucor, alternaria, gelidium, epiphyte, saccharomycetes and the like; the fermented vinegar and vinegar paste not only contain abundant microbial populations such as aspergillus, acetobacter, saccharomycetes and the like, but also contain various active substances with tumor inhibition and treatment effects such as polypeptide, polysaccharide, flavone, polyphenol and the like; various Chinese medicinal materials are rich in various active substances. According to the anticancer pharmaceutical composition provided by the invention, on one hand, the traditional Chinese medicinal materials, the fermented vinegar, the vinegar paste and the fermented grains in the raw materials contain rich active substances with tumor inhibition and treatment effects, and the anticancer pharmaceutical composition can exert a better treatment effect through the mutual synergistic effect of the active substances in the raw materials; on the other hand, the traditional Chinese medicinal materials in the formula are fermented and processed by utilizing the strong capability of decomposing and converting substances of abundant microbial populations in the raw materials, so that the active substances in the traditional Chinese medicinal materials can be better exerted, and the abundant microbial metabolic active substances with the effects of inhibiting and treating tumors are generated, so that the medicine property is enhanced and regulated to the greatest extent, the treatment effect is improved, and the toxic and side effects are reduced. The anticancer pharmaceutical composition provided by the invention can reach tumor focus and act on cancerated tissues, change the growth microenvironment of the tumor focus, regulate tumor immune metabolism, and inhibit proliferation and metastasis of tumor cells, thereby effectively inhibiting the growth of the cancer cells and inducing apoptosis of the cancer cells.

The preparation method of the anticancer pharmaceutical composition provided by the invention comprises the steps of firstly crushing the traditional Chinese medicinal materials to enable the powdery traditional Chinese medicinal materials to be in more complete contact with other raw materials, and then soaking the traditional Chinese medicinal material powder in fermented vinegar, so that active substances in the traditional Chinese medicinal materials are favorably dissolved and activated through the fermented vinegar, enzymes, microorganisms and microorganism metabolites in the fermented vinegar are favorably subjected to chemical reaction and biological catalysis with various substances in the traditional Chinese medicinal material powder, and the effects of enhancing the effect and reducing the toxicity of the traditional Chinese medicinal materials are achieved. And the fermented vinegar and the vinegar paste are added, and through the fermentation, conversion and decomposition of abundant microbial colonies in the raw materials, active substances in the raw materials can exert better treatment effects, and abundant metabolites with tumor inhibition and treatment effects are generated, so that the drug properties are greatly enhanced and/or blended, the treatment effect is improved, and the toxic and side effects are reduced. And finally, extracting to obtain the anticancer pharmaceutical composition. The preparation process is easy to operate, has high utilization rate of raw materials, can be used for simultaneously preparing in large batch, and is favorable for industrial production.

Drawings

FIG. 1 is an LC-MS spectrum of the methylene chloride extract component of vinegar paste provided in example 1 of the present invention.

Detailed Description

In order to make the purpose, technical solution and technical effect of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention is clearly and completely described, and it is obvious that the described embodiments are a part of the embodiments of the present invention, but not all embodiments. All other embodiments obtained by a person of ordinary skill in the art without any inventive step in connection with the embodiments of the present invention shall fall within the scope of protection of the present invention.

In the description of the present invention, it is to be understood that the terms "first", "second" and the like are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implying any number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of the present invention, "a plurality" means two or more unless specifically defined otherwise.

The embodiment of the invention provides an anticancer pharmaceutical composition, which comprises an anticancer extracting solution and an anticancer Chinese medicinal material composition, and the anticancer pharmaceutical composition comprises the following raw materials in parts by weight: 20-80 parts of fermented grains, 50-300 parts of fermented vinegar, 5-30 parts of vinegar paste and 49-121 parts of traditional Chinese medicines;

The anticancer pharmaceutical composition provided by the embodiment of the invention takes fermented grains, fermented vinegar, vinegar paste and traditional Chinese medicines as raw materials, has extremely small toxic and side effects of the raw materials, has good curative effect and is easily accepted by patients. Wherein the fermented grains contain various microorganisms such as lactococcus, enterococcus, Xanthomonas, Acetobacter gluconicum, Bacillus, lactobacillus, Acetobacter, Aspergillus, Mucor, Alternaria, Geospora, Acidococcus, and yeast; the fermented vinegar and vinegar paste not only contain abundant microbial populations such as aspergillus, acetobacter, saccharomycetes and the like, but also contain various active substances with tumor inhibition and treatment effects such as polypeptide, polysaccharide, flavone, polyphenol, antioxidant enzyme and the like; various Chinese medicinal materials are rich in various active substances. According to the anticancer pharmaceutical composition provided by the embodiment of the invention, on one hand, the traditional Chinese medicinal materials, the fermented vinegar, the vinegar paste and the fermented grains in the raw materials contain rich active substances with tumor inhibition and treatment effects, and the possibility of drug resistance is reduced, the dosage of the medicine is reduced, the toxic and side effects of the medicine are reduced, and the anticancer pharmaceutical composition can exert a better treatment effect through the mutual synergistic effect among the active substances in the raw materials; on the other hand, the traditional Chinese medicinal materials in the formula are fermented and processed by utilizing the strong capability of decomposing and converting substances of abundant microbial populations in the raw materials, so that the active substances in the traditional Chinese medicinal materials can be better exerted, and the abundant microbial metabolic active substances with the effects of inhibiting and treating tumors are generated, so that the medicine property is enhanced and regulated to the greatest extent, the treatment effect is improved, and the toxic and side effects are reduced. The anti-cancer pharmaceutical composition provided by the embodiment of the invention can reach the tumor focus to act on the cancerated tissue, change the growth microenvironment of the tumor focus, regulate the tumor immune metabolism, and inhibit the proliferation and the metastasis of tumor cells, thereby effectively inhibiting the growth of the cancer cells and inducing the apoptosis of the cancer cells.

As a preferred embodiment, the preparation of the fermented grains at least comprises the following steps: firstly, obtaining grain raw materials, adding water into the grain raw materials for soaking, steaming, adding water accounting for 140-260% of the weight of the grain raw materials, and stewing to obtain stewed materials; secondly, obtaining famous wine fungus series yeast, adding 20-70% of the famous wine fungus series yeast in weight of the cereal raw material into the stewing material, mixing, adding water in weight of 40-70% of the cereal raw material, and sequentially performing fermentation treatment and aging treatment to obtain a primary fermented product; thirdly, adding grain skin materials accounting for 100 to 300 percent of the weight of the grain raw materials into the primary fermented product, mixing, and then sequentially performing fermentation treatment and aging treatment to obtain fermented grains. Wherein the famous wine in the famous wine strain Daqu is selected from the following raw materials: at least one of Maotai, wuliangye, Luzhou Laojiao, Jiannanchun, Fenjiu, Yanghe Daqu, Lang liquor, Gujing tribute liquor, Dong liquor, Xifeng liquor and Shuanggou Daqu is prepared in the environment of famous liquor production or is directly purchased from a local Daqu manufacturer. The cereal raw material comprises Oryza Glutinosa, semen Tritici Aestivi, jowar, semen Maydis, testa Tritici, rice, potato, such as sweet potato, rhizoma Solani Tuber osi, fine testa oryzae, jowar bran, etc., or vegetables and fruits. The fermented grains adopted by the embodiment of the invention contain various microorganisms such as lactococcus, enterococcus, xanthomonas, gluconacetobacter, bacillus, lactobacillus, acetic acid bacteria, aspergillus, mucor, alternaria, gelidium, epipococcus, yeast and the like, and the microorganisms have strong decomposition and transformation capability on traditional Chinese medicinal materials in raw materials. The traditional Chinese medicinal materials in the raw materials are fermented and processed by utilizing the strong capability of decomposing and converting substances of microbial populations, so that the active substances in the traditional Chinese medicinal materials can be better treated, and the toxic and side effects of the medicines are reduced; on the other hand, the composition can generate abundant microbial metabolites and further enrich the types and the content of active substances in the anticancer pharmaceutical composition, thereby greatly enhancing and harmonizing the drug property and improving the treatment effect.

In some embodiments, the preparation of the fermented substrate comprises at least the steps of: firstly, obtaining a grain raw material, adding water into the grain raw material for soaking, steaming for 90-180 minutes after the grain raw material fully absorbs water, then adding water accounting for 140-260% of the weight of the grain raw material, and stewing for 15-80 minutes at the stewing temperature of 100 ℃ to obtain a stewing material; secondly, obtaining famous wine fungus series yeast, adding 20-70% of the famous wine fungus series yeast by weight of the cereal raw material into the stewing material, mixing, adding 40-70% of water by weight of the cereal raw material, fermenting for 1-15 days at 15-40 ℃, and aging for 15-360 days to obtain a primary fermented product; thirdly, adding a loose material of grain skins accounting for 100-300% of the weight of the grain raw materials into the primary fermented product, mixing, fermenting for 8-15 days, and aging for 30-180 days to obtain fermented grains.

Specifically, the fermented vinegar adopted in the embodiment of the invention is prepared by fermenting glutinous rice, sorghum, rice, corn or wheat and the like. In some embodiments, the fermented vinegar may be one or more of zhangjiajiuquxiangzhi vinegar, shanxi mature vinegar, zhenjiang aromatic vinegar, fujia yongchun old vinegar, langzhonggunning vinegar, henna soft-shelled turtle special vinegar, tianjin uniflow old vinegar, lianyuanchong vinegar, and beijing longmen rice vinegar. Preferably, the vinegar is Zhang Jiajie Jiuqu aromatic ester vinegar. The total flavone in the Zhang Jiajiu Jiuqu aromatic ester vinegar reaches 1800mg/100mL, and the content of lactic acid accounts for not less than 25% of the total acid; the soluble salt-free solid is not less than 25g/100mL and is far higher than the national standard 1.0g/100 mL; the content of the characteristic active peptide is not less than 4.5g/100 mL. In addition, the aspongopus aromaticus ester vinegar also contains active substances such as polysaccharide, amino acid, ferulic acid, gamma-aminobutyric acid, ligustrazine, catechin, epicatechin and the like, and the active substances have high abundance degree and high medicinal value.

As a preferred embodiment, the preparation of the fermented vinegar at least comprises the steps of: firstly, obtaining fermented grains, frying 30-50% of the fermented grains with slow fire to prepare the fermented grains with scorched aroma and slight yellow color, mixing with the rest fermented grains, carrying out water extraction treatment on the mixture of the fermented grains at 35-85 ℃, and collecting water extract to obtain a water extraction product; ② freezing and concentrating the water extraction product to obtain the fermented vinegar. The fermented vinegar adopted in the embodiment of the invention is not only rich in various microbial populations such as aspergillus, acetobacter, saccharomycetes and the like, but also contains a large number of components with medicinal effects such as polypeptide, polysaccharide, flavone, polyphenol, antioxidant enzyme, polyunsaturated fatty acid, lactic acid, gluconic acid, amino acid, calcium, phosphorus, magnesium, iron, B vitamins and the like. Wherein the polysaccharide has effects of reducing blood sugar, reducing blood lipid, resisting oxidation, improving immunity, resisting virus and tumor, etc. The flavonoids have strong biological activity, have the functions of reducing blood fat and blood sugar, resisting inflammation and allergy, resisting bacteria and viruses, can remove free radicals, resist oxidation and carcinogenic factors, inhibit blood flow of tumor tissues to supply nutrition required by the tumor tissues, improve immunity and the like, and further achieve the effects of inhibiting and preventing cancers, particularly cancers which are considered to be related to hormone secretion of human bodies, such as breast cancer, ovarian cancer, prostate cancer and the like. The polyphenol has strong oxidation resistance, can play a good role in preventing the diseases, and simultaneously has good functions in the aspects of resisting mutagenesis, resisting virus, inhibiting bacteria and diminishing inflammation, and the like. On one hand, the microbial community contained in the fermented vinegar can enrich the microbial community in the pharmaceutical composition, enhance the metabolic effects of fermentation, decomposition, conversion and the like of the microbes and the raw materials, make the pharmaceutical raw materials more fully utilized and play a better treatment effect; on the other hand, polypeptides, polysaccharides, flavones, polyphenols, antioxidases and the like with medicinal effects in the fermented vinegar can further enrich active substances in the medicine and improve the treatment effect.

In some embodiments, the preparation of the fermented vinegar comprises at least the steps of: obtaining fermented grains, frying 30-50% of the fermented grains with slow fire until the fermented grains have burnt fragrance and are yellowish, mixing the fried grains with the rest fermented grains, and performing dynamic circulation extraction for 2-3 times by using water accounting for 200-300% of the weight of the fermented grains at the temperature of 35-85 ℃ to obtain a water extraction product, wherein preferably the content of soluble salt-free solids in the water extraction product is 8-13 g/100 ml; and (3) under the conditions that the temperature of a refrigerant is-4 ℃ to-7 ℃ and the scraper speed is 30r/min to 50r/min, freezing and concentrating the water extract for 8 hours to 12 hours to obtain the fermented vinegar. In some embodiments, the step of cold-concentration processing comprises: and (3) freezing the water extraction product into a solid block at the temperature of-25 to-18 ℃, placing the solid block of the extracting solution at room temperature to slowly melt the solid block, collecting the molten liquid, and stopping collecting when the solid block becomes white.

In a preferred embodiment, the vinegar paste is prepared by sealing and ageing for 6-48 months, and the obtained semi-solid paste is the vinegar paste. On one hand, the vinegar paste adopted by the embodiment of the invention contains a large amount of components with medicinal effects, such as organic acid, polysaccharide, polypeptide, alcohol, aldehyde, lactone, saccharide, nitrogen-containing compound and the like, such as: inositol, 9, 12-octadecadienoic acid, ferulic acid, 5-hydroxymethyl furfural, veratraldehyde and other active substances, wherein the inositol is a nutrient for promoting cell growth and maintaining the physiological function of animals, is particularly important for the growth of liver and bone marrow cells, and has the effects of resisting oxidation, resisting thrombus, reducing blood fat, preventing and treating coronary heart disease and the like. On the other hand, the semi-solid vinegar paste obtained by ageing the fermented vinegar for a long time has better astringency and drug property compared with the fermented vinegar, and has the effects of dissipating blood stasis, relieving pain, soothing liver, promoting qi circulation, clearing heat, cooling blood and reducing toxic and side effects of other medicinal materials.

In some embodiments, the vinegar paste may be processed or aged with one or more of Zhangjiajiuquxiangzhi vinegar, Shanxi mature vinegar, Zhenjiang aromatic vinegar, Fujian Yongchun old vinegar, Langzhong Baoning vinegar, Henan old turtle one-time vinegar, Tianjin uniflow old vinegar, Liyuanchong drop vinegar, and Beijing Longmen rice vinegar.

Specifically, in the raw materials of the anti-cancer pharmaceutical composition provided by the embodiment of the invention, the traditional Chinese medicinal materials of frankincense, myrrh, zedoary and rhizoma sparganii belong to the medicines for promoting blood circulation and removing blood stasis, and have the effects of promoting blood circulation and removing blood stasis, eliminating swelling and promoting granulation, breaking blood and promoting qi circulation, and removing food retention and relieving pain; ginseng, radix Codonopsis, and radix astragali belong to qi invigorating medicine, and have effects of invigorating spleen, benefiting lung, nourishing blood, promoting fluid production, inducing diuresis, and relieving swelling; the rhizoma Osmundae and radix patriniae have the effects of clearing away heat and toxic materials; radix Euphorbiae Fischerianae and radix Phytolaccae are purgatives, and have the effects of eliminating edema, and promoting diuresis; in addition, tuckahoe, radix aconiti lateralis praeparata, radix aconiti lateralis preparata, rhizoma cyperi, turtle shell, rhizoma cyperi, carapax amydae, liver calming, wind calming, venenum bufonis, detoxifying and pain relieving can be used for clearing damp-heat and promoting diuresis.

Furthermore, carapax Trionycis has effects of clearing away low fever, strengthening body resistance, and resisting cancer, and can be used for treating lung cancer, hepatocarcinoma, intestinal cancer, ovarian cancer, cervical cancer, bone tumor, etc.; the frankincense contains 11-carbonyl-beta-acetyl boswellic acid and other active ingredients, and can inhibit the growth of tumors by inhibiting the angiogenesis of the tumors; the active components of zedoary turmeric oil, curcumenol, zedoary turmeric diketone, etc. in zedoary turmeric oil not only can change and enhance the immunogenicity of tumor cells, thereby inducing and promoting the immunological rejection reaction of antibody to tumor, but also has direct destructive effect to cancer cells, and can make them denaturalized and necrotized. Has good therapeutic effect on tumors such as lymph cancer, cervical cancer, skin cancer, etc.; the endothelium corneum Gigeriae Galli has effects of inhibiting tumor cells, increasing gastric secretion, acidity and digestive ability, strengthening stomach movement, and accelerating evacuation rate; rhizoma Cyperi has anticancer pharmacological effects of inducing cancer cell apoptosis, resisting oxidation, etc., and can be used for treating thyroid cancer, gastric cancer, hepatocarcinoma, breast cancer, etc., and relieving pain of pain parts. Radix Euphorbiae Fischerianae contains sterol, phenolic components, amino acids, triterpenes, diterpene lactone compounds, etc., and has effect in inhibiting hepatocarcinoma. The pokeberry root polysaccharide also has a certain anti-tumor effect. The total alkaloids in radix Aconiti lateralis can improve breast cancer, and improve life quality of patients by directly inhibiting or killing tumor cells, inducing tumor cell differentiation and apoptosis, and reversing biological behavior change of tumor cells. Rhizoma Osmundae contains aspic acid compounds, and has effects of inhibiting and treating tumors such as cervical cancer, lung cancer, breast cancer, etc. The patrinia is suitable for various tumors, such as cervical cancer, ovarian tumor, chorionic epithelial cancer, liver cancer, leukemia and the like, and is particularly suitable for treating the liver cancer with accumulated heat toxin and retention of damp evil by matching with other medicinal materials. Rabdosia rubescens contains active ingredients such as terpenoid rubescensin and volatile oil, has obvious symptom relieving effects on esophageal cancer, cardiac cancer, primary liver cancer, breast cancer and the like, has the effects of stabilizing and reducing tumor bodies and prolonging the life of patients, can relieve adverse reactions of chemotherapy medicaments and improve curative effect when being used together with chemotherapy, and also has certain curative effect on severe hyperplasia of esophageal epithelium. The gambogic acid and other active substances in gamboge can play a role in various tumor cells through different mechanisms, and have the effects of inducing apoptosis, inhibiting the activity of telomere terminal metastasis and topoisomerase, inhibiting the expression of heat shock protein and channel protein, inhibiting tumor angiogenesis and metastasis and the like. The fucoxanthin and other active substances in the kelp have good treatment effect on leukemia, breast cancer, liver cancer, cervical cancer, lymphoma and other tumors. Atractylodis rhizoma contains volatile oil, atractylenolide, Atractylodis rhizoma polysaccharide, glycosides, amino acids, etc., and has diuretic, antibacterial, antiaging, and antitumor effects. The venenum bufonis contains active ingredients such as bufotoxin ligands, bufotoxin tryptamine and the like, and has obvious inhibition and treatment effects on tumors such as leukemia, liver cancer and the like. The 24 traditional Chinese medicinal materials adopted in the embodiment of the invention have reasonable medicine proportion and contain rich active substances which have an inhibiting effect on tumors. In addition, the active substances in the traditional Chinese medicinal materials have synergistic effect by fermenting, decomposing, converting and the like of the microorganisms in the raw materials, directly generate the effects of inhibiting, inducing and killing cancer cells, and enhance the curative effect of the medicine. In addition, the adopted traditional Chinese medicinal materials can enhance the immunity of the organism and condition the organism to achieve a balanced and steady state, thereby better enhancing the treatment effect of cancer, improving the life quality of patients and prolonging the life cycle.

In some embodiments, the raw materials of the anticancer pharmaceutical composition include fermented vinegar for providing fermented liquid medicine, vinegar paste for providing fermented paste for the composition, and fermented grains for providing fermented microorganisms for the composition. The anti-cancer pharmaceutical composition provided by the embodiment of the invention is rich in original active substances in fermented grains, fermented vinegar, vinegar paste and traditional Chinese medicinal materials and is rich in newly-generated microbial metabolic active substances after fermentation, so that the active substance components in the composition are optimized, the drug property of the composition is enhanced and/or blended, and the pharmaceutical efficacy of the composition is improved.

As a preferred embodiment, the anticancer pharmaceutical composition further comprises pharmaceutically acceptable excipients, wherein the pharmaceutically acceptable excipients comprise: at least one of a solvent, a solubilizer, an emulsifier, an adhesive, a disintegrant, a filler, a lubricant, a stabilizer, a glidant, a flavoring agent, a preservative, a suspending agent, a coating material, an anti-adhesive, a penetration enhancer, a pH regulator, a buffer, a surfactant, a thickener, a humectant, an absorbent, a diluent, a flocculant, and a deflocculant. The auxiliary materials have the effects of stabilizing, emulsifying, bonding, disintegrating, filling and the like on the anticancer medicinal composition, are beneficial to improving the stability of the traditional Chinese medicine extract and meet the requirements of different preparations.

As a preferred embodiment, the present invention provides an anticancer pharmaceutical composition useful for treating at least: leukemia, lymphoma, gastric cancer, colon cancer, and oral cancer. The active pharmaceutical ingredients in the anticancer pharmaceutical composition provided by the invention have treatment and inhibition effects on various tumor diseases, and especially have better inhibition and treatment effects on leukemia, lymphoma, gastric cancer, colon cancer and oral cancer.

The embodiment of the invention also provides a preparation method of the anticancer pharmaceutical composition, which comprises the following steps:

s10, obtaining traditional Chinese medicinal materials in a formula amount, and crushing to obtain traditional Chinese medicinal material powder;

s20, adding the fermented vinegar obtained according to the formula amount into the traditional Chinese medicine powder for soaking treatment, and then frying with slow fire to obtain a product fried with slow fire;

s30, adding the fermented grains and the vinegar paste with the formula amount into the product stir-fried with slow fire, mixing, and performing fermentation treatment to obtain a fermented product;

s40, adding water with the weight ratio of 3-9 times of that of the raw materials into the fermentation product, and extracting to obtain an anticancer pharmaceutical composition, wherein the anticancer pharmaceutical composition comprises: anticancer extractive solution and anticancer Chinese medicinal composition.

According to the preparation method of the anticancer pharmaceutical composition provided by the embodiment of the invention, firstly, the traditional Chinese medicinal materials are crushed to enable the powdery traditional Chinese medicinal materials to be in more complete contact with other raw materials, and then the traditional Chinese medicinal material powder is soaked in the fermented vinegar, so that the active substances in the traditional Chinese medicinal materials are favorably dissolved and activated by the fermented vinegar, enzymes, microorganisms and microbial metabolites in the fermented vinegar are favorably subjected to chemical reaction and biological catalysis with various substances in the traditional Chinese medicinal material powder, and the effects of enhancing the effect and reducing the toxicity of the traditional Chinese medicinal materials are achieved. And the fermented vinegar and the vinegar paste are added, and through the fermentation, conversion and decomposition of abundant microbial colonies in the raw materials, active substances in the raw materials can exert better treatment effects, and the abundant microbial metabolic active substances with tumor inhibition and treatment effects are generated, so that the drug properties are greatly enhanced and blended, the treatment effect is improved, and the toxic and side effects are reduced. Finally, the anticancer pharmaceutical composition is obtained through extraction treatment. The preparation process is easy to operate, has high utilization rate of raw materials, can be used for simultaneously preparing in large batch, and is favorable for industrial production.

Specifically, in step S10, the Chinese medicinal materials are obtained according to the formula ratio, and are pulverized to obtain the Chinese medicinal material powder. According to the embodiment of the invention, the traditional Chinese medicine powder is obtained through crushing treatment, so that on one hand, the surface area of the medicine is increased, the medicine is favorable for being mixed and contacted with other raw materials subsequently, and the dissolution and absorption of the traditional Chinese medicine are favorable, thereby being favorable for improving the efficiency of the mutual synergistic effect of active substances in the traditional Chinese medicine and active substances in other raw materials and improving the treatment effect of the pharmaceutical composition. Preferably, after the crushing treatment, the particle size of the traditional Chinese medicine powder is not more than 180 microns and is less than or equal to 180 microns, so that the specific surface area is effectively increased, and the subsequent treatment process is facilitated. More preferably, after the pulverization treatment, the particle size of the Chinese medicinal material powder is not more than 100 microns.

Specifically, in the step S20, the fermented vinegar obtained according to the formula amount is added into the traditional Chinese medicine powder for soaking treatment, and then the stir-fried product is obtained by stir-frying with slow fire. The majority of the traditional Chinese medicinal materials are dry products, the traditional Chinese medicinal materials are dry and have fine and hard texture, active ingredients are crystallized or precipitated in cells in a set shape, the fermented vinegar is not easy to permeate, the medicinal materials can be softened and the cell tissues are expanded by soaking, the bidirectional migration of the active ingredients is involved, the fermented vinegar fully permeates into the medicinal materials, and partial active substances in the traditional Chinese medicinal materials are dissolved out of the fermented vinegar. The enzymes, microorganisms and microbial metabolites (such as acids, alcohols, esters, polypeptides, amino acids and the like) in the fermented vinegar and active substances in the traditional Chinese medicinal materials have complex chemical reaction and biological catalysis, so that the effects of enhancing the efficacy and reducing the toxicity of the medicinal materials are achieved. After the soaking treatment, the soaked product containing the traditional Chinese medicinal materials and the fermented vinegar is fried by slow fire, partial water in the soaked product is removed, so that the effective components in the soaked product are concentrated, the volume of the soaked product is reduced, the concentration of the soaked product is increased, and the subsequent processes of fermentation treatment and the like are facilitated. As a preferred embodiment, after the stir-frying with slow fire, a stir-fried product with slow fire with the water content of 15% -25% is obtained, and the stir-fried product with slow fire with the water content is beneficial to being uniformly mixed with other subsequently added raw material components, so that an environment is provided for subsequent fermentation.

In a preferred embodiment, the soaking time is 1 to 15 days. If the soaking time is too short, the bidirectional migration of the effective components in the fermented vinegar and the traditional Chinese medicinal materials is insufficient, the reactions between the active substances and the microbial colonies are insufficient, the processes such as subsequent fermentation are not facilitated, and the effects of enhancing the efficacy and reducing the toxicity of the traditional Chinese medicinal materials cannot be obtained. If the soaking time is too long, not only the preparation time and the economic cost of the pharmaceutical composition are increased, but also microorganisms such as harmful bacteria in the environment can easily enter the soaking solution and breed and propagate after being soaked for too long time, and the raw materials deteriorate.

Specifically, in step S30, the fermented grains and the vinegar paste are obtained according to the formula amount, mixed with the stir-fried product with slow fire, and then fermented to obtain a fermented product. Wherein the fermented grains contain various microorganisms such as lactococcus, enterococcus, Xanthomonas, Acetobacter gluconicum, Bacillus, lactobacillus, Acetobacter, Aspergillus, Mucor, Alternaria, Geospora, Acidococcus, and yeast; the vinegar paste contains microbial strains such as yeast, aspergillus and acetobacter. According to the embodiment of the invention, the product stir-fried by slow fire is fermented by abundant microbial populations provided by fermented grains, fermented vinegar and vinegar paste, and the raw materials are processed and fermented by strong decomposition, conversion and other capabilities of microbes, so that on one hand, the utilization rate of the raw materials is improved, and active ingredients in the raw materials are excited to have better activity, so that the drug effect is enhanced and the drug treatment effect is improved; on the other hand, in the fermentation process, the microbial population in the raw materials and each active substance generate synergistic interaction to generate abundant microbial metabolites, so that the active ingredients in the medicine are greatly enhanced, and the effects of enhancing and harmonizing the medicine property, improving the treatment effect and reducing the toxic and side effects are achieved.

As a preferred embodiment, the conditions of the fermentation process include: fermenting for 15-120 days in an environment with the temperature of 15-40 ℃ and the humidity of 60% -80%. Under the fermentation treatment conditions, the fermentation reaction between the microorganisms and other active substances in the raw material is sufficiently completed. The temperature is 15-40 ℃, and the humidity is 60-80%, which is most suitable for the survival of microbial populations in the fermented vinegar, the fermented grains and the vinegar paste adopted in the embodiment of the invention, so that the microbial populations keep the optimal activity, and the smooth and full progress of the fermentation reaction is facilitated.

Specifically, in the step S40, water in an amount which is 3 to 9 times the weight of the raw material is added to the fermentation product, and the fermentation product is extracted to obtain an anticancer pharmaceutical composition, wherein the anticancer pharmaceutical composition comprises: anticancer extractive solution and anticancer Chinese medicinal composition. After the fermentation is completed, water is added for extraction treatment, so that on one hand, active substances in the traditional Chinese medicinal materials are further dissolved into the extracting solution, the content of the active substances in the extracting solution is enriched, and the medicinal curative effect of the anticancer medicinal composition is improved; on the other hand, in the extraction process, the active substances in the fermentation product are further reacted, the synergistic compatibility among the active substances is further enhanced, and the drug effect is enhanced. The product obtained by extraction treatment comprises an anticancer extracting solution and an anticancer traditional Chinese medicine composition, wherein the anticancer traditional Chinese medicine composition is a raw material after extraction treatment.

As a preferred embodiment, the step of extracting process comprises: decocting the mixture for 15-60 minutes by slow fire, and filtering to obtain filtrate as the anticancer extracting solution and filter residues as the anticancer Chinese medicinal material composition. According to the embodiment of the invention, as the traditional Chinese medicinal materials are subjected to crushing, soaking, fermentation and other treatment processes, active substances in the raw materials can be fully dissolved out by decocting the traditional Chinese medicinal materials for 15-60 minutes with slow fire, and the extracted products are filtered after the decoction treatment, wherein the filtrate is the anticancer extract and contains abundant active substances, so that the medicinal value is high, and the further processing processes of subsequent preparations and the like are easy; the filter residue is the anticancer traditional Chinese medicinal material composition, the raw materials in the filter residue still contain rich active substances, and the filter residue also has high medicinal value and can be further processed into a proper preparation for use.

In some embodiments, the time for the soaking treatment when the particle size of the traditional Chinese medicine powder is not more than 900 micrometers is 1-15 days; the water content of the product fried by slow fire is 15 to 25 percent; the conditions of the fermentation treatment include: fermenting for 15-120 days in an environment with the temperature of 15-40 ℃ and the humidity of 60% -80%; the step of extracting processing includes: decocting the mixture for 15-60 minutes by slow fire, and filtering to obtain filtrate as the anticancer extracting solution and filter residues as the anticancer Chinese medicinal material composition.

As a preferred embodiment, the preparation method of the anticancer pharmaceutical composition further comprises: concentrating the anticancer extracting solution to obtain a thick anticancer extracting solution, drying the thick anticancer extracting solution, and crushing to obtain a powdery anticancer extract. Specifically, the anticancer extracted thick paste obtained by concentration treatment is rich in high-concentration active substances with tumor inhibition and treatment effects, and the anticancer extracted powder is obtained by drying and crushing, so that the preparation process is facilitated, and different preparation requirements can be met. Preferably, the anticancer extracting solution is subjected to reduced pressure concentration to obtain anticancer extracting thick paste, the anticancer extracting thick paste is dried and crushed to obtain anticancer extracting powder with the particle size of 125-150 microns. More preferably, the anticancer extracting solution is subjected to reduced pressure concentration to obtain anticancer extracting thick paste, the anticancer extracting thick paste is dried and crushed to obtain anticancer extracting powder with the particle size of 75-90 microns.

As a preferred embodiment, the preparation method of the anticancer pharmaceutical composition further comprises: drying the anticancer traditional Chinese medicine composition, and then crushing to obtain a powdery anticancer traditional Chinese medicine composition. The anticancer Chinese medicinal material composition is a raw material after fermentation and extraction treatment, wherein the content of active substances is high, and the anticancer Chinese medicinal material composition powder obtained after crushing treatment is more beneficial to a preparation process, can be prepared into different preparations for use, and improves the utilization rate of the preparations. The medicine composition is prepared into powder for direct taking, and the microbes and the pharmacodynamic active substances contained in the medicine composition have good treatment effect on tumor focus and good effects on enhancing appetite and regulating intestinal microbes. Preferably, the anticancer Chinese medicinal material composition is dried and then crushed into fine powder to obtain anticancer Chinese medicinal material composition powder with the particle size of 125-150 microns. More preferably, the anticancer traditional Chinese medicine composition is dried and then crushed into superfine powder to obtain anticancer traditional Chinese medicine composition powder with the particle size of 75-90 microns.

In some embodiments, the method for preparing the anticancer pharmaceutical composition further comprises: concentrating the anticancer extracting solution to obtain a thick paste anticancer extract, drying the thick paste anticancer extract, and crushing to obtain a powdery anticancer extract; drying the anticancer traditional Chinese medicine composition, and then crushing to obtain a powdery anticancer traditional Chinese medicine composition.

As a preferred embodiment, the preparation method of the anticancer pharmaceutical composition further comprises: in the anticancer pharmaceutical composition, auxiliary materials allowed in a pharmaceutical range are added to prepare a pharmaceutically acceptable dosage form, wherein the pharmaceutically acceptable dosage form comprises: at least one of oral liquid, capsule, tablet, unguent, powder, granule, pill, suppository and extract injection. The dosage forms with different requirements are prepared by adding auxiliary materials, so that the utilization effect of the anticancer pharmaceutical composition is improved, and the use feeling of the medicine is improved. The embodiment of the invention can prepare the anticancer pharmaceutical composition into various dosage forms, has flexible and convenient preparation, no special limitation, can meet the requirements of different dosage forms, and has convenient preparation and wide applicability.

In order to make the details and operation of the above-mentioned embodiments of the present invention clearly understood by those skilled in the art and to make the progress of the anti-cancer pharmaceutical composition according to the embodiments of the present invention obvious, the above-mentioned technical solution is illustrated by the following examples.

Example 1

The embodiment of the invention provides an anticancer pharmaceutical composition, which specifically comprises the following steps:

1. preparation of the fermentation

1) Mixing sorghum and rice, pulverizing, soaking in water, steaming for 120 min, adding water 180 wt% into steamed raw material, and stewing for 60min at 100 deg.C;

2) crushing Maotai Daqu, adding 50% of the raw materials into the raw materials, uniformly stirring, adding 60% of water, fermenting for 3 days at 15-40 ℃ in a cylinder, performing primary fermentation, and performing sealed aging for 360 days to obtain a primary fermented product;

3) adding 150 wt% of grain skin material into the primary fermented product, mixing, subpackaging in shallow jar, covering with straw mat, fermenting for 10 days, turning layer by layer each day, performing primary fermentation, sealing, aging for 90 days, and obtaining secondary fermented product, i.e. fermented grain.

2. Preparation of fermented vinegar

1) Evenly mixing 1/2 of the fermented seed culture stir-fried by mild fire with the rest of the fermented seed culture, and performing warm-soaking dynamic circulation extraction on the evenly mixed fermented seed culture by hot water with the weight of 2-3 times, wherein the extraction temperature is 80 ℃, and the extraction times are 3 times to obtain an extraction liquid, and the content of soluble salt-free solid matters is 10.5g/100 ml;

2) freezing and concentrating the extractive solution at initial temperature of 4 deg.C, refrigerant temperature of-4 deg.C, scraper speed of 30r/min, and concentrating for 12h to obtain fermented vinegar.

3. Preparation of vinegar paste

Removing the fermented vinegar, sealing and aging for 36 months, wherein the semisolid paste at the bottom is vinegar paste.

4. Preparation of anticancer medicine composition

1) Crushing 6 parts of turtle shell, 2 parts of frankincense, 2 parts of myrrh, 3 parts of rhizoma sparganii, 3 parts of curcuma zedoary, 3 parts of endothelium corneum gigeriae galli, 3 parts of rhizoma cyperi, 1 part of radix euphorbiae lantu, 3 parts of pokeberry root, 3 parts of monkshood, 8 parts of astragalus mongholicus, 8 parts of codonopsis pilosula, 3 parts of ginseng, 3 parts of pseudo-ginseng, 6 parts of poria cocos, 3 parts of cyrtomium rhizome, 3 parts of patrinia heterophylla, 10 parts of rabdosia rubescens, 1 part of gamboge, 3 parts of kelp, 4 parts of bighead atractylodes rhizome, 3 parts of earthworm, 5 parts of American sickle and 0.3 part of venenum bufonis into coarse powder, adding 200 parts by weight of fermentation vinegar, soaking for 7;

2) uniformly mixing the fried medicinal materials with 20 parts by weight of vinegar paste and 80 parts by weight of fermented grains, sealing the mixture in a shallow pottery jar of 40cm, and fermenting the mixture for 30 days at the temperature of 15-40 ℃ and the humidity of 60-80% to obtain a raw material of the medicinal composition which is yellowish brown in appearance, has unique medicinal fragrance and is slightly sour and bitter in taste;

3) adding water 5 times the weight of the raw materials into the raw materials, decocting with slow fire for 30min, filtering the decoction fermented vinegar, concentrating the filtrate under reduced pressure to obtain anticancer extract, and vacuum drying to obtain anticancer extract powder;

4) vacuum drying the residue of the decocted fermented vinegar, and pulverizing the dried residue to obtain anticancer Chinese medicinal composition powder;

5) mixing 100g of anticancer Chinese medicinal composition powder with 20g of Chinese honey, kneading the refined honey and the medicinal powder at the temperature of 60 ℃ and the honey, and making into water-honeyed pill with weight of 0.5g by a pill making machine;

6) mixing 2g of the anticancer extract powder with 8ml of PEG6000 matrix, heating to 80 deg.C, dispersing completely, titrating to 10 deg.C coolant liquid paraffin by titration method, wherein the drop distance is 7cm, the drop speed is 60 drops/min, and the pill weight is 35 mg.

5. Detection of anticancer pharmaceutical composition ingredients

The fermented vinegar and vinegar paste prepared in this example were tested for their components, and found to be rich in polysaccharides, polypeptides, organic acids, flavones and polyphenols, as shown in table 1. LC-MS analysis (shown in figure 1 and Table 2) shows that the vinegar paste dichloromethane extract has active substances such as 9, 12-octadecadienoic acid, inositol, ferulic acid, 5-hydroxymethyl furfural, veratraldehyde, etc., such as inositol is a nutrient for promoting cell growth and maintaining animal physiological functions, is especially important for growth of liver and bone marrow cells, and ferulic acid has the effects of resisting oxidation, resisting thrombus, reducing blood lipid, preventing and treating coronary heart disease, etc.

TABLE 1 active substance content in fermented Vinegar

Inspection item	Unit of measurement	Content (wt.)
			Total polysaccharides	g/100ml	12.80
Total Flavonoids	mg/ml	2.72
			Total polyphenols	mg/ml	6.75
Total acid	g/100ml	12.2
			Non-volatile acid	g/100ml	5.08
Total polypeptides	g/100g	5.70
			Ligustrazine	mg/L	101.03
Soluble salt-free solid	g/100ml	26.31

TABLE 2 analysis of the composition of the vinegar extract dichloromethane extract

Example 2

1. preparation of fermented grains

1) Mixing sorghum and rice, pulverizing, soaking in water, steaming for 180 min, adding 150 wt% water, and stewing at 100 deg.C for 30 min;

2) crushing Luzhou Daqu, adding 40% of the raw material by weight into the raw material, uniformly stirring, adding 70% of water by weight, fermenting for 3 days in a cylinder at the fermentation temperature of 15-40 ℃, and sealing and aging for 180 days after primary fermentation to obtain a primary fermented product;

3) adding grain skin substances accounting for 120% of the weight of the raw materials into the primary fermented product, uniformly mixing, subpackaging in shallow jars, covering with straw mats, fermenting for 15 days, turning layer by layer every day, performing primary fermentation, sealing and aging for 60 days to obtain secondary fermented product, namely fermented grains.

2. Preparation of fermented vinegar

1) Evenly mixing 1/3 fermented grains fried by mild fire with the rest fermented grains, and performing warm-soaking dynamic circulation extraction on the evenly mixed fermented grains with hot water of 3 times of the weight of the evenly mixed fermented grains, wherein the extraction temperature is 70 ℃, and the extraction times are 3 times to obtain an extraction liquid, and the content of soluble salt-free solid matters is 9.5g/100 ml;

2) freezing and concentrating the extractive solution at initial temperature of 4 deg.C, refrigerant temperature of-6 deg.C, scraper speed of 40r/min, and concentrating for 12h to obtain fermented vinegar.

3. Preparation of vinegar paste

Taking the fermented vinegar, sealing and aging for 30 months, wherein the semisolid paste at the bottom is vinegar paste.

4. Preparation of anticancer medicine composition

1) Removing impurities from carapax Trionycis 8, Olibanum 2, Myrrha 2, rhizoma Sparganii 3, Curcumae rhizoma 2, endothelium corneum Gigeriae Galli 3, rhizoma Cyperi 2, radix Euphorbiae Fischerianae 1, radix Phytolaccae 3, radix Aconiti lateralis Preparata 3, radix astragali 10, radix Codonopsis 10, Ginseng radix 3, Notoginseng radix 3, Poria 13, rhizoma Osmundae 2, radix patriniae 3, Rabdosia rubescens 12, resina garciniae 0.5, thallus laminariae 2, Atractylodis rhizoma 2, Lumbricus 2, American sickle 3, and Bufonis venenum 0.5, pulverizing into coarse powder, adding 300 weight parts of fermented vinegar, soaking for 15 days, parching with slow fire, and controlling water content to 20%;

2) uniformly mixing the fried medicinal materials with 30 parts by weight of vinegar paste and 60 parts by weight of fermented grains, sealing the mixture in a shallow pottery jar of 50cm, and fermenting the mixture for 60 days at the temperature of 15-40 ℃ and the humidity of 60-80% to obtain a raw material of the medicinal composition with a yellow brown appearance, unique medicinal fragrance and slightly sour and bitter taste;

3) taking the raw materials of the medicinal composition, adding water with the weight 6 times of the raw materials, decocting with slow fire for 60min, filtering the decocted fermented vinegar, and concentrating the filtrate under reduced pressure to 1/3 volumes to obtain the raw materials of the traditional Chinese medicine oral liquid;

4) taking the raw materials of the traditional Chinese medicine oral liquid, adding 0.1 percent of sodium carboxymethylcellulose and 0.04 percent of xanthan gum, homogenizing under ultrahigh pressure, subpackaging into 50ml of oral liquid and sterilizing to obtain the anticancer oral liquid.

Furthermore, in order to verify the property of the fermented product prepared in the embodiment of the present invention in anticancer, animal efficacy experiments and human efficacy experiments are performed in the embodiment of the present invention.

Example 3

1. Experimental methods

Taking L on day 6 of inoculation₆₁₅Killing leukemia mice after dislocation of cervical vertebrae, taking a proper amount of spleen, placing a small amount of sterile normal saline for homogenate to prepare cell suspension, diluting to 8-9 ml, taking a proper amount of diluted cell suspension, adding 0.2% of taloprene blue buffer saline solution to enable the final concentration of taloprene blue to be 0.02%, calculating the number of living cells of the suspension, and properly diluting to enable the concentration of the living cell suspension to be 4 × 10¹⁰·L^-1. The cell suspension was inoculated subcutaneously into 150 healthy L615 mice,each 0.1ml, mice were randomly divided into 5 groups. The model group was administered by gavage with 0.4 ml/physiological saline, the positive control group was administered by gavage with 0.4 ml/one (containing homoharringtonine 10mg), the high dose group was administered by gavage with 0.4 ml/one example 2 oral liquid, the middle dose group was administered by gavage with 0.2 ml/one example 2 oral liquid, the low dose group was administered by gavage with 0.1 ml/one example 2 oral liquid, the remaining solution was made up with physiological saline, 15 sacrificed weight groups were taken after continuous administration for 15 days, the liver and spleen were dissected and weighed, and the liver coefficient and spleen coefficient of the mice were calculated based on the ratio of the weight of the organ to the weight. After 60 days of continuous administration (the mice with a survival time longer than 60 days, and considered to be cured), the life extension rate of the mice was calculated, and the life extension rate was 1 [ average survival days of administration group/average survival days of control group ]]×100％。

2. Results of the experiment

The influence of the oral liquid on the liver and spleen of the leukemia mice is shown in table 3, and the liver index of the mice can be improved in the oral liquid high-dose group, so that the oral liquid has significant difference. On the other hand, the oral liquid can reduce spleen indexes to different degrees, wherein the high and medium doses have significant difference, so the result shows that the oral liquid has a certain protection effect on the spleen of a leukemia mouse, so that the obviously enlarged mouse spleen is reduced, and the immunity of the organism is enhanced.

TABLE 3 Effect of oral liquid on liver and spleen of leukemia mice

Group of	Body weight (g)	Liver index	Spleen index
				Model set	19.45±1.52	44.84±1.03	17.35±3.12
Positive control group	20.16±1.82	49.12±1.24^*	6.37±2.14^**
				Oral liquid high dose group	20.18±1.56	54.32±3.18^**	9.05±2.82^*
Oral liquid medium dose group	19.88±1.76	45.52±1.36	9.79±3.14^*
				Oral liquid low dose group	20.02±1.63	46.69±1.41	14.05±3.07

Note that:^*P<0.05，^**P<0.01vs. model set

The influence of the oral liquid on the survival cycle of the leukemia mice is shown in table 4, the high, medium and low doses of the oral liquid can obviously prolong the survival cycle of the leukemia mice, compared with a model group, the high, medium and low doses have very obvious difference, and the life prolonging rate of the high dose group reaches 91.89%.

TABLE 4 Effect of oral liquid on the survival cycle of leukemic mice

Group of	Number of animals	Average life cycle (d)	Life extension Rate (%)	P value
					Model set	15	7.4±2.5
Positive control group	15	14.2±4.7	91.89	＜0.01
					Oral liquid high dose group	15	13.4±3.9	81.08	＜0.01
Oral liquid medium dose group	15	11.6±3.5	56.75	＜0.01
					Oral liquid low dose group	15	10.5±2.8	41.89	＜0.01

Example 4

1. Experimental methods

150 male mice of an SPF grade C57BL/6 lymphoma model are purchased, 6-8 weeks old and 18-20 g, and are randomly divided into five groups: the mice in the blank control group are subjected to intragastric administration according to 0.8ml of physiological saline; the positive drug control group is perfused with 0.8ml per stomach (containing 25.78 mug methotrexate) for 1 time per 2 days; high dose groups 2 pellets of 35mg anti-cancer pills prepared in example 1 were dissolved in 10ml water and administered by gavage at 0.8 ml/tube; the middle dose group is perfused with 0.4ml per stomach; the low dose group was gavaged at 0.2 ml/stomach; the rest volume is supplemented with physiological saline, the administration is continuously carried out for 60 days, the tumor volume is calculated on the 3 rd, 6 th, 9 th, 12 th and 24 th days, and the survival rate and the median survival time of each group of mice for 60 days are calculated.

2. Results of the experiment

The change of the tumor volume of the mice is shown in a table 5, the high, medium and low doses have different degrees of inhibition on the tumor volume, wherein the inhibition of the medium dose group on the tumor volume is similar to that of a positive control group, and the significant difference is achieved.

TABLE 5 tumor volume changes (mm) in groups of mice³)

Note that:^*P<0.05，^**P<0.01vs. model set;^#P<0.05，^##P<0.01vs. Positive control

The survival rate of the mice in 60 days and the median survival time are shown in a table 6, compared with the model group, the survival rate of each group is greatly improved, the effect of the medium dose group is best, the survival rate of the 60d group is 23.3 percent and is slightly weaker than that of the positive control group, but the median survival time is 45 days and is close to that of the positive control group, the effect of the high dose group is better, the survival rate is 20 percent, and the median survival time is 42 days.

TABLE 6 Effect of anticancer pellets on 60d survival and median survival time of groups of mice

Group of	Number only	Survival Rate of 60d (%)	Median survival time (d)
				Model set	30	0	20
Positive control group	30	40	49
				High dose set of dropping pills	30	20.0	42
Medium dosage group of dropping pills	30	23.3	45
				Low dose composition of drop pills	30	10.0	31

Example 5

Typical cases are: zhoushan, male, 47 years old, in No. 7, 08 in 2017, the Huxiang traditional Chinese medicine tumor hospital bone puncture shows that primitive granulocytes are 35%, promyelocytes are 14%, AML-m2a is confirmed, chemotherapy in the Huxiang traditional Chinese medicine tumor hospital achieves partial relief, in No. 09, 15 in 2017, the anti-cancer pills in example 1 are taken 10 pills/time, 3 times a day, one treatment course is carried out for four weeks, 4 treatment courses are taken, and blood routine smear is carried out every half a month, all the courses are normal. The anticancer oral liquid of example 2 is taken instead, the treatment is consolidated for 6 courses of treatment, and the administration is stopped after the bone puncture is normal. The patient underwent bone puncture in No. 9/25 of 2018 in Huxiang traditional Chinese medicine tumor hospital to show that 1% of primitive granulocytes and 2% of early granulocytes had recovered to normal values.

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.

Claims

1. The anticancer pharmaceutical composition is characterized by comprising an anticancer extracting solution and an anticancer traditional Chinese medicine composition, and the anticancer pharmaceutical composition comprises the following raw materials in parts by weight: 20-80 parts of fermented grains, 50-300 parts of fermented vinegar, 5-30 parts of vinegar paste and 49-121 parts of traditional Chinese medicines;

2. The anticancer pharmaceutical composition of claim 1, wherein said preparation of fermented grains comprises at least the steps of:

3. The anticancer pharmaceutical composition according to claim 1, wherein said fermented vinegar is prepared by at least the steps of:

4. The anticancer pharmaceutical composition as set forth in claim 1, wherein the preparation of the vinegar paste at least comprises: and (3) sealing and ageing the fermented vinegar for 6-48 months to obtain semi-solid paste, namely vinegar paste.

5. The anticancer pharmaceutical composition of any one of claims 1 to 4, further comprising pharmaceutically acceptable excipients, wherein the pharmaceutically acceptable excipients comprise: at least one of a solvent, a solubilizer, an emulsifier, an adhesive, a disintegrant, a filler, a lubricant, a stabilizer, a glidant, a flavoring agent, a preservative, a suspending agent, a coating material, an anti-adhesive, a penetration enhancer, a pH regulator, a buffer, a surfactant, a thickener, a humectant, an absorbent, a diluent, a flocculant, and a deflocculant.

6. The anti-cancer pharmaceutical composition of claim 5, useful for the treatment of at least: leukemia, lymphoma, gastric cancer, colon cancer, and oral cancer.

7. The preparation method of the anticancer pharmaceutical composition is characterized by comprising the following steps:

8. The method of preparing the anticancer pharmaceutical composition according to claim 7,

the particle size of the traditional Chinese medicine powder is not more than 180 microns; and/or the presence of a gas in the gas,

the soaking time is 1-15 days; and/or the presence of a gas in the gas,

9. The method of preparing the anticancer pharmaceutical composition of claim 7 or 8, further comprising: concentrating the anticancer extracting solution to obtain a thick anticancer extracting solution, drying the thick anticancer extracting solution, and crushing to obtain a powdery anticancer extract; and/or the presence of a gas in the gas,

10. The method of preparing the anticancer pharmaceutical composition of claim 9, further comprising: in the anticancer pharmaceutical composition, auxiliary materials allowed in a pharmaceutical range are added to prepare a pharmaceutically acceptable dosage form, wherein the pharmaceutically acceptable dosage form comprises: at least one of oral liquid, capsule, tablet, unguent, powder, granule, pill, suppository and extract injection.