Anti-tumor Chinese medicine composition and its preparation method and application

Abstract

The invention belongs to the field of medicine, and discloses an anti-tumor Chinese medicine composition, a preparation method and an application thereof. The Chinese medicine composition is prepared from Chinese medicines such as Herba Agrimoniae, Rhizoma Smilacis Glabrae, Polyporus, Herba Hedyotis Diffusae, and Herba Cat's Claw, giving full play to the characteristics of Chinese medicine "strengthening the body and eliminating evil" and the advantages of multi-component, multi-target, multi-pathway, multi-link synergistic effect and overall treatment, and can effectively inhibit tumor growth, enhance immune function, reduce the toxic and side effects of radiotherapy and chemotherapy, and has a synergistic effect on radiotherapy and chemotherapy. The preparation method of the composition of the present invention is stable and feasible, with controllable quality, and is suitable for large-scale industrial production.

Description

Technical Field

[0001] The invention belongs to the field of medicine, and specifically relates to an anti-tumor Chinese medicine composition and a preparation method and application thereof. Background Art

[0002] Malignant tumors are one of the major diseases that seriously threaten human life and health. Statistics from the World Health Organization show that the number of cancer cases in the world reaches 10 million and the number of deaths reaches 7 million each year. Cancer is the second largest killer of humans after cardiovascular disease. In recent years, the incidence of malignant tumors has further increased, and the need to find ideal tumor treatment drugs has become more urgent.

[0003] Modern medicine believes that the onset of tumors involves multiple factors such as physics, chemistry, biology, genetics, hormones, nutrition, and immunity. The development of anti-tumor drugs has gone through alkylating agents from the 1940s to the 1950s, herbal medicines, antimetabolites, antibiotics, and platinum drugs from the 1960s to the 1990s, and biological drugs and biological treatment methods in recent years, such as antibody drugs and cell therapy. As human beings gradually deepen their understanding of the etiology and pathogenesis of malignant tumors, they have further developed treatment ideas. The rich theoretical and practical experience of traditional Chinese medicine in the field of tumor treatment has gradually attracted the attention of the medical community. Traditional Chinese medicine believes that unfavorable qi movement, blood stasis, phlegm coagulation, toxic evil cohesion, and deficiency of positive qi are the main mechanisms of tumor occurrence. Practice has proved that traditional Chinese medicine has incomparable advantages over chemical synthetic drugs in inhibiting tumors, enhancing patients' immune function, enhancing radiotherapy and chemotherapy sensitivity, reducing chemotherapy adverse reactions, improving patients' quality of life, and prolonging survival.

[0004] Studies have shown that the anti-tumor effects of traditional Chinese medicine are multifaceted, including: 1. Inhibiting the synthesis of DNA and RNA; 2. Inhibiting the activity of microtubules; 3. Inhibiting the activity of protein tyrosine kinase; 4. Inhibiting the activity of telomerase; 5. Inhibiting the formation of tumor blood vessels; 6. Inducing the differentiation of tumor cells; 7. Reversing the drug resistance of tumor cells; 8. Regulating the body's immune function; 9. Destroying cell junctions and directly killing tumor cells; 10. Anti-mutation and anti-oncogenic promoter effects. One of the main directions of research and development of anti-tumor traditional Chinese medicine is to give full play to the advantages of traditional Chinese medicine in the treatment of malignant tumors, use drugs rationally according to the etiology and pathogenesis of malignant tumors, and improve symptoms, improve the quality of life, and prolong survival in the entire comprehensive treatment process. Summary of the invention

[0005] The purpose of the present invention is to provide an anti-tumor Chinese medicine composition which can "strengthen the body's resistance and eliminate evil" and has a synergistic effect of multiple components, multiple targets, multiple pathways, and multiple links and an overall therapeutic advantage, as well as a preparation method and application thereof.

[0006] The objective of the present invention is achieved through the following technical solutions:

[0007] On the one hand, the present invention provides an anti-tumor Chinese medicine composition, which is prepared from the following Chinese medicine components in parts by weight: 20-600 parts of agrimony, 1-100 parts of scutellaria, 5-200 parts of oldenlandia diffusa, 5-200 parts of salvia miltiorrhiza, 5-200 parts of lithospermum officinale, 20-600 parts of cucurbita chinensis roots, 5-200 parts of smilax china, 5-200 parts of smilax glabra, 1-100 parts of bupleurum, 5-200 parts of cyperus rotundus, 5-200 parts of cat's claw, 5-200 parts of millettia reticulata, 5-200 parts of umbellata, 5-200 parts of goat's milk, 2-200 parts of mistletoe, 5-200 parts of gynostemma pentaphyllum, 5-200 parts of turtle shell, 5-200 parts of oyster, 2-120 parts of honeycomb, 2-120 parts of bombyx batryticatus, 5-200 parts of chicken's gizzard lining, and 1-100 parts of smilax glabra.

[0008] Preferred are: 40-320 parts of Agrimoniae, 2-50 parts of Scutellariae, 10-80 parts of Hedyotis diffusa, 10-80 parts of Salvia miltiorrhiza, 10-80 parts of Ilex erythrorhizon, 40-320 parts of Cudrania tricuspidata, 10-80 parts of Smilax china, 10-80 parts of Smilax glabra, 2-50 parts of Bupleurum, 10-80 parts of Semen euphorbiae, 10-80 parts of Cat's Claw, 10-80 parts of Millettia reticulata, 10-100 parts of Polyporus, 10-80 parts of Goat's milk, 5-80 parts of Mistletoe, 10-80 parts of Gynostemma pentaphyllum, 10-100 parts of Carapace of Turtle, 10-100 parts of Oyster, 5-60 parts of Honeycomb, 5-60 parts of Bombyx batryticatus, 10-80 parts of Gallus gallus domesticus, and 2-50 parts of Dendrobium officinale.

[0009] More preferably, the following ingredients are used: 80-160 parts of Agrimoniae, 5-25 parts of Scutellariae, 20-40 parts of Hedyotis diffusa, 20-40 parts of Salvia miltiorrhiza, 20-40 parts of Ilex erythrorhizon, 80-160 parts of Cudrania tricuspidata, 20-40 parts of Smilax china, 20-40 parts of Smilax glabra, 5-25 parts of Bupleurum, 20-40 parts of Fructus cyrtonemae, 20-40 parts of Cat's Claw, 20-40 parts of Millettia reticulata, 30-70 parts of Polyporus, 20-40 parts of Goat's milk, 10-40 parts of Mistletoe, 20-40 parts of Gynostemma pentaphyllum, 30-70 parts of Carapace of Turtle, 30-70 parts of Oyster, 10-30 parts of Beehive, 10-30 parts of Bombyx batryticatus, 20-40 parts of Gallus gallus domesticus, and 5-25 parts of Dendrobium officinale.

[0010] The most preferred are: 120 parts of Herba Agrimoniae, 10 parts of Scutellariae, 30 parts of Hedyotis diffusa, 30 parts of Salvia miltiorrhiza, 30 parts of Lithospermum officinale, 120 parts of Cuscuta australis, 30 parts of Smilax china, 30 parts of Smilax glabra, 10 parts of Bupleurum, 30 parts of Fructus Preparata, 30 parts of Cat's Claw, 30 parts of Millettia reticulata, 50 parts of Polyporus, 30 parts of Goat's Milk, 20 parts of Mistletoe, 30 parts of Gynostemma pentaphyllum, 50 parts of Carapace of Turtle, 50 parts of Oyster, 15 parts of Honeycomb, 15 parts of Bombyx batryticatus, 30 parts of Gallus gallus domesticus, and 10 parts of Dracaena.

[0011] The Chinese medicine composition of the present invention is prepared by extracting the raw materials of the above formula into active substances, and the active substances are used as raw materials to prepare any pharmaceutically acceptable dosage form according to conventional preparation techniques when necessary. The active substances can be obtained by crushing or extracting them separately, or by crushing or extracting them together, such as by crushing, grinding, percolation, water extraction, alcohol extraction, etc. These active substances can be in the form of powder or extract, and can be dry extract or fluid extract, and different concentrations can be prepared according to different preparation requirements.

[0012] On the other hand, the Chinese medicine composition of the present invention can be made into any pharmaceutically acceptable oral dosage form. The oral dosage form is selected from the group consisting of tablets, capsules, granules, pills, powders, oral liquids, pastes, suspensions, and solutions. Tablets, capsules, granules, pills, and powders are preferred. Granules are most preferred.

[0013] The oral dosage form is prepared by conventional methods in the pharmaceutical field, and pharmaceutically acceptable excipients may be added when necessary. The pharmaceutically acceptable excipients are selected from dextrin, starch, lactose, micropowdered silica gel, mannitol, magnesium stearate, hydroxypropyl cellulose, microcrystalline cellulose, calcium phosphate, sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, talc, hydroxypropyl methylcellulose, citric acid, ethyl cellulose, etc.

[0014] In another aspect, the present invention provides a method for preparing the Chinese medicine composition, comprising the following steps:

[0015] Take the medicinal material, add 8 to 20 times of water by weight of the medicinal material, perform decoction or reflux extraction 1 to 3 times, each time for 1 to 4 hours, filter, combine the filtrates, concentrate, and dry to obtain a Chinese medicine composition;

[0016] Or take the medicinal material, add 8 to 20 times of water by weight of the medicinal material, extract by steam distillation 1 to 3 times, each time for 1 to 4 hours, collect the volatile oil, filter, combine the filtrate, concentrate, dry, and mix with the volatile oil to obtain a Chinese medicine composition;

[0017] Or take the medicinal material, add 8 to 20 times of water by weight of the medicinal material, decoct or reflux extract 1 to 3 times, each time for 1 to 4 hours, filter, combine the filtrates, concentrate to 1.05 to 1.30, add 50% to 95% ethanol to precipitate to 30% to 85% alcohol, let stand for 6 to 24 hours, concentrate the supernatant, dry, and obtain the Chinese medicine composition;

[0018] Or take the medicinal material, add 8 to 20 times of water by weight of the medicinal material, extract 1 to 3 times by steam distillation, each time for 1 to 4 hours, collect the volatile oil, filter, combine the filtrates, concentrate to 1.05 to 1.30, add 50% to 95% ethanol to precipitate to 30% to 85% alcohol, let stand for 6 to 24 hours, concentrate the supernatant, dry, and mix with the volatile oil to obtain a Chinese medicine composition;

[0019] Or take the medicinal material, add 6 to 20 times of 30% to 95% ethanol, heat and reflux 1 to 4 times, each time for 1 to 3 hours, filter, combine the filtrates, concentrate, and dry to obtain a Chinese medicine composition;

[0020] Or take the medicinal material, add 30% to 95% ethanol 6 to 20 times, percolate or cold soak 2 to 4 times, filter, combine the filtrates, concentrate, and dry to obtain a Chinese medicine composition, wherein the percolation rate is 1 to 5 ml / min until no percolate flows out, and the cold soaking extraction time is 6 to 24 hours each time;

[0021] Or take medicinal materials, group them, extract them by one or more of the above methods, respectively obtain components of the Chinese medicine composition, mix them evenly, and obtain the Chinese medicine composition.

[0022] Preferably, the method for preparing the Chinese medicine composition of the present invention comprises the following steps:

[0023] Take the medicinal material, add water 12 times the weight of the medicinal material, reflux extract 3 times, each time for 1.5 hours, filter, combine the filtrates, concentrate, and dry to obtain a Chinese medicine composition;

[0024] Or take the medicinal material, add 10 times of water by weight of the medicinal material, decoct it 3 times by decoction method, each time for 1 hour, filter, combine the filtrates, concentrate to 1.20-1.25 at 60-65°C, add 95% ethanol to precipitate until the alcohol content reaches 60%, let stand for 12 hours, concentrate the supernatant, dry, and obtain the Chinese medicine composition;

[0025] Or take the medicinal material, add 10 times of water by weight of the medicinal material, decoct it 3 times by decoction method, each time for 1.5 hours, filter, combine the filtrates, concentrate to 1.18-1.22 at 50-60°C, add 95% ethanol to precipitate to 60% alcohol content, let stand for 12 hours, concentrate the supernatant, dry, and obtain the Chinese medicine composition;

[0026] Or take the medicinal material, add water 10 times the weight of the medicinal material, extract by reflux method 3 times, 2 hours each time, filter, combine the filtrates, concentrate to 1.15-1.20 at 50-60°C, add 95% ethanol to precipitate to 60% alcohol content, let stand for 12 hours, concentrate the supernatant, dry, and obtain the Chinese medicine composition;

[0027] Or take the medicinal material, add 10 times of 70% ethanol, reflux extract twice, each time for 2 hours, filter, combine the filtrates, concentrate to 1.20-1.25 at 60-75°C, dry, and obtain a Chinese medicine composition;

[0028] Or take the medicinal materials, add 60% ethanol 10 times, cold soak twice, each time for 12 hours, filter, combine the filtrates, concentrate, and dry to obtain a Chinese medicine composition;

[0029] Or take medicinal materials, group them, extract them by one or more of the above methods, respectively obtain components of the Chinese medicine composition, mix them evenly, and obtain the Chinese medicine composition.

[0030] In another aspect, the present invention provides use of the above-mentioned Chinese medicine composition in the preparation of a drug for treating cancer or assisting in the treatment of cancer.

[0031] Preferably, the cancer is liver cancer or lung cancer, more preferably liver cancer or lung cancer in the advanced stage with no indication for surgery, radiotherapy or chemotherapy or with cachexia;

[0032] The adjuvant cancer treatment is treatment after surgery, radiotherapy, chemotherapy and the like, more preferably treatment after radiotherapy, chemotherapy and the like.

[0033] The present invention adopts agrimony, scutellaria, oldenlandia diffusa, salvia miltiorrhiza, lycopodiella ciliata, cucurbita chinensis root, smilax china, smilax glabra, bupleurum, euphorbia pruriens, cat's claw, millet vine, umbellate, goat milk, mistletoe, gynostemma pentaphyllum, turtle shell, oyster, honeycomb, bombyx batryticatus, chicken's gizzard lining, and smilax glabra, and has the effects of strengthening the body, removing blood stasis, eliminating symptoms and dispersing nodules. Among them:

[0034] Agrimony, bitter, astringent, neutral. Enters the lung, heart, and liver meridians. Detoxifies and removes blood stasis, astringes and stops bleeding, strengthens the body and replenishes deficiency. "Bai Cao Jing" says: "It can lower qi and activate blood circulation, cure all diseases, and relieve fullness and distension." "Guizhou Folk Prescriptions" says: "It can treat pulmonary tuberculosis and hemoptysis." "Compendium of Materia Medica" says: "It can treat carbuncle, ulcer, and lung abscess." "Huangdi Neijing" says: "If the bitter qi of the lungs goes up, eat bitter food to relieve it."

[0035] Cudrania root, sweet, neutral. Enters the lung, stomach, and liver meridians. Disperses blood stasis and stops bleeding, resolves phlegm and resolves knots, replenishes fatigue and nourishes deficiency. "New Selection of Practical Chinese Herbal Medicines in Guangxi" says: "It clears away heat and activates blood circulation, stops coughing and eliminates phlegm. It treats coughing and bleeding due to fatigue." "Selected Chinese Herbal Medicines in Yunnan" says: "It can reduce inflammation and relieve pain, and treat furuncles and carbuncles."

[0036] Danshen, bitter, slightly cold. Enters the heart and liver meridians. Removes blood stasis and relieves pain, activates blood circulation and unblocks meridians. Shennong's Herbal Classic says: "It cures cold and heat accumulation, dissolves tumors and tonifies qi". Bencao Zhengyi says: "It enters the blood, and its function is to activate blood circulation, dissolve internal stasis, and unblock meridians."

[0037] Millettia reticulata is bitter, sweet and warm. It enters the liver, kidney and meridians. It nourishes blood, activates blood circulation and dredges the meridians. The ancients also said: "Drinking Danshen alone has the same effect as Siwu Decoction."

[0038] Lithospermum officinale is bitter, pungent and neutral. It enters the lung, stomach and liver meridians. It can detoxify and reduce swelling, resolve phlegm and resolve knots, and promote blood circulation and relieve pain. "Suzhou Native Medicinal Materials" says: "It can treat choking, phlegm and asthma." "Compendium of Materia Medica" says: "It can treat stomachache and carbuncle caused by wind." "Jiangsu Medicinal Materials" says: "It can treat scrofula."

[0039] Prescription seeds are bitter and neutral. They enter the lung, stomach, liver and bladder meridians. They soothe the liver and stomach, promote blood circulation and relieve pain, soften and disperse lumps. Zhu Liangchun, an old Chinese doctor, believes that it has no disadvantages of being fragrant and dry, regulates qi without hurting it, and has the effect of stimulating appetite.

[0040] Chicken gizzard lining, sweet, neutral. Enters spleen, stomach, small intestine, bladder meridians. Strengthens the stomach and helps digestion. "Medical Records of Chinese and Western Medicine" says: "It can not only eliminate the accumulation of spleen and stomach, but also eliminate the accumulation of any internal organs. Long-term use can cure male lumps and female masses. Chicken gizzard lining can also be added to dissolve the stagnation of meridians." Raw use retains its properties, but roasting reduces its effect.

[0041] Raw oysters are salty and slightly cold. They enter the liver, gallbladder, and kidney meridians. They can suppress yang and replenish yin, soften and disperse masses. The Compendium of Materia Medica says: "It can dissolve phlegm and soften masses, eliminate hernia, lumps, goiter, and tuberculosis." The Essentials of Materia Medica says: "Salty can soften and dissolve phlegm, eliminate scrofula, tuberculosis, and old blood hernia."

[0042] Bupleurum, bitter, slightly cold. Enters the liver and gallbladder meridians. Reconciles the exterior and interior, soothes the liver, and raises yang. "Sisheng Materia Medica" says: "It treats phlegm and chest and flank distension."

[0043] Beast shell, salty, slightly cold. Enters the liver and kidney meridians. Nourishes yin and suppresses yang, softens and disperses lumps. Shennong's Herbal Classic says: "It is used to treat abdominal masses, hard masses, polyps, genital erosion, hemorrhoids and malignant flesh." Yaoxing Lun says: "It is used to treat masses, lumps, and cold masses."

[0044] Cat's Claw, sweet, pungent, warm. Enters the lung and liver meridians. Reduces swelling and resolves nodules, relieves cough and eliminates phlegm. The Handbook of Chinese Medicinal Materials says: "It can treat scrofula and tuberculosis on the neck." The Handbook of Henan Chinese Herbal Medicine says: "It can reduce swelling and stop symptoms, treat scrofula and tuberculosis."

[0045] Bombyx batryticatus, salty, pungent, neutral. Enters the lung, stomach, and liver meridians. Dispels wind and calms nerves, resolves phlegm and disperses stagnation. Compendium of Materia Medica says: "It can disperse wind, phlegm, tuberculosis, scrofula, phlegm syndrome, all wounds, carbuncle, wind hemorrhoids."

[0046] Sheep milk, pungent, sweet, neutral. Enter the lung, liver, spleen, large intestine meridians. Detoxify and reduce swelling, remove phlegm and resolve knots, replenish qi and nourish blood. "Compendium of Materia Medica" says: "It can treat swelling, toxins, scrofula." "Collecting Medicinal Book" says: "It can treat bayberry sores."

[0047] Gynostemma pentaphyllum, sweet, slightly bitter, slightly cold. Replenishes Qi and nourishes the heart, clears heat and resolves phlegm. Enters the heart, stomach, and kidney meridians. Polyporus umbellatus, sweet, bland. Promotes diuresis and eliminates dampness, removes phlegm and resolves stagnation. Enters the kidney and bladder meridians.

[0048] Poria has the effect of diuresis and dampness-removing, and can reduce or eliminate edema caused by cancer.

[0049] Hedyotis diffusa is sweet, light, slightly bitter and slightly cold. It clears away heat and detoxifies, promotes blood circulation and removes blood stasis, eliminates dampness and eliminates carbuncle. It enters the lung, liver, large intestine and bladder meridians. "Quanzhou Materia Medica" says: "It clears away heat and dissipates blood stasis, eliminates carbuncle and detoxifies. It treats carbuncle, ulcer, and scrofula. It can also clear lung fire and relieve lung heat. It treats shortness of breath due to lung heat, cough and chest tightness."

[0050] Smilax china, sweet, sour, neutral. Enters the lung, stomach, liver, and kidney meridians. Clears away heat and detoxifies, astringes and stops bleeding, reduces swelling and relieves pain. "Pin Hui Jing Yao" says: "Disperses swelling and toxins" "Sichuan Chinese Medicine Records" says: "Treats hematuria, scrofula, and traumatic injuries."

[0051] Smilax glabra, sweet, light, neutral. Enters the liver and stomach meridians. Removes dampness and detoxifies. "Compendium of Materia Medica" says: "It can treat waxberry sores, scrofula, sores and swellings." "Compendium of Materia Medica" says: "It can strengthen the spleen and stomach, and treat malignant sores and carbuncles."

[0052] Tianlong, salty, cold, slightly toxic. Enters the liver meridian. Expels wind and calms the nerves, detoxifies and disperses stagnation. "Compendium of Materia Medica" says: "It can treat blood stasis and lumps, and leukorrhea and scrofula."

[0053] Beehive, sweet, neutral. Enters the stomach meridian. Expels wind and poison, dissipates swelling and relieves pain. "Bie Lu" says: "It can treat toxic swelling." "Rihuazi Bencao" says: "It can treat breast pain and malignant sores." "Bencao Shu" says: "It can treat chronic cough with phlegm accumulation."

[0054] Mistletoe, bitter, neutral. Enters the liver and kidney meridians. Nourishes the liver and kidneys, strengthens the tendons and bones.

[0055] Scutellaria baicalensis, bitter, cold. Enter the lung, gallbladder, spleen, large intestine, small intestine meridians. Clear away heat and dampness, purge fire and detoxify, stop bleeding.

[0056] The composition of the present invention has the effects of strengthening the body and removing blood stasis, eliminating symptoms and dispersing nodules, can effectively inhibit the growth of tumors, enhance immune function, have a broad-spectrum synergistic effect on anti-tumor chemotherapy drugs, and can reduce the toxicity of chemotherapy drugs. The composition of the present invention is also safe and has no toxic side effects when used for a long time. Clinical studies have shown that the composition of the present invention can effectively alleviate and inhibit tumors, improve the quality of life of patients, and prolong the survival period. In combination with radiotherapy and chemotherapy, it can not only reduce the toxic and side effects of radiotherapy and chemotherapy, but also has a synergistic effect on radiotherapy and chemotherapy. DETAILED DESCRIPTION

[0057] The present invention will be further described in detail below in conjunction with specific embodiments. The examples given are intended to illustrate the present invention rather than to limit the scope of the present invention.

[0058] Example 1 :

[0059] Mix the following Chinese medicinal materials according to weight ratio:

[0060] Take 600g of Herba Agrimoniae, 100g of Radix Scutellariae, 200g of Herba Hedyotis Diffusae, 200g of Radix Salviae Miltiorrhizae, 200g of Lithospermum Officinale, 600g of Cuscuta Australis, 200g of Smilax Chinensis, 200g of Rhizoma Smilacis Glabrae, 100g of Radix Bupleuri, 200g of Fructus Preparata, 200g of Herba Cat's Claw, 5g of Caulis Spatholobi, 5g of Polyporus, 5g of Goat's Milk, 2g of Viscum Album, 5g of Gynostemma Pentaphyllum, 5g of Carapace of Turtle, 5g of Concha Oyster, 2g of Honeycomb, 2g of Bombyx Batryticatus, 5g of Endothelium Gallifoliae and 1g of Rhizoma Cibotii, add 8 times of the weight of the medicinal materials of water, decoct 3 times by decoction method, each time for 1 hour, filter, combine the filtrates, concentrate to 1.10-1.20 (60°C), add 95% ethanol to precipitate until the alcohol content reaches 80%, let stand for 6 hours, concentrate the supernatant, and dry to obtain a Chinese medicine composition.

[0061] Example 2 :

[0062] According to the weight ratio, divide the following Chinese medicinal materials into two parts and mix them separately:

[0063] Take 20g of Agrimoniae, 1g of Scutellariae, 5g of Hedyotis diffusa, 5g of Salvia miltiorrhiza, 5g of Lithospermum officinale, 20g of Cudrania tricuspidata root, 5g of Smilax china, 5g of Smilax glabra, 1g of Bupleurum chinense, and 5g of Semen euphorbiae, add 20 times of water by weight of the medicinal materials, extract once by steam distillation for 4 hours, collect volatile oil, filter, concentrate, dry, and mix with volatile oil to obtain Chinese medicine composition I;

[0064] Take 5g of cat's claw, 200g of Millettia reticulata, 200g of Polyporus umbellatus, 200g of goat's milk, 200g of mistletoe, 200g of Gynostemma pentaphyllum, 200g of turtle shell, 200g of oyster, 120g of honeycomb, 120g of Bombyx batryticatus, 200g of chicken's gizzard lining, and 100g of Tianlong, crush them, add 30% ethanol 6 times, cold soak 4 times, filter, combine the filtrates, concentrate, and dry to obtain Chinese medicine composition II;

[0065] The Chinese medicine composition I and II are mixed evenly to obtain the Chinese medicine composition.

[0066] Example 3 :

[0067] Mix the following Chinese medicinal materials according to weight ratio:

[0068] Take 80g of Herba Agrimoniae, 5g of Scutellariae, 20g of Hedyotis diffusa, 20g of Salvia miltiorrhiza, 20g of Lithospermum officinale, 80g of Cuscuta australis, 20g of Smilax china, 20g of Smilax glabra, 5g of Bupleurum, 20g of Semen Preparata, 20g of Cat's Claw, 40g of Millettia reticulata, 70g of Poria, 40g of Goat's Milk, 40g of Mistletoe, 40g of Gynostemma pentaphyllum, 70g of Trionycis, 70g of Oyster, 30g of Beehive, 30g of Bombyx batryticatus, 40g of Chicken's Gizzard Stone, and 25g of Dendrobium, crush them, add 20 times of 95% ethanol, heat and reflux once, reflux for 1 hour, filter, concentrate, and dry to obtain a Chinese medicine composition.

[0069] Example 4 :

[0070] Divide the following Chinese medicinal materials into three parts according to weight ratio and mix them separately:

[0071] Take 160g of Agrimoniae, 25g of Scutellariae, 40g of Hedyotis diffusa, 40g of Salvia miltiorrhiza, and 40g of Ipomoea aquatica, add 10 times of water by weight of the medicinal materials, decoct for 3 times, each time for 1.5 hours, filter, combine the filtrates, concentrate to 1.20-1.30 (65°C), add 95% ethanol to precipitate until the alcohol content reaches 60%, let stand for 12 hours, concentrate the supernatant, and dry to obtain Chinese medicine composition I;

[0072] Take 160g of Cudrania root, 40g of Smilax china, 40g of Smilax glabra, 25g of Bupleurum, 40g of Semen euphorbiae, 40g of Radix Cat's Claw, 20g of Millettia reticulata, 30g of Polyporus umbellatus, 20g of Goat's milk, and 10g of Viscum album, add 10 times of 50% ethanol, percolate twice at a percolation rate of 5ml / min until no percolate flows out, combine the percolate, concentrate, and dry to obtain Chinese medicine composition II;

[0073] Take 20g of Gynostemma pentaphyllum, 30g of turtle shell, 30g of oyster, 10g of honeycomb, 10g of Bombyx batryticatus, 20g of chicken gizzard lining, and 5g of Tianlong, add 15 times of water by weight of the medicinal materials, reflux extraction twice, each time for 3 hours, filter, combine the filtrates, concentrate, and dry to obtain Chinese medicine composition III;

[0074] The Chinese medicine composition I, II and III are mixed evenly to obtain the Chinese medicine composition.

[0075] Example 5 :

[0076] Mix the following Chinese medicinal materials according to weight ratio:

[0077] Take 120g of Herba Agrimoniae, 10g of Baical Scutellariae, 30g of Herba Hedyotis Diffusae, 30g of Radix Salviae Miltiorrhizae, 30g of Herba Lithospermi, 120g of Cuscuta Australis, 30g of Herba Smilax Chinensis, 30g of Rhizoma Smilacis Glabrae, 10g of Radix Bupleuri, 30g of Fructus Preparata, 30g of Herba Cat's Claw, 30g of Caulis Spatholobi, 50g of Polyporus, 30g of Herba Goats' Milk, 20g of Viscum Alpiniae, 30g of Gynostemma Pentaphyllum, 50g of Carapace of Turtle, 50g of Concha Oyster, 15g of Honeycomb, 15g of Bombyx Batryticatus, 30g of Gallinae Giardiae and 10g of Rhizoma Cibotii, add water 10 times of the weight of the medicinal materials, decoct 3 times by decoction method, each time for 1.5 hours, filter, combine the filtrates, concentrate to 1.18-1.22 (50-60° C.), add 95% ethanol to precipitate until the alcohol content reaches 60%, let stand for 12 hours, concentrate the supernatant, and dry to obtain a Chinese medicine composition.

[0078] Example 6 :

[0079] Divide the following Chinese medicinal materials into four parts according to weight ratio and mix them separately:

[0080] Take 120g of Agrimoniae, 10g of Scutellariae, 30g of Hedyotis diffusa and 30g of Salvia miltiorrhiza, add 10 times of water by weight of the medicinal materials, decoct for 3 times by decoction method, each time for 1 hour, filter, combine the filtrates, concentrate to 1.20-1.25 (65°C), add 95% ethanol to precipitate until the alcohol content reaches 60%, let stand for 12 hours, concentrate the supernatant, and dry to obtain Chinese medicine composition I;

[0081] Take 30g of Lithospermum officinale, 120g of Cuscuta australis root, 30g of Smilax glabra and 30g of Smilax glabra, add 10 times of 60% ethanol, soak twice for 12 hours each time, filter, combine the filtrates, concentrate and dry to obtain Chinese medicine composition II;

[0082] Take 10g of bupleurum, 30g of euphorbia pulex, 30g of cat's claw, 30g of millettia reticulata, 50g of umbellatus, and 30g of goat milk, extract twice with 70% ethanol, each time for 2 hours, the amount of solvent used is 10 times the weight of the medicinal materials, filter, combine the filtrates, concentrate to 1.20-1.25 (75°C), and dry to obtain Chinese medicine composition III;

[0083] Take 20g of mistletoe, 30g of Gynostemma pentaphyllum, 50g of turtle shell, 50g of oyster, 15g of honeycomb, 15g of Bombyx batryticatus, 30g of chicken gizzard lining, and 10g of Tianlong, add 10 times of water by weight of the medicinal materials, extract 3 times by reflux method, each time for 2 hours, filter, combine the filtrates, concentrate to 1.15-1.20 (50°C), add 95% ethanol to precipitate to 60% alcohol content, let stand for 12 hours, concentrate the supernatant, and dry to obtain Chinese medicine composition IV;

[0084] The Chinese medicine composition I-IV is mixed evenly to obtain the Chinese medicine composition.

[0085] Example 7 :

[0086] Divide the following Chinese medicinal materials into three parts according to weight ratio and mix them separately:

[0087] Take 120g of Agrimoniae, 10g of Scutellariae, and 30g of Hedyotis diffusa, extract twice with 70% ethanol, each time for 2 hours, with the amount of solvent used being 10 times the weight of the medicinal materials, filter, combine the filtrates, concentrate to 1.20-1.25 (60°C), and dry to obtain Chinese medicine composition I;

[0088] Take 30g of salvia miltiorrhiza, 30g of lycopodiella ciliata, 120g of chushu root, 30g of smilax china, 30g of smilax glabra, 10g of bupleurum, 30g of euphorbia pulex, 30g of cat's claw, and 30g of millettia reticulata, add 10 times of water by weight of the medicinal materials, decoct for 3 times, each time for 1 hour, filter, combine the filtrates, concentrate to 1.20-1.25 (65°C), add 95% ethanol to precipitate until the alcohol content reaches 60%, let stand for 12 hours, concentrate the supernatant, and dry to obtain Chinese medicine composition II;

[0089] Take 50g of Polyporus umbellatus, 30g of goat milk, 20g of mistletoe, 30g of Gynostemma pentaphyllum, 50g of turtle shell, 50g of oyster, 15g of honeycomb, 15g of Bombyx batryticatus, 30g of chicken gizzard lining, and 10g of Tianlong, add 12 times of water by weight of the medicinal materials, reflux extraction 3 times, each time for 1.5 hours, filter, combine the filtrates, concentrate, and dry to obtain Chinese medicine composition III;

[0090] The Chinese medicine composition I, II and III are mixed evenly to obtain the Chinese medicine composition.

[0091] Example 8 : Mix the following Chinese medicinal materials according to weight ratio:

[0092] Take 50g of Herba Agrimoniae, 10g of Scutellariae, 50g of Hedyotis diffusa, 25g of Salvia miltiorrhiza, 25g of Ishiba, 20g of Cuscuta root, 5g of Smilax glabra, 15g of Smilax glabra, 10g of Bupleurum, 15g of Seed of the Premonition, 15g of Cat's Claw, 20g of Millettia reticulata, 15g of Polyporus, 20g of Goat's milk, 20g of Mistletoe, 20g of Gynostemma pentaphyllum, 10g of Turtle Shell, 10g of Oyster, 15g of Beehive, 10g of Bombyx batryticatus, 15g of Chicken's gizzard lining, 10g of Tianlong 0g of medicinal material, add 14 times the weight of water, extract once by steam distillation, extract for 2 hours, collect volatile oil, filter, extract the residue twice by reflux method, each time for 1 hour, filter, combine all filtrates, concentrate to 1.20-1.25 (50℃), add 95% ethanol to precipitate to 70% alcohol content, let stand for 18 hours, concentrate the supernatant to 1.10-1.15 (55℃), and obtain concentrated solution.

[0093] Take another volatile oil and add PEG400 in an amount of 0.01% by weight of the medicinal material to dissolve and mix, stir and add to the concentrate, add appropriate amount of water, sweetener (white sugar, etc.), flavor, preservative, filter, and make an oral liquid or syrup.

[0094] Example 9 :

[0095] The Chinese medicinal extracts of Examples 1-7 were taken and crushed, and lactose and aspartame were added respectively, mixed, made into granules, and dried to obtain granules.

[0096] Example 10:The inhibitory effect of the Chinese medicine composition of the present invention on the growth of mouse tumors (S180, HepS, U14)

[0097] Reagents: Sodium chloride injection (normal saline), ampoule, 10 ml / vial, product of Tianjin Amino Acid Company People's Pharmaceutical Factory, product batch number: 20010212. Used for tumor cell inoculation and control group administration.

[0098] Cyclophosphamide, powder injection in ampoule, 200 mg / ampoule, product of Shanghai Hualian Pharmaceutical Co., Ltd., product batch number: 030501; product of Jiangsu Hengrui Medicine Co., Ltd., product batch number: 04111221. Prepare the required concentration of drug solution with normal saline, prepare it fresh before use, and complete the injection within 1 hour after preparation.

[0099] Test drug: the composition obtained in Example 7.

[0100] Experimental animals: Kunming mice (KM), grade 2 experimental animals, both male and female, purchased from the Department of Laboratory Animal Science, Peking University Health Science Center, Laboratory Animal Certificate Numbers: 0042174, 0042219, 0042264, 0034800, 0034708, 0049157, 0049156, 0049228, 0042287.

[0101] Animal tumor sources include S180 (sarcoma 180), HepA (hepatocarcinoma ascites), and U14 (cervical cancer 14).

[0102] Test method:

[0103] Tumor inoculation: Take a tumor-bearing (ascites type) animal that is in good condition 7 to 10 days after tumor inoculation, extract a small amount of ascites after routine disinfection, and extract the ascites after the slide Wright staining cell classification confirms that the number of tumor cells is not less than 75%. Dilute the ascites with a ratio of 1:4 to saline to prepare a tumor cell suspension for inoculation. The preparation of the tumor cell suspension is completed under sterile conditions (in a clean bench). Take 0.2 ml of the above-prepared tumor cell suspension and inoculate it subcutaneously in the right armpit of the mouse. The process from taking out the tumor ascites to the completion of tumor inoculation is completed within 60 minutes.

[0104] Grouping and administration: Animals were randomly divided into groups 24 hours after tumor cell inoculation, with 10 to 12 animals in each group. The experimental groups were: saline control group (NS group), positive drug (cyclophosphamide) control group, high-dose group (134.0 g crude drug / kg), medium-dose group (67.0 crude drug / kg) and low-dose group (33.5 crude drug / kg). The drug group was then gavaged according to the dose, and the administration volume was 0.4 ml / 20 g; the NS group was gavaged with the corresponding volume of saline; the positive drug (cyclophosphamide) control group was intraperitoneally injected with cyclophosphamide 50 mg / kg (0.4 ml / 20 g); except for cyclophosphamide, which was administered once, the test drugs were administered once a day for 7 consecutive days.

[0105] Evaluation of efficacy: 24 hours after the last administration, the animals were killed, weighed, dissected and the tumor tissue was removed, and the tumor weight was weighed. The average tumor weight and tumor growth inhibition rate were used to evaluate the in vivo anticancer effect of the drug. The calculation formula was: Tumor growth inhibition rate = (1-T / C) × 100%, where T is the average tumor weight of the treatment group, and C is the average tumor weight of the control group.

[0106] The above tumor inhibition test was repeated three times for each tumor (S180, HepA, U14).

[0107] Test results: The results show that the composition of the present invention has a certain inhibitory effect on the growth of mouse tumors S180, HepA and U14. The tumor inhibition rate of three experiments has good reproducibility. The tumor inhibition rate of the 134.0g crude drug / kg dosage group for S180 is 31.6%; the tumor inhibition rate for HepA is 30.9%; and the tumor inhibition rate for U14 is 26.1%. As a traditional Chinese medicine preparation, its inhibition rate for various tumors is about 30%, indicating that its anti-cancer effect is significant.

[0108] Table 1 Preliminary observation of the inhibitory effect of the tested drugs on the growth of mouse tumor S180 (solid)

[0109]

[0110]

[0111] Note: 1. Statistical analysis was performed using t-test, and compared with the control group, ***p<0.001, *p<0.05.

[0112] 2. Test drugs: high dose 134.0g crude drug / kg; medium dose 67.0g crude drug / kg; low dose 33.5 crude drug / kg

[0113] Table 2 Preliminary observation of the inhibitory effect of the tested drugs on the growth of mouse tumor HepA (liver cancer entity),

[0114]

[0115]

[0116] Note: 1. Statistical analysis was performed using t-test, and compared with the control group, ***p<0.001, **p<0.01, *p<0.05.

[0117] 2. Test drugs: high dose 134.0g crude drug / kg; medium dose 67.0g crude drug / kg; low dose 33.5 crude drug / kg

[0118] Table 3 Preliminary observation of the inhibitory effect of the tested drugs on the growth of mouse tumor U14

[0119]

[0120]

[0121] Note: 1. Statistical analysis was performed using t-test, and compared with the control group, ***p<0.001, **p<0.01, *p<0.05.

[0122] 2. Test drugs: high dose 134.0g crude drug / kg; medium dose 67.0g crude drug / kg; low dose 33.5 crude drug / kg

[0123] Embodiment 11 :Anticancer synergistic effect of the Chinese medicine composition of the present invention

[0124] Reagents: Sodium chloride injection (normal saline), ampoule, 10 ml / vial, product of Tianjin Amino Acid Company People's Pharmaceutical Factory, product batch number: 20010212. Used for tumor cell inoculation and control group administration.

[0125] Cyclophosphamide, powder injection in ampoule, 200 mg / ampoule, product of Shanghai Hualian Pharmaceutical Co., Ltd., product batch number: 030501; product of Jiangsu Hengrui Medicine Co., Ltd., product batch number: 04111221.

[0126] Cisplatin injection, 30 mg / vial, product of Yunnan Biovalley Dengzhanhua Pharmaceutical Co., Ltd., product batch number: 20040702.

[0127] Fluorouracil injection, 250 mg / ampoule, product of Tianjin Jinyao Amino Acid Co., Ltd., product batch number: 0501172.

[0128] The above three experimental drugs were prepared into the required concentrations with physiological saline. Cyclophosphamide was freshly prepared before use and injected within 1 hour after preparation. Cisplatin and fluorouracil were stored in a refrigerator at 4°C for future use.

[0129] Test drug: the composition obtained in Example 7.

[0130] Experimental animals: Kunming mice (KM), grade 2 experimental animals, both male and female, purchased from the Department of Laboratory Animal Science, Peking University Health Science Center, Laboratory Animal Certificate Numbers: 0042174, 0042219, 0042264, 0034800, 0034708, 0049157, 0049156, 0049228, 0042287.

[0131] The animal tumor source is HepA (hepatocarcinoma ascites).

[0132] Test method:

[0133] Tumor inoculation: Take a tumor-bearing HepA (liver cancer ascites) animal that is in good condition 7 to 10 days after tumor inoculation, extract a small amount of ascites after routine disinfection, and extract the ascites after the slide Wright staining cell classification confirms that the number of tumor cells is not less than 75%. Dilute the ascites with a ratio of 1:4 to saline to prepare a tumor cell suspension for inoculation. The preparation of the tumor cell suspension is completed under sterile conditions (in a clean bench). Take 0.2 ml of the above-prepared tumor cell suspension and inoculate it subcutaneously in the right armpit of the mouse. The process from taking out the tumor ascites to completing the tumor inoculation is completed within 60 minutes.

[0134] 1) Cyclophosphamide synergistic experiment:

[0135] 24 hours after tumor cell inoculation, animals were randomly divided into groups, with the number of animals in each group ranging from 10 to 14. The experimental groups were: normal saline control group (NS group), cyclophosphamide 80 mg / kg group, cyclophosphamide 40 mg / kg group, cyclophosphamide 20 mg / kg group, cyclophosphamide 40 mg / kg combined with 67.0 g crude drug / kg group of the test drug, and cyclophosphamide 20 mg / kg combined with 67.0 g crude drug / kg group of the test drug. Drugs were administered immediately after grouping (i.e. 24 hours after tumor inoculation), cyclophosphamide was administered by intraperitoneal injection, and the test drug was administered by gavage. Cyclophosphamide was administered once, and the test drug was administered once a day for 7 consecutive days.

[0136] 2) Cisplatin synergistic experiment:

[0137] 24 hours after tumor cell inoculation, animals were randomly divided into groups, with the number of animals in each group ranging from 10 to 14. The experimental groups were: normal saline control group (NS group), cisplatin 2 mg / kg × 2d group, cisplatin 2 mg / kg group, cisplatin 1 mg / kg group, cisplatin 2 mg / kg combined with 67.0 g crude drug / kg group and cisplatin 1 mg / kg combined with 67.0 g crude drug / kg group. Drugs were administered immediately after grouping (i.e. 24 hours after tumor inoculation), cisplatin was intraperitoneally injected, and the test drugs were administered by gavage. Except for the cisplatin 2 mg / kg × 2d group, cisplatin was administered once. The second administration of the cisplatin 2 mg / kg × 2d group was 72 hours after the first administration. The administration of the test drugs was the same as the cyclophosphamide enhancement experiment.

[0138] 3) Fluorouracil synergistic experiment:

[0139] 24 hours after tumor cell inoculation, animals were randomly divided into groups, with the number of animals in each group ranging from 10 to 14. The experimental groups were: normal saline control group (NS group), fluorouracil 40 mg / kg×4d group, fluorouracil 25 mg / kg×4 group, fluorouracil 15 mg / kg×4d group, fluorouracil 25 mg / kg×4d combined with test drug 67.0 g / kg group, and fluorouracil 15 mg / kg×4d combined with test drug 67.0 g / kg group. Immediately after grouping (i.e., 24 hours after tumor inoculation), fluorouracil was intraperitoneally injected once a day for 4 consecutive days. The test drug was administered as before.

[0140] Evaluation of therapeutic efficacy: 24 hours after the last administration, the animals were killed, their bodies were weighed, and the tumor tissues were dissected and removed. The tumor weight was weighed, and the tumor growth inhibition rate was used to evaluate the in vivo anticancer effect of the drug. The calculation formula was: Tumor growth inhibition rate = (1-T / C) × 100%, where T was the average tumor weight of the drug-treated group, and C was the average tumor weight of the control group.

[0141] Test results: The results show that the composition of the present invention has a synergistic effect on cyclophosphamide in the fight against mouse tumors: From the results in Table 4, it can be seen that the tumor growth inhibition rates of the cyclophosphamide 40 mg / kg group and the cyclophosphamide 20 mg / kg group were 70.18% and 20.69%, respectively, and the tumor growth inhibition rates of the cyclophosphamide 40 mg / kg combined with the test drug 67.0 g crude drug / kg group and the cyclophosphamide 20 mg / kg combined with the test drug 67.0 g crude drug / kg group were 91.02% and 50.67%, respectively, which were increased by 20.84% ​​and 29.98%, respectively, and the synergistic effect was statistically significant.

[0142] The composition of the present invention has a synergistic effect on cisplatin against mouse tumors: from the results in Table 5, it can be seen that the tumor growth inhibition rates of the cisplatin 2 mg / kg group and the 1 mg / kg group were 31.01% and 15.20%, respectively. After the two-dose combination was used with the test drug, the tumor growth inhibition rates were 41.38% and 35.63%, respectively, which were increased by 10.37% and 20.43%, respectively, and the synergistic effect on the cisplatin 1 mg / kg dosage group was statistically significant.

[0143] The composition of the present invention has a synergistic effect on the anti-tumor effect of fluorouracil on mice: as shown in Table 6, the tumor growth inhibition rates of the fluorouracil 25 mg / kg×4d group and the fluorouracil 15 mg / kg×4d group were 43.05% and 19.30%, respectively. The tumor growth inhibition rates after the two-dose combination was used with the test drug were 50.94% and 33.77%, respectively, which were increased by 7.89% and 14.47%, respectively.

[0144] Conclusion: The composition of the present invention has significant synergistic effects on cyclophosphamide and cisplatin, and has a certain synergistic trend on fluorouracil, indicating that the composition of the present invention may have a broad-spectrum synergistic effect on anti-tumor chemotherapy drugs.

[0145] Table 4 The synergistic effect of the tested drugs on cyclophosphamide

[0146]

[0147] Note: 1. The dosage of the test drug is 67.0g / kg.

[0148] 2. Statistical analysis: t test, all groups were compared with group ①***p<0.001,

[0149] 3. Comparison between Group ⑤ and Group ③ △△△ p<0.001, group ⑥ compared with group ④ ▲▲ p<0.01

[0150] Table 5 The synergistic effect of the tested drugs on cisplatin

[0151]

[0152] Note: 1. The dosage of the test drug is 67.0g / kg.

[0153] 2. Statistical analysis: t test, all groups were compared with group ①***p<0.001,

[0154] 3.Compared with group ④,△p<0.05.

[0155] Table 6 The synergistic effect of the tested drugs on fluorouracil

[0156]

[0157]

[0158] Note: 1. The dosage of the test drug is 67.0g / kg.

[0159] 2. Statistical analysis: t-test, all groups were compared with group ①, ***p<0.001, **p<0.01.

[0160] Example 12 :The toxicity-reducing effect of the Chinese medicine composition of the present invention

[0161] Reagents: Sodium chloride injection (normal saline), ampoule, 10 ml / vial, product of Tianjin Amino Acid Company People's Pharmaceutical Factory, product batch number: 20010212. Used for tumor cell inoculation and control group administration.

[0162] Cyclophosphamide, powder injection in ampoule, 200 mg / ampoule, product of Shanghai Hualian Pharmaceutical Co., Ltd., product batch number: 030501; product of Jiangsu Hengrui Medicine Co., Ltd., product batch number: 04111221.

[0163] Weixuening granules (sugar-free), 8g / bag, produced by Changzhou Jiuding Pharmaceutical Co., Ltd., product batch number 030706. When used, prepare a suspension of the required concentration with physiological saline for oral administration to animals, store in a refrigerator at 4°C after preparation, and shake well when administering.

[0164] Test drug: the composition obtained in Example 7.

[0165] Experimental animals: Kunming mice (KM), grade 2 experimental animals, both male and female, purchased from the Department of Laboratory Animal Science, Peking University Health Science Center, Laboratory Animal Certificate Numbers: 0042174, 0042219, 0042264, 0034800, 0034708, 0049157, 0049156, 0049228, 0042287.

[0166] Experimental method: Animals were randomly divided into 6 groups, namely, normal saline control group, cyclophosphamide control group, cyclophosphamide combined with Weixuening granules (positive control drug) group, and cyclophosphamide combined with the test drug high, medium and low dose groups. The test drug was given by gavage at 134.0g crude drug / kg, 67.0g crude drug / kg and 33.5g crude drug / kg; Weixuening granules were given by gavage at 4.8g / kg (12 times the human dose, equivalent to the human equivalent dose), once a day for 9 consecutive days, and cyclophosphamide was intraperitoneally injected at 100mg / kg, once a day for 2 consecutive days, and was given on the 8th and 9th days after the above drugs were administered. 24 hours after the last cyclophosphamide administration, blood was collected from the animal's orbital venous plexus for white blood cell count determination, and then the animal was killed, the right femur was dissected, and bone marrow cell smears were obtained for bone marrow nucleated cell counts. White blood cell and bone marrow nucleated cell counts were counted by microscope.

[0167] Test results: As shown in Table 7, the white blood cell count and bone marrow nucleated cell count of the animals were significantly reduced under the action of cyclophosphamide, indicating that the model was successfully established. The administration of the composition of the present invention to the animals had no effect on the reduction of bone marrow nucleated cells in the animals, but had a significant protective effect on the reduction of the number of white blood cells.

[0168] The above results show that the composition of the present invention has a significant protective effect on the toxic reaction of leukopenia caused by intraperitoneal injection of cyclophosphamide, and has a stronger attenuating effect than Weixuening.

[0169] Table 7 Effects of the tested drugs on cyclophosphamide-induced decrease in peripheral blood leukocytes and bone marrow nucleated cells in mice

[0170]

[0171]

[0172] Note: 1. Statistical analysis: t-test. Comparison between cyclophosphamide and saline groups: △△△p<0.001,

[0173] 2. Comparison between the combined drug group and the cyclophosphamide group *p<0.05, **p<0.01,

[0174] Embodiment 13 : Experimental study on the effect of the Chinese medicine composition of the present invention on the carbon particle clearance function of normal mice and tumor-bearing mice

[0175] Reagents: Sodium chloride injection (normal saline), ampoule, 10 ml / vial, product of Tianjin Amino Acid Company People's Pharmaceutical Factory, product batch number: 20010212. Used for tumor cell inoculation and control group administration.

[0176] Zhenqi Fuzheng Capsule, capsule, 48 capsules / bottle, specification: 12.5g crude drug / 6 capsules, Gansu Sanyao Pharmaceutical Group Co., Ltd. product, batch number: 20050107. When using, take out the powder in the capsule and prepare it into a concentration of 2.08g crude drug / ml.

[0177] Indian ink, Beijing Zhongyuweike Bioengineering Company, batch number 20040204.

[0178] Test drug: the composition obtained in Example 7.

[0179] Experimental animals: Kunming mice (KM), grade 2 experimental animals, both male and female, purchased from the Department of Laboratory Animal Science, Peking University Health Science Center, Laboratory Animal Certificate Numbers: 0042174, 0042219, 0042264, 0034800, 0034708, 0049157, 0049156, 0049228, 0042287.

[0180] The animal tumor source is HepA (hepatocarcinoma ascites).

[0181] Test method:

[0182] The tumor-bearing animal group was first inoculated with tumors: 0.2 ml of liver cancer ascites (HepA) diluted 1:4 (equivalent to 5×106 cells) was inoculated into the abdominal cavity of each mouse. The animals were randomly divided into groups 24 hours after inoculation, with 10 animals in each group. The normal animal group was also divided into groups at the same time: ① blank control group, no tumor inoculation, no drug administration. ② tumor-bearing control group, tumor inoculation, no drug administration. ③ Zhenqi Fuzheng Capsule, a positive drug tumor-bearing control group. ④~⑥ non-tumor-bearing drug administration groups. ⑦~⑨ tumor-bearing drug administration groups.

[0183] Each group of mice was given medication the day after inoculation of liver cancer ascites. The dosage is shown in Table 8. Each group was given medication once a day for 7 consecutive days. 24 hours after the last medication, each group of mice was intravenously injected with 0.1 ml / 10 g of India ink (diluted at 1:3). 0.025 ml of blood was collected from the retrobulbar venous plexus of the mouse orbit at 2 minutes and 10 minutes after the injection of ink. The blood was immediately blown into 2 ml of 0.1% Na2CO3 solution. The color was measured by spectrophotometer (λ=650 nm), and the OD value was recorded. The phagocytic index K value and the phagocytic coefficient (corrected phagocytic index) α value were calculated by the following formula. After blood collection, the animals were killed and the liver and spleen were weighed.

[0184]

[0185] Test results: The results showed that the composition of the present invention had no significant effect on the carbon particle clearance function of normal mice and tumor-bearing (HepA) mice.

[0186] Table 8 Effects of the tested drugs on carbon particle clearance in tumor-bearing mice

[0187]

[0188] Embodiment 14 :The effect test of the Chinese medicine composition of the present invention on delayed hypersensitivity (DTH) in tumor-bearing mice

[0189] Reagents: Sodium chloride injection (normal saline), ampoule, 10 ml / vial, product of Tianjin Amino Acid Company People's Pharmaceutical Factory, product batch number: 20010212. Used for tumor cell inoculation and control group administration.

[0190] Zhenqi Fuzheng Capsule, capsule, 48 capsules / bottle, specification: 12.5g crude drug / 6 capsules, Gansu Sanyao Pharmaceutical Group Co., Ltd. product, batch number: 20050107. When using, take out the powder in the capsule and prepare it into a concentration of 2.08g crude drug / ml.

[0191] 2,4-Dinitrochlorobenzene (DNCB), Tianjin Reagent Factory No. 1, was prepared into 1% and 5% acetone sesame oil solutions when used.

[0192] Test drug: the composition obtained in Example 7.

[0193] Experimental animals: Kunming mice (KM), grade 2 experimental animals, both male and female, purchased from the Department of Laboratory Animal Science, Peking University Health Science Center, Laboratory Animal Certificate Numbers: 0042174, 0042219, 0042264, 0034800, 0034708, 0049157, 0049156, 0049228, 0042287.

[0194] The animal tumor source is HepA (hepatocarcinoma ascites).

[0195] Test method:

[0196] Grouping and tumor inoculation: 0.2 ml of liver cancer ascites diluted 1:4 (equivalent to 5×106 cells) was inoculated into the abdominal cavity of each mouse. 24 hours after inoculation, the mice were randomly divided into 5 groups: ① tumor-bearing control group, ② Zhenqi Fuzheng capsule, which was the positive drug control group. ③~⑤ were the test drug administration groups. The mice in each group began to be administrated the day after tumor inoculation, with a dose of 8.33 g / kg Zhenqi Fuzheng capsule. The high, medium and low doses of the test drug were 134.0 g crude drug / kg, 67.0 g crude drug / kg and 33.5 g crude drug / kg, respectively, once a day for 7 consecutive days. 24 hours after the first administration, each group of mice was subcutaneously injected with 5% DNCB acetone sesame oil solution 0.02 ml / mouse for sensitization. Half an hour after the last administration, 0.05 ml / mouse 1% DNCB acetone sesame oil solution was evenly applied to the left ear shell of the mouse.

[0197] Test observation indicators:

[0198] (1) Survival status: Observe the survival status and general condition of the animals daily, and record the number and time of death.

[0199] (2) Ear swelling: 24 hours after the left ear of each group of mice was attacked, the animals were killed and the left and right ear shells were cut off and the round ear pieces were removed with a 7 mm diameter puncher and weighed with an electronic balance. The difference in weight between the left and right ear pieces was the swelling degree (mg), which was the main observation indicator of DTH.

[0200] (3) Spleen index: The spleens of mice in each group were removed after being sacrificed and weighed using an electronic balance. The spleen weight per 10 g body weight was used as the spleen index (mg / 10 g).

[0201] (4) Thymus index: The thymus of each group of mice was removed after being sacrificed, and the weight of thymus per 10 g body weight was used as the thymus index (mg / 10 g).

[0202] Test results: The degree of swelling of the ear shell indicates the ability of cellular immune response, and a high degree of swelling indicates that the immune cells have better functions. As shown in Table 9, the degree of swelling of the ear shells of animals in the three dose groups of the composition of the present invention is higher than that of the normal saline control group, and the high dose group has a significant difference after statistical processing by t test. This shows that the composition of the present invention has an enhancing effect on the T cell immune function of tumor-bearing mice.

[0203] Table 9 Effects of the tested drugs on delayed hypersensitivity (DTH) in tumor-bearing mice

[0204]

[0205] Student's t-test, compared with the tumor-bearing control group, *p<0.05.

[0206] Embodiment 15 :Acute toxicity test

[0207] Reagents: deionized water.

[0208] Test drug: the composition obtained in Example 7.

[0209] Experimental animals: Kunming mice (KM), grade 2 experimental animals, both male and female, purchased from the Department of Laboratory Animal Science, Peking University Health Science Center, Laboratory Animal Certificate Numbers: 0042174, 0042219, 0042264, 0034800, 0034708, 0049157, 0049156, 0049228, 0042287.

[0210] Test method:

[0211] The maximum concentration and volume of the test drug fluid extract was administered to mice once a day, with a dose of 431.76 g crude drug / kg.

[0212] Test results: After administration, the mice had obvious inhibitory symptoms, lying still, moving less, walking unsteadily, and loose stools, which returned to normal after 24 hours. After continuous observation for 14 days, all mice survived without death. Weight gain was normal. Surviving mice were killed on the 14th day, and the main organs were dissected. No obvious lesions were found by naked eye observation. Therefore, the maximum daily dosage of the drug is 431.76g crude drug / kg, which is equivalent to 129.7 times the clinical dosage of humans. This shows that the composition of the present invention is highly safe.

[0213] Example 16 :Long-term toxicity test

[0214] Reagents: deionized water.

[0215] Test drug: Composition obtained in Example 6

[0216] Test animals: SD rats, SPF grade, half male and half female.

[0217] Test method:

[0218] The proposed human dose of the test drug is 200g crude drug / day / person. The long-term toxicity test dose for rats is 70, 140, and 216g crude drug / kg, once a day (twice a day in the late stage of the high-dose male rat test), for 6 consecutive months and 1 month of recovery after drug withdrawal. During the entire dosing period, the general drug toxicity reactions of the animals were observed. At the end of 3 months, 6 months of dosing and the recovery period, 1 / 3 of the rats were killed and various indicators were tested: urine biochemistry, hematology, blood biochemistry, organ coefficients, and pathological histology examinations.

[0219] Test results: The data showed that the general drug toxicity reaction, hematology, urine biochemistry, organ coefficients and pathological histology of the animals in the 70g crude drug / kg dose group did not show changes related to drug toxicity. In the 140g crude drug / kg dose group, except for the active proliferation of bone marrow granulocytes and the increased ratio of granulocytes / erythroid cells in female rats, no obvious abnormalities were found in other test indicators. In the 216g crude drug / kg dose group, the weight gain of male rats was significantly slow, the food consumption was reduced, and the coefficients of organs such as the heart, lungs, kidneys, and brain were relatively large. However, after comprehensive analysis, it was believed that the drug had no substantial damage to the nutritional status and organ development of rats. The proliferation of bone marrow granulocytes in female rats in this dose group was also significantly active, the ratio of granulocytes / erythroid cells was significantly increased, and no abnormalities were found in other tests. The results showed that rats were continuously gavaged with the fluid extract of the composition of the present invention for 6 months, and the 70g crude drug / kg dose was its safe dose, which was equivalent to 21 times the clinical dose. The composition of the present invention can be taken for a long time and is safe and non-toxic.

[0220] Embodiment 17 : Clinical observation test of the composition of the present invention on 418 patients with primary liver cancer

[0221] A clinical study of 418 cases of primary liver cancer using the composition of the present invention showed that in the treatment group (decoction of the composition of Example 7), 15 cases had tumor disappearance, symptom disappearance, or complete remission, 90 cases had partial remission, and the remission rate was 25.1%; in the control group (placebo control), 12 cases had remission, and the remission rate was 10%. The efficacy of the two groups showed significant difference after statistical processing, and the treatment group was significantly better than the control group.

[0222] Comparison of survival rate (patients who died during treatment were also included in the base of survival rate): There were significant differences in the six-month and one-year survival rates between the two groups (P<0.01). The treatment group was significantly better.

[0223] Comparison of changes in quality of life: After treatment, the Karnofsky score increased by 10 points, decreased by 10 points, and was considered stable. After treatment, the score increased in 177 cases, stabilized in 18 cases, and decreased in 58 cases in the treatment group, while the scores were respectively 8, 56, and 56 in the control group. The Karnofsky score in the treatment group was significantly better than that in the control group (P<0.05).

[0224] Comparison of ALB and ALT results before and after treatment: 418 cases in the treatment group, the ALB values ​​before and after treatment were 29.05±5.61g / L and 33.39±5.61g / L respectively; 120 cases in the control group, the ALB values ​​before and after treatment were 29.04±6.94g / L and 30.81±6.09g / L respectively. 418 cases in the treatment group, the ALT values ​​before and after treatment were 48.56±15.14U / L and 40.13±18.56U / L respectively; 120 cases in the control group, the ALT values ​​before and after treatment were 47.75±25.31U / L and 42.40±21.12U / L respectively. Both indicators in the treatment group showed significant improvement after treatment (P<0.05), while there was no significant change in the control group (P>0.05).

[0225] Embodiment 18 Clinical observation test of the Chinese medicine composition of the present invention on 74 patients with lung cancer

[0226] A clinical study on 74 cases of stage III and IV lung cancer showed that among the 41 cases in the treatment group (cisplatin plus the decoction of the composition of Example 7), 6 cases were completely relieved, 12 cases were partially relieved, 9 cases were mildly relieved, 9 cases were stable, and 5 cases were progressive; among the 33 cases in the control group (cisplatin plus placebo control), 2 cases were completely relieved, 5 cases were partially relieved, 4 cases were mildly relieved, 8 cases were stable, and 14 cases were progressive. The effective rates (CR+PR) of the two groups were 43.9% (18 / 41) and 21.2% (7 / 33), respectively, and the difference between the two groups was significant (P<0.05).

[0227] Toxic reactions: Among the 41 cases in the treatment group, 15 cases had gastrointestinal reactions, 11 cases had leukocytopenia, 2 cases had cardiac toxicity, and 18 cases had alopecia. Among the 33 cases in the control group, 18 cases had gastrointestinal reactions, 20 cases had leukocytopenia, 3 cases had cardiac toxicity, and 22 cases had alopecia, indicating that the toxicity in the treatment group was milder than that in the control group.

[0228] Quality of life assessment: in the treatment group, 20 cases improved, 15 cases were stable, and 6 cases decreased, while in the control group, 6 cases improved, 13 cases were stable, and 14 cases decreased. The statistical difference between the two groups was very significant (P<0.01).

[0229] Median survival time: The survival time was calculated from the date of hospitalization to the date of death or the last follow-up. Among the 41 cases in the treatment group, the median survival time was 10 months, and the longest survival time was 49 months. Among the 33 cases in the control group, the median survival time was 5 months. There was a significant difference between the two groups (P<0.05).

[0230] Experimental studies have shown that the composition of the present invention can effectively inhibit tumor growth, enhance immune function, have a broad-spectrum synergistic effect on anti-tumor chemotherapy drugs, and can reduce the toxicity of chemotherapy drugs. The composition of the present invention is also safe and has no toxic side effects when used for a long time. Clinical studies have shown that the composition of the present invention can effectively alleviate and inhibit tumors, improve the quality of life of patients, and prolong the survival period. In combination with radiotherapy and chemotherapy, it can not only reduce the toxic and side effects of radiotherapy and chemotherapy, but also have a synergistic effect on radiotherapy and chemotherapy.

Claims

1. An antitumor Chinese medicine composition, which is made from the following Chinese medicine components in parts by weight: 80-160 parts of Agrimoniae, 5-25 parts of Scutellariae, 20-40 parts of Hedyotis diffusa, 20-40 parts of Salvia miltiorrhiza, 20-40 parts of Lithospermum officinale, 80-160 parts of Cuscuta australis roots, 20-40 parts of Smilax china, 20-40 parts of Smilax glabra, 5-25 parts of Bupleurum, 20-40 parts of Fructus nigra, 20-40 parts of Cat's Claw, 20-40 parts of Millettia reticulata, 30-70 parts of Polyporus, 20-40 parts of Goat's milk, 10-40 parts of Mistletoe, 20-40 parts of Gynostemma pentaphyllum, 30-70 parts of Carapace of Turtle, 30-70 parts of Oyster, 10-30 parts of Beehive, 10-30 parts of Bombyx batryticatus, 20-40 parts of Chicken's gizzard lining, and 5-25 parts of Dendrobium officinale.

2. The Chinese medicine composition according to claim 1, characterized in that The invention is prepared from the following Chinese medicinal components in parts by weight: 120 parts of herba agrimonii, 10 parts of baicalin, 30 parts of oldenlandia diffusa, 30 parts of salvia miltiorrhiza, 30 parts of lithospermum officinale, 120 parts of cucurbita chinensis roots, 30 parts of smilax china, 30 parts of rhizoma smilax, 10 parts of bupleurum, 30 parts of cyperus rotundus, 30 parts of cat's claw, 30 parts of millettia reticulata, 50 parts of umbellate, 30 parts of goat's milk, 20 parts of mistletoe, 30 parts of gynostemma pentaphyllum, 50 parts of turtle shell, 50 parts of oyster, 15 parts of honeycomb, 15 parts of bombyx batryticatus, 30 parts of chicken's gizzard lining and 10 parts of smilax glabra.

3. The Chinese medicine composition according to any one of claims 1 to 2, which can be prepared into any pharmaceutically acceptable oral dosage form.

4. The Chinese medicine composition according to claim 3, characterized in that: The dosage form is selected from tablets, capsules, granules, pills, powders, oral liquids, pastes, suspensions, and solutions.

5. The Chinese medicine composition according to claim 3, characterized in that: The dosage form is selected from tablets, capsules, granules, pills and powders.

6. The Chinese medicine composition according to claim 3, characterized in that: The dosage form is selected from granules.

7. The method for preparing the Chinese medicine composition according to any one of claims 1 to 2, characterized in that: The steps include: Take the medicinal material, add 8 to 20 times of water by weight of the medicinal material, perform decoction or reflux extraction 1 to 3 times, each time for 1 to 4 hours, filter, combine the filtrates, concentrate, and dry to obtain a Chinese medicine composition; Or take the medicinal material, add 8 to 20 times of water by weight of the medicinal material, extract by steam distillation 1 to 3 times, each time for 1 to 4 hours, collect the volatile oil, filter, combine the filtrate, concentrate, dry, and mix with the volatile oil to obtain a Chinese medicine composition; Or take the medicinal material, add 8 to 20 times of water by weight of the medicinal material, decoct or reflux extract 1 to 3 times, each time for 1 to 4 hours, filter, combine the filtrates, concentrate to 1.05 to 1.30, add 50% to 95% ethanol to precipitate to 30% to 85% alcohol content, let stand for 6 to 24 hours, concentrate the supernatant, dry, and obtain the Chinese medicine composition; Or take the medicinal material, add 8 to 20 times of water by weight of the medicinal material, extract by steam distillation for 1 to 3 times, each time for 1 to 4 hours, collect the volatile oil, filter, combine the filtrates, concentrate to 1.05 to 1.30, add 50% to 95% ethanol to precipitate to 30% to 85% alcohol, let stand for 6 to 24 hours, concentrate the supernatant, dry, and mix with the volatile oil to obtain a Chinese medicine composition; Or take the medicinal material, add 6 to 20 times of 30% to 95% ethanol, heat and reflux 1 to 4 times, each time for 1 to 3 hours, filter, combine the filtrates, concentrate, and dry to obtain a Chinese medicine composition; Or take the medicinal material, add 30% to 95% ethanol 6 to 20 times, percolate or cold soak 2 to 4 times, filter, combine the filtrates, concentrate, and dry to obtain a Chinese medicine composition, wherein the percolation rate is 1 to 5 ml / min until no percolate flows out, and the cold soaking extraction time is 6 to 24 hours each time; Or take medicinal materials, group them, extract them by one or more of the above methods, respectively obtain components of the Chinese medicine composition, mix them evenly, and obtain the Chinese medicine composition.

8. The preparation method according to claim 7, characterized in that: The steps include: Take the medicinal material, add water 12 times the weight of the medicinal material, reflux extract 3 times, each time for 1.5 hours, filter, combine the filtrates, concentrate, and dry to obtain a Chinese medicine composition; Or take the medicinal material, add water 10 times the weight of the medicinal material, decoct it 3 times by decoction method, each time for 1 hour, filter, combine the filtrates, concentrate to 1.20-1.25 at 60-65°C, add 95% ethanol to precipitate to 60% alcohol content, let stand for 12 hours, concentrate the supernatant, dry, and obtain the Chinese medicine composition; Or take the medicinal material, add water 10 times the weight of the medicinal material, decoct it 3 times by decoction method, each time for 1.5 hours, filter, combine the filtrates, concentrate to 1.18-1.22 at 50-60°C, add 95% ethanol to precipitate to 60% alcohol content, let stand for 12 hours, concentrate the supernatant, dry, and obtain the Chinese medicine composition; Or take the medicinal material, add water 10 times the weight of the medicinal material, extract by reflux method 3 times, 2 hours each time, filter, combine the filtrates, concentrate to 1.15-1.20 at 50-60°C, add 95% ethanol to precipitate to 60% alcohol content, let stand for 12 hours, concentrate the supernatant, dry, and obtain the Chinese medicine composition; Or take the medicinal material, add 70% ethanol 10 times the weight of the medicinal material, reflux extract twice, each time for 2 hours, filter, combine the filtrates, concentrate to 1.20-1.25 at 60-75°C, and dry to obtain a Chinese medicine composition; Or take the medicinal materials, add 60% ethanol 10 times, cold soak twice, each time for 12 hours, filter, combine the filtrates, concentrate, and dry to obtain a Chinese medicine composition; Or take medicinal materials, group them, extract them by one or more of the above methods, respectively obtain components of the Chinese medicine composition, mix them evenly, and obtain the Chinese medicine composition.

9. Use of the Chinese medicine composition according to any one of claims 1 to 2 in the preparation of a drug for treating cancer or assisting in the treatment of cancer.

10. The use according to claim 9, characterized in that The cancer is liver cancer or lung cancer; the auxiliary cancer treatment is treatment after surgery, radiotherapy or chemotherapy.

11. The use according to claim 9, characterized in that The cancer is liver cancer or lung cancer in the middle or late stage with no indication for surgery, radiotherapy or chemotherapy or with cachexia; the auxiliary cancer treatment is treatment after radiotherapy or chemotherapy.

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