CN1954849A - Antineoplastic medical composite compatibility with oldenlandia, ginseng and astragalus root - Google Patents
Antineoplastic medical composite compatibility with oldenlandia, ginseng and astragalus root Download PDFInfo
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Abstract
A composite medicine for preventing and treating tumor is proportionally prepared from oldenlandia or its extract, ginseng or its extract, and astragalus root or its extract. Its preparing process is also disclosed.
Description
1, technical field
The present invention relates to a kind of pharmaceutical composition of making by Herba Hedyotidis Diffusae, Radix Ginseng and the Radix Astragali or its extract that is used for anti-tumor disease, and its production and use, medical technical field belonged to.
2, background technology
At present, cancer has become human No.1 killer, and the M ﹠ M of nearly many decades cancer all has the trend that obviously increases.Tumor is a normal cell that growing in the human body or sophisticated, under the long term of some undesirable element, and the cell mass of certain one, the hyperplasia of appearance or break up unusually and the neoplasm that generates forms lump in the part.But it with organize sharp cell different normally, not according to the growth of Normocellular metabolism rule, and become unfettered and control, can natural death, caused cell to present unusual form, function and metabolism, so that can destroy the structure of normal histoorgan and influence its function.And malignant cell can also be soaked into towards periphery and spreads, even diffusion transfer continues hypertrophy at double to other organ-tissues, causes human body or life are threatened greatly.The Chinese medicine cancer has successful experience and special advantages, the lethal therapy of right and wrong especially, and the advantage that is showed in the treatment malignant tumor is attracted attention by common people.
Herba Hedyotidis Diffusae (Oldenlandiadiffusa (Willd) Roxb) beginning is stated from " Guangxi Chinese medicinal herbal ", is the whole herb with root of Maguireothamnus speciosus Herba Hedyotidis Diffusae.Its leaf seemingly tang is opened and is spent in vain, so name.Another name Herba Hedyotidis Diffusae, short foot are spent Chinese Lobelia, the livings pearl grass of order order, Herba Hedyotidis Diffusae etc. in vain, are distributed widely on the south the Yangtze river basin reaches ground, its nature and flavor hardships, sweet, cold such as main product Fujian, Guangdong, Guangxi, go into the heart, liver, spleen three warps, the effect heat-clearing and toxic substances removing, blood circulation promoting and blood stasis dispelling, anti-inflammatory analgetic etc.Modern pharmacological research shows that Herba Hedyotidis Diffusae has effects such as anti-inflammation, heat-clearing and toxic substances removing, blood circulation promoting and blood stasis dispelling, relieving stranguria by diuresis and antitumor, can be used for treating gastric cancer, the esophageal carcinoma, rectal cancer, malignant lymphoma, pulmonary carcinoma, hepatocarcinoma, cervical cancer, ovarian cancer, bladder cancer etc., clinical practice is extensive.Flavonoid in the Herba Hedyotidis Diffusae, triterpene mixed acid, Coumarins and polysaccharide are anticancer effective ingredient.
Radix Ginseng is the dry root and rhizome of Araliaceae Radix Ginseng (Panax ginseng C.A.Mey.), is used as medicine with its root, has good actions such as " strongly invigorating primordial QI promote the production of body fluid admittedly take off, the Fructus Alpiniae Oxyphyllae of calming the nerves ", is famous valuable ingredient of Chinese medicine.Studies confirm that through Chinese scholars, contain effective ingredient such as Radix Ginseng total saponins, ginseng polysaccharide, ginseng essential oil in the Radix Ginseng, ginseng polysaccharide's pharmacological experiment study confirms: the ginseng polysaccharide has stimulation to immunologic function, can promote the human body non-specific immunity raising, the ginseng polysaccharide is mainly by galactose, galacturonic acid, compositions such as arabinose and rhamnose, toxicological experiment confirm that it has no side effect; Radix Ginseng total saponins has the inhibition tumor cell proliferation, apoptosis-induced effect.
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.) Bge.), it is a kind of conventional Chinese medicine, sweet in the mouth, warm in nature, tonifying Qi and lifting yang is arranged, strengthening superficial resistance to stop perspiration, effect such as expelling pus and toxin by strengthening QI and granulation promoting, Recent study finds to remove in the Radix Astragali astragaloside, micromolecular compounds such as flavone have stronger biological activity, macromolecular compound such as astragalus polysaccharides (APS) have many-sided activity too, astragalus polysaccharides can improve immune function of human body, strengthen the cell physiological metabolism, improve macrophage activity, it is ideal immunostimulant, it can promote the T cell, the B cell, the function of immunocytes such as NK cell, suppress EAS in addition, effects such as two-ways regulation blood glucose, delaying cell aging helps life lengthening.The Radix Astragali and ginseng compatibility can significantly improve active anticancer, reduce chemotherapy side effect.
But, utilizing the interaction of Herba Hedyotidis Diffusae, Radix Ginseng and the Radix Astragali at present, composition of prescription is used for the medicine of anti-tumor aspect, does not appear in the newspapers as yet.The inventor has done a large amount of pharmacology and drug efficacy study, proves that Herba Hedyotidis Diffusae has better curative effect at anti-tumor aspect, and the Radix Ginseng and the Radix Astragali can significantly improve active anticancer as adjuvant drug, reduces chemotherapy side effect.
3, summary of the invention
In order to meet clinical needs, better treat Cancerous disease etc., improve the people ' s health level, the invention provides a kind of new pharmaceutical composition and preparation method thereof.
Pharmaceutical composition of the present invention is made by following bulk drugs: Herba Hedyotidis Diffusae, Radix Ginseng and the Radix Astragali, and its parts by weight are: 50～800 parts of Herba Hedyotidis Diffusaes, 25～1600 parts of Radix Ginsengs, 75～1600 parts of the Radixs Astragali; Be preferably: 100～400 parts of Herba Hedyotidis Diffusaes, 50～800 parts of Radix Ginsengs, 150～800 parts of the Radixs Astragali; Optimum is: 200 parts of Herba Hedyotidis Diffusaes, 100～400 parts of Radix Ginsengs, 300～400 parts of the Radixs Astragali.
Crude drug in the aforementioned pharmaceutical compositions can singly be carried or mix to obtain through refining and obtain extract fully with The suitable solvent and method, and total extract is made arbitrary preparation with mixing acceptable accessories again.Effective ingredient main in the total extract of compositions is: Herba Hedyotidis Diffusae total flavones, ginseng polysaccharide or saponin, astragalus polysaccharides or saponin, the main total content of effective ingredient is not less than 30% in the total extract.
Herba Hedyotidis Diffusae mentioned above can obtain Herba Hedyotidis Diffusae extract through extracting processing with The suitable solvent, wherein solvent preferred water or alcohol, the extracting method of Herba Hedyotidis Diffusae can be infusion process, percolation, decocting method, reflux extraction or continuous extraction.As preparing Herba Hedyotidis Diffusae extract by water extract-alcohol precipitation, ethanol percolation, alcohol extraction upper prop.The invention provides a kind of preferred extraction process of Herba Hedyotidis Diffusae extract, detailed process is as follows:
Get Herba Hedyotidis Diffusae, be ground into coarse powder,, make solvent with 80% ethanol according to the percolation (appendix IO) under fluid extract and the extractum item, flooded 24 hours, percolation slowly, the liquid of filtering are evaporated to does not have the alcohol flavor, and thin up becomes every 1ml to be equivalent to the amount of 1g crude drug, cold preservation, left standstill 12 hours, and filtered, filtrate adds ethanol and carries out three subgradient precipitate with ethanol, make for the first time the alcohol amount 60% that contains, make for the second time to contain alcohol amount 70%, make the alcohol amount 80% that contains for the third time, each all cold preservation 24 hours, filter, filtrate decompression is concentrated into relative density 1.10～1.15, spray drying, promptly.
The Herba Hedyotidis Diffusae extract yield that makes by this technology is 0.5～1.5%; General flavone content (in rutin): be no less than 50%.
Herba Hedyotidis Diffusae also can be by following prepared, but is not limited only to following method:
Technology one: get Herba Hedyotidis Diffusae, be ground into coarse powder, according to the percolation under fluid extract and the extractum item (appendix IO), make solvent with 75% ethanol, flooded 12 hours, percolation slowly, the liquid of filtering are evaporated to does not have the alcohol flavor, thin up becomes every 1ml to be equivalent to the amount of 1g crude drug, cold preservation was left standstill 12 hours, filtered, filtrate is added on the polyamide of having handled well, earlier with the water of 2～3 times of column volumes towards post, reuse 10% ethanol discards cleaning mixture towards post, use 80% ethanol elution of 3～4 times of column volumes at last, collect eluent.Eluent is evaporated to relative density 1.10～1.15, spray drying, promptly.The Herba Hedyotidis Diffusae extract yield that makes by this technology is 0.5～1.5%; General flavone content (in rutin): be no less than 45%.
Technology two: get Herba Hedyotidis Diffusae, be ground into coarse powder, 80% alcohol reflux secondary, each 2 hours, filter, filtrate decompression is concentrated into does not have the alcohol flavor, thin up becomes every 1ml to be equivalent to the amount of 1g crude drug, and cold preservation was left standstill 12 hours, filter, filtrate adds ethanol and carries out two subgradient precipitate with ethanol, makes the alcohol amount 60% that contains for the first time, make for the second time the alcohol amount 80% that contains, each all cold preservation 12 hours filters, filtrate decompression is concentrated into relative density 1.10～1.15, spray drying, promptly.The Herba Hedyotidis Diffusae extract yield that makes by this technology is 0.5～1.5%; General flavone content (in rutin): be no less than 40%.
Radix Ginseng mentioned above can obtain Radix Ginseng extract through extracting processing with The suitable solvent, extract solvent preferred water or ethanol, extracting method can be infusion process, percolation, decocting method, reflux extraction or continuous extraction, the effective ingredient of extract is Radix Ginseng total saponins or ginseng polysaccharide, and content of effective preferably is not less than 50%.
But also reference literature method preparation of the extracting method of Radix Ginseng: can be as Radix Ginseng total saponins according to Chinese patent application CN00110418.7 preparation, the ginseng polysaccharide can prepare according to Chinese patent application CN200410000209.4.
The invention provides the preferred extraction process of Radix Ginseng, detailed process is as follows:
With polysaccharide be main effective ingredient Radix Ginseng extract (hereinafter to be referred as: the preferred for preparation technology ginseng polysaccharide) is as follows:
Get the ginseng crude drug, 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.
Content by ginseng polysaccharide in the Radix Ginseng extract of this prepared is not less than 50%, and the Radix Ginseng extract yield is 0.5-2%.
The ginseng polysaccharide also can be by following prepared, but is not limited only to following method:
Method one: get Radix Ginseng, chopping adds the water reflux, extract, three times, each 2 hours, add 10 times of amounts of water for the first time, two, three times is 8,8 times of amounts, collecting decoction, filter, it is 1.16～1.24 that filtrate decompression is concentrated into relative density, crosses macroporous resin column, collect effluent, be evaporated to the thick paste shape, vacuum drying, promptly.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%.
The invention provides with total saponins be main effective ingredient Radix Ginseng extract (hereinafter to be referred as Radix Ginseng total saponins) preferred for preparation technology, specific as follows:
Get the ginseng crude drug, be ground into particulate, add 10 times of amount alcohol reflux secondaries, each 3 hours, merge extractive liquid,, cold preservation filters, and filtrate recycling ethanol also is concentrated into thick paste, add water to an amount of (making every 1ml be equivalent to crude drug 1g), stir evenly, cold preservation filters, filtrate is added on the macroporous resin column of having handled well, water with 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.
The Radix Ginseng total saponins extract yield that obtains by this prepared is 1～2%, and Radix Ginseng total saponins content is not less than 50%, and ginsenoside Re, ginsenoside Rg1's content are not less than 30%.
Radix Ginseng total saponins also can be by following prepared, but is 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 1.5～1.20, 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 Rg1's content and be not less than 20%.
Method two: get the ginseng crude drug, be ground into particulate, add the ethanol cocurrent flow and extract 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, with receiving ethanol and being 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, decompression is with receiving n-butyl alcohol 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 Rg1's content and be no less than 20%.
The Radix Astragali can obtain Radix Astragali extract through extracting processing with The suitable solvent, extracts solvent preferred water or ethanol, and the extracting method of the Radix Astragali can be infusion process, percolation, decocting method, reflux extraction or continuous extraction.As preparing Radix Astragali extract by water extract-alcohol precipitation, can also be by preparing according to literature method.
The invention provides a kind of with polysaccharide be main effective ingredient Radix Astragali extract (hereinafter to be referred as astragalus polysaccharides) preferred for preparation technology, specific as follows:
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 70%, and yield is 0.5～2%.
Astragalus polysaccharides also can be by following prepared, but is not limited only to following method:
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 invention provides a kind of with total saponins be main effective ingredient Radix Astragali extract (hereinafter to be referred as Radix Astragali total saponins) preferred for preparation technology, specific as follows:
Get the Radix Astragali, decoct with water three times, each 1.5 hours, add for the first time 10 times of amounts of water, be 8 times of amounts two, 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%.Radix Astragali total saponins also can be prepared by following method, but is not limited only to following method:
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 is equivalent to crude drug 10g with receiving ethanol and being concentrated into every 1ml, 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%.
Pharmaceutical composition of the present invention except that available above-mentioned medical material directly feeds intake make, can also feed intake by the extract of Herba Hedyotidis Diffusae, Radix Ginseng, the Radix Astragali and make, its main effective ingredient is respectively: Herba Hedyotidis Diffusae total flavones, ginseng polysaccharide or saponin, astragalus polysaccharides or saponin, Herba Hedyotidis Diffusae extract contains total flavones (in rutin) and preferably is not less than 20%, Radix Ginseng extract contains Radix Ginseng total saponins and preferably is not less than 20% or contain the ginseng polysaccharide and preferably be not less than 20%, and Radix Astragali extract contains Radix Astragali total saponins and preferably is not less than 20% or contain astragalus polysaccharides and preferably be not less than 20%.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: 5～80 parts of Herba Hedyotidis Diffusae extracts, 2～40 parts of ginseng polysaccharides, 7～120 parts of astragalus polysaccharidess; Be preferably: 10～40 parts of Herba Hedyotidis Diffusae extracts, 5～20 parts of ginseng polysaccharides, 15～60 parts of astragalus polysaccharidess; Optimum is: 20 parts of Herba Hedyotidis Diffusae extracts, 10 parts of ginseng polysaccharides, 30 parts of astragalus polysaccharidess;
Proportioning 2: 5～80 parts of Herba Hedyotidis Diffusae extracts, 10～160 parts of Radix Ginseng total saponinss, 10～160 parts of Radix Astragali total saponinss; Be preferably: 10～40 parts of Herba Hedyotidis Diffusae extracts, 20～80 parts of Radix Ginseng total saponinss, 20～80 parts of Radix Astragali total saponinss; Optimum is: 20 parts of Herba Hedyotidis Diffusae extracts, 40 parts of Radix Ginseng total saponinss, 40 parts of Radix Astragali total saponinss;
Proportioning 3: 5～80 parts of Herba Hedyotidis Diffusae extracts, 10～160 parts of Radix Ginseng total saponinss, 7～120 parts of astragalus polysaccharidess; Be preferably: Herba Hedyotidis Diffusae extract 10-40 part, 20～80 parts of Radix Ginseng total saponinss, 15～60 parts of astragalus polysaccharidess; Optimum is: 20 parts of Herba Hedyotidis Diffusae extracts, 40 parts of Radix Ginseng total saponinss, 30 parts of astragalus polysaccharidess;
Proportioning 4: 5～80 parts of Herba Hedyotidis Diffusae extracts, 2～40 parts of ginseng polysaccharides, 10～160 parts of Radix Astragali total saponinss; Be preferably: 10～40 parts of Herba Hedyotidis Diffusae extracts, 5～20 parts of ginseng polysaccharides, 20～80 parts of Radix Astragali total saponinss; Optimum is: 20 parts of Herba Hedyotidis Diffusae extracts, 10 parts of ginseng polysaccharides, 40 parts of Radix Astragali total saponinss.
Above-mentioned 4 kinds of total extracts that proportioning obtains, the main total content of effective ingredient all is not less than 30%.
More than form to be by weight as proportioning, when producing, can or reduce according to the corresponding proportion increase, as large-scale production can be raw material with the kilogram, or be unit with the ton, small-scale production can be unit with the gram also, weight can increase or reduce, but the constant rate of weight proportion between each composition.
More than form,, can make the preparation of 100～10000 consumptions,, can be made into 100～10000,1～10 of each consumption as injection as if being unit with the gram.As tablet, can be made into 100～10000, take 1～10 at every turn.
The ratio of above weight proportion obtains through science screening, and for especial patient, the ratio of can corresponding adjustment forming increases or reduce being no more than 100%.
The consumption of drug component of the present invention is groped to sum up to draw through the inventor in a large number, and each amounts of components all has better curative effect in above-mentioned weight portion scope.
The invention provides a kind of medicine that is used to prepare aspect diseases such as treatment tumor.Pharmaceutical composition of the present invention has antitumor action, Herba Hedyotidis Diffusae is the karyokinesis of anticancer directly, makes its forfeiture fertility, and the oxygen-consuming capacity of cancerous cell is had direct repression, the Radix Ginseng and the Radix Astragali are done to assist and can be significantly improved active anticancer, reduce chemotherapy side effect.Be mainly used in malignant tumor such as treatment gastric cancer, the esophageal carcinoma, rectal cancer, malignant lymphoma, pulmonary carcinoma, hepatocarcinoma, cervical cancer, ovarian cancer, bladder cancer.
Said composition can add one or more pharmaceutically acceptable carriers, with oral, snuffing is gone into or the mode of parenteral is applied to the patient who needs this treatment.Be used for when oral, can be made into conventional solid preparation, as tablet, capsule, soft capsule, dispersible tablet, oral liquid, granule, chewable tablet, oral cavity disintegration tablet, drop pill, slow releasing tablet, slow releasing capsule, controlled release tablet, controlled release capsule, make liquid preparation such as water or oil-suspending agent or other liquid preparation such as syrup etc.; When being used for parenteral, can be made into solution, water or the oil-suspending agent etc. of injection, as liquid drugs injection, freeze-dried powder, aseptic powder injection, transfusion etc.The preferred dosage form of this compositions is 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.
Pharmaceutical composition of 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, sodium lactate, glucose, xylitol, sorbitol and dextran etc., preferred sodium chloride or glucose.Can add excipient in the powder pin, for example, mannitol, glucose etc.
The present invention shows through pharmaceutical research and drug effect animal experiment study result, is the medicine that main component is made by Herba Hedyotidis Diffusae, Radix Ginseng and the Radix Astragali, to S
180Sarcoma has certain inhibitory action; Life span to the EAC mice has tangible prolongation effect in addition; With chemotherapeutic (CTX) and radiotherapy (
60Co irradiation) share and to increase antitumor (S
180Sarcoma) effect.Experimental studies results of the present invention proves that Herba Hedyotidis Diffusae, Radix Ginseng and Radix Astragali drug combination are synergism, and drug effect obviously strengthens.
The present composition has the following advantages:
(1) provides a kind of pharmaceutical composition that is used for anti-tumor disease and its production and use, satisfied urgent clinical needs;
(2) interaction and the composition of prescription to Herba Hedyotidis Diffusae, Radix Ginseng and the Radix Astragali carried out pharmacodynamic study, found that compositions has obvious antineoplastic and radiotherapy, chemotherapeutic sensitivity effect, to S
180The tumour inhibiting rate of sarcoma is respectively and has surpassed 45%, increase in life span to the EAC mice is respectively above 30%, the tumor potentiation rate that presses down to chemotherapy is respectively above 35%, the tumor potentiation rate that presses down to radiotherapy is respectively above 30%, show three medicine Synergistics, evident in efficacy, obviously be better than single Herba Hedyotidis Diffusae extract of using, significant difference is (p＜0.01) extremely significantly, and consequently those skilled in the art institute is beyond thought;
(3) each proportioning of the present composition is carried out pharmacodynamic study, drawn the optimal proportion of the present composition;
(4) the present invention can directly feed intake with raw material or extract, and preparation technology is simple, can make between the different batches medicine mass discrepancy little, and drug quality is more uniform and stable;
(5) stability experiment that carries out shows that the every index of medicine composition injection of the present invention is all more stable, has guaranteed safety of clinical administration;
(6) the Herba Hedyotidis Diffusae antitumor action is obvious, and the Radix Ginseng and the Radix Astragali are done to assist and can be significantly improved active anticancer, reduce chemotherapy side effect, the drug combination determined curative effect, and reduced relative dosage, be with a wide range of applications.
Below example is further set forth the beneficial effect of medicine of the present invention by experiment, and these experimental examples comprise the pharmacodynamic experiment of pharmaceutical composition of the present invention, the compositions of Herba Hedyotidis Diffusae extract, ginseng polysaccharide and astragalus polysaccharides hereinafter to be referred as
The BRH composition I, the compositions of Herba Hedyotidis Diffusae extract, Radix Ginseng total saponins and Radix Astragali total saponins hereinafter to be referred as
BRH composition I I, the compositions of Herba Hedyotidis Diffusae extract, Radix Ginseng total saponins and astragalus polysaccharides hereinafter to be referred as
BRH composition I II, the compositions of Herba Hedyotidis Diffusae extract, ginseng polysaccharide and Radix Astragali total saponins hereinafter to be referred as
BRH composition I VUsed Herba Hedyotidis Diffusae extract is taken from the 2nd crowd of embodiment 1 in the experimental example, and the ginseng polysaccharide takes from the 2nd crowd of embodiment 2, Radix Ginseng total saponins is taken from the 1st crowd of embodiment 3; Astragalus polysaccharides is taken from the 1st crowd of embodiment 4, Radix Astragali total saponins is taken from the 2nd crowd of embodiment 5.
Experimental example 1 BRH compositions drug combination drug efficacy study
Test sample: blank group: 0.9% normal saline solution, self-control;
Positive controls: cyclophosphamide Injection, self-control;
Herba Hedyotidis Diffusae extract group: Herba Hedyotidis Diffusae extract injection, self-control;
BRH composite injection I group, self-control (preparation method is referring to embodiment 7);
BRH composite injection II group, self-control (preparation method is referring to embodiment 7);
BRH composite injection III group, self-control (preparation method is referring to embodiment 7);
BRH composite injection IV group, self-control (preparation method is referring to embodiment 7).
Animal subject: ICR kind mice, body weight 18～22g, male, 270, be divided into 27 groups at random.
Tumor kind: S
180Tumor liquid.
Experimental technique: get 270 of ICR mices, all subcutaneous vaccination S
180Tumor liquid (2 * 10
7/ ml) 0.2ml/, be divided into 27 groups next day at random, weighs.Intraperitoneal injection, dosage sees Table 1, and totally 10 days, drug withdrawal was weighed next day, put to death mice and peeled off the subcutaneous tumors piece, claimed tumor heavy, and calculated tumour inhibiting rate.The results are shown in Table 1.
Experimental result: each administration group all has obvious suppression S
180The tumor growth effect (
*P＜0.05,
* *P＜0.01 He
* *P＜0.001).Wherein BRH composite injection I organizes, BRH composite injection II organizes, BRH composite injection III organizes, the effect of BRH composite injection IV group all obviously is better than the list Herba Hedyotidis Diffusae extract (
#P＜0.01), tumour inhibiting rate is respectively 47.00%～59.00%, 49.00%～60.00%, 47.50%～57.50%, 47.50%～58.50%.The proof Herba Hedyotidis Diffusae, Radix Ginseng and Radix Astragali compatibility have the effect of good restraining tumor growth, and relevant with the dosage ratio of compositions, Herba Hedyotidis Diffusae extract+ginseng polysaccharide+astragalus polysaccharides=20mg+10mg+30mg among the BRH composite injection I, Herba Hedyotidis Diffusae extract+Radix Ginseng total saponins+Radix Astragali total saponins=20mg+40mg+40mg among the BRH composite injection II, Herba Hedyotidis Diffusae extract+Radix Ginseng total saponins+astragalus polysaccharides=20mg+40mg+30mg among the BRH composite injection III, effect is best during Herba Hedyotidis Diffusae extract+ginseng polysaccharide among the BRH composite injection IV+Radix Astragali total saponins=20mg+10mg+40mg.
Table 1 BRH composite injection is to S
180The influence of solid tumor growth (X ± SD)
| Group | Dosage ratio | Number of animals (only) | Dosage (mg/kg) | Tumor heavy (g) | Tumour inhibiting rate (%) |
| The blank group | - | 10 | - | 2.00±0.31 | - |
| Positive controls | - | 10 | 100 | 0.19±0.21 *** | 90.50 |
| The Herba Hedyotidis Diffusae extract group | - | 10 | 20 | 1.45±0.34 * | 27.50 |
| BRH composite injection I organizes (Herba Hedyotidis Diffusae extract+ginseng polysaccharide+astragalus polysaccharides) | 10mg+5mg+15mg | 10 | 20 | 1.06±0.27 **# | 47.00 |
| 20mg+10mg+20mg | 10 | 20 | 0.98±0.34 **# | 51.00 | |
| 20mg+10mg+30mg | 10 | 20 | 0.82±0.42 **# | 59.00 | |
| 30mg+15mg+40mg | 10 | 20 | 0.86±0.24 **# | 57.00 | |
| 30mg+20mg+50mg | 10 | 20 | 0.92±0.51 **# | 54.00 | |
| 40mg+20mg+60mg | 10 | 20 | 0.95±0.32 **# | 52.50 | |
| BRH composite injection II organizes (Herba Hedyotidis Diffusae extract+Radix Ginseng total saponins+Radix Astragali total saponins) | 10mg+20mg+20mg | 10 | 20 | 1.02±0.23 **# | 49.00 |
| 20mg+30mg+30mg | 10 | 20 | 0.96±0.35 **# | 52.00 | |
| 20mg+40mg+40mg | 10 | 20 | 0.80±0.16 **# | 60.00 | |
| 30mg+50mg+60mg | 10 | 20 | 0.85±0.35 **# | 57.50 | |
| 30mg+60mg+60mg | 10 | 20 | 0.89±0.31 **# | 55.50 | |
| 40mg+80mg+80mg | 10 | 20 | 0.97±0.42 **# | 51.50 | |
| BRH composite injection III organizes (Herba Hedyotidis Diffusae extract+Radix Ginseng total saponins+astragalus polysaccharides) | 10mg+20mg+15mg | 10 | 20 | 1.05±0.32 **# | 47.50 |
| 20mg+30mg+20mg | 10 | 20 | 0.96±0.25 **# | 52.00 | |
| 20mg+40mg+30mg | 10 | 20 | 0.85±0.35 **# | 57.50 | |
| 30mg+50mg+40mg | 10 | 20 | 0.89±0.15 **# | 55.50 | |
| 30mg+60mg+50mg | 10 | 20 | 0.95±0.61 **# | 52.50 | |
| 40mg+80mg+60mg | 10 | 20 | 1.00±0.32 **# | 50.00 | |
| BRH composite injection IV organizes (Herba Hedyotidis Diffusae extract+ginseng polysaccharide+Radix Astragali total saponins) | 10mg+5mg+20mg | 10 | 20 | 1.03±0.35 **# | 48.50 |
| 20mg+10mg+30mg | 10 | 20 | 0.98±0.15 **# | 51.00 | |
| 20mg+10mg+40mg | 10 | 20 | 0.83±0.24 **# | 58.50 | |
| 30mg+15mg+50mg | 10 | 20 | 0.91±0.32 **# | 54.50 | |
| 30mg+20mg+60mg | 10 | 20 | 0.98±0.41 **# | 51.00 | |
| 30mg+20mg+80mg | 10 | 20 | 1.05±0.14 **# | 47.50 |
Annotate:
*P＜0.05,
*P＜0.01,
* *P＜0.001 is compared with matched group;
#P＜0.01 is compared with the Herba Hedyotidis Diffusae extract group
Experimental example 2 BRH compositionss are to the influence of ehrlich carcinoma (EAC) mice increase in life span
Test sample: blank group: 0.9% normal saline solution, self-control;
Positive controls: cyclophosphamide Injection, self-control;
Herba Hedyotidis Diffusae extract group: Herba Hedyotidis Diffusae extract injection, self-control;
BRH composite injection I group (Herba Hedyotidis Diffusae extract+ginseng polysaccharide+astragalus polysaccharides=20mg+10mg+30mg): be divided into basic, normal, high three dosage groups, self-control (preparation method is referring to embodiment 7);
BRH composite injection II group (Herba Hedyotidis Diffusae extract+Radix Ginseng total saponins+Radix Astragali total saponins=20mg+40mg+40mg): be divided into basic, normal, high three dosage groups, self-control (preparation method is referring to embodiment 7);
BRH composite injection III group (Herba Hedyotidis Diffusae extract+Radix Ginseng total saponins+astragalus polysaccharides=20mg+40mg+30mg): be divided into basic, normal, high three dosage groups, self-control (preparation method is referring to embodiment 7);
BRH composite injection IV group (Herba Hedyotidis Diffusae extract+ginseng polysaccharide+Radix Astragali total saponins=20mg+10mg+40mg): be divided into basic, normal, high three dosage groups, self-control (preparation method is referring to embodiment 7).
Animal subject: ICR kind mice, body weight 18～22g, male, 150, be divided into 15 groups at random.
Tumor kind: EAC ascites.
Experimental technique: get 150 of ICR mices, aseptic extraction EAC ascites, with 1: 2 times of dilution of normal saline, every Mus abdominal cavity inoculation 0.2ml, be divided into 15 groups in 24 hours at random, be respectively blank group, positive controls, Herba Hedyotidis Diffusae extract group, basic, normal, high three the dosage groups of BRH composite injection I, basic, normal, high three the dosage groups of BRH composite injection II, basic, normal, high three the dosage groups of BRH composite injection III, basic, normal, high three the dosage groups of BRH composite injection IV, weigh.Intraperitoneal injection, dosage sees Table 2, and totally 10 days, the death time of after this observing mice, the result represented with average survival natural law and increase in life span.The results are shown in Table 2.
Table 2 BRH compositions is to the influence of EAC ehrlich ascites carcinoma mice increase in life span (X ± SD)
| Group | Number of animals (only) | Dosage (mg/kg) | The existence natural law | Increase in life span (%) |
| The blank group | 10 | - | 12.60±4.00 | - |
| Positive controls | 10 | 100 | 19.50±5.20 ** | 54.76 |
| The Herba Hedyotidis Diffusae group | 10 | 20 | 14.50±2.00 * | 15.08 |
| BRH composite injection I organizes (low dosage) | 10 | 10 | 17.00±2.80 **# | 34.92 |
| BRH composite injection I organizes (middle dosage) | 10 | 15 | 18.00±3.10 **# | 42.86 |
| BRH composite injection I organizes (high dose) | 10 | 20 | 19.00±3.70 **# | 50.79 |
| BRH composite injection II organizes (low dosage) | 10 | 10 | 16.50±2.60 **# | 30.95 |
| BRH composite injection II organizes (middle dosage) | 10 | 15 | 17.50±3.10 **# | 38.89 |
| BRH composite injection II organizes (high dose) | 10 | 20 | 18.50±3.20 **# | 46.82 |
| BRH composite injection III organizes (low dosage) | 10 | 10 | 17.00±2.50 **# | 34.92 |
| BRH composite injection III organizes (middle dosage) | 10 | 15 | 18.50±4.00 **# | 46.82 |
| BRH composite injection III organizes (high dose) | 10 | 20 | 19.00±3.00 **# | 50.79 |
| BRH composite injection IV organizes (low dosage) | 10 | 10 | 17.00±2.30 **# | 34.92 |
| BRH composite injection IV organizes (middle dosage) | 10 | 15 | 18.00±3.20 **# | 42.86 |
| BRH composite injection IV organizes (high dose) | 10 | 20 | 19.50±2.00 **# | 54.76 |
Annotate:
*P＜0.05,
*P＜0.01 is compared with matched group;
#P＜0.01 is compared with the Herba Hedyotidis Diffusae extract group
Experimental result: each administration group all have the increase in life span that obviously makes the EAC mice improve (
*P＜0.05 He
*P＜0.01).Wherein BRH composite injection I organizes, BRH composite injection II organizes, BRH composite injection III organizes, the effect of BRH composite injection IV group all obviously is better than the list Herba Hedyotidis Diffusae extract (
#P＜0.01), increase in life span is respectively 34.92%～50.79%, 30.95%～46.82%, 34.92%～50.79%, 34.92%～58.54%.Proof Herba Hedyotidis Diffusae, Radix Ginseng and Radix Astragali compatibility have the good restraining tumor growth, prolong the effect of mice life, and relevant with the dosage of each compositions, dosage during for 20mg/kg effect all best.
Experimental example 3 BRH compositionss are to the potentiation of chemotherapy
Test sample: blank group: 0.9% normal saline solution, self-control;
Positive controls: cyclophosphamide (CTX) injection, self-control;
CTX+ Herba Hedyotidis Diffusae extract group: CTX+ Herba Hedyotidis Diffusae extract injection, self-control;
CTX+BRH composite injection I group (Herba Hedyotidis Diffusae extract+ginseng polysaccharide+astragalus polysaccharides=20mg+10mg+30mg): be divided into basic, normal, high three dosage groups, self-control (preparation method is referring to embodiment 7);
CTX+BRH composite injection II group (Herba Hedyotidis Diffusae extract+Radix Ginseng total saponins+Radix Astragali total saponins=20mg+40mg+40mg): be divided into basic, normal, high three dosage groups, self-control (preparation method is referring to embodiment 7);
CTX+BRH composite injection III group (Herba Hedyotidis Diffusae extract+Radix Ginseng total saponins+astragalus polysaccharides=20mg+40mg+30mg): be divided into basic, normal, high three dosage groups, self-control (preparation method is referring to embodiment 7);
CTX+BRH composite injection IV group (Herba Hedyotidis Diffusae extract+ginseng polysaccharide+Radix Astragali total saponins=20mg+10mg+40mg): be divided into basic, normal, high three dosage groups, self-control (preparation method is referring to embodiment 7).
Animal subject: ICR kind mice, body weight 18～22g, male, 150, be divided into 15 groups at random.
Tumor kind: S
180Tumor liquid.
Experimental technique: get 150 of ICR mices, all subcutaneous vaccination S
180Tumor liquid (2 * 10
7/ ml) 0.2ml/, be divided into 15 groups next day at random, be respectively blank group, positive controls, CTX+ Herba Hedyotidis Diffusae extract group, basic, normal, high three the dosage groups of CTX+BRH composite injection I, basic, normal, high three the dosage groups of CTX+BRH composite injection II, basic, normal, high three the dosage groups of CTX+BRH composite injection III, basic, normal, high three the dosage groups of CTX+BRH composite injection IV, weigh.Except that the blank group, all the other each groups are the 2nd, the 6th day intraperitoneal injection of cyclophosphamide (CTX) 30mg/kg after inoculation all, administration group gastric infusion next day, and dosage sees Table 3, totally 10 days, drug withdrawal was weighed next day, put to death animal, peel off the subcutaneous tumors piece, claim tumor heavy, and calculate tumour inhibiting rate and potentiation rate.The results are shown in Table 3.Potentiation rate (%)=(chemotherapeutic adds the average tumor weight-chemotherapeutic of water group and adds the average tumor of administration group heavily)/chemotherapeutic adds the average tumor of water group heavy * 100%.
Experimental result: each administration group and cyclophosphamide share all tangible chemotherapeutic sensitivity effect (
*P＜0.05 He
*P＜0.01).Wherein BRH composite injection I organizes, BRH composite injection II organizes, BRH composite injection III organizes, the potentiation of BRH composite injection IV group all obviously is better than the list Herba Hedyotidis Diffusae extract (
#P＜0.01), it presses down tumor potentiation rate and is respectively 36.57%～38.69%, 35.47%～39.54%, 36.7%～38.69%, 35.47%～38.06%.Proof Herba Hedyotidis Diffusae, Radix Ginseng and Radix Astragali compatibility have share good chemotherapeutic sensitivity effect with the chemotherapeutic cyclophosphamide, and relevant with the dosage of each compositions, and dosage acts on during for 20mg/kg all best.
Table 3 BRH compositions is to the potentiation of chemotherapy (X ± SD)
| Group | Number of animals (only) | Dosage (mg/kg) | Tumor heavy (g) | Tumour inhibiting rate (%) | Potentiation rate (%) |
| The blank group | 10 | - | 1.77±0.26 | - | - |
| Positive controls | 10 | 30 | 0.95±0.30 | 46.33 | - |
| CTX+ Herba Hedyotidis Diffusae extract group | 10 | 20 | 0.69±0.16 * | 61.02 | 26.05 |
| CTX+BRH composite injection I organizes (low dosage) | 10 | 10 | 0.55±0.21 ** | 68.93 | 36.57 |
| CTX+BRH composite injection I organizes (middle dosage) | 10 | 15 | 0.53±0.18 **# | 70.06 | 36.85 |
| CTX+BRH composite injection I organizes (high dose) | 10 | 20 | 0.50±0.19 **# | 71.75 | 38.69 |
| CTX+BRH composite injection II organizes (low dosage) | 10 | 10 | 0.56±0.19 **# | 68.36 | 35.47 |
| CTX+BRH composite injection II organizes (middle dosage) | 10 | 15 | 0.52±0.19 **# | 70.62 | 37.24 |
| CTX+BRH composite injection II organizes (high dose) | 10 | 20 | 0.49±0.16 **# | 72.32 | 39.54 |
| CTX+BRH composite injection III organizes (low dosage) | 10 | 10 | 0.55±0.18 **# | 68.93 | 36.57 |
| CTX+BRH composite injection III organizes (middle dosage) | 10 | 15 | 0.52±0.21 **# | 70.62 | 37.24 |
| CTX+BRH composite injection III organizes (high dose) | 10 | 20 | 0.50±0.17 **# | 71.75 | 38.69 |
| CTX+BRH composite injection IV organizes (low dosage) | 10 | 10 | 0.56±0.20 **# | 68.36 | 35.47 |
| CTX+BRH composite injection IV organizes (middle dosage) | 10 | 15 | 0.54±0.19 **# | 69.49 | 36.12 |
| CTX+BRH composite injection IV organizes (high dose) | 10 | 20 | 0.51±0.17 **# | 71.18 | 38.06 |
Annotate:
*P＜0.05,
*P＜0.01 is compared with matched group;
#P＜0.01 is compared with CTX+ Herba Hedyotidis Diffusae extract group
Experimental example 4 BRH compositionss are to the potentiation of radiotherapy
Test sample: blank group: 0.9% normal saline solution, self-control;
Positive controls:
60The Co group;
60Co+ Herba Hedyotidis Diffusae extract group:
60Co+ Herba Hedyotidis Diffusae extract injection, self-control;
60Co+BRH composite injection I group (Herba Hedyotidis Diffusae extract+ginseng polysaccharide+astragalus polysaccharides=20mg+10mg+30mg): be divided into basic, normal, high three dosage groups, self-control (preparation method is referring to embodiment 7);
60Co+BRH composite injection II group (Herba Hedyotidis Diffusae extract+Radix Ginseng total saponins+Radix Astragali total saponins=20mg+40mg+40mg): be divided into basic, normal, high three dosage groups, self-control (preparation method is referring to embodiment 7);
60Co+BRH composite injection III group (Herba Hedyotidis Diffusae extract+Radix Ginseng total saponins+astragalus polysaccharides=20mg+40mg+30mg): be divided into basic, normal, high three dosage groups, self-control (preparation method is referring to embodiment 7);
60Co+BRH composite injection IV group (Herba Hedyotidis Diffusae extract+ginseng polysaccharide+Radix Astragali total saponins=20mg+10mg+40mg): be divided into basic, normal, high three dosage groups, self-control (preparation method is referring to embodiment 7).
Animal subject: ICR kind mice, body weight 18～22g, male, 150, be divided into 15 groups at random.
Tumor kind: S
180Tumor liquid.
Experimental technique: get 150 of ICR mices, all subcutaneous vaccination S
180Tumor liquid (2 * 10
7/ ml) 0.2ml/, be divided into 15 groups next day at random, be respectively blank group, positive controls, Herba Hedyotidis Diffusae extract group, basic, normal, high three the dosage groups of BRH composite injection I, basic, normal, high three the dosage groups of BRH composite injection II, basic, normal, high three the dosage groups of BRH composite injection III, basic, normal, high three the dosage groups of BRH composite injection IV, weigh.Except that the blank group, all the other each groups are the 3rd, the 6th day usefulness after inoculation all
60Co total irradiation, exposure dose are 0.05Gy/min.Administration group gastric infusion next day, dosage sees Table 4, and totally 10 days, drug withdrawal was weighed next day, put to death animal, peeled off the subcutaneous tumors piece, claimed tumor heavy, and calculated tumour inhibiting rate and potentiation rate.The results are shown in Table 4.
Table 4 BRH compositions is to the potentiation of radiotherapy (X ± SD)
| Group | Number of animals (only) | Dosage (mg/kg) | Tumor heavy (g) | Tumour inhibiting rate (%) | Potentiation rate (%) |
| The blank group | 10 | - | 2.88±0.10 | - | - |
| 60The Co irradiation | 10 | 0.05Gy/min | 2.55±0.36 | 11.45 | - |
| 60Co Herba Hedyotidis Diffusae group | 10 | 20 | 2.08±0.51 * | 27.77 | 25.20 |
| 60Co+BRH composite injection I organizes (low dosage) | 10 | 10 | 1.88±0.46 **# | 34.72 | 32.34 |
| 60Co+BRH composite injection I organizes (middle dosage) | 10 | 15 | 1.86±0.35 **# | 35.42 | 33.64 |
| 60Co+BRH composite injection I organizes (high dose) | 10 | 20 | 1.82±0.47 **# | 36.80 | 34.51 |
| 60Co+BRH composite injection II organizes (low dosage) | 10 | 10 | 1.86±0.36 **# | 35.42 | 33.64 |
| 60Co+BRH composite injection II organizes (middle dosage) | 10 | 15 | 1.84±0.38 **# | 36.11 | 34.02 |
| 60Co+BRH composite injection II organizes (high dose) | 10 | 20 | 1.81±0.40 **# | 37.15 | 34.85 |
| 60Co+BRH composite injection III organizes (low dosage) | 10 | 10 | 1.87±0.51 **# | 35.07 | 33.52 |
| 60Co+BRH composite injection III organizes (middle dosage) | 10 | 15 | 1.83±0.42 **# | 36.46 | 34.31 |
| 60Co+BRH composite injection III organizes (high dose) | 10 | 20 | 1.79±0.35 **# | 37.85 | 35.34 |
| 60Co+BRH composite injection IV organizes (low dosage) | 10 | 10 | 1.88±0.52 **# | 34.72 | 32.34 |
| 60Co+BRH composite injection IV organizes (middle dosage) | 10 | 15 | 1.85±0.34 **# | 35.76 | 33.15 |
| 60Co+BRH composite injection IV organizes (high dose) | 10 | 20 | 1.80±0.32 **# | 37.50 | 35.05 |
Annotate:
*P＜0.05,
*P＜0.01 is compared with matched group;
#P＜0.01, with
60Co+ Herba Hedyotidis Diffusae extract group is compared
Experimental result: each administration group and radiotherapy
60The Co irradiation is share all tangible radiotherapy potentiation (
*P＜0.05 He
*P＜0.01).Wherein BRH composite injection I organizes, BRH composite injection II organizes, BRH composite injection III organizes, the potentiation of BRH composite injection IV group all obviously is better than the list Herba Hedyotidis Diffusae extract (
#P＜0.01), it presses down tumor potentiation rate and is respectively 32.34%～34.51%, 33.64%～34.85%, 33.52%～35.34%, 32.34%～35.05%.Proof Herba Hedyotidis Diffusae, Radix Ginseng and Radix Astragali compatibility and radiotherapy
60Good radiotherapy potentiation has been share in Co irradiation, and relevant with the dosage of compositions, dosage during for 20mg/kg effect all best.
Experimental example 5 injected in mice administration acute toxicity testings
(1) experimental technique
Test sample: BRH composite injection I group (self-control, 1ml: Herba Hedyotidis Diffusae extract+ginseng polysaccharide+astragalus polysaccharides=20mg+10mg+30mg);
BRH composite injection II group (self-control, 1ml: Herba Hedyotidis Diffusae extract+Radix Ginseng total saponins+Radix Astragali total saponins=20mg+40mg+40mg);
BRH composite injection III group (self-control, 1ml: Herba Hedyotidis Diffusae extract+Radix Ginseng total saponins+astragalus polysaccharides=20mg+40mg+30mg);
BRH composite injection IV group (self-control, 1ml: Herba Hedyotidis Diffusae extract+ginseng polysaccharide+Radix Astragali total saponins=20mg+10mg+40mg).
Animal subject: mice, each 5 of every group of male and female, male body weight 25～28g, female body weight 21～24g.
Route of administration: intravenous injection, lumbar injection.
Observation item: death toll, general state, body weight, cut open inspection, half lethal dose.
(2) experimental result
Require to carry out prerun according to acute toxicity testing, 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 maximum dosage-feeding experiment in a day.Dosage: the tail vein is injected BRH composite injection I, BRH composite injection II, BRH composite injection III, each 0.1ml/10g of BRH composite injection IV respectively, the abdominal cavity is injected BRH composite injection I, BRH composite injection II, BRH composite injection III, each 0.1ml/10g of BRH composite injection IV, 2 times on the one respectively.
Death toll: do not occur dead.
General state: no abnormality seen changes.
Body weight: in administration preceding 1 day, administration day, measured in 1,3,7,14 day 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, infer that BRH composite injection I, II, III, IV are 0.2ml/10g to the maximum tolerated dose of male and female mouse vein and intraperitoneal injection, are equivalent to 100 times of maximum consumption 10ml of the 50kg body weight day for human beings.Show this product low toxicity, safe.
Experimental example 6 BRH composite injection stability experiments
Test sample: BRH composite injection I group (self-control, 1ml: Herba Hedyotidis Diffusae extract+ginseng polysaccharide+astragalus polysaccharides=20mg+10mg+30mg);
BRH composite injection II group (self-control, 1ml: Herba Hedyotidis Diffusae extract+Radix Ginseng total saponins+Radix Astragali total saponins=20mg+40mg+40mg);
BRH composite injection III group (self-control, 1ml: Herba Hedyotidis Diffusae extract+Radix Ginseng total saponins+astragalus polysaccharides=20mg+40mg+30mg);
BRH composite injection IV group (self-control, 1ml: Herba Hedyotidis Diffusae extract+ginseng polysaccharide+Radix Astragali total saponins=20mg+10mg+40mg).
Investigation project: character, pH value, clarity
Long-time stability experimental technique and result: each compositions of this product is put under the condition of 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10% and placed 6 months, 12 months, every index has no significant change, and experimental result shows that the long-term placement of each composite injection of this product is basicly stable.
4, the specific embodiment
The specific embodiment of form is described in further detail foregoing of the present invention by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.The adjuvant of each dosage form can be replaced with acceptable accessories in following examples, perhaps reduces, increases.Used Herba Hedyotidis Diffusae extract is taken from the 2nd crowd of embodiment 1 among the embodiment 4～13, and the ginseng polysaccharide takes from the 2nd crowd of embodiment 2, Radix Ginseng total saponins is taken from the 1st crowd of embodiment 3; Astragalus polysaccharides is taken from the 1st crowd of embodiment 4, Radix Astragali total saponins is taken from the 2nd crowd of embodiment 5.
The preparation of embodiment 1 Herba Hedyotidis Diffusae extract
The preparation technology of Herba Hedyotidis Diffusae extract:
Get Herba Hedyotidis Diffusae, be ground into coarse powder,, make solvent with 80% ethanol according to the percolation (appendix IO of Chinese Pharmacopoeia version in 2000) under fluid extract and the extractum item, flooded 24 hours, percolation slowly, the liquid of filtering are evaporated to does not have the alcohol flavor, and thin up becomes every 1ml to be equivalent to the amount of 1g crude drug, cold preservation, left standstill 12 hours, and filtered, filtrate adds ethanol and carries out three subgradient precipitate with ethanol, make for the first time the alcohol amount 60% that contains, make for the second time to contain alcohol amount 70%, make the alcohol amount 80% that contains for the third time, each all cold preservation 24 hours, filter, filtrate decompression is concentrated into relative density 1.10～1.15, spray drying, promptly.
The Herba Hedyotidis Diffusae extract yield that makes by this technology is 0.5～1.5%; General flavone content (in rutin): be no less than 50%.
The assay of Herba Hedyotidis Diffusae extract
The preparation precision of reference substance solution takes by weighing at the control substance of Rutin 10mg of 120 ℃ of drying under reduced pressure to constant weight, puts in the 50ml measuring bottle, adds an amount of 70% ethanol, put that slight fever makes dissolving in the water-bath, put coldly, add 70% ethanol to scale, shake up, promptly get (containing anhydrous rutin 0.2mg among every 1ml).
The preparation precision of standard curve is measured reference substance solution 0.0,1.0,2.0,3.0,4.0,5.0 and 6.0ml, put respectively in the 25ml measuring bottle, respectively add 70% ethanol to 6ml, add 5% sodium nitrite solution 1ml, shake up, placed 6 minutes, add 10% aluminum nitrate solution 1ml, shake up, placed 6 minutes, hydro-oxidation sodium test solution 10ml adds ethanol again to scale, shake up, placed 15 minutes, and, measured trap at the wavelength place of 507nm according to spectrophotography (appendix VB of Chinese Pharmacopoeia version in 2000), with the trap is that vertical coordinate, concentration are abscissa, the drawing standard curve.
It is an amount of that the algoscopy precision is measured this product, is added on the polyamide column (50 orders, the 2g that have handled well, internal diameter 12～15mm, wet method dress post) on, use the 50ml water elution, discard eluent, use 70% ethanol elution, collect the about 25ml of eluent, put in the 25ml measuring bottle, add 70% ethanol dilution, shake up to scale, precision is measured 5ml respectively, puts first, in two 25ml measuring bottles of second, add 5% sodium nitrite solution 1ml in the first bottle, shake up, placed 6 minutes, add 10% aluminum nitrate solution 1ml, shake up, placed 6 minutes, in first, each hydro-oxidation sodium test solution 10ml in two bottles of the second adds ethanol dilution again to scale, shake up, placing 15 minutes, according to spectrophotography (appendix VB of Chinese Pharmacopoeia version in 2000), is blank with the second bottle, wavelength place at 507nm measures trap, read the amount of rutin the need testing solution from standard curve, calculate, promptly.
This product is pressed dry product and is calculated, and contains total flavones in rutin (C27H30016), should be no less than 50%.
According to above-mentioned technology, make Herba Hedyotidis Diffusae extract three batch samples, its content and yield see the following form.
Astragalus polysaccharides content and yield in the Herba Hedyotidis Diffusae extract
| Lot number | General flavone content (in rutin) (%) | Yield (%) |
| 1 | 55.50 | 0.76 |
| 2 | 59.00 | 1.03 |
| 3 | 62.15 | 1.38 |
| On average | 58.88 | 1.06 |
Embodiment 2 is that the Radix Ginseng extract of main effective ingredient is ginseng polysaccharide's preparation with polysaccharide
Ginseng polysaccharide preparation technology:
Get Radix Ginseng, 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 the precipitation washing with acetone, drain acetone, take out and be deposited in 60～80 ℃ of dryings, pulverize promptly.
Ginseng polysaccharide's identification experiment
(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.
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 spectrophotography (appendix VB of Chinese Pharmacopoeia version in 2000) experiment, calculate, promptly.
According to above-mentioned technology, make Radix Ginseng extract three batch samples, its content and yield see the following form.By the result as can be seen, the content by ginseng polysaccharide in ginseng polysaccharide's extract of this prepared is not less than 50%, and extract yield is 0.5～2%.
Ginseng polysaccharide's content and yield in the Radix Ginseng extract
| Lot number | Ginseng polysaccharide's content (%) | Yield (%) |
| 1 | 85 | 0.95 |
| 2 | 90 | 1.11 |
| 3 | 93 | 1.38 |
| On average | 89 | 1.15 |
Embodiment 3 is that the Radix Ginseng extract of main effective ingredient is the preparation of Radix Ginseng total saponins with total saponins
Radix Ginseng total saponins preparation technology:
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 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, Rg1 reference substance, adds methanol and makes the mixed solution that every 1ml contains 2mg, in contrast product solution.Draw above-mentioned two kinds of each 2ul of solution, put respectively on same silica gel g thin-layer plate, (15: 40: 22: 10) lower floor's solution of placing below 10 ℃ was developing solvent with chloroform-ethyl acetate-methanol-water, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, it is clear to be heated to speckle colour developing at 105 ℃, puts under the ultra-violet lamp (365nm) and inspects.In the test sample chromatograph, with reference substance chromatograph relevant position on show the fluorescence speckle of same color.
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 2000), measure trap at 560nm wavelength place, calculate, promptly.
Ginsenoside Re, ginsenoside Rg
1Assay
Chromatographic condition and system suitability experiment 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 results are shown in following table.
According to above-mentioned technology, make Radix Ginseng total saponins three batch samples, its content and yield see the following form.By the result as can be seen, the Radix Ginseng total saponins extract yield that obtains by this prepared is 1～2%, and Radix Ginseng total saponins content is not less than 50%, ginsenoside Re, ginsenoside Rg
1Content is not less than 30%.
Radix Ginseng extract assay result and yield
| Lot number | Radix Ginseng total saponins content (%) | Ginsenoside Re, ginsenoside Rg 1Content (%) | Yield (%) |
| 1 | 71 | 38 | 1.12 |
| 2 | 68 | 41 | 1.08 |
| 3 | 74 | 46 | 1.14 |
| On average | 71 | 41.7 | 1.11 |
Embodiment 4 is that the Radix Astragali extract of main effective ingredient is the preparation of astragalus polysaccharides with polysaccharide
Astragalus polysaccharides preparation technology:
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.
The assay of astragalus polysaccharides
The preparation of standard solution is learnt from else's experience 105 ℃ and is dried to the glucose 100mg of constant weight, 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
(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.
According to above-mentioned technology, make Radix Astragali extract three batch samples, its content and yield see the following form.By the result as can be seen, the 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%.
The content of astragalus polysaccharides and yield
| Lot number | Astragalus polysaccharides content (%) | Yield (%) |
| 1 | 80.40 | 1.02 |
| 2 | 89.56 | 1.58 |
| 3 | 91.13 | 1.92 |
| On average | 87.03 | 1.51 |
Embodiment 5 is that the Radix Astragali extract of main effective ingredient is the preparation of Radix Astragali total saponins with total saponins
Radix Astragali total saponins preparation technology:
Get the Radix Astragali, decoct with water three times, each 1.5 hours, add for the first time 10 times of amounts of water, be 8 times of amounts two, 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 is equivalent to crude drug 10g with receiving ethanol and being concentrated into every 1ml, 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.
The Radix Astragali total saponins identification experiment
Identification experiment one is got this product 0.01g, adds methanol 20ml, heating cocurrent flow 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.
Identification experiment 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 in on-the 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 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 experiment are filler with the octadecyl silane; With second eyeball-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.
According to above-mentioned technology, make Radix Astragali extract three batch samples, its content and yield see the following form.By the result as can be seen, the 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%.
The content of Radix Astragali total saponins and astragaloside and yield
| Lot number | Radix Astragali total saponins content (%) | Astragaloside content (%) | Yield (%) |
| 1 | 55.64 | 2.15 | 0.85 |
| 2 | 58.94 | 2.38 | 1.00 |
| 3 | 63.57 | 3.05 | 1.72 |
| On average | 59.38 | 2.53 | 1.19 |
The preparation of embodiment 6 BRH composition powder injections
1, prescription:
BRH composition I prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Astragalus polysaccharides 30g
Mannitol 300g
Sterile water for injection adds to 3000ml
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 74.87%
BRH composition I I prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Radix Astragali total saponins 40g
Mannitol 300g
Sterile water for injection adds to 3000ml
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 63.78%
BRH composition I II prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Astragalus polysaccharides 30g
Mannitol 300g
Sterile water for injection adds to 3000ml
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 71.47%
BRH composition I V prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Radix Astragali total saponins 40g
Mannitol 300g
Sterile water for injection adds to 3000ml
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 63.39%
2, concrete steps:
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) water for injection of getting dosing amount 40% adds the Herba Hedyotidis Diffusae extract of recipe quantity, and the heated and stirred dissolving fully.Ginseng polysaccharide's (or Radix Ginseng total saponins) and astragalus polysaccharides (or Radix Astragali total saponins) add a small amount of water for injection, make it dissolving after the heating.Merge above-mentioned solution, add the dissolving of mannitol heated and stirred more fully, add sterile water for injection to full dose.
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 7 BRH compositions aqueous injection
1, prescription:
BRH composition I prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Astragalus polysaccharides 30g
Water for injection adds to 1000ml
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 74.87%
BRH composition I I prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Radix Astragali total saponins 40g
Water for injection adds to 1000ml
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 63.78%
BRH composition I II prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Astragalus polysaccharides 30g
Water for injection adds to 1000ml
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 71.47%
BRH composition I V prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Radix Astragali total saponins 40g
Water for injection adds to 1000ml
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 63.39%
2, concrete steps:
1) carries and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) get the water for injection of dosing amount 40%, add the Herba Hedyotidis Diffusae extract of recipe quantity, the heated and stirred dissolving fully.Ginseng polysaccharide's (or Radix Ginseng total saponins) and astragalus polysaccharides (or Radix Astragali total saponins) add a small amount of water for injection, and heating makes it dissolving.
3) merge above-mentioned solution, benefit adds to the full amount of 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 0.45um.
7) clarity of inspection solution, the semi-finished product chemical examination.
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 8 BRH compositions sodium chloride transfusion
1, prescription:
BRH composition I prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Astragalus polysaccharides 30g
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Annotate: the total content of total effective ingredient can reach 74.87%
BRH composition I I prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Radix Astragali total saponins 40g
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Annotate: the total content of total effective ingredient can reach 63.78%
BRH composition I II prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Astragalus polysaccharides 30g
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Annotate: the total content of total effective ingredient can reach 71.47%
BRH composition I V prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Radix Astragali total saponins 40g
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Annotate: the total content of total effective ingredient can reach 63.39%
2, concrete steps:
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) get the water for injection of dosing amount 40%, add the Herba Hedyotidis Diffusae extract of recipe quantity, the heated and stirred dissolving fully.Ginseng polysaccharide's (or Radix Ginseng total saponins) and astragalus polysaccharides (or Radix Astragali total saponins) add a small amount of water for injection, and heating makes it dissolving.Sodium chloride is complete with the water for injection dissolving of dosing amount 40%.
3) merge above-mentioned solution, benefit adds to the full amount of 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 0.45um.
7) clarity of inspection solution, the semi-finished product chemical examination.
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.
The preparation of embodiment 9 BRH compositions glucose infusion liquids
1, prescription:
BRH composition I prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Astragalus polysaccharides 30g
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Annotate: the total content of total effective ingredient can reach 74.87%
BRH composition I I prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Radix Astragali total saponins 40g
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Annotate: the total content of total effective ingredient can reach 63.78%
BRH composition I II prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Astragalus polysaccharides 30g
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Annotate: the total content of total effective ingredient can reach 71.47%
BRH composition I V prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Radix Astragali total saponins 40g
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Annotate: the total content of total effective ingredient can reach 63.39%
2, concrete steps:
1) carries and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) get the water for injection of dosing amount 40%, add the Herba Hedyotidis Diffusae extract of recipe quantity, the heated and stirred dissolving fully.Ginseng polysaccharide's (or Radix Ginseng total saponins) and astragalus polysaccharides (or Radix Astragali total saponins) add a small amount of water for injection, make it dissolving after the heating.Glucose is complete with the water for injection dissolving of dosing amount 40%.
3) merge above-mentioned solution, benefit adds to the full amount of 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 0.45um.
7) clarity of inspection solution, the semi-finished product chemical examination.
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.
The preparation of embodiment 10 BRH composition tablets
1, prescription:
BRH composition I prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Astragalus polysaccharides 30g
Starch 100.0g
Microcrystalline Cellulose 40.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 2.0g
Carboxymethylstach sodium 4.0g
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 74.87%
BRH composition I I prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Radix Astragali total saponins 40g
Starch 100.0g
Microcrystalline Cellulose 40.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 2.0g
Carboxymethylstach sodium 4.0g
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 63.78%
BRH composition I II prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Astragalus polysaccharides 30g
Starch 100.0g
Microcrystalline Cellulose 40.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 2.0g
Carboxymethylstach sodium 4.0g
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 71.47%
BRH composition I V prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Radix Astragali total saponins 40g
Starch 100.0g
Microcrystalline Cellulose 40.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 2.0g
Carboxymethylstach sodium 4.0g
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 63.39%
2, concrete steps:
1) it is standby Herba Hedyotidis Diffusae extract, ginseng polysaccharide's (or Radix Ginseng total saponins) and astragalus polysaccharides (or 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 Herba Hedyotidis Diffusae extract, ginseng polysaccharide's (or Radix Ginseng total saponins), astragalus polysaccharides (or Radix Astragali total saponins), starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material.
5) cross 20 sieve series 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 11 BRH composition capsules
1, prescription:
BRH composition I prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Astragalus polysaccharides 30g
Starch 60.0g
Microcrystalline Cellulose 20.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 1.0g
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 74.87%
BRH composition I I prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Radix Astragali total saponins 40g
Starch 60.0g
Microcrystalline Cellulose 20.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 1.0g
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 63.78%
BRH composition I II prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Astragalus polysaccharides 30g
Starch 60.0g
Microcrystalline Cellulose 20.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 1.0g
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 71.47%
BRH composition I V prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Radix Astragali total saponins 40g
Starch 60.0g
Microcrystalline Cellulose 20.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 1.0g
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 63.39%
2, concrete steps:
1) it is standby Herba Hedyotidis Diffusae extract, ginseng polysaccharide's (or Radix Ginseng total saponins) and astragalus polysaccharides (or 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 Herba Hedyotidis Diffusae extract,, ginseng polysaccharide's (or Radix Ginseng total saponins), astragalus polysaccharides (or Radix Astragali total saponins), starch, microcrystalline Cellulose mix homogeneously, it is an amount of to add the 2%HPMC aqueous solution, 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 12 BRH composition soft agent
1, prescription:
BRH composition I prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Astragalus polysaccharides 30g
Soybean oil 500.0g
Soybean phospholipid 50g
Cera Flava 50g
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 74.87%
BRH composition I I prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Radix Astragali total saponins 40g
Soybean oil 500.0g
Soybean phospholipid 50g
Cera Flava 50g
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 63.78%
BRH composition I II prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Astragalus polysaccharides 30g
Soybean oil 500.0g
Soybean phospholipid 50g
Cera Flava 50g
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 71.47%
BRH composition I V prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Radix Astragali total saponins 40g
Soybean oil 500.0g
Soybean phospholipid 50g
Cera Flava 50g
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 63.39%
2, concrete steps:
Herba Hedyotidis Diffusae extract and ginseng polysaccharide's (or Radix Ginseng total saponins) and astragalus polysaccharides (or Radix Astragali total saponins) pulverize separately are crossed 100 mesh sieves, with the soybean oil of recipe quantity and soybean phospholipid, Cera Flava heating and melting, mixing, put cold, add Herba Hedyotidis Diffusae extract, ginseng polysaccharide's (or Radix Ginseng total saponins) and astragalus polysaccharides (or Radix Astragali total saponins) and grind well, be pressed into soft capsule and get final product.
The preparation of embodiment 13 BRH composition granules
1, prescription:
BRH composition I prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Astragalus polysaccharides 30g
Icing Sugar 1000.0g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Annotate: the total content of total effective ingredient can reach 74.87%
BRH composition I I prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Radix Astragali total saponins 40g
Icing Sugar 1000.0g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Annotate: the total content of total effective ingredient can reach 63.78%
BRH composition I II prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Astragalus polysaccharides 30g
Icing Sugar 1000.0g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Annotate: the total content of total effective ingredient can reach 71.47%
BRH composition I V prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Radix Astragali total saponins 40g
Icing Sugar 1000.0g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Annotate: the total content of total effective ingredient can reach 63.39%
2, concrete steps:
1) it is standby sucrose to be pulverized 100 mesh sieves.It is standby that Herba Hedyotidis Diffusae extract and ginseng polysaccharide's (or Radix Ginseng total saponins) and astragalus polysaccharides (or 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 Herba Hedyotidis Diffusae extract, ginseng polysaccharide's (or Radix Ginseng total saponins) and astragalus polysaccharides (or Radix Astragali total saponins) and Icing Sugar are progressively increased with equivalent, adding 2%HPMC50% alcoholic solution is an amount of, 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 14 BRH composition dripping agent
1, prescription:
BRH composition I prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Astragalus polysaccharides 30g
Polyethylene glycol 6000 600g
Annotate: the total content of total effective ingredient can reach 74.87%
BRH composition I I prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Radix Astragali total saponins 40g
Polyethylene glycol 6000 600g
Annotate: the total content of total effective ingredient can reach 63.78%
BRH composition I II prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Astragalus polysaccharides 30g
Polyethylene glycol 6000 600g
Annotate: the total content of total effective ingredient can reach 71.47%
BRH composition I V prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Radix Astragali total saponins 40g
Polyethylene glycol 6000 600g
Annotate: the total content of total effective ingredient can reach 63.39%
2, concrete steps:
With polyethylene glycol 6000 heating and melting in water-bath, treat to add Herba Hedyotidis Diffusae extract, ginseng polysaccharide's (or Radix Ginseng total saponins) and astragalus polysaccharides (or Radix Astragali total saponins) after whole fusions, stirring and dissolving, 60 mesh sieves are filtered, and keep 60 ℃ to splash in the liquid paraffin that is chilled to below 10 ℃ and make ball.
The preparation of embodiment 15 BRH polysaccharide composition oral liquids
1, prescription:
BRH composition I prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Astragalus polysaccharides 30g
Polyoxyethylene sorbitan monoleate 50g
Sodium hydroxide is an amount of
Sodium benzoate 15g
Stevioside 10g
Water adds to 10000ml
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 74.87%
BRH composition I I prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Radix Astragali total saponins 40g
Polyoxyethylene sorbitan monoleate 50g
Sodium hydroxide is an amount of
Sodium benzoate 15g
Stevioside 10g
Water adds to 10000ml
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 63.78%
BRH composition I II prescription
Herba Hedyotidis Diffusae extract 20g
Radix Ginseng total saponins 40g
Astragalus polysaccharides 30g
Polyoxyethylene sorbitan monoleate 50g
Sodium hydroxide is an amount of
Sodium benzoate 15g
Stevioside 10g
Water adds to 10000ml
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 71.47%
BRH composition I V prescription
Herba Hedyotidis Diffusae extract 20g
Ginseng polysaccharide 10g
Radix Astragali total saponins 40g
Polyoxyethylene sorbitan monoleate 50g
Sodium hydroxide is an amount of
Sodium benzoate 15g
Stevioside 10g
Water adds to 10000ml
Prepare 1000 altogether
Annotate: the total content of total effective ingredient can reach 63.39%
2, concrete steps:
1) earlier that polyoxyethylene sorbitan monoleate is complete with the water dissolution of dosing amount 40%, again Herba Hedyotidis Diffusae extract is added the heated and stirred dissolving fully.Ginseng polysaccharide's (or Radix Ginseng total saponins) and astragalus polysaccharides (or Radix Astragali total saponins) add that to add an amount of dissolution of sodium hydroxide after the low amounts of water heating complete.
2) sodium benzoate and stevioside is complete with the water dissolution of dosing amount 20%.
3) merge above-mentioned solution, mend and add water to full dose.
4) filtering with microporous membrane of mistake 0.8um.
5) semi-finished product chemical examination, fill, finished product is examined entirely, the packing warehouse-in.
Claims (11)
1. pharmaceutical composition, it is characterized in that said composition is made by following bulk drugs: Herba Hedyotidis Diffusae, Radix Ginseng and the Radix Astragali, its parts by weight are: 50～800 parts of Herba Hedyotidis Diffusaes, 25～1600 parts of Radix Ginsengs, 75～1600 parts of the Radixs Astragali.
2. pharmaceutical composition as claimed in claim 1 is characterized in that, the parts by weight of crude drug are: 200 parts of Herba Hedyotidis Diffusaes, 100～400 parts of Radix Ginsengs, 300～400 parts of the Radixs Astragali.
3. as the described arbitrary preparation of drug combination method of claim 1-2, it is characterized in that, crude drug wherein can singly be carried or mix to obtain through refining and obtain extract fully with The suitable solvent and method, and total extract is made arbitrary preparation with mixing acceptable accessories again.
4. preparation of drug combination method as claimed in claim 3 is characterized in that, main effective ingredient contained in the total extract is: Herba Hedyotidis Diffusae total flavones, ginseng polysaccharide or saponin, astragalus polysaccharides or saponin.
5. preparation of drug combination method as claimed in claim 4 is characterized in that the total content of the main effective ingredient in the total extract is not less than 30%.
6. pharmaceutical composition as claimed in claim 1, it is characterized in that, said composition can also be made approximately by following raw materials according: Herba Hedyotidis Diffusae extract, the extract of Radix Ginseng, the Radix Astragali, its main effective ingredient is respectively: Herba Hedyotidis Diffusae total flavones, ginseng polysaccharide or saponin, astragalus polysaccharides or saponin, and the weight proportion of its crude drug is: 5～80 parts of Herba Hedyotidis Diffusae extracts, be that the Radix Ginseng extract of main effective ingredient is 2～40 parts of ginseng polysaccharides, is that the Radix Astragali extract of main effective ingredient is 7～120 parts of astragalus polysaccharidess with polysaccharide with polysaccharide; Perhaps be: 5～80 parts of Herba Hedyotidis Diffusae extracts, be that the Radix Ginseng extract of main effective ingredient is 10～160 parts of Radix Ginseng total saponinss, is that the Radix Astragali extract of main effective ingredient is 10～160 parts of Radix Astragali total saponinss with saponin with saponin; Perhaps be: 5～80 parts of Herba Hedyotidis Diffusae extracts, be that the Radix Ginseng extract of main effective ingredient is 10～160 parts of Radix Ginseng total saponinss, is that the Radix Astragali extract of main effective ingredient is 7～120 parts of astragalus polysaccharidess with polysaccharide with saponin; Perhaps be: 5～80 parts of Herba Hedyotidis Diffusae extracts, be that the Radix Ginseng extract of main effective ingredient is 2～40 parts of ginseng polysaccharides, is that the Radix Astragali extract of main effective ingredient is 10～160 parts of Radix Astragali total saponinss with saponin with polysaccharide.
7. pharmaceutical composition as claimed in claim 6 is characterized in that, the weight proportion of its crude drug is: 20 parts of Herba Hedyotidis Diffusae extracts, 10 parts of ginseng polysaccharides, 30 parts of astragalus polysaccharidess; Perhaps be: 20 parts of Herba Hedyotidis Diffusae extracts, 40 parts of Radix Ginseng total saponinss, 40 parts of Radix Astragali total saponinss; Perhaps be: 20 parts of Herba Hedyotidis Diffusae extracts, 40 parts of Radix Ginseng total saponinss, 30 parts of astragalus polysaccharidess; Perhaps be: 20 parts of Herba Hedyotidis Diffusae extracts, 10 parts of ginseng polysaccharides, 40 parts of Radix Astragali total saponinss.
8. as claim 6,7 described arbitrary pharmaceutical compositions, it is characterized in that the total content of main effective ingredient is not less than 30% in the total extract.
9. as claim 6,7 described arbitrary pharmaceutical compositions, it is characterized in that, described Herba Hedyotidis Diffusae extract contains total flavones and is not less than 20%, Radix Ginseng extract contains Radix Ginseng total saponins and is not less than 20% or contain the ginseng polysaccharide and be not less than 20%, and Radix Astragali extract contains Radix Astragali total saponins and is not less than 20% or contain astragalus polysaccharides and be not less than 20%.
10. as claim 1,2,6,7 described arbitrary pharmaceutical compositions, it is characterized in that said composition can add that acceptable accessories is made clinically or pharmaceutically acceptable arbitrary dosage form.
11. pharmaceutical composition as claimed in claim 10 is characterized in that clinically or pharmaceutically acceptable dosage form is injection or oral formulations.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510104352 CN1954849A (en) | 2005-10-26 | 2005-10-26 | Antineoplastic medical composite compatibility with oldenlandia, ginseng and astragalus root |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510104352 CN1954849A (en) | 2005-10-26 | 2005-10-26 | Antineoplastic medical composite compatibility with oldenlandia, ginseng and astragalus root |
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| Publication Number | Publication Date |
|---|---|
| CN1954849A true CN1954849A (en) | 2007-05-02 |
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|---|---|---|---|
| CN 200510104352 Pending CN1954849A (en) | 2005-10-26 | 2005-10-26 | Antineoplastic medical composite compatibility with oldenlandia, ginseng and astragalus root |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102058871A (en) * | 2010-11-25 | 2011-05-18 | 代龙 | Chinese medicine effective part composition with antitumor effect and preparation method thereof |
| CN103626883A (en) * | 2012-08-29 | 2014-03-12 | 奇复康药物研发(苏州)有限公司 | Extraction method for hedyotis diffusa polysaccharide |
| CN104352603A (en) * | 2014-09-30 | 2015-02-18 | 青岛市中心医院 | Anti-tumor traditional Chinese medicine capable of enhancing immunity of human body |
| CN105250440A (en) * | 2015-11-04 | 2016-01-20 | 刘宇清 | Pain-alleviating traditional Chinese medicine composition and application thereof |
| CN106421134A (en) * | 2016-10-20 | 2017-02-22 | 李晓 | Anti-cancer radix ginseng tea and preparation method thereof |
-
2005
- 2005-10-26 CN CN 200510104352 patent/CN1954849A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102058871A (en) * | 2010-11-25 | 2011-05-18 | 代龙 | Chinese medicine effective part composition with antitumor effect and preparation method thereof |
| CN102058871B (en) * | 2010-11-25 | 2013-04-17 | 代龙 | Chinese medicine effective part composition with antitumor effect and preparation method thereof |
| CN103626883A (en) * | 2012-08-29 | 2014-03-12 | 奇复康药物研发(苏州)有限公司 | Extraction method for hedyotis diffusa polysaccharide |
| CN104352603A (en) * | 2014-09-30 | 2015-02-18 | 青岛市中心医院 | Anti-tumor traditional Chinese medicine capable of enhancing immunity of human body |
| CN105250440A (en) * | 2015-11-04 | 2016-01-20 | 刘宇清 | Pain-alleviating traditional Chinese medicine composition and application thereof |
| CN105250440B (en) * | 2015-11-04 | 2019-03-22 | 刘宇清 | A kind of lenitive Chinese medicine composition and its application |
| CN106421134A (en) * | 2016-10-20 | 2017-02-22 | 李晓 | Anti-cancer radix ginseng tea and preparation method thereof |
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