CN100534493C

CN100534493C - Novel antineoplastic compound medicine

Info

Publication number: CN100534493C
Application number: CNB2006100432655A
Authority: CN
Inventors: 黄振华
Original assignee: Shandong Xuanzhu Pharma Co Ltd
Current assignee: Jiangyin Tianjiang Pharmaceutical Co Ltd
Priority date: 2006-03-24
Filing date: 2006-03-24
Publication date: 2009-09-02
Anticipated expiration: 2026-03-24
Also published as: CN101041004A

Abstract

The invention discloses an antineoplastic medicinal composition containing at least ginseng or its extract, ophiopogon root or its extract, schisandra fruit or its extract, the process for preparation and use thereof, wherein the medicament is one or two selected from cantharidin or derivatives or analogues, and toad venoms. The composition can be used for treating hepatic carcinoma, esophagus cancer, cardiac cancer, lung carcinoma, breast cancer, intestinal cancer, malignant lymphoma, hepatitis and cirrhosis.

Description

A kind of new anti-tumor compound medicine

1, technical field

The present invention relates to a kind of Radix Ginseng or its extract, Radix Ophiopogonis or its extract, Fructus Schisandrae Chinensis or its extract and at least a composition and method of making the same and purposes that is used for the anti-tumor drug composition of containing, belong to medical technical field.

2, background technology

Cancer is a class serious threat human life and healthy disease.Data show according to statistics, the annual newfound cancer patient of China is about about 1,000,000, and every year is seized about 6,000,000 people's life in the whole world, and 1,000 ten thousand people are placed dead edge, along with going from bad to worse of environment for human survival, the incidence rate of cancer is ascendant trend year by year.World Health Organization's prediction 21 century cancer will become human " first killer ".Modern medicine mainly is that the operative treatment cooperation is put, chemotherapy to treatment for cancer at present, though operation can be removed primary lesion, can not fundamentally stop the regeneration and the breeding of cancerous cell; Though put, chemotherapy can kill cancerous cell, simultaneously a large amount of normal tissue cells suffered damage, and brings out gastrointestinal reaction, bone marrow depression and Liver and kidney, impairment of cardiac function, makes patient's health weak more, be difficult to further treatment.And the Chinese traditional treatment cancer has long history, has formed the theoretical system and the treatment rule of own uniqueness.Work through vast medical worker has in recent years confirmed that the Chinese medicine cancer has outstanding effect, has particularly brought into play important effect to the rehabilitation behind the cancer operation and to the efficacy enhancing and toxicity reducing aspect of chemicotherapy.

Mylabris (Canthari) is the dry Scorpio of Meloidae insecticide south mylabris phalerata Mylabris phalerala Pallas or yellow black mylabris cichorii Mylabris cichoriiLinnaeus.Main product in Liaoning, area such as Henan, Guangxi, Anhui, Jiangsu, Hunan, Guizhou, be a kind of important insect drug.Modern pharmacy studies show that its main medicinal ingredient is a cantharidin.Clinically, cantharidin is demonstrating its unique curative effect aspect treatment cancer and some difficult miscellaneous diseases, but because of its toxicity has substantive damage to heart kidney organ, cantharidin is very limited on using.At present, along with the further investigation of people to cantharidin, synthesized multiple cantharidin derivative in succession, these chemical compounds reduce greatly than cantharidin toxicity, and pharmacological action is clearer and more definite.Existing each derivant of cantharidin has all been taken in national medicinal chemicals standard, norcantharidin records into the chemical drugs terrestrial reference and rises 1 24 pages of GBs, disodium cantharidinate records into the chemical drugs terrestrial reference and rises 1 239 pages of GBs, and N-methylcantharidimide records into the chemical drugs terrestrial reference and rises 6 47 pages of GBs.Modern pharmacology and clinical research show that all cantharidin or derivatives thereof or analog have stronger antitumor action, and body is not had tangible immunosuppressive action.Cantharidin or derivatives thereof or analog structural formula are as follows:

R=CH ₃, be cantharidin R=OH, be the N-hydroxycantharidin disodium cantharidinate

R=H is norcantharidin R=CH ₃, be N-methylcantharidimide

Venenum Bufonis is the dry secretions of Bufonidae animal Bufo siccus Bufo bufo gargarixans Cantor or Bufo melanostictus Bufo melanostictus Schneider.Suffering, temperature; Poisonous.The GUIXIN warp.Has detoxifcation, pain relieving, the effect of the refreshment of having one's ideas straightened out.Be mainly used in carbuncle and treat skin ulcer, laryngopharynx swelling and pain, the heatstroke coma, stomachache is vomited and diarrhoea.The Venenum Bufonis ingredient is negative assorted, has determined that now its main chemical constituent is following a few class: 1. by bufotoxin (bufotoxins, BTXs) hydrolysis obtain 20 surplus kind of bufotalin class; 2. newfound five kind 20, and 21-epoxy bufogenin (20,21-epoxybufenolides); 3. indole derivatives: bufotenine, bufotenidine etc.; 4. other: 5-hydroxy tryptamine, epinephrine etc.Its effective ingredient belongs to the indole alkali derivant, has the effect of detoxicating, relieving inflammation, clinical acute and chronic suppurative infection and antitumor, the radiation-resistant adjuvant drug of being used for the treatment of.

Radix Ginseng is the dry root of Araliaceae Radix Ginseng Panax ginseng C.A.Mey., and sweet, the little hardship of property is flat, returns spleen, lung, heart channel, has that strongly invigorating primordial QI, multiple arteries and veins take off admittedly, an invigorating the spleen to benefit the lung, the effect of promoting the production of body fluid, calming the nerves.Radix Ginseng mainly contains effective ingredient such as ginseng polysaccharide, ginsenoside, ginseng polypeptide and volatile oil, several amino acids, fatty acid and vitamin, trace element.The ginsenoside, content is about ginseng crude drug's 4%, separates to such an extent that the ginsenoside has Ra at present _1～6, Rb _1～3, kind surplus Rc, Rd, Re, the Rf etc. 20.Radix Ginseng is enhancing body's immunological function comprehensively, and its active component mainly is saponin and polysaccharide.Ginseng polysaccharide and saponin also can make the caused by cyclophosphamide leukocyte count reduce, and it is normal that macrophage and humoral immunization and cellular immune function inhibition etc. recover; Ginsenoside and ginseng polysaccharide all have the anti-experimental character function of tumor, ginsenoside's antitumor action is relevant with the differentiation again of its inducing cancer cell, the ginseng polysaccharide has direct or indirect anti-tumor activity, vitro cytotoxicity test evidence: ginseng polysaccharide's sensitization serum all has killing and wounding and inhibitory action in various degree to the tumor cell line of people and Mus, also can make it that tangible hemorrhagic necrosis takes place to transplantation tumor in the body.

Be the dried root of liliaceous plant Ophiopogon Radix Ophiopogonis japonicus (Thunb.) Ker-Gawl. Radix Ophiopogonis.Pharmacological research shows to have multiple pharmacological effect Radix Ophiopogonis, mainly concentrate on improve immunity, antitumor, resist myocardial ischemia, aspects such as antithrombotic formation, anoxia enduring, defying age, blood sugar lowering and radioprotective.

Fructus Schisandrae Chinensis is the dry mature fruit of magnoliaceae schisandra Schisandra chinensis (Turcz.) Baill. and schisandra chinensis Schisandra sphenantheraRehd.et Wils..Sour in the mouth, sweet, warm in nature, return lung, the heart, kidney channel, have the convergence astringent or styptic treatment for spontaneous sweating, supplementing QI for promoting the production of body fluid, the effect of kidney calming.Modern study shows that Fructus Schisandrae Chinensis has following pharmacological action: 1. can strengthen cerebral cortex excitement and process of inhibition, make its mutual balance.2. obvious sedation, with synergism such as pentobarbital sodium, chlorpromazine, the convulsions that the antagonism beta stimulant causes has the characteristics of tranquilizer.3. regulate immunity, stablize the liver cell film, protect organelle, nucleus, promote pathological repair, improve liver function.

Utilize one or both the interaction in Radix Ginseng, Radix Ophiopogonis, Fructus Schisandrae Chinensis and cantharidin or derivatives thereof or its analog, the Venenum Bufonis at present, composition of prescription is used to prepare the medicine of anti-tumor aspect, does not appear in the newspapers as yet.

3, summary of the invention

In order to meet clinical needs, better treat cancer, improve patient's quality of life, the invention provides a kind of new pharmaceutical composition and preparation method thereof, said composition contains Radix Ginseng, Radix Ophiopogonis, the Fructus Schisandrae Chinensis of effective dose, with at least a anti-tumor drug that is used for, wherein be used for anti-tumor drug and be selected from: one or both of cantharidin or derivatives thereof or its analog, Venenum Bufonis.

Aforementioned pharmaceutical compositions, the parts by weight of its crude drug are: 500～15000 parts of Radix Ginsengs, 1000～30000 parts of Radix Ophiopogonis, 500～15000 parts of Fructus Schisandrae Chinensis, antitumor drug is different and different according to medicine, for 0.02～5000 part of cantharidin or derivatives thereof or its analog, it is 1～50 part for Venenum Bufonis.

Aforementioned pharmaceutical compositions, the parts by weight of its crude drug are preferably: 1500～6000 parts of Radix Ginsengs, 3000～12000 parts of Radix Ophiopogonis, 1500～6000 parts of Fructus Schisandrae Chinensis, antitumor drug is different and different according to medicine, for cantharidin or derivatives thereof or its analog is 0.05～2000 part, is 4～16 parts for Venenum Bufonis.

Aforementioned pharmaceutical compositions, the parts by weight of its crude drug are more preferably; 3000 parts of Radix Ginsengs, 6000 parts of Radix Ophiopogonis, 3000 parts of Fructus Schisandrae Chinensis, antitumor drug are different and different according to medicine, are 0.1～1000 part for cantharidin or derivatives thereof or its analog, are 8 parts for Venenum Bufonis.

Aforementioned pharmaceutical compositions, its crude drug are formed and parts by weight are particularly preferred is: the compositions of 3000 parts of Radix Ginsengs, 6000 parts of Radix Ophiopogonis, 3000 parts of Fructus Schisandrae Chinensis, 10 parts of norcantharidin; It perhaps is the compositions of 3000 parts of Radix Ginsengs, 6000 parts of Radix Ophiopogonis, 3000 parts of Fructus Schisandrae Chinensis, 8 parts of Venenum Bufoniss.

Preparation of drug combination method of the present invention is, described Radix Ginseng, Radix Ophiopogonis, Fructus Schisandrae Chinensis, Venenum Bufonis can singly be carried or mix to obtain through refining and obtain extract fully with The suitable solvent and method, Radix Ginseng, Radix Ophiopogonis and Fructus Schisandrae Chinensis singly carry thing or mix carry thing again with cantharidin or derivatives thereof or its analog, Venenum Bufonis extract in one or both and mixing acceptable accessories make arbitrary preparation; Wherein the main effective ingredient of Radix Ginseng extract is saponin or polysaccharide, and the effective ingredient of Fructus Schisandrae Chinensis extrat is a schisandrin, and the main effective ingredient of Venenum Bufonis extract is indoles total alkaloids, cinobufagin and bufogenin.Wherein the total content of main effective ingredient is not less than 20% in the total extract, preferably is not less than 50%.

Cantharidin or derivatives thereof or its analog are norcantharidin, disodium cantharidinate, N-methylcantharidimide, N-hydroxycantharidin, acrylic cantharidimide etc., preferred norcantharidin.Radix Ginseng, Radix Ophiopogonis, Fructus Schisandrae Chinensis, Venenum Bufonis are Chinese crude drug, feed intake after must extracting, below be the extraction process of each medical material:

The preferred extraction process of Venenum Bufonis is as follows:

Get Venenum Bufonis, be ground into fine powder, add the soak with ethanol of 20 times of amounts 80%, grind, cold preservation is spent the night, filter next day, and filtrate recycling ethanol adds 10 times of water gagings again and stirs evenly to there not being the alcohol flavor, and cold preservation was left standstill 24 hours, filter, it is 1.10～1.15 that filtrate is concentrated into relative density, spray drying, promptly.The yield of the Venenum Bufonis extract by this prepared is 6.0～8.0%, and wherein the content of indoles alkaloid is not less than 10%, the content of cinobufagin and bufogenin and be not less than 30%.

Except that adopting said method, also can obtain by the following method, but be not limited only to following method:

Method one: get Venenum Bufonis, be ground into fine powder, add 15 times of amounts of ethanol and soak after 1 hour, the reflux, extract, secondary 2 hours for the first time, adds 10 times of amount alcohol refluxs 1 hour for the second time, merge extractive liquid, filters, and filtrate recycling ethanol is to there not being the alcohol flavor, the water that adds 10 times of amounts stirs, and cold preservation was left standstill 24 hours, filter, it is 1.08～1.15 that filtrate is concentrated into relative density, spray drying, promptly.The yield of the Venenum Bufonis extract by this prepared is 8.0～10.0%, and wherein the content of indoles alkaloid is not less than 4%, and the content of cinobufagin and bufogenin is not less than 20%.

Method two: get Venenum Bufonis, be ground into fine powder and put in the percolation vessel, add 10 times of amounts of ethanol soaked overnight, add ethanol percolation next day to colourless, the ethanol percolation of reuse 75% is to colourless, merge percolate, filter filtrate recycling ethanol, and to be concentrated into relative density be 1.10～1.20, put cold, spray drying, promptly.The yield of the Venenum Bufonis extract by this prepared is 6.5～9.0%, and wherein the content of indoles alkaloid is not less than 2%, and the content of cinobufagin and bufogenin is not less than 10%.

Above-mentioned Radix Ginseng can obtain Radix Ginseng total saponins or polysaccharide through extracting processing with The suitable solvent, extract solvent preferred water or ethanol, extracting method can be infusion process, percolation, decocting method, reflux extraction or continuous extraction, and the effective ingredient of extract is total saponins and/or polysaccharide.Because Radix Ginseng total saponins and ginseng polysaccharide all have activity at enhancing immunity and anti-tumor aspect,, as follows respectively so " extracting separately " method of Radix Ginseng can adopt different extracting method because of the difference of its main effective ingredient:

The preferred extraction process one of Radix Ginseng (is main effective ingredient with total saponins) is as follows:

Get the ginseng crude drug, be ground into particulate, add 10 times of amount alcohol reflux secondaries, each 3 hours, merge extractive liquid,, cold preservation filters, and filtrate recycling ethanol also is concentrated into thick paste, add water to an amount of (making every 1ml be equivalent to crude drug 1g), stir evenly, cold preservation filters, filtrate is added on the macroporous resin column of having handled well, water with 2 times～3 times of column volumes carries out eluting earlier, discards water lotion, 80% ethanol elution of 3 times of column volumes of reuse, collect eluent, reclaim ethanol and be evaporated to the thick paste of relative density 1.30～1.35, vacuum drying, promptly.Radix Ginseng total saponins yield by this prepared is 1%～2%, and the content of total saponins is not less than 50%, ginsenoside Re, ginsenoside Rg ₁Total content be not less than 30%.

Radix Ginseng can also extract preparation by following technology, but is not limited only to following technology:

Technology one: get the ginseng crude drug, be ground into particulate, add alcohol reflux three times, add for the first time 10 times of amounts of alcohol, two, three times is 8,8 times of amounts, each 2 hours, merge extractive liquid, filters, and reclaims ethanol and is concentrated into thick paste, add water in right amount, stir evenly cold preservation, filter, filtrate adds 1/2 times of saturated n-butanol extraction of water gaging three times, merges n-butyl alcohol liquid, the reclaim under reduced pressure n-butyl alcohol is to the thick paste shape, vacuum drying, promptly.Radix Ginseng total saponins yield by this prepared is 3～5%, and the content of total saponins is not less than 40%, ginsenoside Re, ginsenoside Rg ₁Total content be not less than 20%.

Technology two: get the ginseng crude drug, be ground into particulate, add the alcohol reflux secondary, each 4 hours, add 10 times of amounts of alcohol, merge extractive liquid, at every turn, cold preservation filters, and filtrate recycling ethanol also is concentrated into thick paste, thin up to relative density is 1.15～1.20, add 1/2 times of saturated n-butanol extraction of water gaging three times, merge n-butyl alcohol liquid, the reclaim under reduced pressure n-butyl alcohol is to the thick paste shape, vacuum drying, promptly.Radix Ginseng total saponins yield by this prepared is 4～5%, and the content of total saponins is not less than 35%, ginsenoside Re, ginsenoside Rg ₁Total content be not less than 20%.

The preferred extraction process two of Radix Ginseng (is main effective ingredient with polysaccharide) is as follows:

Get the ginseng crude drug, chopping, with 75% alcohol reflux 4 hours, filtration, medicinal residues dry, decoct with water five times, and each 1 hour, collecting decoction, add 0.3% active carbon, stirred 30 minutes, standing over night filters, filtrate is crossed resin column, collects effluent, and concentrating under reduced pressure adds ethanol and makes and contain the alcohol amount and reach 95%, cold preservation filters, and gets precipitation and uses washing with acetone, drains acetone, get and be deposited in 60～80 ℃ of dryings, pulverize, promptly.Ginseng polysaccharide's yield by this prepared is 0.5%～2%, and the content of polysaccharide is not less than 50%.

Radix Ginseng also can extract preparation by following technology, but is not limited only to following technology:

Technology one: get the ginseng crude drug, chopping was with 80% alcohol reflux 3 hours, filter, medicinal residues dry, and decoct with water three times, each 2 hours, add 10 times of amounts of water, collecting decoction, filter, it is 1.15～1.20 that filtrate decompression is concentrated into relative density, crosses macroporous resin, and effluent is evaporated to the thick paste shape, vacuum drying, promptly.Ginseng polysaccharide's yield by this prepared is 2～4%, and the content of polysaccharide is not less than 40%.

Technology two: get the ginseng crude drug, chopping, extracting in water three times, each 2 hours, add 10 times of amounts of water for the first time, two, three times is 8,8 times of amounts, merge extractive liquid,, filter, it is 1.16～1.24 that filtrate decompression is concentrated into relative density, crosses macroporous resin column, collect effluent, be evaporated to the thick paste shape, vacuum drying, promptly.Ginseng polysaccharide's yield by this prepared is 3～5%, and the content of polysaccharide is not less than 30%.

The preferred extraction process of Radix Ophiopogonis is as follows:

Get medical material Radix Ophiopogonis, be ground into particulate, add 8 times of water gagings and decoct secondary, each 1 hour, collecting decoction filters, and filtrate is concentrated into the thick paste shape, adds ethanol and makes and contain the alcohol amount and reach 80%, cold preservation was placed 24 hours, filtered, and filtrate recycling ethanol also is concentrated into the thick paste shape, added ethanol and made and contain the alcohol amount and reach 85%, cold preservation was placed 24 hours, filtered, and reclaimed ethanol and was concentrated into the thick paste shape, add water to an amount of (making every 1ml be equivalent to crude drug 2g), stir evenly cold preservation, filter, the filtrate spray drying, promptly.Radix Ophiopogonis extract yield by this prepared is 1～2%.

Can also extract preparation Radix Ophiopogonis by following technology, but be not limited only to following technology:

Technology one: get medical material Radix Ophiopogonis, be ground into particulate, add 80% alcohol reflux three times, each 1 hour, merge extractive liquid, filters, and filtrate recycling ethanol adds water to an amount of to the thick paste shape, stir evenly, cold preservation filters, and filtrate is concentrated into the thick paste shape, add ethanol and make and contain alcohol amount and reach 85%, cold preservation was placed 24 hours, filtered, and reclaimed ethanol and also was concentrated into the thick paste shape, add water in right amount, stir evenly cold preservation, filter, the filtrate spray drying, promptly.Radix Ophiopogonis extract yield by this prepared is 2～4%.

Technology two: get medical material Radix Ophiopogonis, be ground into particulate, add 50% alcohol reflux secondary, each 1 hour under 60 ℃, merge extractive liquid, filters, and filtrate recycling ethanol adds water to an amount of to the thick paste shape, stir evenly, cold preservation filters, and filtrate is concentrated into the thick paste shape, add ethanol and make and contain alcohol amount and reach 85%, cold preservation was placed 24 hours, filtered, and reclaimed ethanol and also was concentrated into the thick paste shape, add water in right amount, stir evenly cold preservation, filter, the filtrate spray drying, promptly.Radix Ophiopogonis extract yield by this prepared is 2～4%.

The preferred extraction process of Fructus Schisandrae Chinensis (is main effective ingredient with schisandrin) is as follows:

Get schisandra chinensis medicinal material, be ground into coarse powder, decoct with water secondary, each 2 hours, collecting decoction filtered, filtrate is concentrated into relative density 1.10～1.15, adds ethanol and makes and contain alcohol amount and reach 60%, and cold preservation was placed 24 hours, filter, filtrate recycling ethanol also is concentrated into relative density 1.10～1.15, adds ethanol again and makes and contain the alcohol amount and reach 80%, cold preservation was placed 24 hours, filtered, and filtrate recycling ethanol also is concentrated into relative density 1.30～1.35, vacuum drying, promptly.Fructus Schisandrae Chinensis extrat yield by this prepared is 2～4%, and the content of schisandrin is not less than 10%.

Fructus Schisandrae Chinensis can also extract preparation by following technology, but is not limited only to following technology:

Technology one: get schisandra chinensis medicinal material, be ground into coarse powder, decoct with water three times, each 1 hour, collecting decoction filtered, filtrate is concentrated into relative density 1.10～1.15, adds ethanol and makes and contain alcohol amount and reach 60%, and cold preservation was placed 24 hours, filter, filtrate recycling ethanol also is concentrated into relative density 1.10～1.15, adds ethanol again and makes and contain the alcohol amount and reach 80%, cold preservation was placed 24 hours, filtered, and filtrate recycling ethanol also is concentrated into relative density 1.30～1.35, vacuum drying, promptly.By the Fructus Schisandrae Chinensis extrat of this prepared, yield is 3～5%, and the content of schisandrin is not less than 8%.

Technology two: get schisandra chinensis medicinal material, be ground into coarse powder, add 80% alcohol reflux secondary, each 2 hours, the inferior for the first time 6 times of amounts of alcohol that add add 4 times of amounts of alcohol for the second time, and merge extractive liquid, filters, filtrate recycling ethanol also is concentrated into relative density 1.10～1.15, adds water in right amount, stirs evenly, cold preservation filters, and filtrate is concentrated into the thick paste shape, add ethanol again and make and contain alcohol amount and reach 80%, cold preservation was placed 24 hours, filtered, filtrate recycling ethanol also is concentrated into relative density 1.30～1.35, vacuum drying, promptly.Fructus Schisandrae Chinensis extrat yield by this prepared is 4～6%, and the content of schisandrin is not less than 5%.

Pharmaceutical composition of the present invention is except that available method for preparing obtains, also the medical material in the crude drug directly can be replaced feeding intake with extract, promptly can be by Radix Ginseng, Radix Ophiopogonis, Fructus Schisandrae Chinensis extrat, and in the two one or both of cantharidin or derivatives thereof or its analog, Venenum Bufonis extract feed intake and make.Cantharidin derivative wherein is norcantharidin, disodium cantharidinate, N-methylcantharidimide, N-hydroxycantharidin, acrylic cantharidimide etc., preferred norcantharidin.

Calculate with respect to the yield of medical material according to extract, the parts by weight of pharmaceutical composition of the present invention are:

Proportioning 1: 5～300 parts of Radix Ginseng total saponinss, 10～600 parts of Radix Ophiopogonis extracts, 10～600 parts of Fructus Schisandrae Chinensis extrats, with be selected from following bulk drugs: one or both in 0.02～5000 part of cantharidin or derivatives thereof or its analog, 0.05～5 part of Venenum Bufonis extract; Be preferably: 10～150 parts of Radix Ginseng total saponinss, 30～200 parts of Radix Ophiopogonis extracts, 30～200 parts of Fructus Schisandrae Chinensis extrats, with be selected from following bulk drugs: one or both in 0.05～2000 part of cantharidin or derivatives thereof or its analog, 0.2～1 part of Venenum Bufonis extract; More preferably: 30～60 parts of Radix Ginseng total saponinss, 60～120 parts of Radix Ophiopogonis extracts, 60～120 parts of Fructus Schisandrae Chinensis extrats, with be selected from following bulk drugs: one or both in 0.1～1000 part of cantharidin or derivatives thereof or its analog, 0.4～0.7 part of Venenum Bufonis extract.

Proportioning 2: 2～300 parts of ginseng polysaccharides, 10～600 parts of Radix Ophiopogonis extracts, 10～600 parts of Fructus Schisandrae Chinensis extrats, with be selected from following bulk drugs: one or both in 0.02～5000 part of cantharidin or derivatives thereof or its analog, 0.05～5 part of Venenum Bufonis extract; Be preferably: 5～150 parts of ginseng polysaccharides, 30～200 parts of Radix Ophiopogonis extracts, 30～200 parts of Fructus Schisandrae Chinensis extrats, with be selected from following bulk drugs: one or both in 0.05～2000 part of cantharidin or derivatives thereof or its analog, 0.2～1 part of Venenum Bufonis extract; More preferably: 10～60 parts of ginseng polysaccharides, 60～120 parts of Radix Ophiopogonis extracts, 60～120 parts of Fructus Schisandrae Chinensis extrats, with be selected from following bulk drugs: one or both in 0.1～1000 part of cantharidin or derivatives thereof or its analog, 0.4～0.7 part of Venenum Bufonis extract.

Aforementioned pharmaceutical compositions, its parts by weight are particularly preferred to be: the compositions of 30～60 parts of Radix Ginseng total saponinss, 60～120 parts of Radix Ophiopogonis extracts, 60～120 parts of Fructus Schisandrae Chinensis extrats, 10 parts of norcantharidin; Perhaps be: the compositions of 30～60 parts of Radix Ginseng total saponinss, 60～120 parts of Radix Ophiopogonis extracts, 60～120 parts of Fructus Schisandrae Chinensis extrats, 0.4～0.7 part of Venenum Bufonis extract; Perhaps be: the compositions of 10～60 parts of ginseng polysaccharides, 60～120 parts of Radix Ophiopogonis extracts, 60～120 parts of Fructus Schisandrae Chinensis extrats, 10 parts of norcantharidin; Perhaps be: the compositions of 10～60 parts of ginseng polysaccharides, 60～120 parts of Radix Ophiopogonis extracts, 60～120 parts of Fructus Schisandrae Chinensis extrats, 0.4～0.7 part of Venenum Bufonis extract.

In the aforementioned pharmaceutical compositions, the indoles total alkaloid contents is not less than 2% in the Venenum Bufonis extract, preferably is not less than 10%, and the content of cinobufagin and bufogenin is not less than 10%, preferably is not less than 30%; The main effective ingredient of Radix Ginseng total saponins is a total saponins, and the content of total saponins is not less than 30%, preferably is not less than 50%, ginsenoside Re, ginsenoside Rg ₁Total content be not less than 20%, preferably be not less than 30%; Ginseng polysaccharide's main effective ingredient be polysaccharide, the content of polysaccharide is not less than 30%, preferably is not less than 50%; The main effective ingredient of Fructus Schisandrae Chinensis extrat is a schisandrin, and the content of schisandrin is not less than 5%, preferably is not less than 10%.

More than form to be by weight as proportioning, when producing, can or reduce according to the corresponding proportion increase, as large-scale production can be unit with the kilogram, or be unit with the ton, small-scale production can be unit with the gram also, weight can increase or reduce, but the constant rate of weight proportion between each composition.If with the gram is unit, can make the preparation of 100～10000 consumptions, as injection, can be made into 100～10000,1～10 of each consumption as tablet, can be made into 100～10000, takes 1～10 at every turn.

The ratio of above weight proportion obtains through science screening, and for especial patient, the ratio of can corresponding adjustment forming increases or reduce being no more than 100%.

Pharmaceutical composition of the present invention can be used for the treatment of hepatocarcinoma, esophageal carcinoma, harmonization of the stomach carcinoma of gastric cardia, pulmonary carcinoma, breast carcinoma, intestinal cancer, malignant lymphoma etc. and low leukocyte counts, also can be used for hepatitis, liver cirrhosis, hepatitis b virus carrier, acute or chronic purulent infection, or can be used as the preceding medication of cancer operation or be used for combined chemotherapy, or can be used as used as adjuvant drug for antitumor.

Pharmaceutical composition of the present invention can add one or more pharmaceutically acceptable carriers, is applied to the patient of this treatment of needs in the mode of oral or parenteral.Be used for when oral, can be made into conventional solid preparation, as tablet, capsule, soft capsule, dispersible tablet, oral liquid, granule, chewable tablet, oral cavity disintegration tablet, drop pill, slow releasing tablet, slow releasing capsule, controlled release tablet, controlled release capsule, make liquid preparation such as water or oil-suspending agent or other liquid preparation such as syrup etc.; When being used for parenteral, can be made into solution, water or the oil-suspending agent etc. of injection, as liquid drugs injection, freeze-dried powder, aseptic powder injection, transfusion etc.The preferred dosage form of this compositions is oral formulations or injection, as sheet, capsule, granule, powder pin, liquid drugs injection, transfusion etc.

Pharmaceutical composition of the present invention can adopt the conventional method production in the existing pharmaceutical field, can add various pharmaceutically acceptable carriers when needing.Described carrier comprises excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier, lubricant of pharmaceutical field routine etc.

Pharmaceutical composition of the present invention is when making oral formulations, and selectable filler has: starch, Icing Sugar, calcium phosphate, calcium sulfate two water things, dextrin, microcrystalline Cellulose, lactose, pregelatinized Starch, mannitol etc.; Selectable binding agent has: sodium carboxymethyl cellulose, PVP-K30, hydroxypropyl cellulose, starch slurry, methylcellulose, ethyl cellulose, hypromellose, gelling starch etc.; Selectable disintegrating agent has: dried starch, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose etc.; Selectable lubricant has: magnesium stearate, Pulvis Talci, sodium lauryl sulphate, micropowder silica gel etc.

Pharmaceutical composition of the present invention in order to increase its dissolubility, can add solubilizing agents such as polyoxyethylene sorbitan monoleate when making injection.Can add the isoosmotic adjusting agent that is used to regulate osmotic pressure in the transfusion, for example, sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium lactate, glucose, xylitol, sorbitol and dextran etc., preferred sodium chloride or glucose.Can add excipient in the powder pin, for example, mannitol, glucose etc.

The present composition has the following advantages:

(1) provide first a kind of Radix Ginseng, Radix Ophiopogonis, Fructus Schisandrae Chinensis and cantharidin or derivatives thereof or its analog especially norcantharidin, Venenum Bufonis one or both compatibilities in the two be used to prepare the pharmaceutical composition of anti-tumor aspect, satisfied urgent clinical needs.

(2) interaction and the composition of prescription to pharmaceutical composition of the present invention carried out pharmaceutical research, found that the present composition is to mice S ₁₈₀Growth of tumor has significant inhibitory effect, and tumour inhibiting rate all can reach more than 50%, but significant prolongation ehrlich ascites carcinoma U ₁₄The existence natural law of mice, increase in life span also significantly increases, both can significantly strengthen the effect of radiotherapy, also can significantly strengthen the curative effect of chemotherapy, liver tumor growth to the qi-deficiency type rat also has significant inhibitory effect, but and the survival natural law of significant prolongation rat, lotus tumor SRS-82 mice blood leukocytes number is raise, macrophage phagocytic function significantly strengthens; And compare with norcantharidin, Venenum Bufonis with single, be applied to antitumor behind the compatibility, evident in efficacy, consequently those skilled in the art institute is beyond thought.

(3) the present invention can directly feed intake with raw material or extract, and preparation technology is simple, can make between the different batches medicine mass discrepancy little, and drug quality is more uniform and stable.

(4) stability experiment that carries out shows that the every index of medicine composition injection of the present invention is all more stable, has guaranteed safety of clinical administration.

(5) present composition drug combination determined curative effect, and reduced relative dosage, be with a wide range of applications.

Below routine by experiment beneficial effect of further setting forth medicine of the present invention.In the following experimental example: the compositions of norcantharidin, Radix Ginseng (extract is main effective ingredient with total saponins), Radix Ophiopogonis, Fructus Schisandrae Chinensis hereinafter to be referred as BRMW ICompositions; The compositions of norcantharidin, Radix Ginseng (extract is main effective ingredient with polysaccharide), Radix Ophiopogonis, Fructus Schisandrae Chinensis hereinafter to be referred as BRMW IICompositions; The compositions of Venenum Bufonis, Radix Ginseng (extract is main effective ingredient with total saponins), Radix Ophiopogonis, Fructus Schisandrae Chinensis hereinafter to be referred as CRMW ICompositions; The compositions of Venenum Bufonis, Radix Ginseng (extract is main effective ingredient with polysaccharide), Radix Ophiopogonis, Fructus Schisandrae Chinensis hereinafter to be referred as CRMW IICompositions.Used Venenum Bufonis extract is taken from embodiment 1 in the following experimental example, Radix Ginseng total saponins is taken from the preparation of Radix Ginseng total saponins among the embodiment 2, the ginseng polysaccharide takes from the preparation of ginseng polysaccharide among the embodiment 2, and Radix Ophiopogonis extract is taken from embodiment 3, and Fructus Schisandrae Chinensis extrat is taken from embodiment 4.

Test example 1 present composition is to mice S ₁₈₀ The tumor growth inhibitory action

Test sample: matched group: normal saline, commercial;

Norcantharidin group: Injectio natarii norcantharidatis injection, specification 2ml:10mg;

Venenum Bufonis group: Venenum Bufonis Injection, specification 2ml: be equivalent to Venenum Bufonis medical material 8mg;

Radix Ginseng total saponins group: Radix Ginseng total saponins injection, self-control, specification 5ml: be equivalent to ginseng crude drug 3g;

Ginseng polysaccharide's group: ginseng polysaccharide injection, self-control, specification 5ml: be equivalent to ginseng crude drug 3g;

Radix Ophiopogonis group: Radix Ophiopogonis injection, self-control, specification 5ml: be equivalent to medical material 6g Radix Ophiopogonis;

Fructus Schisandrae Chinensis group: Fructus Schisandrae Chinensis injection, self-control, 5ml: be equivalent to schisandra chinensis medicinal material 3g;

BRMW I injection group: self-control (prescription and preparation method are referring to aqueous injection prescription 1 among the embodiment 6) is divided into basic, normal, high three dosage groups;

BRMWII injection group: self-control (prescription and preparation method are referring to aqueous injection prescription 2 among the embodiment 6) is divided into basic, normal, high three dosage groups;

CRMW I injection group: self-control (prescription and preparation method are referring to aqueous injection prescription 3 among the embodiment 6) is divided into basic, normal, high three dosage groups;

CRMWII injection group: self-control (prescription and preparation method are referring to aqueous injection prescription 4 among the embodiment 6) is divided into basic, normal, high three dosage groups.

Animal subject: 190 of healthy mices, body weight 16～20g, male and female half and half, 10 every group.

Tumor strain: mice S ₁₈₀Sarcoma

Test method: get and inoculate the mice S that goes down to posterity ₁₈₀Tumor adds normal saline in homogenizer, make mice S ₁₈₀The tumor homogenate, again with normal saline 1: 3 dilution, getting 0.2ml then, to inject oxter, a mice left side subcutaneous, weighed in 24 hours, mice intraperitoneal injection every day once, administration volume identical (0.5ml/ is only), totally 7 days.Next day is put to death mice in drug withdrawal, and the subcutaneous tumors piece is peeled off in the also carefulness of weighing, and takes by weighing tumor in the EM50 electronic balance and weighs, and calculate tumour inhibiting rate.

Table 1 present composition injection is to mice S ₁₈₀The tumor growth inhibitory action (x ± s, n=10)

Annotate: compare with the normal saline matched group, ^*P＜0.05, ^*P＜0.01; Compare with the norcantharidin group, ^aP＜0.01, ^gP＜0.05; Compare with the Venenum Bufonis group, ^bP＜0.01, ^hP＜0.05; Compare with the Radix Ginseng total saponins group, ^cP＜0.01; Compare with ginseng polysaccharide's group, ^dP＜0.01; Compare with Radix Ophiopogonis group, ^eP＜0.01; Compare with the Fructus Schisandrae Chinensis group, ^fP＜0.01.

Result of the test and conclusion: result of the test sees Table 1.

(1) compare with the normal saline matched group, norcantharidin group, Venenum Bufonis group, Radix Ginseng total saponins group and ginseng polysaccharide organize all can obviously suppress mice S ₁₈₀The growth of sarcoma (p＜0.05); BRMW I, BRMW II, CRMW I, each dosage group of CRMW II injection all can significantly suppress mice S ₁₈₀The growth of sarcoma (p＜0.01).

(2) compare with the norcantharidin group, BRMW I, BRMWII injection low dose group all can obviously suppress mice S ₁₈₀The growth of sarcoma (p＜0.05), tumour inhibiting rate significantly increases; BRMW I, the middle and high dosage group of BRMW II injection all can significantly suppress mice S ₁₈₀The growth of sarcoma (p＜0.01), tumour inhibiting rate significantly increases.

(3) compare with the Venenum Bufonis group, CRMW I, CRMWII injection low dose group all can obviously suppress mice S ₁₈₀The growth of sarcoma (p＜0.05), tumour inhibiting rate significantly increases; CRMW I, the middle and high dosage group of CRMW II injection all can significantly suppress mice S ₁₈₀The growth of sarcoma (p＜0.01), tumour inhibiting rate significantly increases.

(4) compare with the Radix Ginseng total saponins group, BRMW I, the basic, normal, high dosage group of CRMW I injection all can significantly suppress mice S ₁₈₀The growth of sarcoma (p＜0.01), tumour inhibiting rate significantly increases.

(5) compare with ginseng polysaccharide's group, BRMW II, the basic, normal, high dosage group of CRMWII injection all can significantly suppress mice S ₁₈₀The growth of sarcoma (p＜0.01), tumour inhibiting rate significantly increases.

(6) compare with Radix Ophiopogonis group, BRMW I, BRMWH, CRMW I, the basic, normal, high dosage group of CRMWII injection all can significantly suppress mice S ₁₈₀The growth of sarcoma (p＜0.01), tumour inhibiting rate significantly increases.

(7) compare with Fructus Schisandrae Chinensis, BRMW I, BRMWII, CRMW I, the basic, normal, high dosage group of CRMWII injection all can significantly suppress mice S ₁₈₀The growth of sarcoma (p＜0.01), tumour inhibiting rate significantly increases.

Result of the test shows, compares with norcantharidin, Venenum Bufonis, Radix Ginseng total saponins, ginseng polysaccharide, Radix Ophiopogonis, Fructus Schisandrae Chinensis with single, and any compatibility in Radix Ginseng, Radix Ophiopogonis, Fructus Schisandrae Chinensis and norcantharidin and the Venenum Bufonis is used, and all can significantly suppress mice S ₁₈₀The growth of sarcoma is significantly increased the tumour inhibiting rate of mice, and tumour inhibiting rate all reaches more than 50%, and effect is relevant with dosage, and effect is best during high dose.Prompting, Radix Ginseng, Radix Ophiopogonis, Fructus Schisandrae Chinensis and norcantharidin and/or Venenum Bufonis associating compatibility have the effect of Synergistic when using.

Test example 2 present compositions are to the influence of ehrlich ascites carcinoma U14 mice increase in life span

Test sample: matched group: normal saline, commercial;

BRMW II injection group: self-control (prescription and preparation method are referring to aqueous injection prescription 2 among the embodiment 6) is divided into basic, normal, high three dosage groups;

Animal subject: healthy mice, 150, body weight 20～25g, the male and female dual-purpose is divided into 15 groups at random, 10 every group.

Tumor strain: mouse ascites cancer U ₁₄

Test method: mouse peritoneal inoculation ehrlich ascites carcinoma U ₁₄Tumor strain bacteria suspension (suspension concentration 2 * 10 ⁷/ ml, inoculum concentration 0.5ml/ are only).Inoculate next day, the mice random packet is weighed in, and presses table 2 intraperitoneal injection, every day 1 time, continuous 10 days.After this observe the death time of mice, the result represents [increase in life span=(test group The average survival time natural law-matched group The average survival time natural law)/matched group The average survival time natural law * 100%] with average survival natural law and increase in life span.

Result of the test and conclusion: result of the test sees Table 2.

(1) compare with the normal saline matched group, norcantharidin group, Venenum Bufonis group and BRMW I, BRMWII, CRMW I, CRMWII injection low dose group all can obviously prolong the existence natural law (p＜0.05) of mice; But BRMW I, BRMW II, CRMW I, the middle and high dosage group of CRMWII injection significant prolongation ehrlich ascites carcinoma U ₁₄The existence natural law of mice (p＜0.01).

(2) compare with the norcantharidin group, BRMW I, BRMWII injection low dose group all can obviously prolong ehrlich ascites carcinoma U ₁₄The existence natural law of mice (p＜0.05), increase in life span also obviously increase (p＜0.05); But BRMW I, the middle and high dosage group of BRMW II injection significant prolongation ehrlich ascites carcinoma U ₁₄The existence natural law of mice (p＜0.01), increase in life span also significantly increase (p＜0.01).

(3) compare with the Venenum Bufonis group, but BRMW I, the basic, normal, high dosage group of BRMWII injection significant prolongation ehrlich ascites carcinoma U ₁₄The existence natural law of mice (p＜0.01), increase in life span also significantly increase (p＜0.01).

Result of the test shows, compares with norcantharidin, Venenum Bufonis with single, and the compositions that Radix Ginseng, Radix Ophiopogonis, Fructus Schisandrae Chinensis and norcantharidin, Venenum Bufonis are formed all can prolong ehrlich ascites carcinoma U ₁₄The existence natural law of mice, increase in life span also increases; And action effect is relevant with dosage, and effect is best during high dose.Prompting, Radix Ginseng, Radix Ophiopogonis, Fructus Schisandrae Chinensis and norcantharidin, Venenum Bufonis associating compatibility have the effect of Synergistic when using.

Table 2 present composition injection is to ehrlich ascites carcinoma U ₁₄The influence of mice increase in life span (x ± s, n=10)

Annotate: compare with the normal saline matched group ^*P＜0.05, ^*P＜0.01; Compare with the norcantharidin group, ^aP＜0.05, ^bP＜0.01; Compare with the Venenum Bufonis group, ^cP＜0.01.

Test example 3 present compositions are to the potentiation of radiotherapy

Test sample: matched group: normal saline, commercial;

CRMW II injection group: self-control (prescription and preparation method are referring to aqueous injection prescription 4 among the embodiment 6) is divided into basic, normal, high three dosage groups.

Animal subject: healthy mice, 140, body weight 20～25g, the male and female dual-purpose is divided into 14 groups at random, 10 every group.

Tumor strain: mice S ₁₈₀Sarcoma.

Test method: every mice left fore oxter subcutaneous vaccination S ₁₈₀Tumor strain cell suspension (suspension concentration 2 * 10 ⁷/ ml, inoculum concentration 0.2ml/ are only), weigh in during 24h.Inoculate next day, random packet, except that the blank group, all the other each groups are the 3rd day, the 6th day usefulness after inoculation all ⁶⁰Co total irradiation, exposure dose are 0.05Gy/min.Inoculate next day, mice is pressed table 3 intraperitoneal injection, every day 1 time, continuous 10 days.Weigh in every day, observes the mice with tumor body weight change.24h after the last administration, weigh in, put to death animal, peel off the subcutaneous tumors piece, take by weighing the tumor body weight, calculate tumor control rate and potentiation rate [potentiation rate=(the average tumor of average tumor weight-radiotherapy of combination radiotherapy group and composite injection therapeutic alliance group is heavy)/average tumor of combination radiotherapy group heavy * 100%].

Table 3 present composition to the potentiation of radiotherapy (x ± s, n=10)

Compare with the blank group, ^*P＜0.01, ^*P＜0.001; With ⁶⁰Co irradiation group is compared, ^aP＜0.05, ^bP＜0.01.

Result of the test and conclusion result of the test see Table 3.

(1) compare with the normal saline matched group, ⁶⁰Co irradiation group is to mice S ₁₈₀Sarcoma has significant inhibitory effect (p＜0.01); ⁶⁰Co irradiation and BRMW I, BRMW II, CRMW I, the therapeutic alliance of CRMW II injection are to mice S ₁₈₀Sarcoma has utmost point significant inhibitory effect (p＜0.001).

(2) with ⁶⁰Co irradiation group is compared, ⁶⁰Co irradiation and low dosage BRMW I, BRMWII, CRMW I, the therapeutic alliance of CRMWII injection are to mice S ₁₈₀The inhibitory action of sarcoma obviously strengthens (p＜0.05), and tumour inhibiting rate obviously increases (p＜0.05); ⁶⁰Co irradiation and middle and high dosage BRMW I, BRMWII, CRMW I, the therapeutic alliance of CRMWII injection are to mice S ₁₈₀The inhibitory action of sarcoma significantly strengthens (p＜0.01), and tumour inhibiting rate significantly increases (p＜0.01).

Result of the test shows that BRMW I, BRMWII, CRMW I, CRMWII injection can significantly strengthen ⁶⁰The radiotherapy effect of Co irradiation, prompting, Radix Ginseng, Radix Ophiopogonis, Fructus Schisandrae Chinensis and norcantharidin, Venenum Bufonis drug combination have the effect that strengthens radiotherapy effect.

Test example 4 present compositions are to the potentiation of chemotherapy (Cy)

Test sample: matched group: normal saline, commercial

Cyclophosphamide for injection: commercial, 100mg, the pharmacy of Hua Lian, Shanghai;

Tumor strain: mice S ₁₈₀Sarcoma.

Test method: every mice left fore oxter subcutaneous vaccination S ₁₈₀Tumor strain cell suspension (suspension concentration 2 * 10 ⁷/ ml, inoculum concentration 0.2ml/ are only).The inoculation next day, the mice random packet is weighed in, and presses table 4 dosage intraperitoneal injection, the next day 1 time, continuous 10 days.Weigh in every day, observes the mice with tumor body weight change.24h after the last administration, weigh in, put to death animal, peel off the subcutaneous tumors piece, take by weighing the tumor body weight, calculate tumor control rate and potentiation rate [potentiation rate=(the average tumor of average tumor weight-chemotherapy of chemotherapy group and composite injection drug combination group is heavy)/average tumor of chemotherapy group heavy * 100%].

Table 4 present composition to the potentiation of chemotherapy (x ± s, n=10)

Compare with the blank group, ^*P＜0.01, ^*P＜0.001; Compare with the Cyclophosphamide for injection group, ^aP＜0.05, ^bP＜0.01.

Result of the test and conclusion: result of the test sees Table 4.

(1) compare with the normal saline matched group, Cyclophosphamide for injection group, cyclophosphamide and BRMW I, BRMWII, CRMW I, CRMW II drug combination low dose group are to mice S ₁₈₀Sarcoma has significant inhibitory effect (p＜0.01); Cyclophosphamide and BRMW I, BRMWII, CRMW I, the middle and high dosage group of CRMW II drug combination are to mice S ₁₈₀Sarcoma has utmost point significant inhibitory effect (p＜0.001).

(2) compare with the Cyclophosphamide for injection group, cyclophosphamide and BRMW I, BRMWII, CRMW I, CRMWII drug combination low dose group are to mice S ₁₈₀Sarcoma has obvious suppression effect (p＜0.05), and tumour inhibiting rate obviously increases (p＜0.05); Cyclophosphamide and BRMW

I, BRMWII, CRMW I, the middle and high dosage group of CRMWII drug combination are to mice S ₁₈₀Sarcoma has significant inhibitory effect (p＜0.01), and tumour inhibiting rate also significantly increases (p＜0.01).

Result of the test shows, when cyclophosphamide and BRMW I, BRMWII, CRMW I, CRMWII compositions drug combination, can significantly strengthen the curative effect of chemotherapy, and can alleviate the toxicity of chemotherapy.Prompting, Radix Ginseng, Radix Ophiopogonis, Fructus Schisandrae Chinensis and norcantharidin, Venenum Bufonis drug combination have the effect that strengthens chemotherapeutic efficacy.

Test example 5 present compositions are to qi-deficiency type rats'liver tumor inhibition effect

Test sample: normal saline matched group: normal saline, commercial;

Animal subject: 150 of rats, body weight 150～180g, makes model of qi-asthenia by 10 every group.

Test method: get rat and do inoculation in the liver of W256, inoculate after 7 days, press the dosage intraperitoneal injection of anesthesia of 35mg/kg with pentobarbital sodium, fixing, cutting open the belly exposes liver, and tumor surface maximum diameter (a) and path (b) are pressed (a * b on the measurement liver ²)/2=V (gross tumor volume).Separate stomach, arteria duodenalis, common hepatic artery and proper hepatic artery, ligation stomach, arteria duodenalis are long-range, with silver brain clip blocking-up common hepatic artery, in sending into proper hepatic artery again at stomach, arteria duodenalis upper cut and after inserting external diameter 0.3mm conduit under the operating loupe, inject respectively by the test grouping then and be subjected to the reagent thing, postoperative tube drawing ligation stomach, arteria duodenalis, decontrol the common hepatic artery silver brain clip, sew up the incision again, place animal housing to wait to revive rat, continue breeding observing, performed the operation back 8 days, detect gross tumor volume by last method.And carry out the survival natural law of experimental observation rat as stated above again.

Table 5 present composition to the rats'liver tumor and the survival natural law influence (x ± s, n=10)

Compare with the normal saline matched group, ^*P＜0.05, ^*P＜0.01, ^{* *}P＜0.001; Compare with the norcantharidin group, ^aP＜0.05, ^bP＜0.01; Compare with the Venenum Bufonis group, ^cP＜0.05, ^dP＜0.01.

Result of the test and conclusion: test result sees Table 5.

(1) compare with the normal saline matched group, gross tumor volume significantly reduces after norcantharidin group, the administration of Venenum Bufonis group, and volume change enlarges markedly (p＜0.01); The survival natural law of rat obviously prolongs (p＜0.05).Gross tumor volume extremely significantly reduces after BRMW I, BRMWII, CRMW I, the administration of CRMWII composite injection, and the volume change utmost point enlarges markedly (p＜0.001); BRMW I, BRMW II, CRMWI, CRMW II composite injection low dose group survival of rats natural law significant prolongation (p＜0.01), BRMW I, BRMWII, CRMWI, the middle and high dosage group of CRMW II composite injection survival of rats natural law utmost point significant prolongation (p＜0.001).

(2) compare with the norcantharidin group, gross tumor volume obviously reduces after BRMW I, the administration of BRMW II composite injection low dose group, volume change obviously increases (p＜0.05), the survival of rats natural law obviously prolongs (p＜0.05), gross tumor volume significantly reduces after BRMW I, the administration of the middle and high dosage group of BRMWII composite injection, volume change enlarges markedly (p＜0.01), survival of rats natural law significant prolongation (p＜0.01).

(3) compare with the Venenum Bufonis group, gross tumor volume obviously reduces after CRMW I, the administration of CRMWII composite injection low dose group, volume change obviously increases (p＜0.05), the survival of rats natural law obviously prolongs (p＜0.05), gross tumor volume significantly reduces after CRMW I, the administration of the middle and high dosage group of CRMWII composite injection, volume change enlarges markedly (p＜0.01), survival of rats natural law significant prolongation (p＜0.01).

Result of the test shows that the rats'liver gross tumor volume reduces behind Radix Ginseng, Radix Ophiopogonis, Fructus Schisandrae Chinensis and norcantharidin, the Venenum Bufonis combination drug, and volume change increases, and the existence natural law of rat prolongs, prompting, and the present composition has the effect of Synergistic.

Experimental example 6 pharmaceutical compositions of the present invention are to lotus SRS-82 sarcoma effect of immunologic function

Animal subject: ICR kind mice, body weight 18～23g, 8 ages in week, male and female half and half.

Tumor kind and reagent: mice SRS-82 cell strain is available from Shanghai cell biological institute

Interleukin II (1L-2) injection, Ke Xing biotech company in Shenzhen produces;

Test sample: normal saline matched group: normal saline, commercial;

CRMWII injection group; Self-control (prescription and preparation method are referring to aqueous injection prescription 4 among the embodiment 6) is divided into basic, normal, high three dosage groups.

Test method:

Tumor inoculation: with behind the SRS-82 cell inoculation kunming mice of cultivating the 8th day, extract the about 15ml of ascites in 4 mouse peritoneals respectively, being diluted to cell number with normal saline is 1.0 * 10 ⁷Behind/the ml (30ml altogether), every mice left side groin subcutaneous injection 0.2ml (2.0 * 10 ⁶/ only).Administering mode and time: every mouse peritoneal injection (ip) administration, the beginning administration in the 2nd day behind inoculated tumour, 1 time/day, totally 10 days.

1, quantity of leucocyte of the present invention changes: solid tumor mice the 11st day behind inoculated tumour, eye socket rear vein beard about 100 μ l that take a blood sample, respectively organize the leukocyte count of mice with Japanese F-800 hemocyte automatic analyzer detection.The results are shown in Table 6.

2, the macrophages in vitro phagocytic function detects: each organizes white mice in the cold DMEM culture medium of experiment the 11st day difference intraperitoneal injection 5ml, and peritoneal fluid is extracted in soft abdominal cavity out behind the 10min, and the centrifugal 10min of 1000r/min abandons the part supernatant, stays about 2ml.Add 1% Sanguis Gallus domesticus ball 2ml then behind the mixing.Put in the constant incubator behind the 60min, the mixing smear, Wright's staining calculates 100 macrophage phagocytic percentage rate (what cytophagies erythrocyte) and phagocytic index (having engulfed what erythrocyte altogether).The results are shown in Table 6.

Result of the test and conclusion: result of the test sees Table 6.

(1) compares with the normal saline matched group, after norcantharidin group, Venenum Bufonis group and BRMW I, BRMWII, CRMW I, the administration of the basic, normal, high dosage group of CRMWII composite injection, all can make lotus tumor SRS-82 mice blood leukocytes number rising (p＜0.05, p＜0.01), can make lotus tumor SRS-82 macrophage phagocytosis of mice obviously strengthen (p＜0.05, p＜0.01).

(2) compare with the norcantharidin group, BRMW I, BRMWII composite injection low dose group can make lotus tumor SRS-82 mice blood leukocytes number obviously raise (p＜0.05), make lotus tumor SRS-82 macrophage phagocytosis of mice obviously strengthen (p＜0.05); BRMW I, the middle and high dosage group of BRMWII composite injection can make lotus tumor SRS-82 mice blood leukocytes number significantly raise (p＜0.01), make lotus tumor SRS-82 macrophage phagocytosis of mice significantly strengthen (p＜0.01).

(3) compare with the Venenum Bufonis group, CRMW I, CRMW II composite injection low dose group can make lotus tumor SRS-82 mice blood leukocytes number obviously raise (p＜0.05), make lotus tumor SRS-82 macrophage phagocytosis of mice obviously strengthen (p＜0.05); CRMW I, the middle and high dosage group of CRMWII composite injection can make lotus tumor SRS-82 mice blood leukocytes number significantly raise (p＜0.01), make lotus tumor SRS-82 macrophage phagocytosis of mice significantly strengthen (p＜0.01).

Result of the test shows, lotus tumor SRS-82 mice blood leukocytes number is raise, and lotus tumor SRS-82 macrophage phagocytosis of mice is strengthened.Prompting, Radix Ginseng, Radix Ophiopogonis, Fructus Schisandrae Chinensis and norcantharidin, Venenum Bufonis compatibility have the effect of Synergistic, and curative effect strengthens with the increase of dosage.

Table 6 pharmaceutical composition SRS-82 of the present invention lotus sarcoma mice is from the influence of cell quantity and macrophage phagocytic function

Annotate: compare with the blank group ^*P＜0.05, ^*P＜0.01; Compare with the norcantharidin group, ^aP＜0.05, ^bP＜0.01; Compare with the Venenum Bufonis group, ^cP＜0.05, ^dP＜0.01.

Test example 7 present composition stability experiments

Test sample:

BRMW I injection group: self-control (prescription and preparation method are referring to aqueous injection prescription 1 among the embodiment 6);

BRMW II injection group: self-control (prescription and preparation method are referring to aqueous injection prescription 2 among the embodiment 6);

CRMW I injection group: self-control (prescription and preparation method are referring to aqueous injection prescription 3 among the embodiment 6);

CRMW II injection group: self-control (prescription and preparation method are referring to aqueous injection prescription 4 among the embodiment 6).

Investigation project: character, content, related substance.

Long-time stability experimental technique and result: each compositions of this product is put under the condition of 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10% and placed 6 months, 12 months, every index has no significant change, and experimental result shows that the long-term placement of pharmaceutical composition of the present invention is basicly stable.

4, the specific embodiment

The specific embodiment of form is described in further detail foregoing of the present invention by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.The adjuvant of each dosage form can be replaced with acceptable accessories in following examples, perhaps reduces, increases.

Venenum Bufonis extract in following examples 5～11, Radix Ginseng total saponins, ginseng polysaccharide, Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat come from the 3rd batch among embodiment 1, embodiment 2, embodiment 3 and the embodiment 4.

The preparation of embodiment 1 Venenum Bufonis extract

Get Venenum Bufonis, be ground into fine powder, add the soak with ethanol of 20 times of amounts 80%, grind, cold preservation is spent the night, filter next day, and filtrate recycling ethanol adds 10 times of water gagings again and stirs evenly to there not being the alcohol flavor, and cold preservation was left standstill 24 hours, filter, it is 1.10～1.15 that filtrate is concentrated into relative density, spray drying, promptly.

By three batches of Venenum Bufonis extracts of above-mentioned prepared, yield sees Table 7.

The discriminating of Venenum Bufonis extract

Get Venenum Bufonis extract 0.1g, add ethanol 10ml, reflux 30 minutes filters, and filtrate is put in the 10ml measuring bottle, adds ethanol to scale, as need testing solution.Other gets Venenum Bufonis control medicinal material 0.2g, shines medical material solution in pairs with legal system.Get bufogenin reference substance and cinobufagin reference substance again, add ethanol and make the solution that every 1ml contains 1mg respectively, in contrast product solution.According to thin layer chromatography test, be developing solvent with cyclohexane extraction-chloroform-acetone (4: 3: 3), launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, be heated to the least bit develop the color clear.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color, with the corresponding position of reference substance chromatograph on, show an identical green and punctation.

Above-mentioned three batches of Venenum Bufonis extracts are differentiated, all met the requirements.

The assay of Venenum Bufonis extract bufotenine constituents

The preparation precision of reference substance solution takes by weighing puts 24 hours 5-hydroxy tryptamine reference substance 2.0mg of vacuum drying in the phosphorus pentoxide desiccator, puts in the 50ml measuring bottle, adds water and makes dissolving, and be diluted to scale, shakes up, and promptly gets (containing 5-hydroxy tryptamine 0.040mg among every 1ml).

Accurate reference substance solution 0.5,1.0,2.0,3.0,4.0 and the 5.0ml of drawing of the preparation of standard curve, put respectively in the 10ml measuring bottle, respectively add water to 5.0ml, accurate 15% paradime thylaminobenzaldehyde hydrochloric acid (2 → 3) the solution 5ml that adds, shake up, room temperature (more than 20 ℃) was placed 30 minutes, according to the spectrophotography test, was blank with the reagent corresponding, measure trap at 555nm wavelength place, with the trap is vertical coordinate, and concentration is abscissa, the drawing standard curve.

The accurate this product 0.5mg that draws of algoscopy puts in the 10ml measuring bottle, and the method under the sighting target directrix curve preparation from " add water and make into 5.0ml ", is measured trap in accordance with the law, from the weight that standard curve is read indoles total alkaloids the need testing solution, calculates, promptly.

The Venenum Bufonis extract assay

The assay of middle cinobufagin and bufogenin

Chromatographic condition and system suitability test are filler with the octadecylsilane chemically bonded silica; With 0.5% potassium dihydrogen phosphate-acetonitrile (50: 50) (is 3.2 with the phosphoric acid adjust pH) is mobile phase; The detection wavelength is 296nm; 40 ℃ of column temperatures.Number of theoretical plate calculates by cinobufagin peak, bufogenin peak should be not less than 4000.

The preparation precision of reference substance solution takes by weighing through 24 hours cinobufagin reference substance of phosphorus pentoxide drying under reduced pressure, each 10mg of bufogenin reference substance, puts respectively in the 100ml measuring bottle, adds dissolve with methanol and is diluted to scale, shakes up; Precision is measured 5ml respectively, respectively puts in the 10ml measuring bottle, adds methanol to scale, shakes up, and promptly gets (containing cinobufagin, each 50 μ l of bufogenin among every 1ml).

This product 2mg is got in the preparation of need testing solution, and accurate the title decides, and puts in the 50ml tool plug conical flask, the accurate methanol 20ml that adds, claim decide weight, reflux 1 hour is put coldly, and weight decided in title again, supply the weight that subtracts mistake with methanol, shake up, filter, get subsequent filtrate as need testing solution.

Accurate respectively above-mentioned two kinds of reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.

Above-mentioned three batches of Venenum Bufonis extracts are carried out assay, the results are shown in Table 7.

Venenum Bufonis extract yield by this prepared is 6.0%～8.0%, and indoles alkaloid content is not less than 10%, and the bufotoxin class is not less than 30%.

The assay result and the yield of three batches of Venenum Bufonis extracts of table 7

The preparation of embodiment 2 Radix Ginseng extracts

The preparation of Radix Ginseng total saponins

Get the ginseng crude drug, be ground into particulate, add 10 times of amount alcohol reflux secondaries, each 3 hours, merge extractive liquid,, cold preservation filters, and filtrate recycling ethanol also is concentrated into thick paste, add water to an amount of (making every 1ml be equivalent to crude drug 1g), stir evenly, cold preservation filters, filtrate is added on the macroporous resin column of having handled well, water with 2 times～3 times of column volumes carries out eluting earlier, discards water lotion, 80% ethanol elution of 3 times of column volumes of reuse, collect eluent, reclaim ethanol and be evaporated to the thick paste of relative density 1.30～1.35, vacuum drying, promptly.

Prepare three batches of Radix Ginseng total saponinss respectively, yield sees Table 7.

The discriminating of Radix Ginseng total saponins

Get Radix Ginseng total saponins 0.5g, add water 0.5ml and stir moistening, add water-saturated n-butanol 10ml, supersound process 30 minutes is drawn supernatant and is added 3 times of amount ammonia solutions, shakes up, and places layering, gets upper strata liquid evaporate to dryness, and residue adds methanol 1ml makes dissolving, as need testing solution.Other gets ginsenoside Re, Rg1 reference substance, adds methanol and makes the mixed solution that every 1ml contains 2mg, in contrast product solution.Draw above-mentioned two kinds of each 2ul of solution, put respectively on same silica gel g thin-layer plate, (15: 40: 22: 10) lower floor's solution of placing below 10 ℃ was developing solvent with chloroform-ethyl acetate-methanol-water, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, it is clear to be heated to speckle colour developing at 105 ℃, puts under the ultra-violet lamp (365nm) and inspects.In the test sample chromatograph, with reference substance chromatograph relevant position on show the fluorescence speckle of same color.

Above-mentioned three batches of Radix Ginseng total saponinss are differentiated, all met the requirements.

The Radix Ginseng total saponins assay

The about 10mg of ginsenoside Rg1 reference substance is got in reference substance solution preparation, and through 60 ℃ of vacuum dryings 2 hours, the accurate title put in the 100ml measuring bottle calmly, with anhydrous alcohol solution and be diluted to scale, shakes up, and makes the solution that every 1ml contains Rg1 reference substance 0.1mg, promptly.

Need testing solution prepares precision and takes by weighing Radix Ginseng total saponins 50mg, puts in the 50ml measuring bottle, adds dehydrated alcohol and is diluted to scale, shakes up, and precision is measured 2ml, puts in the 10ml measuring bottle, adds dehydrated alcohol and is diluted to scale, shakes up, promptly.

The algoscopy precision is measured need testing solution and each 1ml of reference substance solution, puts respectively in the 10ml tool plug test tube, and evaporate to dryness in water-bath is put cold, add 5% vanillin glacial acetic acid solution 0.2ml, add perchloric acid 0.8ml again, in 60 ℃ of insulations 15 minutes, be cooled to room temperature, add glacial acetic acid 5ml, shake up; Make blank simultaneously.Spectrophotography is measured trap at 560nm wavelength place, calculates, promptly.

Ginsenoside Re, ginsenoside Rg ₁Assay

Chromatographic condition and system suitability test are filler with the octadecylsilane chemically bonded silica; With acetonitrile-water (22: 78) is mobile phase; The detection wavelength is 203nm.Number of theoretical plate calculates by the ginsenoside Re peak should be not less than 2000.

The preparation precision of reference substance solution takes by weighing ginsenoside Rg1's reference substance, the Re reference substance is an amount of, adds methanol and makes the mixed solution that every 1ml contains 0.2mg.

Radix Ginseng total saponins 0.2g is got in the preparation of need testing solution, and accurate the title decides, the accurate water-saturated n-butanol 30ml that adds, close plug, placement is spent the night, supersound process (power 250W, frequency 50kHz) 30 minutes, filter, discard filtrate just, precision is measured subsequent filtrate 15ml, puts evaporate to dryness in the evaporating dish, and residue adds dissolve with methanol and is transferred in the 5ml volumetric flask, add methanol and be diluted to scale, shake up, filter, get subsequent filtrate promptly.

Accurate respectively reference substance and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.

Above-mentioned three batches of Radix Ginseng total saponinss are carried out assay, the results are shown in Table 7.

Radix Ginseng total saponins yield by this prepared is 1%～2%, and the content of total saponins is not less than 50%, ginsenoside Re, ginsenoside Rg ₁Total content be not less than 30%.

Table 8 Determination of Total Saponin Content in Panax Ginseng result and yield

Ginseng polysaccharide's preparation

Get the ginseng crude drug, chopping, with 75% alcohol reflux 4 hours, filtration, medicinal residues dry, decoct with water five times, and each 1 hour, collecting decoction, add 0.3% active carbon, stirred 30 minutes, standing over night filters, filtrate is crossed resin column, collects effluent, and concentrating under reduced pressure adds ethanol and makes and contain the alcohol amount and reach 95%, cold preservation filters, and gets precipitation and uses washing with acetone, drains acetone, get and be deposited in 60～80 ℃ of dryings, pulverize, promptly.

Prepare three crowdes of ginseng polysaccharides respectively, yield sees Table 9.

Ginseng polysaccharide's discriminating

(1) gets the about 0.2g of ginseng polysaccharide, after adding water 5ml dissolving, add 5 of alkaline cupric tartrate test solutions, heating promptly produces red precipitate, cooling, filter, get filtrate add 1 of hydrochloric acid make acid, heating in water bath 10 minutes, put cold, regulate pH value to neutral, add alkaline cupric tartrate test solution 0.5ml, heating in water bath promptly produces red copper oxidule precipitation.

(2) get the about 0.2g of ginseng polysaccharide, add water 2ml dissolving after, add 5% alpha-Naphthol alcoholic solution 0.5ml and shake up, slowly add sulphuric acid 3ml, two liquid level intersection displaing amaranth rings.

Above-mentioned three crowdes of ginseng polysaccharides are differentiated, all meet the requirements.

Ginseng polysaccharide's assay

The preparation precision of reference substance solution takes by weighing 60 ℃ of vacuum dryings to the about 100mg of the galacturonic acid of constant weight, puts in the 100ml measuring bottle, adds water to scale, shakes up.Precision is measured 10ml, puts in the 100ml measuring bottle, adds water to scale, shakes up, promptly.

The preparation precision of need testing solution takes by weighing ginseng polysaccharide 50mg, puts in the 100ml measuring bottle, is dissolved in water and is diluted to scale, shakes up, promptly.

The algoscopy precision is measured each 1ml of reference substance solution, need testing solution and water, the accurate respectively 0.25mol/L Borax sulfuric acid solution 6ml that adds, put in the water-bath heating 30 minutes, put cold, the accurate respectively again 0.125% carbazole ethanol solution 0.4ml that adds, put in the water-bath and heated 10 minutes, put and be chilled to room temperature, spectrophotography is measured trap at 530nm wavelength place, calculate, promptly.

Above-mentioned three crowdes of ginseng polysaccharides are carried out assay, the results are shown in Table 9.

Ginseng polysaccharide's yield by this prepared is 0.5%～2%, and the content of polysaccharide is not less than 50%.

Table 9 ginseng polysaccharide's assay result and yield

The preparation of embodiment 3 Radix Ophiopogonis extracts

Get medical material Radix Ophiopogonis, be ground into particulate, add 8 times of water gagings and decoct secondary, each 1 hour, collecting decoction filters, and filtrate is concentrated into the thick paste shape, adds ethanol and makes and contain the alcohol amount and reach 80%, cold preservation was placed 24 hours, filtered, and filtrate recycling ethanol also is concentrated into the thick paste shape, added ethanol and made and contain the alcohol amount and reach 85%, cold preservation was placed 24 hours, filtered, and reclaimed ethanol and was concentrated into the thick paste shape, add water to an amount of (making every 1ml be equivalent to crude drug 2g), stir evenly cold preservation, filter, the filtrate spray drying, promptly.

Prepare three batches of Radix Ophiopogonis extracts respectively, yield sees Table 10.

Radix Ophiopogonis extract yield by this prepared is 1～2%.

The yield of table 10 Radix Ophiopogonis extract

The preparation and the assay of embodiment 4 Fructus Schisandrae Chinensis extrats

The preparation of Fructus Schisandrae Chinensis extrat

Get schisandra chinensis medicinal material, be ground into coarse powder, decoct with water secondary, each 2 hours, collecting decoction filtered, filtrate is concentrated into relative density 1.10～1.15, adds ethanol and makes and contain alcohol amount and reach 60%, and cold preservation was placed 24 hours, filter, filtrate recycling ethanol also is concentrated into relative density 1.10～1.15, adds ethanol again and makes and contain the alcohol amount and reach 80%, cold preservation was placed 24 hours, filtered, and filtrate recycling ethanol also is concentrated into relative density 1.30～1.35, vacuum drying, promptly.

Prepare three batches of Fructus Schisandrae Chinensis extrats respectively, yield sees Table 11.

The discriminating of Fructus Schisandrae Chinensis extrat

Get this product 1g, add chloroform 20ml, reflux 20 minutes filters, and filtrate evaporate to dryness, residue add chloroform 1ml makes dissolving, as need testing solution.Other gets Fructus Schisandrae Chinensis control medicinal material 1g, shines medical material solution in pairs with legal system.Get the deoxyschizandrin reference substance again, add chloroform and make the solution that every 1ml contains 1mg, in contrast product solution.According to the thin layer chromatography test, draw each 2 μ l of above-mentioned three kinds of solution, put in same silica gel G F respectively ₂₅₄On the lamellae, be developing solvent, launch, take out, dry, put under the ultra-violet lamp (254nm) and inspect with the upper solution of petroleum ether (30～60 ℃)-Ethyl formate-formic acid (15: 5: 1).In the test sample chromatograph, with control medicinal material and the corresponding position of reference substance chromatograph on, show the speckle of same color.

Above-mentioned three batches of Fructus Schisandrae Chinensis extrats are differentiated, all met the requirements.

The assay of Fructus Schisandrae Chinensis extrat

The assay of schisandrin

Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Methanol-water (13: 7) is a mobile phase; The detection wavelength is 250nm.Number of theoretical plate calculates by the schisandrin peak should be not less than 2000.

Schisandrin reference substance 15mg is got in the preparation of reference substance solution, accurate claims surely, puts in the 50ml measuring bottle, with dissolve with methanol and be diluted to scale, shakes up, and promptly gets (every 1ml contains schisandrin 0.3mg).

The about 0.1g of this product is got in the preparation of need testing solution, and accurate the title decides, and puts in the 25ml measuring bottle, adds the about 20ml of methanol, and supersound process (power 250W, frequency 44kHz) 20 minutes is taken out, and adds methanol to scale, shakes up, and filters, promptly.

Accurate respectively reference substance solution and each the 10 μ l of test solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.

Above-mentioned three batches of Fructus Schisandrae Chinensis extrats are carried out assay, the results are shown in Table 11.

Fructus Schisandrae Chinensis extrat yield by this prepared is 2～4%, and the content of schisandrin is not less than 10%.

The assay result and the yield of table 11 Fructus Schisandrae Chinensis extrat

The preparation of embodiment 5 present composition injectable powder

1, prescription:

Prescription 1:BRMW I compositions

Norcantharidin 10mg; Radix Ginseng total saponins 39.9g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Sodium hydroxide 5g; Polyoxyethylene sorbitan monoleate 50g; Sterile water for injection adds to 3000ml, prepares 1000 altogether.

Prescription 2:BRMW II compositions

Norcantharidin 10mg; Ginseng polysaccharide 22.8g (being equivalent to crude drug 6kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Sodium hydroxide 5g; Polyoxyethylene sorbitan monoleate 50g; Sterile water for injection adds to 3000ml, prepares 1000 altogether.

Prescription 3:CRMW I compositions

Venenum Bufonis extract 708.8mg (being equivalent to crude drug 8g); Radix Ginseng total saponins 39.9g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Polyoxyethylene sorbitan monoleate 50g; HP-β-CD 15g; Sterile water for injection adds to 3000ml, prepares 1000 altogether.

Prescription 4:CRMWII compositions

Venenum Bufonis extract 708.8mg (being equivalent to crude drug 8g); Ginseng polysaccharide 22.8g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Polyoxyethylene sorbitan monoleate 50g; HP-β-CD 15g; Sterile water for injection adds to 3000ml, prepares 1000 altogether.

2, concrete steps:

1) container of at first dosing being used and antibiotic glass bottle, plug etc. carry out aseptic process.

2) take by weighing raw material and adjuvant according to recipe quantity.

3) it is an amount of norcantharidin, sodium hydroxide to be added the injection water, and heated and stirred makes dissolving, and ginsenoside (or ginseng polysaccharide), Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat add a small amount of water for injection, add the polyoxyethylene sorbitan monoleate heated and stirred dissolving of recipe quantity.Merge above-mentioned solution, add sterile water for injection to 3000ml;

Perhaps Venenum Bufonis extract is carried out enclose and heats making dissolving with HP-β-CD with saturated water solution method, ginsenoside (or ginseng polysaccharide), Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat add a small amount of water for injection, add the polyoxyethylene sorbitan monoleate heated and stirred dissolving of recipe quantity.Merge above-mentioned solution, add sterile water for injection to 3000ml.

4) injection-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.

5) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.

6) through the microporous filter membrane fine straining of 0.22 μ m.

7) clarity of inspection solution, the semi-finished product chemical examination.

8) be sub-packed in the antibiotic glass bottle half tamponade.Sample is put into the freeze dryer lyophilization.-40 ℃ of pre-freezes 5 hours ,-45 ℃～0 ℃ low-temperature vacuum drying 25 hours was warming up to 25 ℃ of vacuum dryings 3 hours then.

9) lyophilizing finishes, and lid is rolled in tamponade.

10) finished product is examined entirely, the packing warehouse-in.

The preparation of embodiment 6 present composition aqueous injection

1, prescription:

Prescription 1:BRMW I compositions

Norcantharidin 10mg; Radix Ginseng total saponins 39.9g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Sodium hydroxide 5g; Polyoxyethylene sorbitan monoleate 50g; Sterile water for injection adds to 5000ml, prepares 1000 altogether.

Prescription 2:BRMWII compositions

Norcantharidin 10mg; Ginseng polysaccharide 22.8g (being equivalent to crude drug 6kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Sodium hydroxide 5g; Polyoxyethylene sorbitan monoleate 50g; Sterile water for injection adds to 5000ml, prepares 1000 altogether.

Prescription 3:CRMW I compositions

Venenum Bufonis extract 708.8mg (being equivalent to crude drug 8g); Radix Ginseng total saponins 39.9g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Polyoxyethylene sorbitan monoleate 50g; HP-β-CD 15g; Sterile water for injection adds to 5000ml, prepares 1000 altogether.

Prescription 4:CRMWII compositions

Venenum Bufonis extract 708.8mg (being equivalent to crude drug 8g); Ginseng polysaccharide 22.8g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Polyoxyethylene sorbitan monoleate 50g; HP-β-CD 15g; Sterile water for injection adds to 5000ml, prepares 1000 altogether.

2, concrete steps:

1) carries and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.

2) it is an amount of norcantharidin, sodium hydroxide to be added the injection water, and heated and stirred makes dissolving, and ginsenoside (or ginseng polysaccharide), Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat add a small amount of water for injection, add the polyoxyethylene sorbitan monoleate heated and stirred dissolving of recipe quantity.Merge above-mentioned solution, add water for injection to 5000ml;

Perhaps Venenum Bufonis extract is carried out enclose and heats making dissolving with HP-β-CD with saturated water solution method, ginsenoside (or ginseng polysaccharide), Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat add a small amount of water for injection, add the polyoxyethylene sorbitan monoleate heated and stirred dissolving of recipe quantity.Merge above-mentioned solution, add water for injection to 5000ml.

3) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.

4) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.

5) through the microporous filter membrane fine straining of 0.45 μ m.

6) clarity of inspection solution, the semi-finished product chemical examination.

7) with the solution embedding in glass ampule.

8) 100 ℃ of flowing steam sterilizations are 30 minutes.

9) while hot sample being put into 0.01% methylene blue solution hunts leak.

10) lamp inspection, finished product is examined entirely, the packing warehouse-in.

The preparation of embodiment 7 present composition sodium chloride transfusion

1, prescription:

Prescription 1:BRMW I compositions

Norcantharidin 10mg; Radix Ginseng total saponins 39.9g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Sodium hydroxide 5g; Polyoxyethylene sorbitan monoleate 50g; Sodium chloride 900g; Sterile water for injection adds to 100000ml, prepares 1000 bottles altogether.

Prescription 2:BRMWII compositions

Norcantharidin 10mg; Ginseng polysaccharide 22.8g (being equivalent to crude drug 6kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Sodium hydroxide 5g; Polyoxyethylene sorbitan monoleate 50g; Sodium chloride 900g; Sterile water for injection adds to 100000ml, prepares 1000 bottles altogether.

Prescription 3:CRMW I compositions

Venenum Bufonis extract 708.8mg (being equivalent to crude drug 8g); Radix Ginseng total saponins 39.9g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Polyoxyethylene sorbitan monoleate 50g; HP-β-CD 15g; Sodium chloride 900g; Sterile water for injection adds to 100000ml, prepares 1000 bottles altogether.

Prescription 4:CRMWII compositions

Venenum Bufonis extract 708.8mg (being equivalent to crude drug 8g); Ginseng polysaccharide 22.8g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Polyoxyethylene sorbitan monoleate 50g; HP-β-CD 15g; Sodium chloride 900g; Sterile water for injection adds to 100000ml, prepares 1000 bottles altogether.

2, concrete steps:

1) carry and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse, plug, cillin bottle carry out aseptic process.

2) it is an amount of norcantharidin, sodium hydroxide to be added the injection water, and heated and stirred makes dissolving, and ginsenoside (or ginseng polysaccharide), Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat add a small amount of water for injection, add the polyoxyethylene sorbitan monoleate heated and stirred dissolving of recipe quantity.Sodium chloride is complete with the water for injection dissolving of dosing amount 40%, merge above-mentioned solution, benefit adds to the full amount of water for injection;

Perhaps Venenum Bufonis extract is carried out enclose and heats making dissolving with HP-β-CD with saturated water solution method, ginsenoside (or ginseng polysaccharide), Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat add a small amount of water for injection, add the polyoxyethylene sorbitan monoleate heated and stirred dissolving of recipe quantity.Sodium chloride is complete with the water for injection dissolving of dosing amount 40%, merge above-mentioned solution, benefit adds to the full amount of water for injection.

5) through the microporous filter membrane fine straining of 0.45 μ m.

7) fill is in the infusion bottle of 100ml.

8) 115 ℃ of pressure sterilizings are 30 minutes.

9) lamp inspection, finished product is examined entirely, the packing warehouse-in.

The preparation of embodiment 8 present composition glucose infusion liquids

1, prescription:

Prescription 1:BRMW I compositions

Norcantharidin 10mg; Radix Ginseng total saponins 39.9g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Sodium hydroxide 5g; Polyoxyethylene sorbitan monoleate 50g; Glucose 5000g; Sterile water for injection adds to 100000ml, prepares 1000 bottles altogether.

Prescription 2:BRMWII compositions

Norcantharidin 10mg; Ginseng polysaccharide 22.8g (being equivalent to crude drug 6kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Sodium hydroxide 5g; Polyoxyethylene sorbitan monoleate 50g; Glucose 5000g; Sterile water for injection adds to 100000ml, prepares 1000 bottles altogether.

Prescription 3:CRMW I compositions

Venenum Bufonis extract 708.8mg (being equivalent to crude drug 8g); Radix Ginseng total saponins 39.9g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Polyoxyethylene sorbitan monoleate 50g; HP-β-CD 15g; Glucose 5000g; Sterile water for injection adds to 100000ml, prepares 1000 bottles altogether.

Prescription 4:CRMWII compositions

Venenum Bufonis extract 708.8mg (being equivalent to crude drug 8g); Ginseng polysaccharide 22.8g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Polyoxyethylene sorbitan monoleate 50g; HP-β-CD 15g; Glucose 5000g; Sterile water for injection adds to 100000ml, prepares 1000 bottles altogether.

2, concrete steps:

2) it is an amount of norcantharidin, sodium hydroxide to be added the injection water, and heated and stirred makes dissolving, and ginsenoside (or ginseng polysaccharide), Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat add a small amount of water for injection, add the polyoxyethylene sorbitan monoleate heated and stirred dissolving of recipe quantity.Glucose is complete with the water for injection dissolving of dosing amount 40%, merge above-mentioned solution, benefit adds to the full amount of water for injection;

Perhaps Venenum Bufonis extract is carried out enclose and heats making dissolving with HP-β-CD with saturated water solution method, ginsenoside (or ginseng polysaccharide), Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat add a small amount of water for injection, add the polyoxyethylene sorbitan monoleate heated and stirred dissolving of recipe quantity.Glucose is complete with the water for injection dissolving of dosing amount 40%, merge above-mentioned solution, benefit adds to the full amount of water for injection.

5) through the microporous filter membrane fine straining of 0.45 μ m.

7) fill is in the infusion bottle of 100ml.

8) 115 ℃ of pressure sterilizings are 30 minutes.

The preparation of embodiment 9 present composition tablets

1, prescription:

Prescription 1:BRMW I compositions

Norcantharidin 10mg; Radix Ginseng total saponins 39.9g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Starch 60.0g; Microcrystalline Cellulose 20.0g; The 2%HPMC aqueous solution is an amount of; Magnesium stearate 1.0g; Carboxymethylstach sodium 2.0g; Prepare 1000 altogether.

Prescription 2:BRMWII compositions

Norcantharidin 10mg; Ginseng polysaccharide 22.8g (being equivalent to crude drug 6kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Starch 60.0g; Microcrystalline Cellulose 20.0g; The 2%HPMC aqueous solution is an amount of; Magnesium stearate 1.0g; Carboxymethylstach sodium 2.0g; Prepare 1000 altogether.

Prescription 3:CRMW I compositions

Venenum Bufonis extract 708.8mg (being equivalent to crude drug 8g); Radix Ginseng total saponins 39.9g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); HP-β-CD 15g; Starch 60.0g; Microcrystalline Cellulose 20.0g; The 2%HPMC aqueous solution is an amount of; Magnesium stearate 1.0g; Carboxymethylstach sodium 2.0g; Prepare 1000 altogether.

Prescription 4:CRMWII compositions

Venenum Bufonis extract 708.8mg (being equivalent to crude drug 8g); Ginseng polysaccharide 22.8g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); HP-β-CD 15g; Starch 60.0g; Microcrystalline Cellulose 20.0g; The 2%HPMC aqueous solution is an amount of; Magnesium stearate 1.0g; Carboxymethylstach sodium 2.0g; Prepare 1000 altogether.

2, concrete steps:

1) norcantharidin, Venenum Bufonis extract, Radix Ginseng total saponins (or ginseng polysaccharide), Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat are pulverized, it is standby to cross 100 mesh sieves.

2) take by weighing raw material and adjuvant according to recipe quantity.

3) water-soluble 2% the aqueous solution made of hypromellose is standby.

4) with norcantharidin, Radix Ginseng total saponins (or ginseng polysaccharide), Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat, starch, microcrystalline Cellulose mix homogeneously, the 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material;

Perhaps Venenum Bufonis extract is carried out enclose with saturated water solution method with HP-β-CD and heats making dissolving, the cold preservation of stirring sucking filtration get the Venenum Bufonis clathrate, back and ginsenoside (or ginseng polysaccharide), Radix Ophiopogonis extract, Fructus Schisandrae Chinensis, starch, microcrystalline Cellulose mix homogeneously, the 2%HPMC aqueous solution is an amount of, stir, make suitable soft material.

5) cross 20 mesh sieve system granules.

6) granule is dried under 60 ℃ condition.

7) dry good granule adds magnesium stearate and carboxymethylstach sodium, crosses 18 mesh sieve granulate, mix homogeneously.

8) sampling, the semi-finished product chemical examination.

9) the sheet weight sheet of determining according to chemical examination.

10) finished product is examined entirely, the packing warehouse-in.

The preparation of embodiment 10 present composition capsules

1, prescription:

Prescription 1:BRMW I compositions

Norcantharidin 10mg; Radix Ginseng total saponins 39.9g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Pregelatinized Starch 20.0g; Starch 30.0g; Microcrystalline Cellulose 20.0g; 50% alcoholic solution of 2%HPMC is an amount of; Magnesium stearate 2.0g; Prepare 1000 altogether.

Prescription 2:BRMWII compositions

Norcantharidin 10mg; Ginseng polysaccharide 22.8g (being equivalent to crude drug 6kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Pregelatinized Starch 20.0g; Starch 30.0g; Microcrystalline Cellulose 20.0g; 50% alcoholic solution of 2%HPMC is an amount of; Magnesium stearate 2.0g; Prepare 1000 altogether.

Prescription 3:CRMW I compositions

Venenum Bufonis extract 708.8mg (being equivalent to crude drug 8g); Radix Ginseng total saponins 39.9g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); HP-β-CD 15g; Pregelatinized Starch 20.0g; Starch 30.0g; Microcrystalline Cellulose 20.0g; 50% alcoholic solution of 2%HPMC is an amount of; Magnesium stearate 2.0g; Prepare 1000 altogether.

Prescription 4:CRMWII compositions

Venenum Bufonis extract 708.8mg (being equivalent to crude drug 8g); Ginseng polysaccharide 22.8g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); HP-β-CD 15g; Pregelatinized Starch 20.0g; Starch 40.0g; Microcrystalline Cellulose 20.0g; 50% alcoholic solution of 2%HPMC is an amount of; Magnesium stearate 2.0g; Prepare 1000 altogether.

2, concrete steps:

2) take by weighing raw material and adjuvant according to recipe quantity.

3) hypromellose 2% the aqueous solution made soluble in water is standby.

4) with norcantharidin, Radix Ginseng total saponins (or ginseng polysaccharide), Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat, starch, microcrystalline Cellulose mix homogeneously, 50% alcoholic solution of 2%HPMC is an amount of; In right amount, stir, make suitable soft material;

Perhaps Venenum Bufonis extract is carried out enclose with saturated water solution method with HP-β-CD and heats making dissolving, the cold preservation of stirring sucking filtration get the Venenum Bufonis clathrate, back and ginsenoside (or ginseng polysaccharide), Radix Ophiopogonis extract, Fructus Schisandrae Chinensis, starch, microcrystalline Cellulose mix homogeneously, 50% alcoholic solution of 2%HPMC is an amount of; In right amount, stir, make suitable soft material.

5) cross 20 mesh sieve system granules.

6) granule is dried under 60 ℃ condition.

7) dry good granule adds magnesium stearate, crosses 18 mesh sieve granulate, mix homogeneously.

8) sampling, the semi-finished product chemical examination.

9) according to assay, determine loading amount, granule is sub-packed in the capsule shells.

10) finished product is examined entirely, the packing warehouse-in.

The preparation of embodiment 11 present composition granules

1, prescription:

Prescription 1:BRMW I compositions

Norcantharidin 10mg; Radix Ginseng total saponins 39.9g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Icing Sugar 2000.0g; The 2%HPMC70% alcoholic solution is an amount of; Prepare 1000 bags altogether.

Prescription 2:BRMWII compositions

Norcantharidin 10mg; Ginseng polysaccharide 22.8g (being equivalent to crude drug 6kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); Icing Sugar 2000.0g; The 2%HPMC70% alcoholic solution is an amount of; Prepare 1000 bags altogether.

Prescription 3:CRMW I compositions

Venenum Bufonis extract 708.8mg (being equivalent to crude drug 8g); Radix Ginseng total saponins 39.9g (being equivalent to crude drug 3kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); HP-β-CD 15g; Icing Sugar 2000.0g; The 2%HPMC70% alcoholic solution is an amount of; Prepare 1000 bags altogether.

Prescription 4:CRMWII compositions

Venenum Bufonis extract 708.8mg (being equivalent to crude drug 8g); Ginseng polysaccharide 22.8g (being equivalent to crude drug 6kg); Radix Ophiopogonis extract 74.4g (being equivalent to crude drug 6kg); Fructus Schisandrae Chinensis extrat 76.2g (being equivalent to crude drug 3kg); HP-β-CD 15g; Icing Sugar 2000.0g; The 2%HPMC70% alcoholic solution is an amount of; Prepare 1000 bags altogether.

2, concrete steps:

2) take by weighing raw material and adjuvant according to recipe quantity.

3) the method mix homogeneously that norcantharidin, Radix Ginseng total saponins (or ginseng polysaccharide), Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat and Icing Sugar are progressively increased with equivalent, adding 2%HPMC70% alcoholic solution is an amount of, stirs, and makes suitable soft material;

Perhaps Venenum Bufonis extract is carried out enclose with saturated water solution method with HP-β-CD and heats making dissolving, the cold preservation of stirring sucking filtration get the Venenum Bufonis clathrate, the method mix homogeneously that back and ginsenoside (or ginseng polysaccharide), Radix Ophiopogonis extract, Fructus Schisandrae Chinensis, starch, Icing Sugar progressively increase with equivalent, it is an amount of to add the 2%HPMC70% alcoholic solution, stir, make suitable soft material.

5) 20 mesh sieve system granules.

6) granule is dried under 60 ℃ condition.

7) granule is crossed 18 mesh sieve granulate.

8) sampling, the sign content of principal agent in the semi-finished product chemical examination granule

9) determine loading amount, packing.

10) finished product is examined entirely, the packing warehouse-in.

Claims

1. pharmaceutical composition is characterized in that and can also be made by following bulk drugs:

5～300 parts of Radix Ginseng total saponinss, 10～600 parts of Radix Ophiopogonis extracts, 10～600 parts of Fructus Schisandrae Chinensis extrats, with be selected from following bulk drugs: 0.02～5000 part of cantharidin or derivatives thereof or its analog, one or both of 0.05～5 part of Venenum Bufonis extract;

Perhaps be 2～300 parts of ginseng polysaccharides, 10～600 parts of Radix Ophiopogonis extracts, 10～600 parts of Fructus Schisandrae Chinensis extrats, with be selected from following bulk drugs: 0.02～5000 part of cantharidin or derivatives thereof or its analog, one or both of 0.05～5 part of Venenum Bufonis extract

The indoles total alkaloid contents is not less than 2% in the described Venenum Bufonis extract, and the content of cinobufagin and bufogenin is not less than 10%; The content of total saponins is not less than 30% in the Radix Ginseng total saponins, ginsenoside Re, ginsenoside Rg ₁Total content be not less than 20%; The content of polysaccharide is not less than 30% among the ginseng polysaccharide; The content of schisandrin is not less than 5% in the Fructus Schisandrae Chinensis extrat, and described cantharidin derivative or its analog are norcantharidin.

2. arbitrary pharmaceutical composition as claimed in claim 1 is characterized in that, this pharmaceutical composition and mixing acceptable accessories are made clinically any or pharmaceutically acceptable dosage form.