CN1745843A - Anticancer Chinese medicine compound preparation and its making method thereof - Google Patents
Anticancer Chinese medicine compound preparation and its making method thereof Download PDFInfo
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- CN1745843A CN1745843A CN 200510109374 CN200510109374A CN1745843A CN 1745843 A CN1745843 A CN 1745843A CN 200510109374 CN200510109374 CN 200510109374 CN 200510109374 A CN200510109374 A CN 200510109374A CN 1745843 A CN1745843 A CN 1745843A
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- radix ginseng
- semen coicis
- ethanol
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Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
An anticancer Chinese medicine is prepared from ginseng, brucea fruit, zedoary oil and coix seed. It is possible to use other Chinese-medicinal materials as its raw materials for regulating its action. Its preparing process is also disclosed.
Description
Technical field:
The present invention relates to Chinese medicine medicine for preventing compound preparation and preparation method, it is characterized in that, this compound preparation is made by raw material of Chinese medicine Radix Ginseng, Fructus Bruceae, Oleum Curcumae, Semen Coicis, and said preparation can also add other Chinese medicines as required, to regulate its effect.
Background technology:
According to the research of national treatment and prevention of tumour research office to 20 years malignant tumor death trend of China, China's malignant tumor is adjusted mortality rate seventies 84.58/10 ten thousand, and be 94.36/10 ten thousand the nineties, risen 11.56%.The major malignant tumor that rises is: gastric cancer (9.95%), hepatocarcinoma (41.17%), pulmonary carcinoma (111.85%) and leukemia (30.26%), cause huge life to threaten to the patient, quality of life is had a strong impact on, and causes white elephant also for patient family and even entire society.
At present, the Chinese medicine and western medicine of malignant tumor such as treatment gastric cancer, hepatocarcinoma is a lot, but how many Western medicine has some side effect.Chinese medicine has certain advantage aspect the treatment malignant tumor, utilizes pathogenesis research thinking treatment malignant tumor that certain effect is arranged, and becomes the focus of malignant tumor area research in recent years.
In recent years, along with going deep into of clinical research, also occur the Chinese medicine of some treatment malignant tumor on the market, but existing medicine belongs to a bit and cure the symptoms, not the disease, some uses expensive composition, and some interrupts use because uncertain therapeutic efficacy is cut in application process.
In view of this, the inventor develop a kind of taking convenience, effect steadily, determined curative effect, dosage form is stable, quality controllable and the pure Chinese medicinal preparation that has no side effect, to satisfy the demand of extensive patients.
The present invention with Radix Ginseng, Fructus Bruceae, Rhizoma Curcumae, Semen Coicis for square substantially, the side in the Radix Ginseng strongly invigorating primordial QI, invigorating the spleen to benefit the lung promotes the production of body fluid, the Fructus Alpiniae Oxyphyllae of calming the nerves; Radix Astragali spleen invigorating invigorating middle warmer, ascending up spleen-Qi and Yang, benefit is defended consolidating superficial resistance, diuresis, promoting pus discharge and tissue regeneration strengthening; The Fructus Bruceae heat-clearing and toxic substances removing, dysentery relieving, preventing the attack (or recurrence) of malaria, corrosion wart; The circulation of qi promoting of Rhizoma Curcumae removing blood stasis, the removing food stagnancy pain relieving; Be aided with the Venenum Bufonis detoxifcation, pain relieving, the refreshment of having one's ideas straightened out; The Mylabris removing blood stasis note of the ancient Chinese that disappears, the counteracting toxic substances phagedenoma; The Fructus Liquidambaris dispelling, collateral-activating, diuretic stimulates the menstrual flow; The Ramulus et folium taxi cuspidatae inducing diuresis to remove edema, the kidney warming stimulates the menstrual flow.Many medicines share, and play heat-clearing and toxic substances removing altogether, supplementing QI and nourishing YIN, note of the ancient Chinese eliminating stagnation that disappears, analgesic effect.
The purpose of this invention is to provide a kind of therapeutic domain wide, easily accept, easily absorb, efficient, low dosage, the Chinese medicine preparation that has no side effect, preparation technology and dosage form thereof.
Summary of the invention:
The invention provides a kind of Chinese medicine anticancer preparation, said preparation prepares with Chinese medicine Radix Ginseng, Fructus Bruceae, Rhizoma Curcumae, Semen Coicis, and per 1000 dosage units are made by the following weight proportion raw material:
Radix Ginseng 600-9000 part, Fructus Bruceae 120-2000 part, Rhizoma Curcumae 750-9000 part, Semen Coicis 1500-30000 part.
Preferably 1200 parts of Radix Ginsengs, 250 parts of Fructus Bruceaes, 1500 parts of Rhizoma Curcumae, 3000 parts of Semen Coiciss (being called prescription 1.).
Chinese medicine anticancer preparation of the present invention except that Radix Ginseng, Fructus Bruceae, Rhizoma Curcumae, Semen Coicis, also can add other Chinese medicines with the adjustment of treatment effect in its prescription as required, and described other Chinese medicines are selected from: Bufo siccus, Mylabris, Fructus Liquidambaris, Ramulus et folium taxi cuspidatae.Such Chinese medicine preparation is called plus-minus side of the present invention.Plus-minus side of the present invention is preferably: 6～60 parts of Radix Ginseng 600-9000 parts, Fructus Bruceae 120-2000 part, Rhizoma Curcumae 750-9000 part, Semen Coicis 1500-30000 part, Mylabris.Most preferred proportioning is: 1200 parts of Radix Ginsengs, 250 parts of Fructus Bruceaes, 1500 parts of Rhizoma Curcumae, 3000 parts of Semen Coiciss, 12 parts of Mylabris (being called prescription 2.).
Another preferably the side of plus-minus is: Radix Ginseng 600-9000 part, Fructus Bruceae 120-2000 part, Rhizoma Curcumae 750-9000 part, Semen Coicis 1500-30000 part, Bufo siccus 2-30 part.Most preferred proportioning is 1200 parts of Radix Ginsengs, 250 parts of Fructus Bruceaes, 1500 parts of Rhizoma Curcumae, 3000 parts of Semen Coiciss, 4 parts of Bufo siccuss (being called prescription 3.).
Another preferably the side of plus-minus is: Radix Ginseng 600-9000 part, Fructus Bruceae 120-2000 part, Rhizoma Curcumae 750-9000 part, Semen Coicis 1500-30000 part, Fructus Liquidambaris 3000-9000 part.Most preferred proportioning is 1200 parts of Radix Ginsengs, 250 parts of Fructus Bruceaes, 1500 parts of Rhizoma Curcumae, 3000 parts of Semen Coiciss, 6000 parts of Fructus Liquidambaris (being called prescription 4.).
Another preferably the side of plus-minus is: Radix Astragali 1500-30000 part, Fructus Bruceae 120-2000 part, Rhizoma Curcumae 750-9000 part, Semen Coicis 1500-30000 part, Ramulus et folium taxi cuspidatae 25000-100000 part.Most preferred proportioning is 3000 parts of the Radixs Astragali, 250 parts of Fructus Bruceaes, 1500 parts of Rhizoma Curcumae, 3000 parts of Semen Coiciss, 50000 parts of Ramulus et folium taxi cuspidatae (being called prescription 5.).
In more than forming, the weight of medicine is calculated with crude drug, and per 1 part can be 1 gram, also can be kilogram or ton, if be unit with gram, this prescription composition can be made into 1000 doses of pharmaceutical preparatioies.Described 1000 doses of fingers, the final drug preparation of making, as make 1000 bottles of ejection preparations, 1000 of capsule preparations, 1000 in tablet, granule 1000g, oral liquid 1000ml etc. also can make big packing as granule, as the 100-500 bag, specifically can be 100 bags, 125 bags, 200 bags, 250 bags, 500 bags etc., every bag can be used as taking dose 1 time.
More than form, can be made into the preparation of 50-1000 taking dose, as tablet, make 1000, each taking dose can be the 1-20 sheet, can take 50-1000 time altogether.As granule, make 125 bags, take the 1-2 bag at every turn, can take 62.5-125 time altogether.
More than form to be by weight as proportioning, when producing, can increase or reduce according to corresponding proportion, as large-scale production can be unit with the kilogram, or be unit with the ton, small-scale production can be unit with the milligram also, weight can increase or reduce, but the constant rate of the raw medicinal herbs weight proportion between each composition.
The ratio of above weight proportion obtains through science screening, for especial patient, and as serious symptom or light disease, fat or modest patient, the proportioning of the amount of can corresponding adjustment forming increases or reduces being no more than 100%, and drug effect is constant.
Pharmaceutically active substance in the pharmaceutical preparation of the present invention, its shared percentage by weight in preparation can be 0.1-99.9%, all the other are the medicine acceptable carrier.Pharmaceutical preparation of the present invention exists with unit dosage form, and described unit dosage form is meant the unit of preparation, as every of tablet, capsular every capsules, every of injection etc., in the unit dose, the amount that contains active substance is 5-800mg, preferably 20-500mg.
Pharmaceutical preparation of the present invention can be any pharmaceutically useful dosage form, and these dosage forms comprise: tablet, capsule, oral liquid, syrup, granule, pill, powder, unguentum, sublimed preparation, injection, suppository, cream, spray, drop pill, patch, slow releasing preparation, controlled release preparation.
The form of oral liquid can be aqueous or oily suspensions, solution, Emulsion, syrup or elixir, perhaps can be a kind of available water before use or other suitable composite dry products of carrier.This liquid preparation can contain conventional additive, such as suspending agent, for example sorbitol, syrup, methylcellulose, gelatin, hydroxyethyl-cellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenation edible fat, emulsifying agent, for example lecithin, anhydro sorbitol monooleate or arabic gum; Non-aqueous carrier (they can comprise edible oil), for example almond oil, fractionated coconut oil, such as oily ester, propylene glycol or the ethanol of the ester of glycerol; Antiseptic, for example para hydroxybenzene methyl ester or propyl p-hydroxybenzoate or sorbic acid, and if desired, can contain conventional flavouring agent or coloring agent.
For injection, the liquid unit dosage forms of preparation contains active substance of the present invention and sterile carrier.According to carrier and concentration, this chemical compound can be suspended or dissolving.The preparation of solution is normally by being dissolved in active substance in a kind of carrier filter-sterilized before it is packed into a kind of suitable bottle or ampoule, sealing then.For example a kind of local anesthetic of adjuvant, antiseptic and buffer agent also can be dissolved in this carrier.In order to improve its stability, can be after the bottle of packing into that this compositions is freezing, and under vacuum, water is removed.
Pharmaceutical preparation of the present invention, when being prepared into medicament, optionally add suitable medicine acceptable carrier, described medicine acceptable carrier is selected from: mannitol, sorbitol, sodium pyrosulfite, sodium sulfite, sodium thiosulfate, cysteine hydrochloride, TGA, methionine, vitamin C, the EDTA disodium, EDTA calcium sodium, the alkali-metal carbonate of monovalence, acetate, phosphate or its aqueous solution, hydrochloric acid, acetic acid, sulphuric acid, phosphoric acid, aminoacid, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivative, cellulose and derivant thereof, alginate, gelatin, polyvinylpyrrolidone, glycerol, soil temperature 80, agar, calcium carbonate, calcium bicarbonate, surfactant, Polyethylene Glycol, cyclodextrin, beta-schardinger dextrin-, the phospholipid material, Kaolin, Pulvis Talci, calcium stearate, magnesium stearate etc.
Pharmaceutical preparation of the present invention, active component can extract a few flavor medicines respectively, and extraction also can mix.When extracting respectively, method is as follows:
The preparation method of Radix Ginseng active component is: take by weighing the ginseng crude drug, decoct with water twice, each amount of water is 5～8 times of amounts, and extracting solution is centrifugal by tube centrifuge, and centrifugal liquid is crossed D
101Macroporous resin adsorption is collected effluent, and device is preserved in addition; Macroporous resin washes with water to effluent light color, and reuse 15～80% ethanol carry out eluting, collects eluent, concentrating under reduced pressure, and spray drying, dry powder 90% alcohol reflux, extracting solution reclaims ethanol, is condensed into cream, and drying gets dry powder, gets the Radix Ginseng active components A.Get the macroporous resin effluent, cross ion exchange resin, except that behind the deproteinize, effluent is evaporated in right amount, and adding ethanol to determining alcohol is more than 80%, the leaching precipitation, and precipitate continues and uses washing with acetone, cold drying to get Radix Ginseng active component B with 80% washing with alcohol.
The preparation of Semen Coicis active component: get Semen Coicis, be ground into coarse powder, add the acetone extraction three times of 3 times of amounts, 2.5 times of amounts, 2.5 times of amounts respectively, merge acetone solution, reclaim under reduced pressure acetone, the petroleum ether dissolution that adds 0.5～1 times of amount, the decolorizing with activated carbon of adding 0.5～1.0% is after decarburization, filter, filtrate adds 2% sodium hydroxide solution eluting of 2 times of amounts, 1.5 times of amounts respectively, is washed to neutrality again, reclaimed behind the petroleum ether the Semen Coicis active component.
The preparation of Rhizoma Curcumae active component: get Rhizoma Curcumae, be ground into coarse powder, the water extraction of 10～15 times of amounts 4～10 hours is collected distillate, and distillate carries out the distillation second time, gets Oleum Curcumae.
The preparation of Fructus Bruceae active component: get Fructus Bruceae, be ground into coarse powder, the acetone extraction secondary that adds 3.5 times of amounts, 3.0 times of amounts respectively, merge acetone solution, reclaim under reduced pressure acetone adds the petroleum ether dissolution of 0.5～1 times of amount, the decolorizing with activated carbon of adding 0.5～1.0%, after decarburization, filter, having reclaimed must the Fructus Bruceae active component behind the petroleum ether.
The preparation of Bufo siccus active component: get Bufo siccus and be ground into coarse powder, add an amount of ethanol earlier and run through, in the percolator of packing into, add 4 times of amount soak with ethanol and carry out percolation after 12 hours, percolation to effluent is a light color, collect percolate, reclaim under reduced pressure is finished ethanol, adds the dissolve with ethanol of 0.5～1 times of amount, the decolorizing with activated carbon of adding 0.5～1.0%, after decarburization, filter, having reclaimed must the Bufo siccus active component behind the ethanol.
The preparation of Mylabris active component: get powder of cantharide and be broken into coarse powder, the hydrochloric acid solution that adds 5～15 times of amounts 10% carries out percolation, and the acetone that percolate adds 5～10 times of amounts carries out merceration, filters, acetone solution is recycled to 1/6 of original volume, get grease, place natural crystallize, separate precipitate, with a spot of petroleum ether-dehydrated alcohol (1: 1) washing, oven drying at low temperature gets the Mylabris active component.
The preparation of Fructus Liquidambaris active component: get Fructus Liquidambaris and decoct with water secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, and filtrate is concentrated into the clear paste that relative density is 1.25～1.30 (40 ℃); Add ethanol and make and contain alcohol amount to 75%, left standstill 24 hours, filter, filtrate recycling ethanol also is concentrated into the clear paste that relative density is 1.25～1.30 (40 ℃); Qinghuo reagent adds ethanol to be made and contains alcohol amount to 80%, leaves standstill 24 hours, gets supernatant and reclaims ethanol and be concentrated into the thick paste that relative density is 1.29～1.31 (40 ℃), drying.Promptly get the Fructus Liquidambaris active component.
The preparation of Ramulus et folium taxi cuspidatae active component: get Ramulus et folium taxi cuspidatae, alcohol dipping with 95% is after 48 hours, slowly percolation is collected the liquid of filtering, and 40 ℃ of decompression recycling ethanols are to doing, add water and dichloromethane solution, filter, the reclaim under reduced pressure dichloromethane is to doing, and residue dissolves with ethyl acetate-methanol (3: 1) mixed liquor, adding kieselguhr mixes thoroughly, removal of solvent under reduced pressure in the percolation bucket of packing into, is used earlier the normal hexane percolation, continue and use the dichloromethane percolation, collect the dichloromethane percolate, the reclaim under reduced pressure dichloromethane is to doing, and residue dissolves with ethyl acetate, with silica gel is absorbent, normal hexane-acetone (75: 25) is eluant, and eluting is collected the eluent that contains paclitaxel, reclaim under reduced pressure promptly gets the Ramulus et folium taxi cuspidatae active component to doing.
The active constituents of medicine of the preparation of the present invention that above method obtains is further processed through the galenic pharmacy routine techniques, can be prepared into preparation of the present invention.
Preparation of the present invention, different dosage form method difference below is the preparation method of several preferred dosage form.
(1) preparation of injection
Described injection, wherein the ratio of active component and adjuvant is 1: 0.1～05, and described adjuvant is refining fabaceous lecithin, tween 80, pluronic F-80, Arlacel-80, Arius acid sodium, sodium sulfite, sodium pyrosulfite, Polyethylene Glycol, propylene glycol, ethanol, glycerol or their mixture.Its preparation method is: after water soluble drug active component and an amount of water for injection are fully dissolved, get water-insoluble active component again and must fully dissolve by adjuvant with an amount of liposoluble, the routine fashion by injection behind both mixings is made injection.
(2) preparation of drop pill
Drop pill of the present invention, wherein the ratio of active component and adjuvant is 1: 0.5～10, and preferred ratio is 1: 2～4, and most preferred ratio is 1: 3.The above adjuvant be specially molecular weight polyethylene glycol between 400 to 10000 Polyethylene Glycol and their mixture, as PEG400 (PEG400), Macrogol 2000, Macrogol 4000, polyethylene glycol 6000 or their mixture, or other suitable other auxiliary elements such as glycerol, gelatin or stearic acid sodium etc. of making drop pill.
Following steps are taked in the preparation of drop pill of the present invention:
1. be ready to following raw material: active component, adjuvant and/or other inactive ingredients;
2. with the above-mentioned raw materials mix homogeneously;
3. add the transconversion into heat material, move into the drip irrigation of drop pill machine, medicinal liquid splashes in the liquid sub liquid paraffin by water dropper, removes liquid paraffin, selects ball, promptly.
(3) preparation of soft capsule
Soft capsule preparation of the present invention is that active component and pharmaceutically useful organic solvent and the material of making soft capsule shell are formed.Organic solvent wherein is selected from PEG400, Tween 80, glycerol, propylene glycol, isopropyl alcohol, dehydrogenation soybean oil, vegetable oil, aromatic oil, the material of wherein making soft capsule shell is gelatin or arabic gum, water, plasticizer and antiseptic, the weight ratio of gelatin or arabic gum and plasticizer is 1.0: 0.4～1.0 in the soft capsule shell, and the weight ratio of gelatin and water is 1.0: 0.8～1.2.Wherein the weight proportion between active component and the pharmaceutically useful organic solvent is: the content of active component is 50mg-500mg in every soft capsule.
The preparation method of preparation of the present invention, the process following steps:
A. get gelatin, glycerol, pure water adds thermosol, adds an amount of antiseptic, preparation rubber;
B. get active component and be dissolved in organic solvent, add suitable quantity of water, be prepared into soft capsule through encapsulating machine.
(4) preparation process of granule is as follows: with above-mentioned extract obtained, add a certain amount of correctives, filler, lubricant, granulate, promptly get granule.
(5) preparation method of chewable tablet is as follows: with above-mentioned extract obtained, add a certain amount of correctives, filler, lubricant, granulate, and drying, tabletting promptly gets chewable tablet.
(6) preparation method of oral liquid is as follows: the active component of above-mentioned each medicine gained is added certain amount of fluid dispersion medium, cosolvent, emulsifying agent, correctives composition oral liquid.
Filler described in the preparation such as granule, chewable tablet is selected from one or more the mixture in lactose, sucrose, dextrin, starch, microcrystalline Cellulose, mannitol, pregelatinized Starch, sorbitol, the xylitol etc.; Described correctives one of is selected from Rhizoma et radix valerianae, Fructus Pruni pseudocerasi, Fructus Vitis viniferae, Fructus Citri tangerinae, Fructus Citri Limoniae, Herba Menthae, Fructus Fragariae Ananssae, Fructus Musae, Fructus Ananadis comosi, honey peach essence, maltose alcohol, saccharin sodium, protein sugar, sucrose, aspartame, the stevioside or wherein several mixture; Suitable lubricant comprises wherein one or more such as magnesium stearate, Pulvis Talci, micropowder silica gel.Following data declaration beneficial effect of the present invention by experiment:
In order to prove the Clinical feasibility that changes after the technology, we have carried out the research of its main pharmacodynamics to this medicine is Antitumor Effects, observes its therapeutical effect, and the clinical experimental basis that provides is provided.
1 method
1.1 the foundation of tumor model
With aseptic needle tubing from H
22The tumor strain mouse peritoneal that goes down to posterity extracts ascites 0.2ml, puts into sterile chamber, adds PBS liquid and is diluted to 1: 4 tumor tissue suspension in right amount, regulates with PBS liquid, and making cell number is 20 * 10
6/ mL.The right axil subcutaneous vaccination of mice H
22Cell suspension, 2 * 10
6Individual/only, and 0.1ml/, random packet behind the 24h.
1.2 animal grouping and administration
98 model mices are divided into 7 groups at random, 14 every group.All per os is irritated stomach and is given relative medicine, and 1 time/d, continuous 15d.
1. extractum group: 0.06g/kg writes out a prescription; 2. extractum group: 0.06g/kg writes out a prescription; 3. extractum group: 0.06g/kg writes out a prescription; 4. extractum group 0.13g/kg writes out a prescription; 5. extractum group 0.09g/kg writes out a prescription; Cyclophosphamide group: 0.02g/kg.Other gets 14 of healthy Kunming kind white mice, as the blank group.Model group and blank group all give normal saline, and 0.2mL/10g the weight of animals, administering mode are for irritating stomach, and 15d puts to death all animals in irritating the dislocation of stomach end cervical vertebra next day continuously, strips tumor tissue to fix paraffin embedding.
1.3 light microscopy checking
With 4% formaldehyde fixed, paraffin embedding is cut into slices with the tumor tissue piece, HE dyeing, the pathological change of om observation tumor tissue.
1.4 electron microscopic examination
Get tumor tissues 0.1cm * 0.1cm, fix, 10ml/L osmic acid (O with the glutaraldehyde of 25ml/L
sO
4) back fixedly 1h, the dehydration of ethanol gradient, ultrathin section is made in embedding, observes under transmission electron microscope.
1.5 detection apoptosis cell
Adopt the transferase mediated breach end-labelling (TUNEL method) of dna end to detect apoptotic cell.The conventional dewaxing of paraffin organization section entry, 0.3%H
2O
2(dissolve with methanol) handles 30min, and E.C. 3.4.21.64 was at 37 ℃ of digestion 10min in 1: 100; Every adds 1 μ lTdT enzyme and 9 μ L reaction buffers and places 37 ℃ in wet box, 3h; Every adds 37 ℃ of confining liquid 50 μ L, 30min; Add 40 μ L37 ℃ of chromogenic reaction liquid, 30～60min; Add 40 μ L colour developing liquid 20min; 0.5% C.I. 42590 waits 20s, gummy mounting, and microscopically is observed has blue-purple granule positive.
2 observation index
Overall health of patients: the fur gloss of observation animal, moving situation etc.
The measurement tumor is heavy, calculates tumour inhibiting rate.Tumour inhibiting rate (the %)=heavy oncocyte morphological change of (the average tumor of the average tumor weight-experimental group of matched group is heavy)/average tumor of matched group: observe respectively under light microscopic and the Electronic Speculum.
Apoptotic cell: 400 times of optical microscopes are observed down.5 visuals field of picked at random, 100 cells are calculated in each visual field, in average per 100 cells the number of apoptotic cell be apoptotic index (ApoplOsis Index, AI).
3 statistical procedures
Tumor heavily reaches apoptotic index and all uses (x ± s) expression.Many groups data mean relatively adopts variance analysis.All data are handled with the SPSS10.0 statistical software.
4 results
4.1 overall health of patients
From each group situation, at subcutaneous vaccination H
22Behind the oncocyte, the model group mice hair color shortage gloss that becomes gradually, food-intake obviously reduces, and the mental status is relatively poor, is slow in action.Each prescription group, positive controls mice, its fur become dark and gloomy gradually, but kinestate and food-intake all are better than the model group mice.
4.2 influence heavy to tumor, tumour inhibiting rate
The average tumor weight average of each prescription group and positive controls is lower than model group, with the model group contrast, significant difference (P＜0.01) is arranged.See Table 1.
Table 1 antitumor action comparison sheet (x ± s)
| Group | n | Tumor heavy (g) | Tumour inhibiting rate (%) | Body weight (g) |
| The blank group of the model group medicinal extract group medicinal extract group medicinal extract group medicinal extract group 5. medicinal extract group of writing out a prescription of writing out a prescription 4. of writing out a prescription 3. of writing out a prescription 2. of writing out a prescription 1. | 14 14 12 12 13 13 13 | 2.73±0.48 1.21±0.41 *1.10±0.32 *1.19±0.26 *1.15±0.20 *1.11±0.12 * | 55.79 60.32 56.52 58.32 59.13 | 25.50±0.45 26.60±0.41 24.74±0.38 22.90±0.31 21.90±0.31 22.70±0.11 23.0±0.13 |
| The cyclophosphamide group | 12 | 0.78±0.21 * | 69.04 | 21.15±0.19 |
Annotate: with model group contrast, * P＜0.01.
4.3 om observation result
Under the light microscopic, each group of visible prescription and positive controls part cell volume diminish karyopycnosis, the nuclei dyeing chromaticness concentrates, the limit collection, and part oncocyte differentiation degree is higher, is the lobules of liver shape and changes, and the model group cell is rounded or oval, and nucleus is justified the caryoplasm large percentage greatly.
4.4 electron microscopic observation result
Prescription each group and positive controls part tumor cell nucleus chromatin margination are crescent, and chromatin concentrates, solidifies, nuclear deformity, organelle structural integrities such as mitochondrion, visible apoptotic body.Electromicroscopic photograph can be seen the macrophage phagocytic apoptotic cell, and model group does not see that this phenomenon takes place.
4.5 TUNEL testing result
In each group of prescription and the positive controls part cell, all can see blue-purple granule, and its nucleus also presents different morphological changes.Do not see this phenomenon in the model group cell.Each treatment group apoptotic index all is higher than model group, and difference has significance (P＜0.01).See Table 2.
Table 2 couple H
22The tumor model mouse tumor is organized the influence (x ± s) of apoptotic index
| Group | n | Apoptotic index |
| The blank group of the model group medicinal extract group medicinal extract group medicinal extract group medicinal extract group 5. medicinal extract group endoxan group of writing out a prescription of writing out a prescription 4. of writing out a prescription 3. of writing out a prescription 2. of writing out a prescription 1. | 14 14 11 12 13 13 12 12 | 2.47±1.21 0 22.74±1.71* 24.25±1.34* 20.05±2.23* 21.13±1.30* 22.21±1.31* 26.65±4.16* |
Annotate: with model group contrast, * P＜0.01.
5 these laboratory observations all have obvious inhibitory action to the tumor growth of tumor-bearing mice to each prescription group, its average tumor is heavily compared with model group, and all there were significant differences (P＜0.01), the research of the Chinese medicine compound side of tearing open has two kinds of different approaches, the one, the applied mathematics pattern instructs, the 2nd, cooperate by different method of treatment under the instruction of Chinese Medicine theory and monarch and to carry out prescription research, the latter is at present the most frequently used, and has obtained certain progress.
The specific embodiment:
Specific embodiment is as follows, includes but not limited to the following example.
Embodiment 1
It is characterized in that containing four kinds of Chinese medicines, Radix Ginseng, Fructus Bruceae, Rhizoma Curcumae and Semen Coicis.(prescription 1.)
Being prepared as follows of injection:
The preparation method of Radix Ginseng active component is: take by weighing ginseng crude drug 1200g, decoct with water twice, each amount of water is respectively 8 times of amounts, 6 times of amounts, and extracting solution is centrifugal by tube centrifuge, and centrifugal liquid is crossed D
101Macroporous resin adsorption is collected effluent, and device is preserved in addition; Macroporous resin washes with water to effluent light color, and reuse 70% ethanol carries out eluting, collects eluent, concentrating under reduced pressure, and spray drying, dry powder 90% alcohol reflux, extracting solution reclaims ethanol, is condensed into cream, and drying gets Radix Ginseng active component 22.1g.Get the macroporous resin effluent, cross 732 storng-acid cation exchange resins, effluent is evaporated in right amount, adding ethanol to determining alcohol is more than 80%, the leaching precipitation, and precipitate is with 80% washing with alcohol, continue and use washing with acetone, cold drying to get Radix Ginseng active component 15.9g.
The preparation of Fructus Bruceae active component: get Fructus Bruceae 250g, be ground into coarse powder, the acetone extraction secondary that adds 3.5 times of amounts, 3.0 times of amounts respectively merges acetone solution, reclaim under reduced pressure acetone, the petroleum ether dissolution that adds 1 times of amount, the activated carbon of adding 0.8% reclaimed 30 minutes, and cooling is after decarburization, filter, having reclaimed must Fructus Bruceae active component 28.2ml behind the petroleum ether.
The preparation of Rhizoma Curcumae active component: get Rhizoma Curcumae 1500g, be ground into coarse powder, add the water extraction 6 hours of 15 times of amounts, collect distillate, distillate carries out distillation second time, must Oleum Curcumae 18.4ml.
The preparation of Semen Coicis active component: get Semen Coicis 3000g, be ground into coarse powder, add the acetone extraction three times of 3 times of amounts, 2.5 times of amounts, 2.5 times of amounts respectively, merge acetone solution, reclaim under reduced pressure acetone, the petroleum ether dissolution that adds 1 times of amount, the decolorizing with activated carbon of adding 1.0% is after decarburization, filter, filtrate adds 2% sodium hydroxide solution eluting of 2.0 times of amounts, 1.5 times of amounts respectively, is washed to neutrality again, reclaimed behind the petroleum ether Semen Coicis active component 15.1ml.
Two kinds of active component getting Radix Ginseng add an amount of water for injection and fully dissolve, and get refining fabaceous lecithin 11.0g again and mix twice of usefulness colloid mill homogenize with the water for injection of warm two kinds of Radix Ginseng active component of glycerol 18ml and adding, it is uniformly dispersed, added warm Fructus Bruceae active component, Rhizoma Curcumae active component, Semen Coicis active component insulated and stirred 30 minutes, and made into primary emulsion, add water for injection to 1000ml, change in the colloid mill homogenize again over to three times, filter, get filtrate, embedding, sterilization, promptly.
Being prepared as follows of soft capsule preparation:
The preparation method of Radix Ginseng active component is: take by weighing ginseng crude drug 1200g, decoct with water twice, each amount of water is respectively 8 times of amounts, 6 times of amounts, and extracting solution is centrifugal by tube centrifuge, and centrifugal liquid is crossed D
101Macroporous resin adsorption is collected effluent, and device is preserved in addition; Macroporous resin washes with water to effluent light color, and reuse 70% ethanol carries out eluting, collects eluent, concentrating under reduced pressure, and spray drying, dry powder 90% alcohol reflux, extracting solution reclaims ethanol, is condensed into cream, and drying gets Radix Ginseng active component 21.5g.Get the macroporous resin effluent, cross 732 storng-acid cation exchange resins, effluent is evaporated in right amount, adding ethanol to determining alcohol is more than 80%, the leaching precipitation, and precipitate is with 80% washing with alcohol, continue and use washing with acetone, cold drying to get Radix Ginseng active component 15.1g.
The preparation of Fructus Bruceae active component: get Fructus Bruceae 250g, be ground into coarse powder, the acetone extraction secondary that adds 3.5 times of amounts, 3.0 times of amounts respectively merges acetone solution, reclaim under reduced pressure acetone, the petroleum ether dissolution that adds 1 times of amount, the activated carbon of adding 0.8% reclaimed 30 minutes, and cooling is after decarburization, filter, having reclaimed must Fructus Bruceae active component 27.3ml behind the petroleum ether.
The preparation of Rhizoma Curcumae active component: get Rhizoma Curcumae 1500g, be ground into coarse powder, add the water extraction 6 hours of 15 times of amounts, collect distillate, distillate carries out distillation second time, must Oleum Curcumae 19.0ml.
The preparation of Semen Coicis active component: get Semen Coicis 3000g, be ground into coarse powder, add the acetone extraction three times of 3 times of amounts, 2.5 times of amounts, 2.5 times of amounts respectively, merge acetone solution, reclaim under reduced pressure acetone, the petroleum ether dissolution that adds 1 times of amount, the decolorizing with activated carbon of adding 1.0% is after decarburization, filter, filtrate adds 2% sodium hydroxide solution eluting of 2 times of amounts, 1.5 times of amounts respectively, is washed to neutrality again, reclaimed behind the petroleum ether Semen Coicis active component 15.2ml.
Get above four kinds of active component and add a certain amount of substrate and make emulsion, make 1000 soft capsules with pressing, aluminum-plastic packaged.
Embodiment 2
It is characterized in that containing five kinds of Chinese medicines: Radix Ginseng, Fructus Bruceae, Rhizoma Curcumae, Semen Coicis and Mylabris.(prescription 2.)
Being prepared as follows of injection:
The preparation method of Radix Ginseng active component is: take by weighing ginseng crude drug 1200g, decoct with water twice, each amount of water is respectively 8 times of amounts, 6 times of amounts, and extracting solution is centrifugal by tube centrifuge, and centrifugal liquid is crossed D
101Macroporous resin adsorption is collected effluent, and device is preserved in addition; Macroporous resin washes with water to effluent light color, and reuse 70% ethanol carries out eluting, collects eluent, concentrating under reduced pressure, and spray drying, dry powder 90% alcohol reflux, extracting solution reclaims ethanol, is condensed into cream, and drying gets Radix Ginseng active component 21.8g.Get the macroporous resin effluent, cross 732 storng-acid cation exchange resins, effluent is evaporated in right amount, adding ethanol to determining alcohol is more than 80%, the leaching precipitation, and precipitate is with 80% washing with alcohol, continue and use washing with acetone, cold drying to get Radix Ginseng active component 14.5g.
The preparation of Fructus Bruceae active component: get Fructus Bruceae 250g, be ground into coarse powder, the acetone extraction secondary that adds 3.5 times of amounts, 3.0 times of amounts respectively merges acetone solution, reclaim under reduced pressure acetone, the petroleum ether dissolution that adds 1 times of amount, the activated carbon of adding 0.8% reclaimed 30 minutes, and cooling is after decarburization, filter, having reclaimed must Fructus Bruceae active component 27.6ml behind the petroleum ether.
The preparation of Rhizoma Curcumae active component: get Rhizoma Curcumae 1500g, be ground into coarse powder, add the water extraction 6 hours of 15 times of amounts, collect distillate, distillate carries out distillation second time, must Oleum Curcumae 19.0ml.
The preparation of Semen Coicis active component: get Semen Coicis 3000g, be ground into coarse powder, add the acetone extraction three times of 3 times of amounts, 2.5 times of amounts, 2.5 times of amounts respectively, merge acetone solution, reclaim under reduced pressure acetone, the petroleum ether dissolution that adds 1 times of amount, the decolorizing with activated carbon of adding 1.0% is after decarburization, filter, filtrate adds 2% sodium hydroxide solution eluting of 2 times of amounts, 1.5 times of amounts respectively, is washed to neutrality again, reclaimed behind the petroleum ether Semen Coicis active component 14.8ml.
The preparation of Mylabris active component: get Mylabris 12g and be ground into coarse powder, the hydrochloric acid solution that adds 10 times of amounts 10% carries out percolation, and the acetone that percolate adds 10 times of amounts carries out merceration, and cooling bath filters, reclaim acetone to 1/6 of original volume, get grease, place natural crystallize, separate precipitate, with a spot of petroleum ether-dehydrated alcohol (1: 1) washing, oven drying at low temperature gets Mylabris active component 0.11g.
Two kinds of active component getting Radix Ginseng add an amount of water for injection and fully dissolve, getting refining fabaceous lecithin 11.0g again mixes with the warm glycerol 18ml and the water for injection of two kinds of Radix Ginseng active component of adding, with twice of colloid mill homogenize, it is uniformly dispersed, added warm Fructus Bruceae active component, Rhizoma Curcumae active component, Semen Coicis active component and Mylabris active component insulated and stirred 30 minutes, make into primary emulsion, add water for injection to 1000ml, change in the colloid mill homogenize again over to three times, filter, get filtrate, embedding, sterilization, promptly.
The preparation method of drop pill is as follows:
The preparation method of Radix Ginseng active component is: take by weighing ginseng crude drug 1200g, decoct with water twice, each amount of water is respectively 8 times of amounts, 6 times of amounts, and extracting solution is centrifugal by tube centrifuge, and centrifugal liquid is crossed D
101Macroporous resin adsorption is collected effluent, and device is preserved in addition; Macroporous resin washes with water to effluent light color, and reuse 70% ethanol carries out eluting, collects eluent, concentrating under reduced pressure, and spray drying, dry powder 90% alcohol reflux, extracting solution reclaims ethanol, is condensed into cream, and drying gets Radix Ginseng active component 23.0g.Get the macroporous resin effluent, cross 732 storng-acid cation exchange resins, effluent is evaporated in right amount, adding ethanol to determining alcohol is more than 80%, the leaching precipitation, and precipitate is with 80% washing with alcohol, continue and use washing with acetone, cold drying to get Radix Ginseng active component 14.2g.
The preparation of Fructus Bruceae active component: get Fructus Bruceae 250g, be ground into coarse powder, the acetone extraction secondary that adds 3.5 times of amounts, 3.0 times of amounts respectively merges acetone solution, reclaim under reduced pressure acetone, the petroleum ether dissolution that adds 1 times of amount, the activated carbon of adding 0.8% reclaimed 30 minutes, and cooling is after decarburization, filter, having reclaimed must Fructus Bruceae active component 27.8ml behind the petroleum ether.
The preparation of Rhizoma Curcumae active component: get Rhizoma Curcumae 1500g, be ground into coarse powder, add the water extraction 6 hours of 15 times of amounts, collect distillate, distillate carries out distillation second time, must Oleum Curcumae 18.2ml.
The preparation of Semen Coicis active component: get Semen Coicis 3000g, be ground into coarse powder, add the acetone extraction three times of 3 times of amounts, 2.5 times of amounts, 2.5 times of amounts respectively, merge acetone solution, reclaim under reduced pressure acetone, the petroleum ether dissolution that adds 1 times of amount, the decolorizing with activated carbon of adding 1.0% is after decarburization, filter, filtrate adds 2% sodium hydroxide solution eluting of 2 times of amounts, 1.5 times of amounts respectively, is washed to neutrality again, reclaimed behind the petroleum ether Semen Coicis active component 14.5ml.
The preparation of Mylabris active component: get Mylabris 12g and be ground into coarse powder, the hydrochloric acid solution that adds 10 times of amounts 10% carries out percolation, and the acetone that percolate adds 10 times of amounts carries out merceration, and cooling bath filters, reclaim acetone to 1/6 of original volume, get grease, place natural crystallize, separate precipitate, with a spot of petroleum ether-dehydrated alcohol (1: 1) washing, oven drying at low temperature gets Mylabris active component 0.10g.
Get Fructus Bruceae, Oleum Curcumae and Semen Coicis active component and carry out enclose with 8 times of amount beta-schardinger dextrin-s, the clathrate cold drying promptly, with Radix Ginseng active components A, B, Mylabris mix homogeneously, the PEG400 that adds recipe quantity puts into the vessel in heating dissolving, jolting, make and dissolve into uniform solution, insert in the fluid reservoir.Keep 80 ℃ the system of dripping temperature, and a control speed, condensed fluid is a liquid paraffin, the system of dripping promptly gets 1000.
Embodiment 3
It is characterized in that containing five kinds of Chinese medicines, Radix Ginseng, Fructus Bruceae, Rhizoma Curcumae, Semen Coicis and Bufo siccus.(prescription 3.)
Being prepared as follows of injection:
The preparation method of Radix Ginseng active component is: take by weighing ginseng crude drug 1200g, decoct with water twice, each amount of water is respectively 8 times of amounts, 6 times of amounts, and extracting solution is centrifugal by tube centrifuge, and centrifugal liquid is crossed D
101Macroporous resin adsorption is collected effluent, and device is preserved in addition; Macroporous resin washes with water to effluent light color, and reuse 70% ethanol carries out eluting, collects eluent, concentrating under reduced pressure, and spray drying, dry powder 90% alcohol reflux, extracting solution reclaims ethanol, is condensed into cream, and drying gets Radix Ginseng active component 20.9g.Get the macroporous resin effluent, cross 732 storng-acid cation exchange resins, effluent is evaporated in right amount, adding ethanol to determining alcohol is more than 80%, the leaching precipitation, and precipitate is with 80% washing with alcohol, continue and use washing with acetone, cold drying to get Radix Ginseng active component 13.6g.
The preparation of Fructus Bruceae active component: get Fructus Bruceae 250g, be ground into coarse powder, the acetone extraction secondary that adds 3.5 times of amounts, 3.0 times of amounts respectively merges acetone solution, reclaim under reduced pressure acetone, the petroleum ether dissolution that adds 1 times of amount, the activated carbon of adding 0.8% reclaimed 30 minutes, and cooling is after decarburization, filter, having reclaimed must Fructus Bruceae active component 27.5ml behind the petroleum ether.
The preparation of Rhizoma Curcumae active component: get Rhizoma Curcumae 1500g, be ground into coarse powder, add the water extraction 6 hours of 15 times of amounts, collect distillate, distillate carries out distillation second time, must Oleum Curcumae 18.5ml.
The preparation of Semen Coicis active component: get Semen Coicis 3000g, be ground into coarse powder, add the acetone extraction three times of 3 times of amounts, 2.5 times of amounts, 2.5 times of amounts respectively, merge acetone solution, reclaim under reduced pressure acetone, the petroleum ether dissolution that adds 1 times of amount, the decolorizing with activated carbon of adding 1.0% is after decarburization, filter, filtrate adds 2% sodium hydroxide solution eluting of 2 times of amounts, 1.5 times of amounts respectively, is washed to neutrality again, reclaimed behind the petroleum ether Semen Coicis active component 15.1ml.
Get Bufo siccus 4g and be ground into coarse powder, add an amount of ethanol earlier and run through, in the percolator of packing into, add 4 times of amount soak with ethanol and carry out percolation after 12 hours, percolation to effluent is a light color, collect percolate, reclaim under reduced pressure is finished ethanol, adds the dissolve with ethanol of 0.8 times of amount, the decolorizing with activated carbon of adding 1.0%, after decarburization, filter, having reclaimed must Bufo siccus active component 0.21g behind the ethanol.
Two kinds of active component getting Radix Ginseng add an amount of water for injection and fully dissolve, getting refining fabaceous lecithin 11.0g again mixes with the warm glycerol 18ml and the water for injection of two kinds of Radix Ginseng active component of adding, with twice of colloid mill homogenize, it is uniformly dispersed, added warm Fructus Bruceae active component, Rhizoma Curcumae active component, Semen Coicis active component and Bufo siccus active component insulated and stirred 30 minutes, make into primary emulsion, add water for injection to 1000ml, change in the colloid mill homogenize again over to three times, filter, get filtrate, embedding, sterilization, promptly.
The preparation method of granule:
The preparation method of Radix Ginseng active component is: take by weighing ginseng crude drug 1200g, decoct with water twice, each amount of water is respectively 8 times of amounts, 6 times of amounts, and extracting solution is centrifugal by tube centrifuge, and centrifugal liquid is crossed D
101Macroporous resin adsorption is collected effluent, and device is preserved in addition; Macroporous resin washes with water to effluent light color, and reuse 70% ethanol carries out eluting, collects eluent, concentrating under reduced pressure, and spray drying, dry powder 90% alcohol reflux, extracting solution reclaims ethanol, is condensed into cream, and drying gets Radix Ginseng active component 22.9g.Get the macroporous resin effluent, cross 732 storng-acid cation exchange resins, effluent is evaporated in right amount, adding ethanol to determining alcohol is more than 80%, the leaching precipitation, and precipitate is with 80% washing with alcohol, continue and use washing with acetone, cold drying to get Radix Ginseng active component 14.6g.
The preparation of Fructus Bruceae active component: get Fructus Bruceae 250g, be ground into coarse powder, the acetone extraction secondary that adds 3.5 times of amounts, 3.0 times of amounts respectively merges acetone solution, reclaim under reduced pressure acetone, the petroleum ether dissolution that adds 1 times of amount, the activated carbon of adding 0.8% reclaimed 30 minutes, and cooling is after decarburization, filter, having reclaimed must Fructus Bruceae active component 28.3ml behind the petroleum ether.
The preparation of Rhizoma Curcumae active component: get Rhizoma Curcumae 1500g, be ground into coarse powder, add the water extraction 6 hours of 15 times of amounts, collect distillate, distillate carries out distillation second time, must Oleum Curcumae 19.2ml.
The preparation of Semen Coicis active component: get Semen Coicis 3000g, be ground into coarse powder, add the acetone extraction three times of 3 times of amounts, 2.5 times of amounts, 2.5 times of amounts respectively, merge acetone solution, reclaim under reduced pressure acetone, the petroleum ether dissolution that adds 1 times of amount, the decolorizing with activated carbon of adding 1.0% is after decarburization, filter, filtrate adds 2% sodium hydroxide solution eluting of 2 times of amounts, 1.5 times of amounts respectively, is washed to neutrality again, reclaimed behind the petroleum ether Semen Coicis active component 14.8ml.
Get Bufo siccus 4g and be ground into coarse powder, add an amount of ethanol earlier and run through, in the percolator of packing into, add 4 times of amount soak with ethanol and carry out percolation after 12 hours, percolation to effluent is a light color, collect percolate, reclaim under reduced pressure is finished ethanol, adds the dissolve with ethanol of 0.8 times of amount, the decolorizing with activated carbon of adding 1.0%, after decarburization, filter, having reclaimed must Bufo siccus active component 0.23g behind the ethanol.
Get Fructus Bruceae active component, Oleum Curcumae and Semen Coicis active component and carry out enclose with 8 times of amount beta-schardinger dextrin-s, the clathrate cold drying gets 338.5g, with Radix Ginseng active components A, B active component, Bufo siccus fine powder 4.0g mixing, add a certain amount of adjuvant mix homogeneously, make the 1000g granule, aluminum-plastic packaged.
Embodiment 4
It is characterized in that containing five kinds of Chinese medicines: Radix Ginseng, Fructus Bruceae, Rhizoma Curcumae, Semen Coicis and Fructus Liquidambaris.(prescription 4.)
Being prepared as follows of injection:
The preparation method of Radix Ginseng active component is: take by weighing ginseng crude drug 1200g, decoct with water twice, each amount of water is respectively 8 times of amounts, 6 times of amounts, and extracting solution is centrifugal by tube centrifuge, and centrifugal liquid is crossed D
101Macroporous resin adsorption is collected effluent, and device is preserved in addition; Macroporous resin washes with water to effluent light color, and reuse 70% ethanol carries out eluting, collects eluent, concentrating under reduced pressure, and spray drying, dry powder 90% alcohol reflux, extracting solution reclaims ethanol, is condensed into cream, and drying gets Radix Ginseng active component 22.1g.Get the macroporous resin effluent, cross 732 storng-acid cation exchange resins, effluent is evaporated in right amount, adding ethanol to determining alcohol is more than 80%, the leaching precipitation, and precipitate is with 80% washing with alcohol, continue and use washing with acetone, cold drying to get Radix Ginseng active component 15.0g.
The preparation of Fructus Bruceae active component: get Fructus Bruceae 250g, be ground into coarse powder, the acetone extraction secondary that adds 3.5 times of amounts, 3.0 times of amounts respectively merges acetone solution, reclaim under reduced pressure acetone, the petroleum ether dissolution that adds 1 times of amount, the activated carbon of adding 0.8% reclaimed 30 minutes, and cooling is after decarburization, filter, having reclaimed must Fructus Bruceae active component 27.4ml behind the petroleum ether.
The preparation of Rhizoma Curcumae active component: get Rhizoma Curcumae 1500g, be ground into coarse powder, add the water extraction 6 hours of 15 times of amounts, collect distillate, distillate carries out distillation second time, must Oleum Curcumae 18.5ml.
The preparation of Semen Coicis active component: get Semen Coicis 3000g, be ground into coarse powder, add the acetone extraction three times of 3 times of amounts, 2.5 times of amounts, 2.5 times of amounts respectively, merge acetone solution, reclaim under reduced pressure acetone, the petroleum ether dissolution that adds 1 times of amount, the decolorizing with activated carbon of adding 1.0% is after decarburization, filter, filtrate adds 2% sodium hydroxide solution eluting of 2 times of amounts, 1.5 times of amounts respectively, is washed to neutrality again, reclaimed behind the petroleum ether Semen Coicis active component 14.8ml.
The preparation of Fructus Liquidambaris active component: get Fructus Liquidambaris 6000g and decoct with water secondary, 2 hours for the first time, 1.5 hours for the second time, amount of water was respectively 7 times of amounts, 5 times of amounts, and collecting decoction filters, and filtrate is concentrated into the clear paste that relative density is 1.28 (40 ℃); Add ethanol and make and contain alcohol amount to 75%, left standstill 24 hours, filter, filtrate recycling ethanol also is concentrated into the clear paste that relative density is 1.25 (40 ℃); Qinghuo reagent adds ethanol to be made and contains alcohol amount to 80%, leaves standstill 24 hours, gets supernatant and reclaims ethanol and be concentrated into the thick paste that relative density is 1.29～1.31 (40 ℃), drying.Promptly get Fructus Liquidambaris active component 110.5g.
Getting two kinds of active component of Radix Ginseng and Fructus Liquidambaris active component adds an amount of water for injection and fully dissolves, getting refining fabaceous lecithin 10.0g again mixes with the warm glycerol 16ml and the water for injection of two kinds of Radix Ginseng active component of adding, with twice of colloid mill homogenize, it is uniformly dispersed, added warm Fructus Bruceae active component, Rhizoma Curcumae active component and Semen Coicis active component insulated and stirred 30 minutes, make into primary emulsion, add water for injection to 2000ml, change in the colloid mill homogenize again over to three times, filter, get filtrate, embedding, sterilization, promptly.
Embodiment 5
It is characterized in that containing five kinds of Chinese medicines: Radix Ginseng, Fructus Bruceae, Rhizoma Curcumae, Semen Coicis and Ramulus et folium taxi cuspidatae.(prescription 5.)
Being prepared as follows of injection:
The preparation method of Radix Ginseng active component is: take by weighing ginseng crude drug 1200g, decoct with water twice, each amount of water is respectively 8 times of amounts, 6 times of amounts, and extracting solution is centrifugal by tube centrifuge, and centrifugal liquid is crossed D
101Macroporous resin adsorption is collected effluent, and device is preserved in addition; Macroporous resin washes with water to effluent light color, and reuse 70% ethanol carries out eluting, collects eluent, concentrating under reduced pressure, and spray drying, dry powder 90% alcohol reflux, extracting solution reclaims ethanol, is condensed into cream, and drying gets Radix Ginseng active component 22.4g.Get the macroporous resin effluent, cross 732 storng-acid cation exchange resins, effluent is evaporated in right amount, adding ethanol to determining alcohol is more than 80%, the leaching precipitation, and precipitate is with 80% washing with alcohol, continue and use washing with acetone, cold drying to get Radix Ginseng active component 14.6.0g.
The preparation of Fructus Bruceae active component: get Fructus Bruceae 250g, be ground into coarse powder, the acetone extraction secondary that adds 3.5 times of amounts, 3.0 times of amounts respectively merges acetone solution, reclaim under reduced pressure acetone, the petroleum ether dissolution that adds 1 times of amount, the activated carbon of adding 0.8% reclaimed 30 minutes, and cooling is after decarburization, filter, having reclaimed must Fructus Bruceae active component 28.4ml behind the petroleum ether.
The preparation of Rhizoma Curcumae active component: get Rhizoma Curcumae 1500g, be ground into coarse powder, add the water extraction 6 hours of 15 times of amounts, collect distillate, distillate carries out distillation second time, must Oleum Curcumae 19.0ml.
The preparation of Semen Coicis active component: get Semen Coicis 3000g, be ground into coarse powder, add the acetone extraction three times of 3 times of amounts, 2.5 times of amounts, 2.5 times of amounts respectively, merge acetone solution, reclaim under reduced pressure acetone, the petroleum ether dissolution that adds 1 times of amount, the decolorizing with activated carbon of adding 1.0% is after decarburization, filter, filtrate adds 2% sodium hydroxide solution eluting of 2 times of amounts, 1.5 times of amounts respectively, is washed to neutrality again, reclaimed behind the petroleum ether Semen Coicis active component 14.3ml.
The preparation of Ramulus et folium taxi cuspidatae active component: get Ramulus et folium taxi cuspidatae 50000g, alcohol dipping with 95% is after 48 hours, slowly percolation is collected the liquid of filtering, and 40 ℃ of decompression recycling ethanols are to doing, add water and dichloromethane solution, filter, the reclaim under reduced pressure dichloromethane is to doing, and residue dissolves with ethyl acetate-methanol (3: 1) mixed liquor, adding kieselguhr mixes thoroughly, removal of solvent under reduced pressure in the percolation bucket of packing into, is used earlier the normal hexane percolation, continue and use the dichloromethane percolation, collect the dichloromethane percolate, the reclaim under reduced pressure dichloromethane is to doing, and residue dissolves with ethyl acetate, with silica gel is absorbent, normal hexane-acetone (75: 25) is eluant, and eluting is collected the eluent that contains paclitaxel, reclaim under reduced pressure promptly gets Ramulus et folium taxi cuspidatae active component 50g to doing.
Getting two kinds of active component of Radix Ginseng and Ramulus et folium taxi cuspidatae active component adds an amount of water for injection and fully dissolves, getting refining fabaceous lecithin 12.0g again mixes with the warm glycerol 18ml and the water for injection of two kinds of Radix Ginseng active component of adding, with twice of colloid mill homogenize, it is uniformly dispersed, added warm Fructus Bruceae active component, Rhizoma Curcumae active component and Semen Coicis active component insulated and stirred 30 minutes, make into primary emulsion, add water for injection to 2000ml, change in the colloid mill homogenize again over to three times, filter, get filtrate, embedding, sterilization, promptly.
Claims (10)
1, a kind of Chinese medicine medicine for preventing preparation, its feature is made by following raw material of Chinese medicine, Radix Ginseng, Fructus Bruceae, Rhizoma Curcumae, Semen Coicis also can add in case of necessity and is selected from: the raw material of Chinese medicine of Bufo siccus, Mylabris, Fructus Liquidambaris, Ramulus et folium taxi cuspidatae, prescription is respectively:
The a Radix Ginseng, Fructus Bruceae, Rhizoma Curcumae, Semen Coicis,
The b Radix Ginseng, Fructus Bruceae, Rhizoma Curcumae, Semen Coicis, Bufo siccus,
The c Radix Ginseng, Fructus Bruceae, Rhizoma Curcumae, Semen Coicis, Mylabris,
The d Radix Ginseng, Fructus Bruceae, Rhizoma Curcumae, Semen Coicis, Fructus Liquidambaris,
The e Radix Ginseng, Fructus Bruceae, Rhizoma Curcumae, Semen Coicis, Ramulus et folium taxi cuspidatae.
2, the Chinese medicine preparation of claim 1, it is characterized in that, per 1000 dosage units are made by the following weight proportion raw material: Radix Ginseng 600-9000 part, Fructus Bruceae 120-2000 part, Rhizoma Curcumae 750-9000 part, Semen Coicis 1500-30000 part, 25000～100000 parts of Bufo siccus 2-30 parts, 6～60 parts of Mylabris, Fructus Liquidambaris 3000-9000 part, Ramulus et folium taxi cuspidatae.
3, the Chinese medicine preparation of claim 1, it is characterized in that per 1000 dosage units are made by the following weight proportion raw material: 1200 parts of Radix Ginsengs, 250 parts of Fructus Bruceaes, 1500 parts of Rhizoma Curcumae, 3000 parts of Semen Coiciss, 4 parts of Bufo siccuss, 12 parts of Mylabris, 6000 parts of Fructus Liquidambaris, 50000 parts of Ramulus et folium taxi cuspidatae.
4, the Chinese medicine preparation of claim 1, it is characterized in that, be that described raw material of Chinese medicine is extracted processing, obtain active component, add suitable adjuvant as required, make with the galenic pharmacy routine techniques, wherein said active component is: Radix Ginseng total saponins, ginseng polysaccharide, Oleum Fructus Bruceae, Oleum Curcumae, Semen Coicis oil, bufonin, cantharidin, paclitaxel etc.
5, the Chinese medicine preparation of claim 1 is injection, (soft) capsule, tablet, oral liquid, syrup, granule, pill, powder, unguentum, sublimed preparation, suppository, cream, spray, drop pill, patch, slow releasing preparation or controlled release preparation.
6, the preparation method of the Chinese medicine preparation of claim 4 is characterized in that, described active component prepares through following steps:
The preparation of Radix Ginseng active component: take by weighing the ginseng crude drug, decoct with water twice, each amount of water is 5～8 times of amounts, and extracting solution is centrifugal by tube centrifuge, and centrifugal liquid is crossed D
101Macroporous resin adsorption is collected effluent, and device is preserved in addition; Macroporous resin washes with water to effluent light color, and reuse 50～80% ethanol carry out eluting, collects eluent, concentrating under reduced pressure, and spray drying, dry powder 90% alcohol reflux, extracting solution reclaims ethanol, is condensed into cream, and drying gets dry powder, gets the Radix Ginseng active components A.Get the macroporous resin effluent, cross ion exchange resin, except that behind the deproteinize, effluent is evaporated in right amount, and adding ethanol to determining alcohol is more than 80%, the leaching precipitation, and precipitate continues and uses washing with acetone, cold drying to get Radix Ginseng active component B with 80% washing with alcohol.
The preparation of Semen Coicis active component: get Semen Coicis, be ground into coarse powder, the acetone extraction of 1.5～6 times of amounts three times merges acetone solution, reclaim under reduced pressure acetone, the petroleum ether dissolution that adds 0.5～1 times of amount, the decolorizing with activated carbon of adding 0.5～1.0% is after decarburization, filter, filtrate adds 2% sodium hydroxide solution eluting of 0.5～5 times of amount respectively, is washed to neutrality again, reclaimed behind the petroleum ether the Semen Coicis active component.
The preparation of Fructus Bruceae active component: get Fructus Bruceae, be ground into coarse powder, the acetone extraction secondary that adds 1.5～5 times of amounts respectively, merge acetone solution, reclaim under reduced pressure acetone adds the petroleum ether dissolution of 0.5～1 times of amount, the decolorizing with activated carbon of adding 0.5～1.0%, after decarburization, filter, having reclaimed must the Fructus Bruceae active component behind the petroleum ether.
The preparation of Bufo siccus active component: get Bufo siccus and be ground into coarse powder, add an amount of ethanol earlier and run through, in the percolator of packing into, add 1～5 times of amount soak with ethanol and carry out percolation after 6～15 hours, percolation to effluent is a light color, collect percolate, reclaim under reduced pressure is finished ethanol, adds the dissolve with ethanol of 0.5～1 times of amount, the decolorizing with activated carbon of adding 0.5～1.0%, after decarburization, filter, having reclaimed must the Bufo siccus active component behind the ethanol.
The preparation of Rhizoma Curcumae active component: get Rhizoma Curcumae, be ground into coarse powder, the water extraction of 10～15 times of amounts 4～10 hours is collected distillate, and distillate carries out the distillation second time, gets Oleum Curcumae.
The preparation of Mylabris active component: get powder of cantharide and be broken into coarse powder, the hydrochloric acid solution that adds 5～15 times of amounts 10% carries out percolation, and the acetone that percolate adds 5～10 times of amounts carries out merceration, filters, acetone solution is recycled to 1/6 of original volume, get grease, place natural crystallize, separate precipitate, with a spot of petroleum ether-dehydrated alcohol (1: 1) washing, oven drying at low temperature gets the Mylabris active component.
The preparation of Fructus Liquidambaris active component: get Fructus Liquidambaris and decoct with water secondary, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, and filtrate is concentrated into the clear paste that relative density is 1.25～1.30 (40 ℃); Add ethanol and make and contain alcohol amount to 75%, left standstill 24 hours, filter, filtrate recycling ethanol also is concentrated into the clear paste that relative density is 1.25～1.30 (40 ℃); Qinghuo reagent adds ethanol to be made and contains alcohol amount to 80%, leaves standstill 24 hours, gets supernatant and reclaims ethanol and be concentrated into the thick paste that relative density is 1.29～1.31 (40 ℃), drying.Promptly get the Fructus Liquidambaris active component.
The preparation of Ramulus et folium taxi cuspidatae active component: get Ramulus et folium taxi cuspidatae, alcohol dipping with 75～95% is after 24～50 hours, slowly percolation is collected the liquid of filtering, and 40 ℃ of decompression recycling ethanols are to doing, add water and dichloromethane solution, filter, the reclaim under reduced pressure dichloromethane is to doing, and residue dissolves with ethyl acetate-methanol (3: 1) mixed liquor, adding kieselguhr mixes thoroughly, removal of solvent under reduced pressure in the percolation bucket of packing into, is used earlier the normal hexane percolation, continue and use the dichloromethane percolation, collect the dichloromethane percolate, the reclaim under reduced pressure dichloromethane is to doing, and residue dissolves with ethyl acetate, with silica gel is absorbent, normal hexane-acetone (75: 25) is eluant, and eluting is collected the eluent that contains paclitaxel, reclaim under reduced pressure promptly gets the Ramulus et folium taxi cuspidatae active component to doing.
7, the preparation method of claim 6 also comprises described active component is mixed according to proportioning, adds the medicine acceptable auxiliary, makes the step of pharmaceutical preparation with the galenic pharmacy routine techniques.
8, the preparation method of claim 6, it is characterized in that: the preparation of injection comprises, with water-soluble active ingredient and after water for injection fully dissolves in right amount, getting water-insoluble active component again must fully dissolve by adjuvant with an amount of liposoluble, routine fashion by injection behind both mixings is made injection, wherein the ratio of active component and adjuvant is 1: 0.1～05, and described adjuvant is selected from: refining fabaceous lecithin, tween 80, pluronic F-80, Arlacel-80, Arius acid sodium, sodium sulfite, sodium pyrosulfite, Polyethylene Glycol, propylene glycol, ethanol, glycerol; Wherein the preparation of drop pill comprises, with active constituents of medicine and proper auxiliary materials behind 60-115 ℃ of mix homogeneously, regulate the water dropper size with control drop pill weight, with dimethicone or liquid paraffin is that the coolant system of dripping forms, coolant temperature is-10-5 ℃, wherein the ratio of active component and adjuvant is 1: 0.5～10, described adjuvant be molecular weight between 400 to 10000 Polyethylene Glycol and their mixture, be selected from PEG400 (or 600), Macrogol 2000, Macrogol 4000, polyethylene glycol 6000 or their mixture.Wherein the preparation of soft capsule comprises, with active constituents of medicine and proper auxiliary materials mix homogeneously, obtain uniform suspension and/or solution, regulate content weight, compacting, dry getting final product, its content is made up of active component and suitable substrate, wherein the content of active component is 50mg-500mg in every soft capsule; Substrate wherein is selected from wherein one or more of PEG400, Tween 80, glycerol, propylene glycol, isopropyl alcohol, dehydrogenation soybean oil, vegetable oil, aromatic oil, animal wet goods.
The preparation process of oral liquid: the active component of above-mentioned each medicine gained is added certain amount of fluid dispersion medium, cosolvent, emulsifying agent, correctives composition oral liquid.
The preparation process of granule: with above-mentioned extract obtained, add a certain amount of correctives, filler, lubricant, granulate, promptly get granule.
The preparation process of chewable tablet: with above-mentioned extract obtained, add a certain amount of correctives, filler, lubricant, granulate, drying, tabletting promptly gets chewable tablet.
9, the preparation method of claim 8 is characterized in that: the prescription of the preparation of making is respectively:
The a Radix Ginseng, Fructus Bruceae, Rhizoma Curcumae, Semen Coicis,
The b Radix Ginseng, Fructus Bruceae, Rhizoma Curcumae, Semen Coicis, Bufo siccus,
The c Radix Ginseng, Fructus Bruceae, Rhizoma Curcumae, Semen Coicis, Mylabris,
The d Radix Ginseng, Fructus Bruceae, Rhizoma Curcumae, Semen Coicis, Fructus Liquidambaris,
The e Radix Ginseng, Fructus Bruceae, Rhizoma Curcumae, Semen Coicis, Ramulus et folium taxi cuspidatae.
10, the application of the Chinese medicine preparation of claim 1 in the medicine of multiple malignant tumor such as preparation treatment pulmonary carcinoma, hepatocarcinoma, cervical cancer, digestive tract cancer, leukemia.
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| CN1084206C (en) * | 1999-05-20 | 2002-05-08 | 周金龙 | Cancer treating medicine and its preparation |
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| CN101700394B (en) * | 2009-11-27 | 2013-04-10 | 成都中医药大学 | Pharmaceutical composite for curing colon cancer and preparing method thereof |
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| CN105477554A (en) * | 2015-12-31 | 2016-04-13 | 蒲敬北 | Medicine for treating HPV infection and preventing cervical cancer and preparation method of medicine |
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| CN111346197A (en) * | 2020-01-14 | 2020-06-30 | 河北省沧州中西医结合医院 | Lung tumor stagnation-removing formula |
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