CN1954839B

CN1954839B - Medical composition prepared by caulis Marsdeniae Tenacissimae, ginseng and astragalus root

Info

Publication number: CN1954839B
Application number: CN2005101043560A
Authority: CN
Inventors: 黄振华
Original assignee: Shandong Xuanzhu Pharma Co Ltd
Current assignee: Shandong Xuanzhu Pharma Co Ltd
Priority date: 2005-10-26
Filing date: 2005-10-26
Publication date: 2010-09-08
Anticipated expiration: 2025-10-26
Also published as: CN1954839A

Abstract

A composite medicine for preventing and treating tumor, liver injury and infection is proportionally prepared from caulis marsdeniae tenacissimae or its extract, ginseng or its extract, and astragalus root or its extract. Its preparing process is also disclosed.

Description

The pharmaceutical composition of making by Caulis Marsdeniae Tenacissimae, Radix Ginseng and the Radix Astragali

[technical field]

The invention belongs to medical technical field, relate to a kind of pharmaceutical composition of making by Radix Ginseng or its extract, the Radix Astragali or its extract, Caulis Marsdeniae Tenacissimae or its extract and its production and use.

[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.

Radix Ginseng is the dry root of Araliaceae Radix Ginseng PanaxginsengC.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 is one of genuine medicinal materials of abounding with of Changbaishan area, is used as medicine with its root, and be famous valuable ingredient of Chinese medicine.Mainly contain effective ingredient such as ginseng polysaccharide, ginsenoside, ginseng polypeptide and volatile oil, several amino acids, fatty acid and vitamin, trace element.Main component is the ginsenoside, measures approximately 4%, separates to such an extent that the ginsenoside has Ra at present _1～6, Rb _1～3, Rc, Rd, Re, Rf, Rg _1～3, Rh _1～2, kind surplus the Ro etc. 20.Radix Ginseng is enhancing body's immunological function comprehensively, and its active component mainly is saponin and polysaccharide.The ginsenoside all can strengthen engulf the clean up ability of reticuloendothelial system to carbon granules, antibacterial, chicken red blood cell etc. to multiple animal, the ginseng polysaccharide is in the external NK cells in mice activity that strengthens, 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, think that its antitumor mechanism may be to have induced neoplasm necrosis factor TNF-N.

The Radix Astragali is the dry root of leguminous plant Radix Astagali Astragalus membranaceus (Fisch.) Bge.var.mongholicus (Bge.) Hsiao or Radix Astragali Astragalus membranaceus (Fisch.).Sweet, temperature is returned lung, spleen channel, has the effect of invigorating QI to consolidate the body surface resistance, diuresis detoxification, evacuation of pus, expelling pus and promoting granulation, and it is weak to be mainly used in the deficiency of vital energy, anorexia and loose stool, sinking of QI of middle-JIAO, chronic diarrhea proctoptosis, the metrorrhagia of having blood in stool, exterior deficiency spontaneous perspiration, deficiency of vital energy edema, carbuncle is difficult bursts, and burst for a long time and do not hold back, the blood deficiency dull yellowish colored skin, interior-heat is quenched one's thirst; Chronic nephritis albumen disease, diabetes.Mainly contain compositions such as astragalus polysaccharides, Radix Astragali saponin, flavonoid, alkaloid, glucuronic acid and trace element-selenium.Existing pharmacological testing shows that the Radix Astragali can promote immunologic function, main effective ingredient is polysaccharide and saponin, can significantly increase the total white blood cells in the blood, promote engulfing and sterilizing ability of neutrophilic granulocyte and macrophage, can obviously promote cellular immunization, promote the lymphocyte transformation that PHA, ConA and phytolaccanine (PWM) etc. cause, improve the rat local graft versus host reaction that the malignant neoplastic disease human lymphocyte causes.Astragalus polysaccharides can significantly strengthen the mouse macrophage function, promote IgM to form, improve the haematolysis ability of PFC, the mice swimming time that astragalus polysaccharides can also the significant prolongation hydrocortisone be exhausted, increase its adrenal weight, to the significantly improvement effect of the equal tool of several anoxia model of mice; Can make normal and the cold-resistant life span prolongation of weak mice; Body weight, blood cell count and cellularity to mice after the radiation have obvious protective effect.

Caulis Marsdeniae Tenacissimae is the dry rattan of asclepiadaceae plant Caulis Marsdeniae Tenacissimae Marsdenia tenacissima (Roxb.) Wight et Arn..Hardship is slightly cold.Its local Radix Fissistigmatis Glaucescentis by name, Caulis Marsdeniae Tenacissimae, Marsdenia tenacissima, DAGU rattan etc. originate in Yunnan and South of Guizhou, and medicinal rattan, leaf, stem contain steroidal bitterness ester glycosides, polysaccharide, alkaloid etc.Have anticancer dispersing, the effect of relieving cough and asthma, the results showed has inhibitory action to Diplococcus pneumoniae and hemophilus influenza by antitumaous effect in addition.Also have antihistaminic effect, can alleviate the asthma that causes because of histamine.Pharmacological research show Caulis Marsdeniae Tenacissimae have relieving asthma, blood pressure lowering and effect such as antibacterial, can disturb synthesizing of cancerous cell ribonucleic acid and DNA, stop cancerous cell division, breeding, multiple malignant tumor all there is good efficacy, especially multiple malignant tumor such as pulmonary carcinoma, the esophageal carcinoma, gastric cancer, leukemia, cervical cancer there is certain curative effect, also can cooperate radiotherapy, chemotherapy and post-operative treatment, the heart, liver, kidney and hemopoietic system are not all had obvious toxic-side effects.

Modern pharmacology and pharmacodynamic study show that Caulis Marsdeniae Tenacissimae has better curative effect aspect antitumor, the enhancing immunity, the Caulis Marsdeniae Tenacissimae injection of at present existing single active ingredient (trade name: the cancer that disappears is flat) listing, but utilize the interaction of Radix Ginseng, the Radix Astragali and Caulis Marsdeniae Tenacissimae, composition of prescription is used for the antineoplastic application and yet there are no report.

[summary of the invention]

In order to meet clinical needs, to the invention provides a kind of new antitumor medicine composition that is mainly used in, and its preparation method is provided.

The crude drug of pharmaceutical composition of the present invention is: Caulis Marsdeniae Tenacissimae, Radix Ginseng, the Radix Astragali.Grope summary in a large number through the inventor and draw, each component all has better curative effect in the following portions by weight scope: 2～100 parts of Caulis Marsdeniae Tenacissimaes, 1～200 part of Radix Ginseng, 1～200 part of the Radix Astragali; Preferred umber is 10～50 parts of Caulis Marsdeniae Tenacissimaes, 5～100 parts of Radix Ginsengs, 5～100 parts of the Radixs Astragali; Best umber is 20 parts of Caulis Marsdeniae Tenacissimaes, 40 parts of Radix Ginsengs, 10 parts of the Radixs Astragali.

More than form being by weight as proportioning, can be unit with the kilogram as large-scale production, or is unit with the ton, and small-scale production can be unit with the gram also, and weight can increase or reduce, but each form between the constant rate of weight proportion.

Above parts by weight are for especial patient, and the ratio of can corresponding adjustment forming increases or reduce being no more than 100%.

Caulis Marsdeniae Tenacissimae in the aforementioned pharmaceutical compositions, Radix Ginseng, the Radix Astragali can be with The suitable solvent respectively or mix through extracting processing and obtain its extract.The suitable solvent is meant the solvent that Chinese medicine extraction is commonly used, preferred water or alcohol, especially water or ethanol.Extracting method can adopt the conventional method of Chinese medicine extraction, as infusion process, percolation, decocting method, reflux extraction or continuous extraction.

Be that the preparation technology of Caulis Marsdeniae Tenacissimae extract of main effective ingredient is as follows with total phenolic acid in the present composition: get the Caulis Marsdeniae Tenacissimae medical material, decoct with water three times, 1.5 hours for the first time, second, three times 1 hour, collecting decoction filtered, it is 1.02～1.06 that filtrate is concentrated into relative density, puts coldly, adds 8 times of amounts of 85% ethanol, stir evenly, placed 24 hours, filter at 4 ℃, filtrate recycling ethanol is to there not being the alcohol flavor, filter, add 8 times of amounts of ethanol, stir evenly, placed 48 hours at 4 ℃, filter, filtrate was placed 48 hours at 4 ℃ with receiving ethanol to there not being the alcohol flavor, filter, it is 1.09～1.12 that filtrate is concentrated into relative density, spray drying, promptly.Content by total phenolic acid in the Caulis Marsdeniae Tenacissimae extract of this prepared is not less than 20%, and extract yield is 0.5～2%.

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

Method one: get the Caulis Marsdeniae Tenacissimae medical material, decoct with water secondary, each 2 hours, add 10 times of amounts of water at every turn, collecting decoction filters, and it is 1.08～1.11 that filtrate decompression is concentrated into relative density, and vacuum drying is promptly.Caulis Marsdeniae Tenacissimae extract yield by this prepared is 5～8%, and the content of total phenolic acid is not less than 10%.

Method two: get the Caulis Marsdeniae Tenacissimae medical material, decoct with water three times, 1.5 hours for the first time, second and third time 1 hour, collecting decoction filters, and it is 1.02～1.06 that filtrate is concentrated into relative density, puts cold, add 10 times of amounts of 70% ethanol, stir evenly, cold preservation was placed 24 hours, filtered, filtrate recycling ethanol filters to there not being the alcohol flavor, adds 8 times of amounts of 80% ethanol, stirs evenly, cold preservation was placed 48 hours, filtered, and filtrate recycling ethanol filters to there not being the alcohol flavor, it is 1.10～1.12 that filtrate is concentrated into relative density, spray drying, promptly.Caulis Marsdeniae Tenacissimae extract yield by this prepared is 2～5%, and the content of total phenolic acid is not less than 15%.

Be that the preparation technology of Radix Ginseng extract of main effective ingredient is as follows with total saponins in the present composition: get the ginseng crude drug, be ground into particulate, the alcohol reflux secondary, each 3 hours, add 10 times of amounts of alcohol, merge extractive liquid,, cold preservation at every turn, filter, filtrate recycling ethanol also is concentrated into thick paste, adds water to an amount of (making every 1ml be equivalent to crude drug 1g), stirs evenly, cold preservation, filter, filtrate is added on the macroporous resin column of having handled well, and the water with 2V～3V column volume carries out eluting earlier, discard water lotion, 80% ethanol elution of 3 times of column volumes of reuse is collected eluent, reclaims ethanol and is evaporated to the thick paste of relative density 1.30～1.35, vacuum drying, promptly.The Radix Ginseng total saponins extract yield that obtains by this prepared is 0.5～2%, and Radix Ginseng total saponins content is not less than 50%, ginsenoside Re, ginsenoside Rg ₁Content and be not less than 30%.

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

Method one: 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, filter, filtrate recycling ethanol also is concentrated into thick paste, and thin up to relative density is 1.15～1.20, add 1/2 times of saturated n-butanol extraction of water gaging 3 times, merge n-butyl alcohol liquid, the reclaim under reduced pressure n-butyl alcohol is to the thick paste shape, and spray drying promptly.Radix Ginseng extract yield by this prepared is 4～5%, and Radix Ginseng total saponins content is not less than 35%, ginsenoside Re, ginsenoside Rg ₁Content and be not less than 20%.

Method two: 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 3 concentrating under reduced pressure of 1/2 times of saturated n-butanol extraction of water gaging, merges n-butyl alcohol liquid, the reclaim under reduced pressure n-butyl alcohol is to the thick paste shape, and spray drying promptly.Radix Ginseng extract yield by this prepared is 3～5%, and Radix Ginseng total saponins content is for being not less than 40%, ginsenoside Re, ginsenoside Rg ₁Content and be no less than 20%.

Be that the preparation technology of Radix Ginseng extract of main effective ingredient is as follows with polysaccharide in the present composition: get Radix Ginseng, 75% ethanol is used in chopping, reflux, extract, 4 hours filters, and medicinal residues dry, decoct with water five times, merge decoction liquor, add 0.3% active carbon, stirred 30 minutes, standing over night filters, and filtrate is crossed resin column, collect effluent, concentrating under reduced pressure adds ethanol and makes and contain alcohol amount and reach 95%, cold preservation, filter, get precipitation and use washing with acetone, drain acetone, take out and be deposited in 60～80 ℃ of dryings, pulverize, get powder promptly.Content by ginseng polysaccharide in ginseng polysaccharide's extract of this prepared is not less than 50%, and extract yield is 0.5～2%.

Except that adopting said method, also can pass through literature method (as CN200410000209) preparation, also can obtain by the following method, but be not limited only to following method:

Method one: get Radix Ginseng, chopping adds the water reflux, extract, 3 times, each 2 hours, add 10 times of amounts of water for the first time, two, three times is 8,8 times of amounts, collecting decoction, filter, it is 1.6～1.24 that filtrate decompression is concentrated into relative density, crosses macroporous resin column, collect effluent, be evaporated to the thick paste shape, vacuum drying, promptly.By the Radix Ginseng extract of this prepared, yield is 4～6%, and ginseng polysaccharide's content is not less than 40%.

Method two: get Radix Ginseng, 80% ethanol is used in chopping, reflux, extract, 3 hours filters, and medicinal residues dry, decoct with water three times, each 1.5 hours, add 10 times of amounts of water, merge decoction liquor, filter, it is 1.15～1.20 that filtrate decompression is concentrated into relative density, crosses macroporous resin, effluent is evaporated to the thick paste shape, and spray drying promptly.By the Radix Ginseng extract of this prepared, yield is 2～4%, and ginseng polysaccharide's content is not less than 45%.

Be that the preparation technology of the Radix Astragali extract of main effective ingredient adds down with total saponins in the present composition: get the Radix Astragali, decoct with water three times, each 1.5 hours, add for the first time 10 times of amounts of water, two, be 8 times of amounts for three times, collecting decoction, filter, it is 1.20～1.25 (60 ℃) that filtrate is concentrated into relative density, handles 2 times with ethanol precipitation, containing the alcohol amount in the solution for the first time is 75%, be 85% for the second time, each all cold preservation is placed, and reclaims ethanol and be concentrated into every 1ml to be equivalent to crude drug 10g, be added on the macroporous adsorptive resins of having handled well, earlier with the water of 2 times of volumes towards post, 70% ethanol elution of 4 times of volumes of reuse, collection eluent, concentrating under reduced pressure, vacuum drying, promptly.Radix Astragali total saponins extract yield by this prepared is 0.5～2%, and total saponin content is not less than 50%, and Astragaloside content is not less than 2.0%.

Method one: get the Radix Astragali, decoct with water three times, each 2 hours, collecting decoction, filter, it is 1.20～1.25 (60 ℃) that filtrate is concentrated into relative density, handles 2 times with ethanol precipitation, containing amount of alcohol in the solution for the first time is 60%, be 85% for the second time, each all cold preservation is placed, and reclaims ethanol and be concentrated into every 1ml to be equivalent to crude drug 10g, concentrating under reduced pressure, vacuum drying, promptly.Radix Astragali extract yield by this prepared is 3～5%, and total saponin content is not less than 30%, and Astragaloside content is not less than 1%.

Method two: get the Radix Astragali, decoct with water three times, each 1.5 hours, collecting decoction filtered, it is 1.20～1.25 (60 ℃) that filtrate is concentrated into relative density, handle to make that to contain amount of alcohol be 60% for 1 time with ethanol precipitation, cold preservation is placed, and reclaims ethanol and be concentrated into every 1ml to be equivalent to crude drug 10g, and concentrating under reduced pressure, vacuum drying, promptly.Radix Astragali extract yield by this prepared is 2～4%, and total saponin content is for being not less than 40%, and Astragaloside content is not less than 1%.

Be that the preparation technology of the Radix Astragali extract of main effective ingredient adds down with polysaccharide in the present composition: get Milkvetch Root, add 7 times of amount 70% ethanol extraction secondaries, each 2 hours, extracting solution discards, the slag extracting in water secondary of getting it filled, and extracting solution merges, the ratio that is concentrated into extracting liquid volume and raw medicinal herbs is 1.05: 1, add ethanol precipitation and make and contain the alcohol amount and reach 70%, filter, must precipitate, precipitation 70% washing with alcohol, the dissolving of reuse suitable quantity of water is filtered, and filtrate is crossed macroporous resin, the water eluting, collect water lotion, water lotion is concentrated into medicine liquid volume, add ethanol and make and contain alcohol and measure and reach 70% with the medical material ratio is 1: 2.5, must precipitate, to precipitate with 95% ethanol and washing with acetone dehydration, drying under reduced pressure (60 ℃), promptly.Content by Radix Astragali Mongolici total polysaccharide in the Radix Astragali extract of this prepared is not less than 50%, and extract yield is 0.5～2%.

Method one: get Milkvetch Root, add the water reflux, extract, three times, each 2 hours, merge extractive liquid, filters, and it is 1.15～1.23 that filtrate decompression is concentrated into relative density, add ethanol and make and contain alcohol amount and reach 80%, left standstill 24 hours, filter, precipitation is dissolved in water, and filters, and adds ethanol again and makes and contain the alcohol amount and reach 85%, left standstill 24 hours, filter, collecting precipitation, vacuum drying are promptly.Radix Astragali extract yield by this prepared is 2～4%, and astragalus polysaccharides content is not less than 40%.

Method two: get Milkvetch Root, add 10 times of amount 80% ethanol extractions 4 hours, extracting solution discards, the slag extracting in water secondary of getting it filled, each 2 hours, add 10 times of amounts of water, extracting solution merges at every turn, filters, filtrate adds ethanol to be made and contains alcohol amount and reach 85%, filter, filtrate decompression is concentrated into the thick paste shape, and spray drying promptly.Radix Astragali extract yield by this prepared is 3～4%, and astragalus polysaccharides content is not less than 35%.

The present composition is raw material makes except that available above-mentioned medical material, also can directly feed intake and make by the extract of Caulis Marsdeniae Tenacissimae, Radix Ginseng, the Radix Astragali, its main effective ingredient is respectively: Caulis Marsdeniae Tenacissimae total phenolic acids, ginseng polysaccharide or saponin, astragalus polysaccharides or saponin, Caulis Marsdeniae Tenacissimae extract wherein contain Caulis Marsdeniae Tenacissimae total phenolic acids and are not less than 20%; Radix Ginseng extract contains the ginseng polysaccharide and preferably is not less than 50%, perhaps contains Radix Ginseng total saponins and preferably is not less than 50%, ginsenoside Re wherein and ginsenoside Rg ₁Total content be not less than 30%; Radix Astragali extract contains astragalus polysaccharides and preferably is not less than 50%, perhaps contains Radix Astragali total saponins and preferably is not less than 50%, and Astragaloside content is not less than 2.0% in the Radix Astragali total saponins.Calculate with respect to the yield of medical material according to extract, the present composition can have following 4 kinds of different proportionings, is respectively by ratio of weight and the number of copies:

Proportioning 1: 1～200 part of Caulis Marsdeniae Tenacissimae extract, 1～400 part of ginseng polysaccharide, 1～400 part of astragalus polysaccharides, preferred umber is: 5～100 parts, 2～200 parts, 2～200 parts, optimum umber is: 10～40 parts, 10～100 parts, 10～100 parts;

Proportioning 2: 1～200 part of Caulis Marsdeniae Tenacissimae extract, 1～400 part of ginsenoside, 1～400 part of astragalus polysaccharides, preferred umber is: 5～100 parts, 2～200 parts, 2～200 parts, optimum umber is: 10～40 parts, 10～100 parts, 10～100 parts;

Proportioning 3: 1～200 part of Caulis Marsdeniae Tenacissimae extract, 1～400 part of ginseng polysaccharide, 1～400 part of Radix Astragali saponin, preferred umber is: 5～100 parts, 2～200 parts, 2～200 parts, optimum umber is: 10～40 parts, 10～100 parts, 10～100 parts;

Proportioning 4: 1～200 part of Caulis Marsdeniae Tenacissimae extract, 1～400 part of ginsenoside, 1～400 part of Radix Astragali saponin, preferred umber is: 5～100 parts, 2～200 parts, 2～200 parts, optimum umber is: 10～40 parts, 10～100 parts, 10～100 parts.

The compositions of above-mentioned different proportionings, the total content of main effective ingredient preferably is not less than 50% in the total extract.

Aforementioned pharmaceutical compositions, can make clinically arbitrary or pharmaceutically acceptable dosage form, as injection, oral normal release dosage form, sustained-release and controlled release dosage form, granule, pill, oral fluid agent, eye drop, nasal drop, ear drop, inhalant, suppository, ointment etc.Pharmaceutical composition preferred dosage form of the present invention is injection or oral formulations.

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 diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier, lubricant of pharmaceutical field routine etc.

The present invention in order to increase its dissolubility, can add solubilizing agents such as tween 80 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, lactic acid are received, glucose, xylitol, sorbitol and dextran etc., preferred sodium chloride or glucose.Can add excipient in the powder pin, for example, mannitol, glucose etc.

Aforementioned pharmaceutical compositions has effects such as anti-hepatic injury, infection, antitumor, detoxifcation, antibiotic and enhancing human body immunity power.

The invention has the advantages that:

1. a kind of new Chinese medicine medicine for preventing compound recipe is provided, has satisfied urgent clinical needs.

2. interaction and the composition of prescription to Caulis Marsdeniae Tenacissimae, Radix Ginseng and the Radix Astragali carried out pharmaceutical research, but showing the present composition, the result qi-deficiency type rats'liver tumor is had the existence natural law of obvious suppression effect and significant prolongation rat, the SGC-7901 vitro growth of gastric cancer cell also there is the obvious suppression effect, can obviously reduces mice U ₁₄Ascites cells volume and number, and its effect and single compare effect very remarkable (p＜0.01) with Caulis Marsdeniae Tenacissimae, Radix Ginseng and the Radix Astragali show that Caulis Marsdeniae Tenacissimae, Radix Ginseng and Radix Astragali three have the effect of Synergistic.Simultaneously, three's combination drug can alleviate violent toxicity after the chemical medication, has improved patient's life quality.

3. pass through the different proportionings of the present composition to mice S ₁₈₀The inhibiting pharmacodynamic study of tumor growth has filtered out the optimum ratio of the present composition.

4. the present composition both can have been fed intake by Caulis Marsdeniae Tenacissimae, Radix Ginseng and Milkvetch Root and make, and also can directly be fed intake by Caulis Marsdeniae Tenacissimae extract, Radix Ginseng extract and Radix Astragali extract, met the needs of large-scale production.

5. main content of effective of present composition extract and total content are limited respectively, be convenient to control the quality of product.

6. the present composition has been carried out acute toxicity test, the result shows that present composition toxicity is little, and safety range is big.

7. the stability test result that pharmaceutical composition of the present invention is carried out shows that every index is all more stable, has guaranteed safety of clinical administration.

8. Caulis Marsdeniae Tenacissimae, Radix Ginseng and Radix Astragali clinical application determined curative effect, dosage reduces behind three's drug combination, has broad application prospects.

Below test example is further set forth the beneficial effect of medicine of the present invention, and these test examples comprise the pharmacodynamics test of pharmaceutical composition of the present invention, and pharmaceutical composition of the present invention is hereinafter to be referred as compositions.Below test Caulis Marsdeniae Tenacissimae basis in the example Embodiment 1Make Caulis Marsdeniae Tenacissimae extract, the Radix Ginseng basis Embodiment 2Make Radix Ginseng total saponins and and the ginseng polysaccharide, Radix Astragali basis Embodiment 3Make Radix Astragali total saponins and astragalus polysaccharides.Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide and astragalus polysaccharides compositions are called for short TRH ₁ Group, Caulis Marsdeniae Tenacissimae extract, ginsenoside and astragalus polysaccharides compositions are called for short TRH ₂ Group, Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide and Radix Astragali saponin compositions are called for short TRH ₃ Group, Caulis Marsdeniae Tenacissimae extract, ginsenoside and Radix Astragali saponin compositions are called for short TRH ₄ Group

Test example 1 pharmacodynamics test-compositions is to mice S ₁₈₀The tumor growth inhibitory action

Test sample matched group: sodium chloride injection (Shangdong Changfu Jiejing Pharmaceutical Industry Co., Ltd.)

Caulis Marsdeniae Tenacissimae group: anticancer injection liquid (Shenyuan Pharmaceutical Co., Ltd., Tonghua) 2ml: be equivalent to Caulis Marsdeniae Tenacissimae medical material 10g.

Radix Ginseng total saponins group: Radix Ginseng total saponins injection, self-control, 2ml: be equivalent to ginseng crude drug 1g.

Ginseng polysaccharide's group: ginseng polysaccharide injection, self-control, 2ml: be equivalent to ginseng crude drug 4g.

Radix Astragali total saponins group: Radix Astragali total saponins injection, self-control, 2ml: be equivalent to Milkvetch Root 3g.

Astragalus polysaccharides group: astragalin injection, self-control, 2ml: be equivalent to Milkvetch Root 4g

The compositions group:

TRH ₁Group: self-control (preparation method is referring to the preparation of embodiment 5 aqueous injection prescription 1);

TRH ₂Group: self-control (preparation method is referring to the preparation of embodiment 5 aqueous injection prescription 2);

TRH ₃Group: self-control (preparation method is referring to the preparation of embodiment 5 aqueous injection prescription 3);

TRH ₄Group: self-control (preparation method is referring to the preparation of embodiment 5 aqueous injection prescription 4).

260 of animal subject healthy mices, body weight 16～20g, male and female half and half, 10 every group.

Tumor strain mice S ₁₈₀

Test method is got and is inoculated the mice S that goes down to posterity ₁₈₀, in homogenizer, add normal saline, 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 gastric infusion 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 compositions 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 Caulis Marsdeniae Tenacissimae group, ^#P＜0.01

Result of the test and conclusion are compared TRH with the normal saline matched group by table 1 result as can be seen ₁(Caulis Marsdeniae Tenacissimae extract+ginseng polysaccharide+astragalus polysaccharides) group, TRH ₂(Caulis Marsdeniae Tenacissimae extract+ginsenoside+astragalus polysaccharides) group, TRH ₃(Caulis Marsdeniae Tenacissimae extract+ginseng polysaccharide+Radix Astragali saponin) group, TRH ₄(Caulis Marsdeniae Tenacissimae extract+ginsenoside+Radix Astragali saponin) group, anticancer injection liquid are to mice S ₁₈₀The tumor body all has remarkable inhibitory action (p＜0.05, p＜0.01), though Radix Ginseng total saponins group, ginseng polysaccharide's group, Radix Astragali saponin group and astragalus polysaccharides group are to mice S ₁₈₀The tumor body also has inhibitory action, but DeGrain.Compare with the Caulis Marsdeniae Tenacissimae group, the proportioning of Caulis Marsdeniae Tenacissimae, Radix Ginseng, the Radix Astragali exists in the compositions: (1～5g): (0.5～10g): (difference between the effects very significantly (p＜0.01), wherein Caulis Marsdeniae Tenacissimae 2g 0.5～10g) time: Radix Ginseng 4g: effect is best during Radix Astragali 1g.

Test example 2 compositionss are to qi-deficiency type rats'liver tumor inhibition effect

Caulis Marsdeniae Tenacissimae group: anticancer injection liquid (Shenyuan Pharmaceutical Co., Ltd., Tonghua) 2ml: be equivalent to Caulis Marsdeniae Tenacissimae medical material 10g

Compositions group: TRH ₁Group, TRH ₂Group, TRH ₃Group, TRH ₄Group, self-control, preparation method is respectively referring to the preparation of embodiment 5 aqueous injection prescription 1,2,3,4.

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

Method is got rat and is done inoculation in the liver of W256, inoculate after 7 days, press the dosage intraperitoneal injection of anesthesia of 35mg/kg with pentobarbital sodium, and 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, the ligation stomach, arteria duodenalis is long-range, with silver brain clip blocking-up common hepatic artery, under operating loupe at stomach, the arteria duodenalis upper cut and insert external diameter 0.3mm conduit after send into proper hepatic artery again, 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, volume change=(gross tumor volume after the administration-administration pre-neoplastic volume)/administration pre-neoplastic volume by last method.

Table 2 compositions to the influence of rats'liver tumor (x ± s, n=10)

As stated above, test again, observe the survival of rats natural law.

Table 3 survival of rats natural law relatively

Result of the test and conclusion and are respectively organized the liver tumor volume after the normal saline matched group is compared administration and are obviously reduced by table 2 result as can be seen, and volume change increases (p＜0.05, p＜0.01); Table 3 result shows survival natural law elongated (p＜0.05, p＜0.01) after the administration.And TRH ₁(Caulis Marsdeniae Tenacissimae extract+ginseng polysaccharide+astragalus polysaccharides) group, TRH ₂(Caulis Marsdeniae Tenacissimae extract+ginsenoside+astragalus polysaccharides) group, TRH ₃(Caulis Marsdeniae Tenacissimae extract+ginseng polysaccharide+Radix Astragali saponin) group, TRH ₄(Caulis Marsdeniae Tenacissimae extract+ginsenoside+Radix Astragali saponin) group effect all significantly is better than Caulis Marsdeniae Tenacissimae group (p＜0.01), points out three medicines that the effect of Synergistic is arranged.

Test example 3 compositionss are to SGC-7901 vitro growth of gastric cancer cell inhibitory action

Test sample matched group: sodium chloride injection, Shandong Huaxin Pharmaceutical Co., Ltd.

The compositions group:

Cell human stomach cancer cell line SGC-7901

The cell culture trophophase SGC-7901 cell of taking the logarithm, with behind 0.25% the trypsinization with PBS (pH7.2) washing 3 times, be that 10.00% calf serum RPMI-1640 culture fluid transfers to 2 * 10 with final concentration of cells with containing volume parts ⁸/ L is inoculated in 96 holes or 6 orifice plates.Be divided at random: matched group: the RPMI-1640 culture fluid that adds isodose serum-free; Caulis Marsdeniae Tenacissimae group final concentration is 10mmol/L; TRH ₁, TRH ₂, TRH ₃, TRH ₄Group: final concentration is 10mmol/L.

Method is selected the exponential phase stomach cancer cell, and adjusting cell number is 2 * 10 ⁸/ L is inoculated in 96 well culture plates, every hole 100ul, and other establishes the culture fluid that does not add cell is background, behind the 24h, it is Caulis Marsdeniae Tenacissimae group 400mg/ml that test group gives final concentration respectively, TRH ₁, TRH ₂, TRH ₃, TRH ₄Group 500mg/ml, the cell that does not add medicine is as blank.Each concentration is established 6 multiple holes, and after 24,48,72 and 96 hours, every hole adds the MTT20ul of 5g/L respectively, hatches 4h for 37 ℃, abandons supernatant, and every hole adds 150ulDMSO, and vibration makes the crystallization dissolving.Behind the dull and stereotyped shaking table micro oscillation 20min, survey every hole absorbance (A) at wavelength 490nm place with microplate reader and repeat 3 times, calculate inhibitory rate of cell growth (%)=(1-(medicine group-background values)/(control group A-background values)) * 100.00%

Table 4 compositions is to SGC-7901 vitro growth of gastric cancer cell inhibitory action

Annotate: compare with the normal saline matched group, ^*P＜0.05, ^*P＜0.01; Compare with the Caulis Marsdeniae Tenacissimae group, ^#P＜0.01

Result of the test and conclusion are compared Caulis Marsdeniae Tenacissimae group and TRH with the normal saline matched group by table 4 result as can be known ₁(Caulis Marsdeniae Tenacissimae extract+ginseng polysaccharide+astragalus polysaccharides) group, TRH ₂(Caulis Marsdeniae Tenacissimae extract+ginsenoside+astragalus polysaccharides) group, TRH ₃(Caulis Marsdeniae Tenacissimae extract+ginseng polysaccharide+Radix Astragali saponin) group, TRH ₄(Caulis Marsdeniae Tenacissimae extract+ginsenoside+Radix Astragali saponin) respectively organizes injection all has inhibitory action to the SGC-7901 vitro growth of gastric cancer cell, and TRH ₁, TRH ₂, TRH ₃, TRH ₄The injection group is compared effect more remarkable (p＜0.01) with the Caulis Marsdeniae Tenacissimae group, point out three medicines that the effect of Synergistic is arranged.

Test example 4 compositionss are to mice U ₁₄The influence of ascites cells propagation

The compositions group:

140 of animal subject mices, body weight 22～28g is divided into 5 groups immediately, 10 every group

Cancer strain U ₁₄The ascites cells strain

The method mouse peritoneal once inoculates 1 * 10 ⁷Cell/only, be divided into 5 groups at random on the 3rd day in the inoculation back, i.e. matched group, Caulis Marsdeniae Tenacissimae group, RHT ₁Three dosage groups, RHT ₂Three dosage groups, RHT ₃Three dosage groups, RHT ₄Three dosage groups, and beginning intraperitoneal injection or isopyknic normal saline 0.2ml are only, once a day, for three days on end.In administration the 3rd day 9 hours, 4 days 9 hours, 5 days 9 hours respectively with the animal sacrificed by exsanguination. cut off the abdominal cavity and collect about the about 5ml of ascites cells washing liquid with normal saline flushing.With 1200 rev/mins of low-temperature centrifugation washing secondaries, meter cancerous cell volume; Be settled to 5rrd with cold saline then.Get 20ul dilution carrying out cancerous cell counting.

Table 5 compositions is to mice U ₁₄The influence of ascites cells propagation

Result and conclusion: by table 5 result as can be known, all reduce with cancerous cell volume and the quantity of respectively organizing mice after the normal saline matched group is compared administration.Show TRH ₁(Caulis Marsdeniae Tenacissimae extract+ginseng polysaccharide+astragalus polysaccharides) group, TRH ₂(Caulis Marsdeniae Tenacissimae extract+ginsenoside+astragalus polysaccharides) group, TRH ₃(Caulis Marsdeniae Tenacissimae extract+ginseng polysaccharide+Radix Astragali saponin) group, TRH ₄(Caulis Marsdeniae Tenacissimae extract+ginsenoside+Radix Astragali saponin) group, three dosage groups and Caulis Marsdeniae Tenacissimae group all can suppress mice U ₁₄The propagation of ascites cells, and TRH ₁, TRH ₂, TRH ₃, TRH ₄Group is treated to disappear and obviously is better than singly using Caulis Marsdeniae Tenacissimae, points out three medicines that the effect of Synergistic is arranged.

The 5 injected in mice administration acute toxicity tests of test example

(1) test method

Test sample: composite injection derives from embodiment 5, specification 2ml.

Animal subject: mice, each 60 of every group of male and female, male body weight 25～28g, female body weight 21～24g.

Route of administration: intravenous injection, lumbar injection.

Observe special project: death toll, general state, body weight, cut open inspection, half lethal dose.

(2) result of the test

Require to carry out prerun according to acute toxicity test, lumbar injection and intravenous injection two route of administration all can't be measured the median lethal dose(LD 50) of medicine, also do not see tangible toxic reaction, so carry out a day maximum dosage-feeding test.Dosage: tail vein injection 0.1ml/10g, lumbar injection 0.1ml/10g, 2 times on the one.

Death toll: do not occur dead.

General state: no abnormality seen changes.

Body weight: in administration preceding 1 day, administration day, measured in 2,4,6,8,10,12,14 days after the administration; No abnormality seen changes.

Cut open inspection: the heart, liver, lung, kidney etc. organize no abnormality seen to change.

(3) conclusion

Occur death in this experiment, composite injection is 0.2ml/10g to the maximum tolerated dose of male and female mouse vein and intraperitoneal injection, is equivalent to 140 times of maximum consumption 10ml of the 70kg body weight day for human beings.Show this product low toxicity, safe.

Test example 6 composite injection stability tests

Test sample: the TRH injection derives from embodiment 5, specification 2ml.

Investigation project: character, pH value, clarity, related substance, sign content; And at accelerated test 6 months and the aseptic and pyrogen test of long term test end of term increase.

1, influence factor's test

The strong illumination test: get test sample, putting illumination is interior the placement 10 days of lighting box of 4500Lx.

Hot test: get test sample, place respectively under 40 ℃, the 60 ℃ conditions and placed 10 days.

Low-temperature test: get test sample, in 4 ℃ of refrigerators, placed 10 days.

Above-mentioned test was respectively at the 5th, 10 day sampling and measuring.Relatively test every index after the character, and with result and comparison in 0 day.

The result: placed 10 days under the illumination 4500Lx condition, except that related substance slightly raise, all other indexs had no significant change.Placed 10 days under 60 ℃ of conditions of high temperature, every index does not have significant change.Placed 10 days under 40 ℃ of high temperature, 4 ℃ of conditions of low temperature, every index does not have significant change.

2, accelerated test

Method: put under the condition of 40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5% and placed 6 months.Respectively at taking a sample 1st month, 2 months, 3 months, 6 the end of month, relatively after the outward appearance, test every index at duration of test, with result and comparison in 0 month; And at 6 aseptic and pyrogen tests of increase at the end of month.

Result: placed 6 months under the condition of 40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5%, removing related substance slightly increases, and outside sign content slightly descended, all other indexs had no significant change, at 6 the end of month of accelerated test, pyrogen, sterility test are all up to specification.

3, long term test

Method: put under the condition of 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10% and placed 18 months.Respectively at 3rd month, 6 months, 9 months, 12 months, 18 months, relatively after the outward appearance, test every index, with result and comparison in 0 month; And at 18 aseptic and pyrogen tests of increase at the end of month.

The result: placed under the condition of 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10% 18 months, every index has no significant change, and at 18 the end of month of long term test, pyrogen, sterility test are all up to specification.

Conclusion: reached a conclusion by above-mentioned investigation result, in every test, composite injection is all more stable.

In sum, Caulis Marsdeniae Tenacissimae provided by the invention, people participate in Milkvetch root composition and have synergistic function, obviously are better than the individually dosed drug effect of Caulis Marsdeniae Tenacissimae, Radix Ginseng or the Radix Astragali.The stability test result that composite injection is carried out shows that every index of the injection that compositions provided by the invention is made is all more stable, can be used for amplifying producing.

[specific embodiment]

Come by the following examples further to set forth preparation of drug combination method of the present invention, 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.

Caulis Marsdeniae Tenacissimae extract in following examples 4～6, ginseng polysaccharide, Radix Ginseng total saponins and astragalus polysaccharides, Radix Astragali total saponins derive from the 3rd batch in Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide, Radix Ginseng total saponins and astragalus polysaccharides among the embodiment 1,2,3, three batches of extracts of Radix Astragali total saponins.Caulis Marsdeniae Tenacissimae extract in following examples 7～11, ginseng polysaccharide, Radix Ginseng total saponins and astragalus polysaccharides, Radix Astragali total saponins derive from first in Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide, Radix Ginseng total saponins and astragalus polysaccharides among the embodiment 1,2,3, three batches of extracts of Radix Astragali total saponins.

The preparation of embodiment 1 Caulis Marsdeniae Tenacissimae extract

Get Caulis Marsdeniae Tenacissimae medical material 30kg, decoct with water three times, 1.5 hours for the first time, second and third time 1 hour, collecting decoction filters, it is 1.02～1.06 that filtrate is concentrated into relative density, puts coldly, adds 8 times of amounts of 85% ethanol, stir evenly, placed 24 hours, filter at 4 ℃, filtrate recycling ethanol is to there not being the alcohol flavor, filter, add 8 times of amounts of ethanol, stir evenly, placed 48 hours at 4 ℃, filter, filtrate recycling ethanol was placed 48 hours at 4 ℃ to there not being the alcohol flavor, filter, it is 1.09～1.12 that filtrate is concentrated into relative density, spray drying, promptly.

Prepare three batches of extracts respectively, extract yield and content see the following form 6.

The assay of Caulis Marsdeniae Tenacissimae extract

It is an amount of that the chlorogenic acid reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds ethanol and makes the solution that every 1ml contains 80 μ g, promptly.

This product 50mg is got in the preparation of need testing solution, adds ethanol 25ml, shakes up, and gets 2ml, adds ethanol to 25ml, shakes up, promptly.

The accurate need testing solution of drawing of algoscopy, reference substance solution, each 2ml of ethanol, put respectively in the 25ml tool plug scale test tube, add dehydrated alcohol to 5ml, the accurate respectively again 0.3% sodium dodecyl sulfate solution 2ml that adds, 0.5% potassium ferricyanide-1% ferric chloride (1: 1) mixed solution 2ml, shake up, placed 5 minutes the dark place, add the 0.1mol/L hydrochloric acid solution to 25ml, shake up, placed 20 minutes the dark place, is blank with above-mentioned ethanol pipe, according to spectrophotography (appendix VB of Chinese Pharmacopoeia version in 2000), measure trap at the wavelength place of 764nm respectively, calculate, promptly.

The discriminating of Caulis Marsdeniae Tenacissimae extract

Get this product 50mg, add water 20ml and make dissolving, add strong ammonia solution 1ml, with chloroform jolting washing 2 times, each 20ml discards chloroform layer, water layer reuse n-butyl alcohol jolting washing 2 times, each 15ml, discard n-butanol layer, the water intaking layer is concentrated into dried, and residue adds methanol 1ml makes dissolving, place, get supernatant as need testing solution.Other gets Caulis Marsdeniae Tenacissimae control medicinal material 2g, adds water 50ml, soaks and places 24 hours, and supersound process 20 minutes filters, and filtrate is concentrated into 20ml, shines medical material solution in pairs with legal system.According to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000) test, draw each 5 μ l of above-mentioned two 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 chloroform-acetone-formic acid (15: 3: 2).In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.

Three batches of Caulis Marsdeniae Tenacissimae extract yield of table 6 and assay result

The preparation of embodiment 2 Radix Ginseng extracts

The preparation of Radix Ginseng total saponins

Get ginseng crude drug 40kg, be ground into particulate, add 8 times of amount alcohol reflux 2 times, 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 2V～3V column volume 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.

Make three batches of Radix Ginseng total saponins extracts respectively, extract yield and content see the following form 7.

Determination of Total Saponin Content in Panax Ginseng

Reference substance solution preparation: get ginsenoside R _G1The about 10mg of reference substance through 60 ℃ of vacuum dryings 2 hours, accurately claims surely, puts in the 100ml measuring bottle, with anhydrous alcohol solution and be diluted to scale, shakes up, and makes every 1ml and contains R _G1The solution of reference substance 0.1mg, promptly.

The need testing solution preparation: precision takes by weighing this product 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.According to spectrophotography (appendix VB of Chinese Pharmacopoeia version in 2005), measure trap at 560nm wavelength place, calculate, 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 the ginsenoside Rg ₁Reference substance, Re reference substance are an amount of, add methanol and make the mixed solution that every 1ml contains 0.2mg.

This product 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 20ul of need testing solution of drawing of algoscopy injects chromatograph of liquid, measures, promptly.

The discriminating of Radix Ginseng total saponins

Get this product 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, Rg ₁Reference 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.

Three batches of Radix Ginseng total saponins extract yields of table 7 and assay result

Ginseng polysaccharide's preparation

Get Radix Ginseng 10kg, chopping is used 75% ethanol, reflux, extract, 4 ° hours, filter, medicinal residues dry, and decoct with water five times, merge decoction liquor, 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, taking-up is deposited in 60～80 ℃ of dryings, pulverizes, and gets powder promptly.

Make three batches of ginseng polysaccharide's extracts respectively, extract must be filtered with content and see the following form 8.

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 this product 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,, measure trap at 530nm wavelength place according to the spectrophotography test, calculate, promptly.

Ginseng polysaccharide's discriminating

(1) gets the about 0.2g of this product, 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 this product, 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.

Table 8 ginseng polysaccharide extract yield and assay result

The preparation of embodiment 3 Radix Astragali extracts

The preparation of Radix Astragali total saponins

Get Radix Astragali 40kg, decoct with water three times, each 1.5 hours, collecting decoction filters, and it is 1.20～1.25 (60 ℃) that filtrate is concentrated into relative density, handle 2 times with ethanol precipitation, containing the alcohol amount in the solution for the first time is 75%, is 85% for the second time, each all cold preservation is placed, and reclaims ethanol and be concentrated into every 1ml to be equivalent to crude drug 10g, is diluted to every 1ml with water for injection and is equivalent to crude drug 1g, cold preservation was placed 12 hours, filter, filtrate decompression concentrates, vacuum drying, promptly.

Make three batches of Radix Astragali total saponins extracts respectively, extract yield and content results see the following form 9.

The Radix Astragali total saponins discrimination test

Discrimination test one is got this product 0.01g, adds methanol 20ml, reflux 1 hour, filter, filtrate is added on neutral alumina post (100～120 orders, 5g, on the internal diameter 10～15mm), with 40% methanol 100ml eluting, collect eluent, evaporate to dryness, residue adds water 30ml makes dissolving, extract 2 times with water saturated n-butyl alcohol jolting, each 20ml merges n-butyl alcohol liquid; Wash each 20ml with water 2 times; Discard water liquid, n-butyl alcohol liquid evaporate to dryness, residue add methanol 0.5ml makes dissolving, as need testing solution.Other gets the astragaloside reference substance, adds methanol and makes the solution that every 1ml contains 1mg, in contrast product solution.Drawing each 2 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is developing solvent with lower floor's solution of chloroform-methanol-water (13: 7: 2), launch, take out airing, spray is with 10% ethanol solution of sulfuric acid, and it is clear to be heated to the speckle colour developing at 105 ℃.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, daylight shows down identical sepia speckle; Ultra-violet lamp (365nm) shows identical orange-yellow fluorescence speckle down.

Discrimination test two is got this product 0.01g, adds ethanol 30ml, reflux 20 minutes, filter, filtrate adds 0.3% sodium hydroxide solution 15ml makes dissolving, filters, and filtrate is regulated pH value to 5～6 with dilute hydrochloric acid, extract with ethyl acetate 15ml jolting, divide and get ethyl acetate liquid, filter the filtrate evaporate to dryness with the filter paper that is covered with anhydrous sodium sulfate, residue adds ethyl acetate 1ml makes dissolving, as need testing solution.Other gets Radix Astragali control medicinal material 2g, shines medical material solution in pairs with legal system.Draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate,, launch as developing solvent with chloroform-methanol (10: 1), take out, airing is put in the ammonia steam and is inspected under the smoked rearmounted ultra-violet lamp (365nm).In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence principal spot of same color.

The Radix Astragali total saponins assay

The assay of total saponins

The preparation precision of reference substance solution takes by weighing the about 10mg of astragaloside reference substance that is dried to constant weight in 105 ℃, puts in the 100ml measuring bottle, adds dissolve with methanol and is diluted to scale, shakes up, and promptly gets (every 1ml contains astragaloside dry product 0.1mg).

This product 0.1g is got in the preparation of need testing solution, and accurate the title decides, and adds water 25ml and makes dissolving, move in the separatory funnel, extract 4 times, each 20ml with water saturated n-butyl alcohol jolting, merge n-butyl alcohol liquid, with the saturated water washing twice of n-butyl alcohol, each 10ml, discard water liquid, n-butyl alcohol evaporate to dryness to the water-bath, residue adds dissolve with methanol, move in the 25ml measuring bottle, and add methanol and be diluted to scale, shake up, filter, get subsequent filtrate, promptly.

The algoscopy precision is measured reference substance solution, each 1ml of need testing solution, puts 25ml Na Shi color comparison tube, puts evaporate to dryness in the water-bath, put coldly, add freshly prepared 5% vanillin-glacial acetic acid solution 0.4ml, perchloric acid 1.6ml, shake up, placed 5 minutes, put in the boiling water bath and developed the color 15 minutes, take out, put immediately and be cooled to room temperature in the ice bath, add the 8ml glacial acetic acid, shake up, measure absorbance at 538nm wavelength place, calculate, promptly.

The assay of astragaloside

Chromatographic condition and system suitability test are filler with the octadecyl silane; With acetonitrile-water (32: 68) is mobile phase; Evaporative light scattering detector.Number of theoretical plate calculates with the astragaloside peak and is not less than 4000.

It is an amount of that the preparation precision of reference substance solution takes by weighing the astragaloside reference substance, adds methanol and make the solution that every 1ml contains 0.5mg, promptly.

The preparation precision of need testing solution takes by weighing this product 0.04g, and accurate the title decides, and puts in the apparatus,Soxhlet's, add methanol 40ml, merceration spends the night, and it is an amount of to add methanol again, reflux 4 hours, extracting solution reclaim solvent and are concentrated into driedly, and residue adds water 10ml, slight fever makes dissolving, extracts 4 times with water saturated n-butyl alcohol jolting, each 40ml, merge n-butyl alcohol liquid, use ammonia solution thorough washing 2 times, each 40ml, discard ammoniacal liquor, n-butyl alcohol liquid evaporate to dryness, residue add water 5ml makes dissolving, put cold, by D101 type macroporous adsorptive resins (internal diameter 1.5cm, long 12cm), with water 50ml eluting, discard water liquid, reuse 40% ethanol 30ml eluting, discard eluent, continue with 70% ethanol 80ml eluting, collect eluent, evaporate to dryness, with dissolve with methanol and be transferred in the 5ml measuring bottle, add methanol and be diluted to scale, shake up, promptly.

Accurate respectively reference substance solution 10 μ l, 20 μ l and the need testing solution 20 μ l of drawing of algoscopy inject chromatograph of liquid, measure, and calculate with 2 logarithmic equations of external standard, promptly.

Three batches of Radix Astragali total saponins extractive contents of table 9 and yield

The preparation of astragalus polysaccharides

Get Milkvetch Root 30kg, add 7 times of amount 70% ethanol extraction secondaries, each 2 hours, extracting solution discards, the slag extracting in water secondary of getting it filled, and extracting solution merges, the ratio that is concentrated into extracting liquid volume and raw medicinal herbs is 1.05: 1, add ethanol precipitation and make and contain the alcohol amount and reach 70%, filter, must precipitate, precipitation 70% washing with alcohol, the dissolving of reuse suitable quantity of water is filtered, and filtrate is crossed macroporous resin, the water eluting, collect water lotion, water lotion is concentrated into medicine liquid volume, add ethanol and make and contain alcohol and measure and reach 70% with the medical material ratio is 1: 2.5, must precipitate, to precipitate with 95% ethanol and washing with acetone dehydration, drying under reduced pressure (60 ℃), promptly.

Make three batches of astragalus polysaccharide extracts respectively, extract yield and content results see the following form 10.

Three batches of astragalus polysaccharide extract content of table 10 and yield

The astragalus polysaccharides assay

The preparation of standard solution takes by weighing the glucose 100mg that is dried to constant weight through 105 ℃, and accurate the title decides, and puts in the 100ml measuring bottle, is dissolved in water, and is diluted to scale, shakes up.Precision is measured 10ml, puts in the 100ml measuring bottle, adds water to scale, shakes up, and is standby.

Standard curve drafting precision is measured totally 6 parts of standard solution 0.1ml～0.6ml, put respectively in the 25ml measuring bottle, add water to 2.0ml, and add phenol solution and (get phenol 300g, aluminium flake 0.3g, sodium bicarbonate 0.15g, mix distillation, collect 182 ℃ of fractions, be mixed with 5% aqueous solution) 1.0ml, shake up, drip concentrated sulphuric acid 5.0ml rapidly, shake up, place 5min, put and heat 15min in the water-bath, take out, be cooled to room temperature rapidly, in addition with the same operation repetitive of 2.0ml water as blank, measure absorption value at 490nm wavelength place, calculate regression equation.

Assay method is got Radix Astragali extract 0.5g and is put in the 25ml measuring bottle, and the method under the sighting target directrix curve drafting item is measured absorption value, according to the content of regression equation calculation polysaccharide from " adding water to 2.0ml " in accordance with the law.

The discriminating of astragalus polysaccharides

The preparation of embodiment 4 present composition injectable powder

Prescription:

Prescription 1

Caulis Marsdeniae Tenacissimae extract 23.4g (being equivalent to Caulis Marsdeniae Tenacissimae 2kg)

Ginseng polysaccharide 75.6g (being equivalent to Radix Ginseng 4kg)

Astragalus polysaccharides 18.7g (being equivalent to Radix Astragali 1kg)

Polyoxyethylene sorbitan monoleate 50g

Mannitol 200g

Sterile water for injection adds to 2000ml

Prepare 1000 altogether

Annotate: the total content of main effective ingredient is 50.47% in the total extract.

Prescription 2

Ginsenoside 78.8g (being equivalent to Radix Ginseng 4kg)

Astragalus polysaccharides 18.7g (being equivalent to Radix Astragali 1kg)

Polyoxyethylene sorbitan monoleate 50g

Mannitol 200g

Sterile water for injection adds to 2000ml

Prepare 1000 altogether

Annotate: the total content of main effective ingredient is 50.04% in the total extract.

Prescription 3

Ginseng polysaccharide 75.kg (being equivalent to Radix Ginseng 4kg)

Radix Astragali saponin 5.4g (being equivalent to Radix Astragali 1kg)

Polyoxyethylene sorbitan monoleate 50g

Mannitol 200g

Sterile water for injection adds to 2000ml

Prepare 1000 altogether

Annotate: the total content of main effective ingredient is 53.38% in the total extract.

Prescription 4

Ginsenoside 78.8g (being equivalent to Radix Ginseng 4kg)

Radix Astragali saponin 5.4g (being equivalent to Radix Astragali 1kg)

Polyoxyethylene sorbitan monoleate 50g

Mannitol 200g

Sterile water for injection adds to 2000ml

Prepare 1000 altogether

Annotate: the total content of main effective ingredient is 51.42% in the total extract.

Preparation technology:

1) vessel 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) with Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide, astragalus polysaccharides, perhaps with Caulis Marsdeniae Tenacissimae extract, ginsenoside, astragalus polysaccharides, perhaps with Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide, Radix Astragali saponin, perhaps fully with heated and stirred dissolving in Caulis Marsdeniae Tenacissimae extract, ginsenoside, Radix Astragali saponin and mannitol adding dosing amount 30% sterile water for injection.

4) needle-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 0.22um.

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.Pre-freeze-45 ℃ 5 hours, low-temperature vacuum drying-45 ℃～0 ℃ 20 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 5 present composition aqueous injection

Prescription:

Prescription 1

Ginseng polysaccharide 75.6g (being equivalent to Radix Ginseng 4kg)

Astragalus polysaccharides 18.7g (being equivalent to Radix Astragali 1kg)

Propylene glycol 500ml

Water for injection adds to 2000ml

Prepare 1000 altogether

Prescription 2

Ginsenoside 78.8g (being equivalent to Radix Ginseng 4kg)

Astragalus polysaccharides 18.7g (being equivalent to Radix Astragali 1kg)

Propylene glycol 500ml

Water for injection adds to 2000ml

Prepare 1000 altogether

Prescription 3

Ginseng polysaccharide 75.6g (being equivalent to Radix Ginseng 4kg)

Radix Astragali saponin 5.4g (being equivalent to Radix Astragali 1kg)

Propylene glycol 500ml

Water for injection adds to 2000ml

Prepare 1000 altogether

Prescription 4

Ginsenoside 78.8g (being equivalent to Radix Ginseng 4kg)

Radix Astragali saponin 5.4g (being equivalent to Radix Astragali 1kg)

Propylene glycol 500ml

Water for injection adds to 2000ml

Prepare 1000 altogether

Preparation technology:

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) Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide and astragalus polysaccharides are added in the water for injection of dosing amount 20% and the propylene glycol heated and stirred dissolving fully; Perhaps Caulis Marsdeniae Tenacissimae extract, ginsenoside and astragalus polysaccharides are added in the water for injection of dosing amount 20% and the propylene glycol heated and stirred dissolving fully; Perhaps Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide and Radix Astragali saponin are added in the water for injection of dosing amount 20% and the propylene glycol heated and stirred dissolving fully; Perhaps Caulis Marsdeniae Tenacissimae extract, ginsenoside and Radix Astragali saponin are added in the water for injection of dosing amount 20% and the propylene glycol heated and stirred dissolving fully.

3) benefit adds to the full amount of water for injection.

6) through the microporous filter membrane fine straining of 0.45um.

8) with the solution sealing by fusing in glass ampule.

9) 100 ℃ of flowing steam sterilizations are 30 minutes.

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

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

The preparation of embodiment 6 present compositions transfusion

The sodium chloride transfusion:

Prescription:

Prescription 1

Ginseng polysaccharide 75.6g (being equivalent to Radix Ginseng 4kg)

Astragalus polysaccharides 18.7g (being equivalent to Radix Astragali 1kg)

Polyoxyethylene sorbitan monoleate 50g

Sodium chloride 900g

Water for injection adds to 100000ml

Prepare 1000 bottles altogether

Prescription 2

Ginsenoside 78.8g (being equivalent to Radix Ginseng 4kg)

Astragalus polysaccharides 18.7g (being equivalent to Radix Astragali 1kg)

Polyoxyethylene sorbitan monoleate 50g

Sodium chloride 900g

Water for injection adds to 100000ml

Prepare 1000 bottles altogether

Prescription 3

Ginseng polysaccharide 75.6g (being equivalent to Radix Ginseng 4kg)

Radix Astragali saponin 5.4g (being equivalent to Radix Astragali 1kg)

Polyoxyethylene sorbitan monoleate 50g

Sodium chloride 900g

Water for injection adds to 100000ml

Prepare 1000 bottles altogether

Prescription 4

Ginsenoside 78.8g (being equivalent to Radix Ginseng 4kg)

Radix Astragali saponin 5.4g (being equivalent to Radix Astragali 1kg)

Polyoxyethylene sorbitan monoleate 50g

Sodium chloride 900g

Water for injection adds to 100000ml

Prepare 1000 bottles altogether

Preparation technology:

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

2) Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide, astragalus polysaccharides are added the dissolving of dosing amount 20% water for injection heated and stirred fully, with sodium chloride with the water for injection dissolving of dosing amount 20% fully, polyoxyethylene sorbitan monoleate is made aqueous solution after adding 20% sterile water for injection;

Perhaps Caulis Marsdeniae Tenacissimae extract, ginsenoside, astragalus polysaccharides are added the dissolving of dosing amount 20% water for injection heated and stirred fully, with sodium chloride with the dissolving of the water for injection of dosing amount 20% fully, polyoxyethylene sorbitan monoleate is made aqueous solution after adding 20% sterile water for injection;

Perhaps Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide, Radix Astragali saponin are added the dissolving of dosing amount 20% water for injection heated and stirred fully, with sodium chloride with the dissolving of the water for injection of dosing amount 20% fully, polyoxyethylene sorbitan monoleate is made aqueous solution after adding 20% sterile water for injection;

Perhaps Caulis Marsdeniae Tenacissimae extract, ginsenoside, Radix Astragali saponin are added the dissolving of dosing amount 20% water for injection heated and stirred fully, with sodium chloride with the dissolving of the water for injection of dosing amount 20% fully, polyoxyethylene sorbitan monoleate is made aqueous solution after adding 20% sterile water for injection.

3) merge above-mentioned solution, benefit adds to the full amount of water for injection.

6) through the microporous filter membrane fine straining of 0.45um.

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

9) 115 ℃ of pressure sterilizings are 30 minutes.

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

Glucose infusion liquid:

Prescription:

Prescription 1

Ginseng polysaccharide 75.6g (being equivalent to Radix Ginseng 4kg)

Astragalus polysaccharides 18.7g (being equivalent to Radix Astragali 1kg)

Polyoxyethylene sorbitan monoleate 50g

Glucose 5000g

Water for injection adds to 100000ml

Prepare 1000 bottles altogether

Prescription 2

Ginsenoside 78.8g (being equivalent to Radix Ginseng 4kg)

Astragalus polysaccharides 18.7g (being equivalent to Radix Astragali 1kg)

Polyoxyethylene sorbitan monoleate 50g

Glucose 5000g

Water for injection adds to 100000ml

Prepare 1000 bottles altogether

Prescription 3

Ginseng polysaccharide 75.6g (being equivalent to Radix Ginseng 4kg)

Radix Astragali saponin 5.4g (being equivalent to Radix Astragali 1kg)

Polyoxyethylene sorbitan monoleate 50g

Glucose 5000g

Water for injection adds to 100000ml

Prepare 1000 bottles altogether

Prescription 4

Ginsenoside 78.8g (being equivalent to Radix Ginseng 4kg)

Radix Astragali saponin 5.4g (being equivalent to Radix Astragali 1kg)

Polyoxyethylene sorbitan monoleate 50g

Sodium chloride 900g

Water for injection adds to 100000ml

Prepare 1000 bottles altogether

Preparation technology:

2) with heated and stirred dissolving in Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide, astragalus polysaccharides and polyoxyethylene sorbitan monoleate adding dosing amount 20% water for injection fully, that glucose is complete with the water for injection dissolving of dosing amount 20%, heated and boiled 15 minutes;

Perhaps with heated and stirred dissolving in Caulis Marsdeniae Tenacissimae extract, ginsenoside, astragalus polysaccharides and polyoxyethylene sorbitan monoleate adding dosing amount 20% water for injection fully, that glucose is complete with the water for injection dissolving of dosing amount 20%, heated and boiled 15 minutes;

Perhaps with heated and stirred dissolving in Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide, Radix Astragali saponin and polyoxyethylene sorbitan monoleate adding dosing amount 20% water for injection fully, that glucose is complete with the water for injection dissolving of dosing amount 20%, heated and boiled 15 minutes;

Perhaps with heated and stirred dissolving in Caulis Marsdeniae Tenacissimae extract, ginsenoside, Radix Astragali saponin and polyoxyethylene sorbitan monoleate adding dosing amount 20% water for injection fully, that glucose is complete with the water for injection dissolving of dosing amount 20%, heated and boiled 15 minutes.

6) through the microporous filter membrane fine straining of 0.45um.

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

9) 115 ℃ of pressure sterilizings are 30 minutes.

The preparation of embodiment 7 present composition tablets

Prescription:

Prescription 1

Caulis Marsdeniae Tenacissimae extract 40.2g (being equivalent to Caulis Marsdeniae Tenacissimae 2kg)

Ginseng polysaccharide 48.4g (being equivalent to Radix Ginseng 4kg)

Astragalus polysaccharides 5.5g (being equivalent to Radix Astragali 1kg)

Pregelatinized Starch 40.0g

Microcrystalline Cellulose 40.0g

The 2%HPMC aqueous solution is an amount of

Magnesium stearate 2.0g

Carboxymethylstach sodium 12.0g

Prepare 1000 altogether

Annotate: the total content of main effective ingredient is 52.31% in the total extract.

Prescription 2

Ginsenoside 19.6g (being equivalent to Radix Ginseng 4kg)

Astragalus polysaccharides 5.5g (being equivalent to Radix Astragali 1kg)

Pregelatinized Starch 40.0g

Microcrystalline Cellulose 40.0g

The 2%HPMC aqueous solution is an amount of

Magnesium stearate 2.0g

Carboxymethylstach sodium 12.0g

Prepare 1000 altogether

Annotate: the total content of main effective ingredient is 50.23% in the total extract.

Prescription 3

Ginseng polysaccharide 48.4g (being equivalent to Radix Ginseng 4kg)

Radix Astragali saponin 20.2g (being equivalent to Radix Astragali 1kg)

Pregelatinized Starch 40.0g

Microcrystalline Cellulose 40.0g

The 2%HPMC aqueous solution is an amount of

Magnesium stearate 2.0g

Carboxymethylstach sodium 12.0g

Prepare 1000 altogether

Annotate: the total content of main effective ingredient is 55.61% in the total extract.

Prescription 4

Ginsenoside 19.6g (being equivalent to Radix Ginseng 4kg)

Radix Astragali saponin 20.2g (being equivalent to Radix Astragali 1kg)

Pregelatinized Starch 40.0g

Microcrystalline Cellulose 40.0g

The 2%HPMC aqueous solution is an amount of

Magnesium stearate 2.0g

Carboxymethylstach sodium 12.0g

Prepare 1000 bottles altogether

Annotate: the total content of main effective ingredient is 50.31% in the total extract.

Preparation technology:

1) it is standby Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide, Radix Ginseng total saponins and astragalus polysaccharides, Radix Astragali total saponins to be pulverized 100 mesh sieves.

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 Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide, astragalus polysaccharides, pregelatinized Starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material;

Perhaps with Caulis Marsdeniae Tenacissimae extract, ginsenoside, astragalus polysaccharides, pregelatinized Starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material;

Perhaps with Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide, Radix Astragali saponin, pregelatinized Starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material;

Perhaps with Caulis Marsdeniae Tenacissimae extract, ginsenoside, Radix Astragali saponin, pregelatinized Starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes 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 8 present composition capsules

Prescription:

Prescription 1

Ginseng polysaccharide 48.4g (being equivalent to Radix Ginseng 4kg)

Astragalus polysaccharides 5.5g (being equivalent to Radix Astragali 1kg)

Starch 20.0g

Microcrystalline Cellulose 60.0g

The 2%HPMC aqueous solution is an amount of

Magnesium stearate 2.0g

Prepare 1000 altogether

Prescription 2

Ginsenoside 19.6g (being equivalent to Radix Ginseng 4kg)

Astragalus polysaccharides 5.5g (being equivalent to Radix Astragali 1kg)

Starch 20.0g

Microcrystalline Cellulose 60.0g

The 2%HPMC aqueous solution is an amount of

Magnesium stearate 2.0g

Prepare 1000 altogether

Prescription 3

Ginseng polysaccharide 48.4g (being equivalent to Radix Ginseng 4kg)

Radix Astragali saponin 20.2g (being equivalent to Radix Astragali 1kg)

Starch 20.0g

Microcrystalline Cellulose 60.0g

The 2%HPMC aqueous solution is an amount of

Magnesium stearate 2.0g

Prepare 1000 altogether

Prescription 4

Ginsenoside 19.6g (being equivalent to Radix Ginseng 4kg)

Radix Astragali saponin 20.2g (being equivalent to Radix Astragali 1kg)

Starch 20.0g

Microcrystalline Cellulose 60.0g

The 2%HPMC aqueous solution is an amount of

Magnesium stearate 2.0g

Prepare 1000 altogether

Preparation technology:

1) it is standby Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide, Radix Ginseng total saponins and astragalus polysaccharides, Radix Astragali total saponins to be pulverized 100 mesh sieves.。

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) Caulis Marsdeniae Tenacissimae is got thing, ginseng polysaccharide, astragalus polysaccharides, starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material;

Perhaps Caulis Marsdeniae Tenacissimae is got thing, ginsenoside, astragalus polysaccharides, starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material;

Perhaps Caulis Marsdeniae Tenacissimae is got thing, ginseng polysaccharide, Radix Astragali saponin, starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material;

Perhaps Caulis Marsdeniae Tenacissimae is got thing, ginsenoside, Radix Astragali saponin, starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes 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) loading amount of determining according to chemical examination incapsulates.

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

The preparation of embodiment 9 present composition granules

Prescription:

Prescription 1

Ginseng polysaccharide 48.4g (being equivalent to Radix Ginseng 4kg)

Astragalus polysaccharides 5.5g (being equivalent to Radix Astragali 1kg)

Icing Sugar 2000.0g

The 2%HPMC50% alcoholic solution is an amount of

Prepare 1000 bags altogether

Prescription 2

Ginsenoside 19.6g (being equivalent to Radix Ginseng 4kg)

Astragalus polysaccharides 5.5g (being equivalent to Radix Astragali 1kg)

Icing Sugar 2000.0g

The 2%HPMC50% alcoholic solution is an amount of

Prepare 1000 bags altogether

Prescription 3

Ginseng polysaccharide 48.4g (being equivalent to Radix Ginseng 4kg)

Radix Astragali saponin 20.2g (being equivalent to Radix Astragali 1kg)

Icing Sugar 2000.0g

The 2%HPMC50% alcoholic solution is an amount of

Prepare 1000 bags altogether

Prescription 4

Ginsenoside 19.6g (being equivalent to Radix Ginseng 4kg)

Radix Astragali saponin 20.2g (being equivalent to Radix Astragali 1kg)

Icing Sugar 2000.0g

The 2%HPMC50% alcoholic solution is an amount of

Prepare 1000 bags altogether

Preparation technology:

1) it is standby sucrose to be pulverized 100 mesh sieves.It is standby that Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide, Radix Ginseng total saponins and astragalus polysaccharides, Radix Astragali total saponins were pulverized 100 mesh sieves.

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

3) the method mix homogeneously that Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide, astragalus polysaccharides and Icing Sugar are progressively increased with equivalent, adding 2%HPMC50% alcoholic solution is an amount of, stirs, and makes suitable soft material;

The perhaps method mix homogeneously that Caulis Marsdeniae Tenacissimae extract, ginsenoside, astragalus polysaccharides and Icing Sugar are progressively increased with equivalent, it is an amount of to add the 2%HPMC50% alcoholic solution, stirs, and makes suitable soft material;

The perhaps method mix homogeneously that Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide, Radix Astragali saponin and Icing Sugar are progressively increased with equivalent, it is an amount of to add the 2%HPMC50% alcoholic solution, stirs, and makes suitable soft material;

The perhaps method mix homogeneously that Caulis Marsdeniae Tenacissimae extract, ginsenoside, Radix Astragali saponin and Icing Sugar are progressively increased with equivalent, it is an amount of to add the 2%HPMC50% alcoholic solution, stirs, and makes suitable soft material.

4) cross 20 mesh sieve system granules.

5) granule is dried under 60 ℃ condition.

6) dried granule is crossed 18 mesh sieve granulate.

7) sampling, the content of principal agent is determined loading amount in the semi-finished product chemical examination granule.

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

The preparation of embodiment 10 present composition soft capsules

Prescription:

Prescription 1

Ginseng polysaccharide 48.4g (being equivalent to Radix Ginseng 4kg)

Astragalus polysaccharides 5.5g (being equivalent to Radix Astragali 1kg)

Soybean oil 1000.0g

Soybean phospholipid 500g

Cera Flava 500g

Prepare 1000 altogether

Prescription 2

Ginsenoside 19.6g (being equivalent to Radix Ginseng 4kg)

Astragalus polysaccharides 5.5g (being equivalent to Radix Astragali 1kg)

Soybean oil 1000.0g

Soybean phospholipid 500g

Cera Flava 500g

Prepare 1000 altogether

Prescription 3

Ginsenoside 48.4g (being equivalent to Radix Ginseng 4kg)

Astragalus polysaccharides 20.2g (being equivalent to Radix Astragali 1kg)

Soybean oil 1000.0g

Soybean phospholipid 500g

Cera Flava 500g

Prepare 1000 altogether

Prescription 4

Ginsenoside 19.6g (being equivalent to Radix Ginseng 4kg)

Radix Astragali saponin 20.2g (being equivalent to Radix Astragali 1kg)

Soybean oil 1000.0g

Soybean phospholipid 500g

Cera Flava 500g

Prepare 1000 altogether

Preparation technology:

1) with the soybean oil of recipe quantity and soybean phospholipid, Cera Flava heating and melting, mixing, put cold,

2) adding Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide, astragalus polysaccharides grind well, and are pressed into soft capsule and get final product; Perhaps add Caulis Marsdeniae Tenacissimae extract, ginsenoside, astragalus polysaccharides and grind well, be pressed into soft capsule and get final product; Perhaps add Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide, Radix Astragali saponin and grind well, be pressed into soft capsule and get final product; Perhaps add Caulis Marsdeniae Tenacissimae extract, ginsenoside, Radix Astragali saponin and grind well, be pressed into soft capsule and get final product.

The preparation of embodiment 11 present composition oral liquids

Prescription:

Prescription 1

Ginseng polysaccharide 48.4g (being equivalent to Radix Ginseng 4kg)

Astragalus polysaccharides 5.5g (being equivalent to Radix Astragali 1kg)

Methyl hydroxybenzoate 1.0g

Stevioside 10g

Purified water adds to 10000ml

Prepare 1000 altogether

Prescription 2

Ginsenoside 19.6g (being equivalent to Radix Ginseng 4kg)

Astragalus polysaccharides 5.5g (being equivalent to Radix Astragali 1kg)

Methyl hydroxybenzoate 1.0g

Stevioside 10g

Purified water adds to 10000ml

Prepare 1000 altogether

Prescription 3

Ginseng polysaccharide 48.4g (being equivalent to Radix Ginseng 4kg)

Radix Astragali saponin 20.2g (being equivalent to Radix Astragali 1kg)

Methyl hydroxybenzoate 1.0g

Stevioside 10g

Purified water adds to 10000ml

Prepare 1000 altogether

Prescription 4

Ginsenoside 19.6g (being equivalent to Radix Ginseng 4kg)

Radix Astragali saponin 20.2g (being equivalent to Radix Astragali 1kg)

Methyl hydroxybenzoate 1.0g

Stevioside 10g

Purified water adds to 10000ml

Prepare 1000 altogether

Preparation technology:

1) with heated and stirred dissolving in the purified water of Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide, astragalus polysaccharides adding dosing amount 50% fully; Perhaps fully with heated and stirred dissolving in the purified water of Caulis Marsdeniae Tenacissimae extract, ginsenoside, astragalus polysaccharides adding dosing amount 50%; Perhaps fully with heated and stirred dissolving in the purified water of Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharide, Radix Astragali saponin adding dosing amount 50%; Perhaps fully with heated and stirred dissolving in the purified water of Caulis Marsdeniae Tenacissimae extract, ginsenoside, Radix Astragali saponin adding dosing amount 50%;

2) methyl hydroxybenzoate and stevioside is complete with the water dissolution of dosing amount 20%.

3) merge above-mentioned solution, add purified water water to full dose.

4) filtering with microporous membrane of mistake 0.8um.

5) semi-finished product chemical examination.

6) fill.Finished product is examined entirely, the packing warehouse-in.

Claims

1. one kind is used for antitumor medicine composition, it is characterized in that, said composition is made by following bulk drugs: the extract of Caulis Marsdeniae Tenacissimae, Radix Ginseng, the Radix Astragali, and its main effective ingredient is respectively: Caulis Marsdeniae Tenacissimae total phenolic acids, ginseng polysaccharide or total saponins, astragalus polysaccharides or total saponins; Its weight proportion is: be 10～100 parts of 10～40 parts of Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharides, 10～100 parts of the astragalus polysaccharidess of main effective ingredient with total phenolic acid; Perhaps be: be 10～100 parts of 10～40 parts of Caulis Marsdeniae Tenacissimae extract, ginsenosides, 10～100 parts of the astragalus polysaccharidess of main effective ingredient with total phenolic acid; Perhaps be: be 10～100 parts of 10～40 parts of Caulis Marsdeniae Tenacissimae extract, ginseng polysaccharides, 10～100 parts of the Radix Astragali saponins of main effective ingredient with total phenolic acid; Perhaps be: be 10～100 parts of 10～40 parts of Caulis Marsdeniae Tenacissimae extract, ginsenosides, 10～100 parts of the Radix Astragali saponins of main effective ingredient with total phenolic acid.

2. pharmaceutical composition as claimed in claim 1 is characterized in that described Caulis Marsdeniae Tenacissimae extract contains Caulis Marsdeniae Tenacissimae total phenolic acids and is not less than 20%; Radix Ginseng extract contains the ginseng polysaccharide and is not less than 50% or contain Radix Ginseng total saponins and be not less than 50%, and ginsenoside Re, ginsenoside Rg1's content are not less than 30% in the Radix Ginseng total saponins; Radix Astragali extract contains astragalus polysaccharides and is not less than 50% or contain Radix Astragali total saponins and be not less than 50%, and Astragaloside content is not less than 2.0% in the Radix Astragali total saponins.

3. pharmaceutical composition as claimed in claim 1 is characterized in that, the total content of the main effective ingredient in described each extract is not less than 50% of total extract weight.

4. as claim 1 or 2 or 3 arbitrary described pharmaceutical compositions, it is characterized in that said composition makes injection or oral formulations.