CN100473408C - Heat-clearing and phlegm-resolving medicine composition, preparation and use thereof - Google Patents
Heat-clearing and phlegm-resolving medicine composition, preparation and use thereof Download PDFInfo
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- CN100473408C CN100473408C CNB2005100202235A CN200510020223A CN100473408C CN 100473408 C CN100473408 C CN 100473408C CN B2005100202235 A CNB2005100202235 A CN B2005100202235A CN 200510020223 A CN200510020223 A CN 200510020223A CN 100473408 C CN100473408 C CN 100473408C
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Abstract
A Chinese medicine for antipyresis and resolving phlegm is prepared from fresh P. glauca Mcclure or phyllostachys glance McClure or phyllostanchys nuda McClure and pharmacologically acceptable auxiliary through extracting. Its advantages are high biologic utilization rate, and high quality stability.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition of removing heat-phlegm, particularly, is to be the pharmaceutical composition that feedstock production forms with the plant extract, belongs to drug world.
Background technology
Fresh Succus Bambusae has another name called Succus Bambusae, phyllostachys nigra (lodd.ex lindl.) munro var.henonis (miff.) spapf et rendle drop, vinifera palm oil etc.This product be the bright stalk of grass phyllostachys nigra (lodd.ex lindl.) munro var.henonis (miff.) spapf et rendle or phyllostachys glauca Mcclure with burning roasting bright and effusive juice, be the conventional Chinese medicine of removing heat-phlegm simply.Sweet in the mouth is cold in nature, GUIXIN, lung, stomach warp, the extremely sliding profit of property.The function heat clearing away is separated the sliding expectorant of fire, lung moistening, yin nourishing nourishing, sharp key and is made eye bright, and is usually used in that lung-heat expectorant is stopped up, the expectorant fan is burning hot, the hot infantile convulsion of expectorant, apoplexy locked mouth, unhappiness are quenched one's thirst, all diseases of spontaneous sweating due to deficientcy of blood.According to existing literature report (Zheng Zhanhu etc., " Chinese medicine modern study and application ", medicine garden publishing house), mainly contain several amino acids in the Succus Bambusae, contain the guaiacol of glucose, fructose, sucrose and trace in addition.Aspartic Acid has auxiliary enhance immunity effect, helps the degree of reducing inflammation, so correspondingly secretions reduces.The cystine chemical constitution is similar to expelling phlegm drugses such as acetylcysteine (having another name called acetylcystein) and cysteine tetramethyl esters.When cystine adding reduced glutathion, disulfide bond is reduced to the mercapto key again (SH), can make sputum mucin polypeptide key center disulfide bond (S-S-) short row, thereby make expectorant thinning, viscosity degradation and be easy to expectoration, in addition, methionine can be changed into cysteine and cystine, plays synergism.
The preparation method of tradition Succus Bambusae is bake, is not suitable for the big production of modernization.And volume of production is very little, and through the Succus Bambusae of high temperature bake, the destruction of effective ingredient is a lot, does not meet the effective requirement of medicine.Defective at traditional Succus Bambusae preparation method, the Succus Bambusae production method of existing report, such as: application number: 88102280 " production methods of fresh Succus Bambusae ", this method is that bright bamboo powder is broken, dipping, secondary percolation, percolate are handled fill and formed, this method preparation be Succus Bambusae preparation under the liquid condition.Application number: 90105836 " a kind of preparation methoies of Chinese medicine fresh Succus Bambusae ", this method are that the bamboo stalk is soaked through water or alcohol (in methanol, ethanol, propanol, the n-butyl alcohol any), and ethanol is extracted, reclaimed to heat, liquid Succus Bambusae preparation.Above-mentioned several preparation method all is to extract under the condition of high temperature, is unfavorable for the preservation of effective ingredient, and the processing time is long, causes the loss and the destruction of effective ingredient easily.And present commercially available Succus Bambusae product is prepared by traditional Succus Bambusae method, is oral liquid, and the clinical consumption of its usage is 30ml/ time, Bid, and then every day, amount was 60ml/ people; If people's body weight is in 60kg, then clinical people's consumption is 1.0ml/kg/ day, and clinical consumption is big, and oral liquid carries inconvenience, and dose is difficult for grasping, and liquid preparation is preserved and is difficult for, and easily causes secondary pollution easily in use.
Summary of the invention
Technical scheme of the present invention provides a kind of pharmaceutical composition of removing heat-phlegm, and it is that bright stalk extract with bamboo is the pharmaceutical composition that active component is prepared from, and the present invention also provides this preparation of drug combination method and purposes.
The invention provides a kind of pharmaceutical composition of removing heat-phlegm, it is that water extract by the bright stalk of grass phyllostachys nigra (lodd.ex lindl.) munro var.henonis (miff.) spapf et rendle Phyllostachys nigra (Lodd.) Munro var.henonis (Miff.) Stapfex Rendle or phyllostachys glauca Mcclure Phyllostachys glanca McClure or clean bamboo Phyllostanchys nuda McClure is an active component, adds the preparation that acceptable accessories or complementary composition are prepared from.
Wherein, every 100g contains aspartic acid 80.23mg～110.56mg in the described water extract, cystine 3.54mg～4.98mg, methionine 1.81mg～4.36mg, glutamic acid 53.28mg～85.47mg, serine 8.94mg～11.59mg, valine 5.60mg～7.09mg, isoleucine 2.94mg～3.66mg, tyrosine 6.95mg～8.83mg, phenylalanine-3,4-quinone .94mg～5.50mg, lysine 4.83mg～6.59mg, proline-4 .13mg～6.15mg, threonine 7.01mg～7.98mg, glycine 10.00mg～12.98mg, alanine 20.16mg～25.90mg, leucine 4.85mg～7.16mg, histidine 4.15mg～7.11mg, arginine 3.05mg～4.11mg, total amino acid content 224.41mg～318.02mg; Contain guaiacol 2～10ug in every 1g extract.
Wherein, described preparation is solid preparation, liquid preparation.
Further, described solid preparation is conventional tablet, dispersible tablet, capsule, granule, buccal tablet, slow releasing preparation.Described granule is a sugar-free granule.
Wherein, described slow releasing preparation comprises slow-released part and immediate release section, and wherein slow-released part is to be prepared from by the following weight proportion raw material:
80～120 parts of bamboo extracts, 10～15 parts of ethyl celluloses, 40～60 parts of starch, acrylic acid resin II numbers 10～15 parts.
Further, described slow releasing preparation comprises slow-released part and immediate release section, and wherein slow-released part is to be prepared from by the following weight proportion raw material:
100 parts of bamboo extracts, 15 parts of ethyl celluloses, 50 parts of starch, acrylic acid resin II numbers 10 parts.
Wherein, described dispersible tablet is to contain the following weight proportion raw material to be prepared from:
120～180 parts of bamboo extracts, 6～12 parts of low-substituted hydroxypropyl celluloses, 8～15 parts of microcrystalline Cellulose.
Further, dispersible tablet is to be prepared from by the following weight proportion raw material:
150 parts of bamboo extracts, 9 parts of low-substituted hydroxypropyl celluloses, 12 parts of microcrystalline Cellulose.
Particularly, it is to contain the following weight proportion raw material to be prepared from:
120～180 parts of bamboo extracts, 6～12 parts of low-substituted hydroxypropyl celluloses, 8～15 parts of microcrystalline Cellulose, 4～10 parts of lactose, 4～10 parts in mannitol, 6～12 parts of steviosides, 6～15 parts of magnesium stearate, 60～150 parts of starch.
Further, described dispersible tablet is to contain the following weight proportion raw material to be prepared from:
150 parts of bamboo extracts, 9 parts of low-substituted hydroxypropyl celluloses, 12 parts of microcrystalline Cellulose, 9 parts of lactose, 9 parts in mannitol, 9 parts of steviosides.
The present invention also provides this preparation of pharmaceutical compositions method, and it comprises the steps:
A, get the bright stalk of grass phyllostachys nigra (lodd.ex lindl.) munro var.henonis (miff.) spapf et rendle Phyllostachys nigra (Lodd.) Munro var.henonis (Miff.) Stapfex Rendle or phyllostachys glauca Mcclure Phyllostachys glanca McClure or clean bamboo Phyllostanchysnuda McClure, the decocting that adds 4～8 times of amounts boils, filter, cryoconcentration gets bamboo extract;
B, the bamboo extract that a step is prepared add that acceptable accessories or complementary composition are prepared into solid preparation or liquid preparation pharmaceutically commonly used.
Wherein, the temperature of the described cryoconcentration of step a is: 55～85 ℃, and vacuum pressure: 0.020～0.080MPa.
The present invention also provide described pharmaceutical composition in analgesic, the cough-relieving of preparation, eliminate the phlegm, relieving asthma, the purposes in the antiphlogistic medicine.
Further, described medicine is a lozenge medicine, and described medicine is oral drugs.
Medicine material bamboo extract of the present invention is compared with the fresh Succus Bambusae of traditional bake, raw extract adopts extract at low temperature to concentrate, can avoid the destruction of effective ingredient, can also to greatest extent effective ingredient be kept simultaneously, not only can cover the taste of medicine discomfort, and increased activity, bioavailability improves, wherein, contained Aspartic Acid, cystine, methionine and total amino acid content all is higher than the fresh Succus Bambusae of traditional bake.By pharmacodynamics test explanation, medicine of the present invention has that Succus Bambusae is analgesic, cough-relieving, eliminate the phlegm, relieving asthma, antiphlogistic effect, and refrigeration function is apparently higher than the fresh Succus Bambusae of traditional bake; Medicine material extract of the present invention is prepared into various solid-liquid body preparations, comprise common oral preparation, buccal lozenge, dispersible tablet, slow releasing preparation, the absorption approach is many, the bioavailability height, and steady quality, controllability is strong, and use is carried, be beneficial to and take and take care of, provide new medication to select for clinical.
Obviously, according to foregoing of the present invention,,, can also make modification, replacement or the change of other various ways not breaking away under the above-mentioned basic fundamental thought of the present invention prerequisite according to the ordinary skill knowledge and the customary means of this area.
The specific embodiment of form is described in further detail foregoing of the present invention again 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 example.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.
The specific embodiment
The preparation of embodiment 1 medicine material extract extractum of the present invention
A, phyllostachys glauca Mcclure Fresh bamboo stalk 100g is cut into 2～5cm, put in the 1000ml beaker, add the water of 6 times of amounts, temperature is controlled at 100 ℃, boil and propose decoction in 1.5 hours, decoction liquor is filtered, and filtering residue adds 4 times of water gagings respectively, 100 ℃ of temperature, decocted 1.0 hours, filter, merge filtrate twice, adding distil water is to 1000ml standardize solution (every 1ml is equivalent to bright phyllostachys nigra (lodd.ex lindl.) munro var.henonis (miff.) spapf et rendle 0.1g).
B, the bamboo extract of a step (temperature is below 80 ℃, proportion〉1.01) carried out triple effect concentrate, the Succus Bambusae concentrated solution.Technological parameter: vapour pressure :≤0.10Mpa; Temperature: one imitates: 75--85 ℃; Two imitate: 65--75 ℃; Triple effect: 55--65 ℃; Vacuum: one imitates: 0.020-0.040Mpa; Two imitate: 0.040-0.060Mpa; Triple effect: 0.060-0.080Mpa; Receive cream proportion: 1.10-1.35 (40--80 ℃).
C, drying means: airpillow-dry.
Wherein, the b step adds bamboo extract in the concentrating under reduced pressure jar, and temperature is controlled at 60 ℃, and vacuum pressure is controlled at 0.08Pa, concentrates 6 hours and promptly gets the bamboo extract concentrated solution.
Table 1 contrasts raw material bamboo extract of the present invention and traditional bake Succus Bambusae of embodiment 1 preparation:
| The sample title | Aspartic Acid (mg/100g) | Cystine (mg/100g) | Methionine (mg/100g) | Total amino acid content (mg/100g) |
| Phyllostachys nigra (lodd.ex lindl.) munro var.henonis (miff.) spapf et rendle water extract | 86.94 | 2.84 | 2.21 | 244.94 |
| The fresh Succus Bambusae of tradition bake | 31.64 | 1.90 | Do not detect | 83.61 |
Contain the fresh Succus Bambusae that Aspartic Acid, cystine, methionine and total amino acid content all are higher than traditional bake.
The preparation of embodiment 2 medicine bamboo extract extractum of the present invention
A, Caulis Bambusae In Taeniam Fresh bamboo stalk 100g is cut into 2～5cm, put in the 1000ml beaker, add the water of 6 times of amounts, temperature is controlled at 100 ℃, boil and propose decoction in 1.5 hours, decoction liquor is filtered, and filtering residue adds 4 times of water gagings respectively, 100 ℃ of temperature, decocted 1.0 hours, filter, merge filtrate twice, adding distil water is to 1000ml standardize solution (every 1ml is equivalent to bright phyllostachys nigra (lodd.ex lindl.) munro var.henonis (miff.) spapf et rendle 0.1g).
B, bamboo extract is added in the concentrating under reduced pressure jar, temperature is controlled at 60 ℃, vacuum pressure is controlled at 0.08Pa, concentrates 6 hours and promptly gets the bamboo extract concentrated solution;
C, drying means: airpillow-dry.
By above-mentioned contrast experiment explanation, medicine material extract of the present invention and traditional bake and must fresh Succus Bambusae be incoordinate, raw extract of the present invention obviously is better than traditional Succus Bambusae, and extraction process is simple, cost is low.
The preparation of embodiment 3 medicinal tablets of the present invention
Get an amount of starch and dextrin mixing, spray into the clear paste one-step palletizing of embodiment 1 step b preparation, spraying frequency 4HZ, pressure 0.12MPa, 40～50 ℃ of temperature of charge, 75～85 ℃ of inlet temperature, 70～75 ℃ of leaving air temps.Granule adds 0.5% magnesium stearate mixing, is pressed into 1000, bag film-coat, packing, promptly.
The preparation of embodiment 4 medicinal granules of the present invention (sugar-free)
Get an amount of starch and dextrin mixing, spray into clear paste one-step palletizing, the granulate of embodiment 1 step b preparation, packing, promptly.
The preparation of embodiment 5 medicine dispersible tablets of the present invention
The consumption of supplementary material: Succus Bambusae extractum 150g, low-substituted hydroxypropyl cellulose 9g, microcrystalline Cellulose 12g, lactose 9g, mannitol 9g, stevioside 9g, magnesium stearate 12g, starch 90g, 1%PVP aqueous solution are an amount of, make 1000 altogether, 0.3g/ sheet, every contains Succus Bambusae extractum 150mg.
Preparation method: a, Succus Bambusae extractum, lactose and mannitol mix homogeneously ground 100 mesh sieves jointly, took by weighing low-substituted hydroxypropyl cellulose, starch and microcrystalline Cellulose again and crossed 100 orders respectively, with Succus Bambusae dry extract mixture mix homogeneously, crossed 80 mesh sieves, promptly; B, powder in a step is added 1%PVP solution make soft material, cross 20 mesh sieves and granulate, the grain that will wet is put in the drying baker and is dried to water content less than 9% in 50 ℃-60 ℃.Cross 20 mesh sieve granulate, add magnesium stearate, mixing; C, get granule and carry out semi-finished product inspection in right amount, the qualified back of semi-finished product inspection tabletting is checked tablet weight variation, and is up to specification, makes medicine dispersible tablet of the present invention; D, packing, packing get finished product after the assay was approved.
This reliable preparation process, stable, favorable reproducibility can meet working condition.
Below be kind and the characteristics according to above various dressing, with reference to the prescription of other dispersible tablets, comprehensively the advantage of each prescription is worked out following prescription and is screened.See Table 2
Table 2 medicine dispersible tablet of the present invention prescription screening
Dispersible tablet generally adopts wet granulation technology, and drug dissolution is relevant with the grain diameter size, and particle diameter is small, and the medicine stripping is fast more.The wet grain of dispersible tablet requires below 1mm (about 18 orders), and dried granule granulate requires below 0.6mm (30 order).
Respectively 100 mesh sieves are crossed in extractum pulverizing and adjuvant by each prescription, put mix homogeneously in the container, add the 1%PVP aqueous solution and make soft material, cross 20 mesh sieves and make wet grain, the grain that will wet is put in the drying baker in 50
0C---60
0C is dried to water content less than 9%, crosses 20 mesh sieve granulate, adds magnesium stearate, mix homogeneously, promptly.
Above granule is investigated mobility of particle, investigate indexs such as tablet appearance, disintegration, dispersing uniformity, the results are shown in Table 3.
Table 3 prescription screening result
| The prescription numbering | Outward appearance | Angle of repose | Disintegration | Dispersing uniformity |
| 1 | Yellowish color chips, bright and clean, attractive in appearance | 35 0 | 220s | Up to specification |
| 2 | Yellowish color chips, bright and clean, attractive in appearance | 27.6 0 | 120s | Up to specification |
| 3 | Yellowish color chips, bright and clean, attractive in appearance | 30.2 0 | 156s | Up to specification |
Each achievement data algoscopy side is as follows:
Mobility of particle: usefulness fixedly conical bottom method is measured angle of repose.
Mobile: observe slice, thin piece integrity, fineness, whether bond drift etc.
Disintegration: send out according to Chinese Pharmacopoeia version appendix in 2000 disintegration time mensuration and to measure.
Dispersing uniformity: remove 3 of dispersible tablets, put in the 100ml water and jolt, in 20 ℃ ± 1 ℃ water, all disintegrates and in 3 minutes by No. 2 sieves.
Analysis result: comprehensive 3 prescriptions are investigated the data of index, every indexs such as character, angle of repose, disintegration, dispersing uniformity, and the test result of prescription 2 is ideal, therefore selects prescription 2 for use.Be that Succus Bambusae extractum 150g, low-substituted hydroxypropyl cellulose 9g, microcrystalline Cellulose 12g, lactose 9g, mannitol 9g, stevioside 9g, magnesium stearate 12g, starch 90g, 1%PVP aqueous solution are an amount of, make 1000 altogether, 0.3g/ sheet, every contains Succus Bambusae extractum 150mg, makes 1000.
The preparation of embodiment 6 drug port buccal tablets of the present invention
Raw material and adjuvant: Succus Bambusae extractum 150g, starch 50g, mannitol 75g, citric acid 5g, magnesium stearate 20g, distilled water are an amount of, lemon yellow pigment, essence are an amount of; Make 1000 altogether, the 0.3g/ sheet, every contains Succus Bambusae extractum 150mg.
The screening of supplementary product consumption mainly is in order to regulate the mouthfeel of preparation, getting Succus Bambusae extractum prepares by different amounts with adjuvant, through proportioning repeatedly, the result shows adding starch 50g, mannitol 75g, citric acid 5g, its pelletization of preparation of the ratio preparation of magnesium stearate 20g tablet each side smooth, that extrude all can be up to specification, and sour-sweet suitable, mouthfeel is better.
Preparation method: get Succus Bambusae extractum 150g, add 50-60 ℃ distilled water 1000ml dissolving, filter with 100 mesh sieves the dissolving back, and filtrate is standby as the medicinal liquid slurry.Getting it filled, it is standby to use starch 50g, mannitol 25g, magnesium stearate 20g to cross behind 100 mesh sieves.Operate according to the following steps then: in the material container in the boiling granulating machine of 1, adjuvant being packed into, the medicinal liquid slurry is packed in the transfusion dolly beverage container.2, debugging spray gun: under 0.3～0.4Mpa normal pressure, regulate pump machine flow and nozzle, make evenly no granule of spraying, injection is strong, wide coverage.3, liter opens material container, makes main frame airtight, and temperature controlling range is 25～40 ℃ on the setting temperature controller, opens solenoid valve, heating heat exchange room air.Open the examination air-introduced machine, turn round after 30 seconds, open dry rising, damper mixes the material boiling, when treating that temperature rises to desirable value, sets 18 seconds material shaking time, stops the 100 seconds time of trembling, and setting hydrojet speed is 15～18, begins to granulate.4, drying: 40～45 ℃ of temperature, 1.5～2.5 hours time.5, citric acid, lemon yellow pigment are dissolved in the water, spray into, behind the mix homogeneously, when treating that temperature of charge drops to below 40 ℃, again Fructus Citri Limoniae essence is sprayed into mix homogeneously.Close dry rising and total air door discharging.6, granule is sieved behind the granulate, check, standby.7, tabletting.
The preparation of embodiment 7 slow releasing tablets of the present invention
Prescription:
Make 1000 altogether, the 0.3g/ sheet, every contains Succus Bambusae extractum 150mg
Preparation technology
1, slow-released part is got the fine powder mix homogeneously of ethyl cellulose and acrylic acid resin II number, behind 60% dissolve with ethanol, sprays in the starch, be prepared into fine grained with ebullated bed, then Succus Bambusae extractum medicinal liquid slurry sprayed into, granulate, drying, granulate, standby as the slow-released part granule.
2, immediate release section: Succus Bambusae extractum medicinal liquid slurry is prepared into fine grained with starch through ebullated bed, drying, granulate, standby as the immediate release section granule.
3, granulate: this preparation intends adopting ebullated bed to prepare fine grained, carries out tabletting then.
In the process of granulating with ebullated bed, the concentration of Succus Bambusae extractum medicinal liquid slurry, hydrojet speed, bubbling bed temperature scope are the principal elements that influences granular mass, so we have carried out orthogonal experiment to above factor.
Experimental result shows that ethyl cellulose and acrylic acid resin are 12～15 with hydrojet speed behind 60% dissolve with ethanol II number, and medicinal liquid slurry concentration is 50mg/ml, and hydrojet speed is 15～18, and when the bubbling bed temperature scope was 25～40 ℃, the granular mass of preparation was best.So select above production technology in process of production.
Amino acid whose quality control in embodiment 8 medicines of the present invention:
Glutamic acid reference substance: middle inspection institute lot number: 11576-200201, serine reference substance: middle inspection institute lot number: 624-200104
Get this product 0.5g, add water 20ml, supersound process 10 minutes, filter, filtrate is added on the 732 type cation exchange resin columns of having handled well (internal diameter 1cm, long 10cm), wash with water to eluent sugar-free reaction and (get eluent 1ml, add 3 of a-naphthols test solutions, add 5 in sulphuric acid along tube wall, two liquid answer the redfree ring to produce at the interface), reuse 2mol/L ammonia solution 40ml eluting is collected eluent, evaporate to dryness, residue adds normal propyl alcohol solution (1 → 10) 1ml makes dissolving, as need testing solution.Other gets glutamic acid, serine reference substance, adds normal propyl alcohol solution (1 → 10) and makes the mixed solution that every 1ml contains 1mg, in contrast product solution.According to thin layer chromatography (" appendix VIB of Chinese pharmacopoeia version in 2000) test, draw each 1～2 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate with the preparation of 0.2mol/L potassium dihydrogen phosphate, with n-butyl alcohol-glacial acetic acid-water (8:3:1) is developing solvent, launch, take out, dry, spray is with ninhydrin solution, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show two identical punctations.
Studies show that contain several amino acids in the Succus Bambusae, wherein glutamic acid and serine content are higher, see Table 4.So with reference to the method for Succus Bambusae capsule pharmaceutical standard, adopt thin layer chromatography to differentiate, select the higher glutamic acid of content, serine reference substance for use in contrast, specificity is strong, favorable reproducibility, the sample treatment of selecting for use, can remove interfering components, make thin layer speckle separator well.
Table 4 bamboo juice analysis of amino acids table
Done simultaneously the negative sample of Succus Bambusae again by prescription, negative sample does not produce interference not having corresponding speckle with reference substance chromatograph corresponding position as a result.
The preparation precision of reference substance solution takes by weighing 105 ℃ of glutamic acid reference substance 10mg that are dried to constant weight, puts in the 50ml measuring bottle, is dissolved in water and is diluted to scale, shake up, precision is measured 15ml and is put in the 50ml measuring bottle, and thin up is to scale, shake up, promptly get (every 1ml contains glutamic acid 60 μ g).
The preparation precision of standard curve is measured reference substance solution 0.0,0.2,0.4,0.6,0.8,1.0ml put respectively in the 10ml tool plug test tube, add water and make into 1.0ml, add 0.2mol/L citrate salt buffer (PH5.0) 1.0ml, add 1% ascorbic acid solution 0.1ml and 2% 1,2,3-indantrione monohydrate ethylene glycol monomethyl ether solution 3.0ml, shake up, be covered in tool plug test tube top with a sizeable clean gauze, with linear system tight (avoiding extrusion), put heating taking-up in 15 minutes in the water-bath, put and be chilled to room temperature in the cold water, add 60% ethanol 3.0ml, shake up, with first part is blank, according to spectrophotography (" appendix VB of Chinese pharmacopoeia version in 2000) test, measure trap at 570nm wavelength place, be vertical coordinate with the trap, concentration is abscissa, the drawing standard curve.
Algoscopy is got the content under this product content uniformity, and porphyrize is got about 1g, and accurate the title decides, and puts in the tool plug conical flask, precision adds water 50ml, and supersound process 10 minutes filters, and discards filtrate just, precision is measured subsequent filtrate 3ml, puts in the 25ml measuring bottle, and thin up shakes up to scale.Precision is measured 1ml, puts in the 10ml tool plug test tube method under the sighting target directrix curve preparation, from " adding citrate salt buffer (PH5.0) 1.0ml ", measure trap, the weight (μ g) of reading glutamic acid the need testing solution from standard curve in accordance with the law, calculate, promptly.
Every of this product contains total amino acids with glutamic acid (C
5H
9NO
4) meter, must not be less than 3.0mg.
The method of quality control of embodiment 9 drug extract guaiacol of the present invention
Instrument and Tianjin, reagent island SPD-10A UV-detector; Tianjin, island SPD-10A high performance liquid chromatogram pump; Sartorious CP225-D type electronic balance (100,000/, Germany
Company); KQ-100DE numerical control supersonic washer (Kunshan Ultrasonic Instruments Co., Ltd.).Methanol, acetonitrile are chromatographically pure, double distilled water, and all the other reagent are analytical pure.
[assay] photograph high performance liquid chromatography (" 2000 editions appendix VID of Chinese pharmacopoeia) measure.
Chromatographic condition and system suitability test enlightening agate C
18(15*4.5) post; Octadecyl silane is a filler; The detection wavelength is 276nm; Acetonitrile-water (volume ratio 20: 80) is as mobile phase; Theoretical cam curve guaiacol peak calculates should be lower than 3000.
It is an amount of that the guaiacol reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds methanol and makes the solution that every 1ml contains about 5ug.
The preparation of need testing solution is got the about 10g of capsule 's content and is put in the 250ml beaker, adding water about 100 stirs, supersound process 15 minutes, sucking filtration, filter paper and residue (going in the beaker with a spot of washing) are transferred in the beaker in the lump, in beaker, add about 100ml water again and stirred supersound process 15 minutes, repeated treatments 4 times.Collecting sucking filtration liquid puts in the flask of 1000ml by determination of volatile oil method (appendix XD, add ethyl acetate 1.5ml in the side pipe) measure, extract 5 times, add ethyl acetate 1.5ml at every turn, extracted 1 hour at every turn, treat ethyl acetate layer clarification after, ethyl acetate layer is transferred in the same 10ml measuring bottle, be diluted to scale with ethyl acetate, shake up, promptly.
Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, adopt double pump geopressure gradient elution process, when guaiacol reference substance appearance time, use pure acetonitrile eluting instead after 10 minutes, recover mobile phase, the balance baseline is measured, promptly.
Contain guaiacol 2～10ug in every 1g extract.
It is the index composition that aminoacid and guaiacol are adopted in drug quality control of the present invention simultaneously, and wherein aminoacid is the more composition of content in the medicine material extract of the present invention, but aminoacid is conventional index, only is quality control index with aminoacid, and specific aim is not strong; Though guaiacol content is few, therefore this, measure two constituents simultaneously as effective ingredient, reaches the purpose of quality control, and controllability is strong.
Below prove beneficial effect of the present invention by pharmacodynamics test.
Test example 1 medicine of the present invention is separated heat test
1, is subjected to the reagent thing
Medicine embodiment 1 preparation of the present invention.
Fresh Succus Bambusae: lot number 021201 is given birth to pharmaceutical Co. Ltd by the Sichuan Ji and is produced, and clinical consumption is 30ml/ time, Bid, and then every day, amount was 60ml/ people; If people's body weight is in 60kg, then clinical people's consumption is 1.0ml/kg/ day.
Phenacetin+caffeine+aspirin: lot number 021103, every contains aspirin 0.22g, phenacetin 0.15g, caffeine 0.035g, produced by Chengdu pharmacy one factory, grind to form fine powder, being mixed with every 1ml with distilled water, to contain the suspension of aspirin 0.0075g standby.
2, main agents
Bacterial endotoxin lot number 962, the 7200EU/ ampoule is provided by Nat'l Pharmaceutical ﹠ Biological Products Control Institute.Facing the time spent is diluted with water to 120EU/ml solution with the bacterial endotoxin inspection.
3, animal
Rabbit, body weight 2.45 ± 0.5kg, health, the male and female dual-purpose, female person does not have pregnant, is provided by laboratory animal quality monitoring center, Sichuan Province.
4, method and result
Get rabbit, did the adaptability temperature taking in continuous two days before the administration, choose body temperature in 38.4-39.5 ℃ of scopes, and the body temperature fluctuation is no more than 0.4 ℃ rabbit use in pretest in two days.Administration same day.Test normal body temperature again, select the most last twice body temperature to be no more than 0.2 ℃ of rabbit and be divided into 5 groups at random, every group of 6 rabbit.Gastric infusion: give APC suspension 0.15g (aspirin)/kg (be equivalent to clinical adult's ampoule 20 times) for one group; Give fresh Succus Bambusae 20ml/kg (be equivalent to clinical adult's one consumption per day 20 times) for two groups; Give medicine high concentration suspension 12.4g crude drug in whole/kg of the present invention (be equivalent to clinical adult's one consumption per day 20 times) for three groups; Give medicine low concentration suspension 6.2g crude drug in whole/kg of the present invention for four groups, (be equivalent to clinical adult's one consumption per day 10 times); Make blank to distilled water for five groups, each is organized the administration volume and is 20ml/kg, after the administration, gives every tame rabbit ear vein bacterial injection endotoxin solution, 1ml/kg immediately.Measure injection back 0.5,1,2,3,4,5,6, hour each rabbit body temperature, actual measurement body temperature with each time point deducts the intensification value that the normal body temperature that records before the administration gets each time point rabbit, learn by statistics and handle, investigate each administration group rabbit body temperature rising and compare, there was no significant difference is arranged with the blank group.
Table 5 medicine of the present invention is to the influence of fever in rabbits due to the bacterial endotoxin
*p<0.05 **p<0.01
The result shows: medicine of the present invention has significant difference in the rising of inhibition rabbit body temperature with blank group and fresh Succus Bambusae positive controls.
Test example 2 medicines of the present invention are to the cough-relieving test of mice
1, is subjected to the reagent thing
Medicine embodiment 1 preparation of the present invention (clinical people's consumption is that then clinical people's consumption is 0.62g crude drug in whole/kg/ day in body weight 60kg)
Fresh Succus Bambusae: lot number 021201 is given birth to pharmaceutical Co. Ltd by the Sichuan Ji and is produced, and clinical consumption is 30ml/ time, Bid, and then every day, amount was 60ml/ people; If people's body weight is in 60kg, then clinical people's consumption is 1.0ml/kg/ day.
Cough-relieving: lot number 020914, the 0.3g/ grain, wonderful clever Pharmaceutical Co produces by Guizhou, and the suspension that is mixed with 0.0015g/ml concentration with distilled water is standby.Clinical people's consumption is 0.9g/ time, Bid, and then every day, amount was 1.8g/ people; If people's body weight is in 60kg, then clinical people's consumption is 0.03g/kg/ day.
2, main agents
Ammonia lot number 990505-1, east, Chongqing chemical reagent work produces.
3, animal
Kunming kind white mice, body weight 19-22g, health, male and female half and half are provided by laboratory animal quality monitoring center, Sichuan Province.
4, method
Get 60 of white mice, be divided into 6 groups at random, one or two groups as positive drug control group, and gastric infusion gives cough-relieving 0.3g/kg (be equivalent to clinical people's consumption 10 times) respectively, fresh Succus Bambusae 10ml/kg (be equivalent to clinical people's consumption 10 times); Three, four, five groups respectively as the high, medium and low dosage group of medicine of the present invention, irritates stomach respectively and gives medicine 9.3g 4.65g 2.32g crude drug in whole/kg of the present invention; Six groups as blank, irritates the saline that stomach gives equal volume; Each is organized and only irritates stomach 0.4ml/ every day, and continuous 2 days, after 1 hour, mice is put into container in the last administration, spray into quantitative strong aqua ammonia aerosol at certain hour, observe the cough reaction of mice, the number of times of record cough latent period and cough in 1 minute.
5, result
Table 6 medicine of the present invention is to the antitussive action of mice
| Group | Number of animals (n) | Cough latent period (second) * ± SD | The cough number of times * ± SD |
| Cough-relieving positive drug group | 10 | 18.6±4.38 * | 15.3±6.8 * |
| The positive group of fresh Succus Bambusae | 10 | 19.5±3.92 * | 9.78±2.78 * |
| Medicine high dose group of the present invention | 10 | 18.5±5.64 * | 13.5±6.57 * |
| Dosage group in the medicine of the present invention | 10 | 16.6±3.03 * | 16.8±7.3 * |
| Medicine low dose group of the present invention | 10 | 13.1±3.81 * | 21.5±9.03 * |
| The blank group | 10 | 7.56±2.07 | 40.8±6.99 |
In the table:
*P＜0.01-p〉0.05+p＜0.05
Experimental result shows that through significant t-test the high, medium and low dosage of medicine of the present invention all can prolong the mouse cough latent time and reduce the cough number of times by highly significant; Effect and cough-relieving, fresh Succus Bambusae are identical.
The experiment of eliminating the phlegm of test example 3
1, is subjected to the reagent thing
Medicine of the present invention is by embodiment 1 preparation (clinical people's consumption is that then clinical people's consumption is 0.62g crude drug in whole/kg/ day in body weight 60kg)
Fresh Succus Bambusae: lot number 021201 is given birth to pharmaceutical Co. Ltd by the Sichuan Ji and is produced, and clinical consumption is 30ml/ time, Bid, and then every day, amount was 60ml/ people; If people's body weight is in 60kg, then clinical people's consumption is 1.0ml/kg/ day.
Ammonium chloride: lot number 020931, Chengdu chemical plant are near a river produced, and clinical people's consumption is 0.6g/ time, Bid, and then every day, amount was 1.8g/ people; If people's body weight is in 60kg, then clinical people's consumption is 0.03g/kg/ day.
2, main agents
Phenol red lot number 020716, military medical courses in general institute produces, and is made into 5% phenol red solution with normal saline.
3, animal
Kunming kind white mice, body weight 19-22g, health, male and female half and half are provided by laboratory animal quality monitoring center, Sichuan Province.
4, method
Get 60 of white mice, be divided into 6 groups at random, one or two groups as positive drug control group, and gastric infusion gives ammonium chloride 0.3g/kg (be equivalent to clinical people's consumption 10 times) respectively, fresh Succus Bambusae 10ml/kg (be equivalent to clinical people's consumption 10 times); Three, four, five groups respectively as the high, medium and low dosage group of medicine of the present invention, irritates stomach respectively and gives medicine 9.3g 4.65g 2.32g crude drug in whole/kg of the present invention; Six groups as blank, irritates the saline that stomach gives equal volume; Each is organized and only irritates stomach 0.4ml/ every day.For three days on end, in the last administration after 30 minutes, lumbar injection 0.2ml/20g phenol red solution was injected phenol red back 30 minutes, put to death animal, peel off the trachea surrounding tissue, cut one section trachea down to the trachea bifurcation, put into the test tube that fills the 2ml normal saline, add the 1mol/L sodium hydroxide of 0.1ml again from thyroid cartilage, with Tianjin, island UV-2102 PCS type ultraviolet spectrophotometer, measure trap at wavelength 546nm place.
5, result
Table 7 medicine of the present invention is to the phlegm-dispelling functions of mice
| Group | Number of animals (n) | Phenol red absorption value * ± SD | The P value |
| Ammonium chloride positive drug group | 10 | 0.381±0.149 | <0.01 |
| The positive group of fresh Succus Bambusae | 10 | 0.218±0.047 | <0.01 |
| Medicine high dose group of the present invention | 10 | 0.264±0.089 | <0.01 |
| Dosage group in the medicine of the present invention | 10 | 0.239±0.063 | <0.01 |
| Medicine low dose group of the present invention | 10 | 0.222±0.079 | <0.01 |
| The blank group | 10 | 0.099±0.021 |
Experimental result shows that through significant t-test the high, medium and low dosage of medicine of the present invention all can increase the phenol red secretory volume of mice tunica mucosa tracheae by highly significant, promptly has certain phlegm-dispelling functions.Effect and ammonium chloride, fresh Succus Bambusae are identical.
The test of relievining asthma of test example 4
1, is subjected to the reagent thing
Medicine of the present invention: by embodiment 1 preparation (clinical people's consumption is that then clinical people's consumption is 0.62g crude drug in whole/kg/ day in body weight 60kg)
Fresh Succus Bambusae: lot number 021201 is given birth to pharmaceutical Co. Ltd by the Sichuan Ji and is produced, and clinical consumption is 30ml/ time, Bid, and then every day, amount was 60ml/ people; If people's body weight is in 60kg, then clinical people's consumption is 1.0ml/kg/ day.
Cough-relieving: lot number 020914, the 0.3g/ grain, wonderful clever Pharmaceutical Co produces by Guizhou, and the suspension that is mixed with 0.012g/ml concentration with distilled water is standby.Clinical people's consumption is 0.9g/ time, Bid, and then every day, amount was 1.8g/ people; If people's body weight is in 60kg, then clinical people's consumption is 0.03g/kg/ day.
2, main agents
Phosphoric acid organizes ammonium lot number 0210291 Shanghai Inst. of Biochemistry, Chinese Academy of Sciences to produce, and is mixed with 2mg/ml on probation with distilled water.
3, animal
Cavia porcellus, body weight 150--200g, health, male and female all have, and are provided by laboratory animal quality monitoring center, Sichuan Province.
4, method
Get 60 of Cavia porcelluss, be divided into 6 groups at random, one or two groups as positive drug control group, irritates stomach respectively and gives cough-relieving 0.3g/kg (be equivalent to clinical people's consumption 10 times), fresh Succus Bambusae 6ml/kg (be equivalent to clinical people's consumption 6 times); Three, four, five groups respectively as the high, medium and low dosage group of medicine of the present invention, irritates stomach respectively and gives medicine 5.6g of the present invention, 2.8g, 1.4g crude drug in whole/kg; Six groups as blank, irritates the saline that stomach gives equal volume; Each is organized and irritates stomach 1.5ml/100g every day.Continuous 4 days, in the last administration after 1 hour, Cavia porcellus is put into container, spray into quantitative histamine phosphate aerosol at certain hour, observe the asthma reaction of Cavia porcellus, the record spraying begin to the symptom time of occurrence as latent time, " asthma " reaction follow procedure is divided into level Four: the I level is breathed and is quickened, II level dyspnea, the III level is twitched, and the IV level is fallen.Experimental data is handled with grade preface value method (improvement Kiss level method),
5, result
Table 8 medicine of the present invention is to the antiasthmatic effect of Cavia porcellus
| Group | Number of animals | 0 grade | The I level | The II level | The III level | The IV level | The P value |
| Ammonium chloride positive drug group | 10 | 2 | 2 | 2 | 2 | 2 | <0.05 |
| The positive group of fresh Succus Bambusae | 10 | 2 | 2 | 3 | 0 | 3 | <0.05 |
| Medicine high dose group of the present invention | 10 | 3 | 2 | 2 | 2 | 1 | <0.05 |
| Dosage group in the medicine of the present invention | 10 | 2 | 0 | 1 | 4 | 3 | >0.05 |
| Medicine low dose group of the present invention | 10 | 1 | 0 | 3 | 2 | 4 | >0.05 |
| The blank group | 10 | 1 | 0 | 0 | 1 | 8 |
Experimental result shows that medicine high dose group of the present invention can significantly resist the Cavia porcellus asthma due to the phosphoric acid group, and effect and cough-relieving, fresh Succus Bambusae are identical.
The test of test example 5 antiinflammatories
1, is subjected to the reagent thing
Medicine of the present invention is by embodiment 1 preparation, and the time spent is mixed with high, medium and low three concentration suspensions for test with distilled water.(clinical people's consumption is that then clinical people's consumption is 0.62g crude drug in whole/kg/ day in body weight 60kg).
Fresh Succus Bambusae: lot number 021201 is given birth to pharmaceutical Co. Ltd by the Sichuan Ji and is produced, and clinical consumption is 30ml/ time, Bid, and then every day, amount was 60ml/ people; If people's body weight is in 60kg, then clinical people's consumption is 1.0ml/kg/ day.
Aspirin tablet: lot number 020516-2, the 0.3g/ sheet is produced by Leshan Pharmaceutical Factory, Sichuan Prov., grinds to form behind the fine powder that to be mixed with the suspension of 0.015g/ml concentration with distilled water standby.Clinical people's consumption is 0.6g/ time, Bid, and then every day, amount was 1.8g/ people; If people's body weight is in 60kg, then clinical people's consumption is 0.03g/kg/ day.
2, main agents
The ivens orchid faces the time spent and is made into 05% solution.
3, animal
Kunming kind white mice, body weight 19-22g, health, male and female half and half are provided by laboratory animal quality monitoring center, Sichuan Province.
4, method
Get 60 of white mice, be divided into 6 groups at random, one or two groups as positive drug control group, irritates stomach respectively and gives aspirin tablet 0.3g/kg (be equivalent to clinical people's consumption 10 times), fresh Succus Bambusae 10ml/kg (be equivalent to clinical people's consumption 10 times); Three, four, five groups respectively as the high, medium and low dosage group of medicine of the present invention, irritates stomach respectively and gives medicine 9.3g of the present invention, 4.65g, 2.32g crude drug in whole/kg; Six groups as blank, irritates the saline that stomach gives equal volume; Each is organized and only irritates stomach 0.4ml/ every day.For three days on end, in the last administration after 1 hour, the blue 0.2ml/20g mice of intravenous injection 0.5% ivens, lumbar injection 0.6% acetum 0.2ml/ only puts to death animal after 20 minutes immediately, and intraperitoneal injection of saline 6ml/ only, the washing abdominal cavity, collect cleaning mixture, get supernatant after leaving standstill, measure trap at the 590nm place with UV-2102 PCS type ultraviolet spectrophotometer.
5, result
Table 9 medicine of the present invention is to the antiinflammatory action of mice
| Group | Number of animals | Trap * ± SD | The P value |
| The aspirin tablet group | 10 | 0.199±0.038 | <0.01 |
| The positive group of fresh Succus Bambusae | 10 | 0.281±0.081 | <0.01 |
| Medicine high dose group of the present invention | 10 | 0.277±0.075 | <0.01 |
| Dosage group in the medicine of the present invention | 10 | 0.348±0.085 | <0.01 |
| Medicine low dose group of the present invention | 10 | 0.550±0.189 | <0.05 |
| The blank group | 10 | 0.775±0.176 |
Experimental result shows that through significant t-test the high Chinese herbal medicine dosage of medicine of the present invention group can significantly suppress the mice capillary permeability, has certain antiinflammatory action.Effect and aspirin, fresh Succus Bambusae are identical.
Conclusion: medicine of the present invention can suppress the rabbit body temperature rising that vivotoxin causes, has refrigeration function.Can suppress the mouse cough that ammonia causes, have antitussive effect.Can suppress the Cavia porcellus asthma that histamine phosphate causes, have antiasthmatic effect.Can increase the phenol red amount of mouse breathing road mucosa excretion, have the lung moistening phlegm-dispelling functions.Can suppress the permeability of mice blood capillary, have antiinflammatory action.
To sum up the result shows: effects such as Succus Bambusae extractum has analgesic, antitussive, eliminates the phlegm, antiinflammatory, and be better than traditional baking Succus Bambusae than showing in analgesic effect.
The 6 medicine dispersible tablet pharmacokinetics tests of the present invention of test example
1, material and reagent
1.1 instrument: UV-2102 PCS type ultraviolet spectrophotometer
1.2 reagent: medicine dispersible tablet of the present invention (embodiment 4 preparations, lot number 0030101,0.3g/ sheet)
1.3 laboratory animal: the hybrid dog, 8, body weight 12～20kg, male and female are not limit, provide by laboratory animal quality-monitoring center, Sichuan Province.
1.4 sample collecting and processing
Respectively at after 0 time and the administration 0.17,0.25,0.33,0.42,0.50,0.67,1.00,1.50,2.00,3.50,5.50,7.00h venous blood samples 3.5ml, the blood sample of collection is through anticoagulant heparin, and is centrifugal, puts refrigerator and deposits to be equipped with and survey.
1.5 the mensuration of blood drug level
The accurate absorption of the pretreatment of blood sample blood plasma 0.5ml marks liquid (glutamic acid contrast liquid 202ng/ml) 100ul, the sodium hydroxide 100ul of 2.0mol/L in accurate the adding in 10ml point end test tube.With the normal hexane 3.5ml vortex hybrid extraction 6min that contains 3.5% isoamyl alcohol, centrifugal 5min gets upper strata liquid in point end test tube, puts air blow drying in 50 ℃ of water-baths behind the mixing, and residue is dissolved in 100ul mobile phase.Mixing, the 80ul sample introduction.
2, method and result
2.1 detection method
The preparation precision of glutamic acid reference substance solution is measured the glutamic acid reference substance 0.2g that is dried to constant weight through 105 ℃, puts in the 100ml measuring bottle, is dissolved in water and is diluted to scale, shakes up; Precision is measured 20ml, puts in the measuring bottle of 100ml, adds water to scale, shakes up.Contain glutamic acid 40 μ g among every 1ml.
It is an amount of that the preparation precision of test sample is measured this product, adds water and make the solution that contains 40 μ g among every 1ml.
The preparation precision of standard curve is measured reference substance solution 0.0,0.2,0.4,0.6,0.8,1.0ml, put respectively in the 10ml tool plug test tube, add water to 1.0ml, add 0.2mol/L citrate buffer (pH5.0) 1.0ml, add 1% ascorbic acid solution 0.1ml and 2% triketohydrindene hydrate ethylene glycol monomethyl ether solution 3.0ml, shake up, be covered in tool plug test tube top with a sizeable clean gauze, with linear system tight (avoiding extrusion), put heating taking-up in 15 minutes in the water-bath, put and be chilled to room temperature in the cold water, add 60% ethanol 3.0ml, shake up, with first part be blank, according to spectrophotography (appendix VB of Chinese Pharmacopoeia version in 2000) test, wavelength place at 570nm measures trap, with the trap is vertical coordinate, and concentration is abscissa, the drawing standard curve.
Algoscopy is got the content under this product content uniformity, and porphyrize is got about 0.5g, and accurate the title decides, and puts in the tool plug conical flask, precision adds water 50ml, and supersound process 10 minutes filters, and discards filtrate just, precision is measured subsequent filtrate 3ml, puts in the 25ml measuring bottle, and thin up shakes up to scale.Precision is measured 1ml, puts in the 10ml tool plug test tube method under the sighting target directrix curve preparation, from " adding citrate salt buffer (pH5.0) 1.0ml ", measure trap, the weight (μ g) of reading glutamic acid the need testing solution from standard curve in accordance with the law, calculate, promptly.
Every of this product contains aminoacid with glutamic acid (C
5H
9NO
4) meter, must not be less than 3.0mg.
2.2 the interference measurement of adjuvant
Precision takes by weighing the adjuvant that is equivalent to medicine dispersible tablet 10mg of the present invention in the tablet formulation, with an amount of water stirring and dissolving and be settled to 10ml, get subsequent filtrate direct injected under these conditions, and contrast with the chromatogram of medicine dispersible tablet standard solution of the present invention, visible adjuvant content to medicine dispersible tablet of the present invention under this HPLC condition does not disturb.
2.3 specificity blank and plasma sample chromatograph are as seen, the retention time of determinand and internal standard substance is respectively 4.56min and 7.81min in the plasma sample.Peak shape is good, separate fully, and the free from admixture peak disturbs.
2.4 the response rate
Get blank plasma 0.5mL and put difference in vitro, add not commensurability medicine dispersible tablet standard solution of the present invention respectively, and compare with the medicine dispersible tablet standard solution of the present invention of same concentrations, press the blood plasma quadrat method and handle and measure, calculate recovery rate sees Table 10.
Table 10 recovery test
| Pipe contrast amount (ug) amount of recording (ug) response rate (%) average |
| 1 100 98.37 98.37 2 100 99.56 99.56 100.10±1.27 3 100 101.72 101.72 4 100 100.75 100.75 |
2.4 precision
Get the medicine dispersible tablet plasma sample of the present invention of variable concentrations, after handling as stated above, in different time on the same day, replication is 5 times respectively, calculates relative standard deviation in a few days; In same date not, the same concentrations plasma sample used with method handle and measure, repeat 5, calculate relative standard deviation in the daytime, the results are shown in Table 11.
The test of table 11 precision
| Absolute sample size average 100 300 600 |
| The amount of recording in a few days, (ng) RSD in 90.5 ± 2.54 311.7 ± 3.43 591.9 ± 6.84 days, (%) amount of recording between 2.23 1.42 1.32 1.66 days, (ng) RSD between 87.45 ± 2.04 294.6 ± 5.23 595.3 ± 8.95 days, (%) 4.12 2.15 1.05 2.44 |
2.5 average recovery
Get the dog plasma 0.5mL of concentration known, adding concentration respectively is the medicine dispersible tablet standard solution an amount of of the present invention of 20ug/mL, is equivalent to 6 respectively, 12, the medicine dispersible tablet of the present invention of 20ug is handled by above-mentioned blood sample preprocess method, and measure with the HPLC method, average recovery sees Table 12.
The test of table 12 average recovery
| Blood plasma Chinese medicine amount addition record the total amount amount of recording response rate average recovery rate RSD% (ug) (ug) (ug) (ug) (%) (%) |
| 8.5 4 12.8 4.3 107.5 8.5 4 12.6 4.1 102.5 8.5 5 13.4 4.9 98 8.5 5 13.3 4.8 96 100.67 1.63 8.5 6 14.4 5.9 98.3 8.5 6 14.6 6.1 101.7 |
2.6 pharmacokinetics in medicine dispersible tablet of the present invention and ordinary tablet animal (dog) body
2.6.1 animal subject: select the more approaching dog of digestive system and people as study subject.
2.6.2 medication
Adopt self intersection single oral dose administration, directly tablet is sent into dog throat, 50mL simultaneously feeds water; Dosage 3.75 grams/only, respectively at timing is from the about 2.5mL of hind leg venous blood collection before the administration and after the administration, separated plasma is standby immediately; Fasting 12h before the administration, and fasting to sampling finishes; Dosing interval: 1 week; Plasma sample is used with method and is handled and measure.
Adopt the pharmacokinetic parameter and the statistical result of two kinds of preparations of 3P87 program calculating to see Table 13.
The statistical result of the main pharmacokinetic parameter of two kinds of preparations of table 13
| Major parameter | Ordinary tablet | Dispersible tablet | The P value |
| AUC (0-t)/ng.h.ml -1 | 229.625±36.455 | 303.806±30.419 | P<0.01 |
| AUC (0-inf)/ng.h.ml -1 | 274.787±43.068 | 348.480±20.088 | P<0.05 |
| C max/ng.ml -1 | 85.759±7.512 | 121.679±6.910 | P<0.01 |
| T max/h | 0.410±0.194 | 0.731±0.176 | P<0.05 |
| MRT (0-t)/h | 1.417±0.127 | 2.365±0.059 | P<0.05 |
| T 1/2ke/h | 1.270±0.539 | 2.553±1.198 | P<0.05 |
| MRT (0-inf)/h | 2.378±0.566 | 3.541±1.055 | P<0.05 |
From pharmacokinetic parameters as can be seen, there were significant differences than ordinary tablet for dispersible tablet.
Table 14 medicine dispersible tablet of the present invention and ordinary tablet relative bioavailability are relatively
| F dispersible tablet ordinary tablet |
| F(0-t) 105.5±15.5 93.0±15.8 F(0-inf.) 107.2±18.1 91.3±19.3 |
Bioavailability also meet the requirements (80%---120%).
Conclusion and discussion
Pharmacokinetic parameters statistical result shows: there is significant differences in the peak time of two kinds of preparations, and medicine dispersible tablet peak time of the present invention significantly improves, and indicates that medicine dispersible tablet of the present invention can bring into play drug effect soon; The difference of the peak value blood drug level of two kinds of preparations does not have significance, but there is significant difference in the area under the drug-time curve of the two (AUC), illustrate that medicine dispersible tablet of the present invention can keep higher haemoconcentration for more time than ordinary tablet, this is very important to keeping of the performance of drug effect and drug effect; AUC with ordinary tablet is a reference, and the relative bioavailability of medicine dispersible tablet of the present invention is 143%, illustrates that medicine dispersible tablet of the present invention absorbs fully than ordinary tablet.
The 7 medicament slow release preparation pharmacokinetics tests of the present invention of test example
1, material and reagent
1.1 instrument: UV-2102 PCS type ultraviolet spectrophotometer
1.2 reagent: medicament sustained-release tablets of the present invention (by embodiment 6 preparations, 0.4g/ sheet)
1.3 laboratory animal: the hybrid dog, 6, body weight 8～12kg, male and female are not limit, and are provided by laboratory animal quality-monitoring center, Sichuan Province.
2, method and result
2.1 detection method
The preparation precision of glutamic acid reference substance solution is measured the glutamic acid reference substance 0.2g that is dried to constant weight through 105 ℃, puts in the 100ml measuring bottle, is dissolved in water and is diluted to scale, shakes up; Precision is measured 20ml, puts in the measuring bottle of 100ml, adds water to scale, shakes up.Contain glutamic acid 40 μ g among every 1ml.
It is an amount of that the preparation precision of test sample is measured this product, adds water and make the solution that contains 40 μ g among every 1ml.
The preparation precision of standard curve is measured reference substance solution 0.0,0.2,0.4,0.6,0.8,1.0ml, put respectively in the 10ml tool plug test tube, add water to 1.0ml, add 0.2mol/L citrate buffer (pH5.0) 1.0ml, add 1% ascorbic acid solution 0.1ml and 2% triketohydrindene hydrate ethylene glycol monomethyl ether solution 3.0ml, shake up, be covered in tool plug test tube top with a sizeable clean gauze, with linear system tight (avoiding extrusion), put heating taking-up in 15 minutes in the water-bath, put and be chilled to room temperature in the cold water, add 60% ethanol 3.0ml, shake up, with first part be blank, according to spectrophotography (appendix VB of Chinese Pharmacopoeia version in 2000) test, wavelength place at 570nm measures trap, with the trap is vertical coordinate, and concentration is abscissa, the drawing standard curve.
Algoscopy is got the content under this product content uniformity, and porphyrize is got about 0.5g, and accurate the title decides, and puts in the tool plug conical flask, precision adds water 50ml, and supersound process 10 minutes filters, and discards filtrate just, precision is measured subsequent filtrate 3ml, puts in the 25ml measuring bottle, and thin up shakes up to scale.Precision is measured 1ml, puts in the 10ml tool plug test tube method under the sighting target directrix curve preparation, from " adding citrate salt buffer (pH5.0) 1.0ml ", measure trap, the weight (μ g) of reading glutamic acid the need testing solution from standard curve in accordance with the law, calculate, promptly.
Every of this product contains aminoacid with glutamic acid (C
5H
9NO
4) meter, must not be less than 3.0mg.
2.2 the interference measurement of adjuvant
Precision takes by weighing the adjuvant that is equivalent to medicament sustained-release tablets 10mg of the present invention in the tablet formulation, with an amount of water stirring and dissolving and be settled to 10ml, get subsequent filtrate direct injected under these conditions, and contrast with the chromatogram of medicament sustained-release tablets standard solution of the present invention, visible adjuvant content to medicament sustained-release tablets of the present invention under this HPLC condition does not disturb.
2.3 extraction recovery
Get blank plasma 0.5mL and put difference in vitro, add not commensurability medicament sustained-release tablets standard solution of the present invention respectively, and compare, press the blood plasma quadrat method and handle and measure with the medicament sustained-release tablets standard solution of the present invention of same concentrations, calculate recovery rate the results are shown in Table 15.
Table 15 extraction recovery
| Pipe contrast amount (ug) amount of recording (ug) response rate (%) average |
| 1 100 101.3 103.3 2 100 98.4 98.4 101.23±1.67 3 100 102.5 102.5 4 100 100.7 100.7 |
2.4 precision
Get the medicament sustained-release tablets plasma sample of the present invention of variable concentrations, after handling as stated above, in different time on the same day, replication is 5 times respectively, calculates relative standard deviation in a few days; In same date not, the same concentrations plasma sample used with method handle and measure, repeat 5, calculate relative standard deviation in the daytime, the results are shown in Table 16.
Table 16 precision
| Absolute sample size average 100 300 600 |
| The amount of recording in a few days, (ng) RSD in 88.5 ± 2.74 301.7 ± 3.69 594.9 ± 6.61 days, (%) amount of recording between 2.78 1.22 1.11 1.70 days, (ng) RSD between 97.4 ± 3.04 298.4 ± 5.82 592.3 ± 9.75 days, (%) 3.12 1.95 1.65 2.24 |
2.5 average recovery
Get the dog plasma 0.5mL of concentration known, adding concentration respectively is the medicament sustained-release tablets standard solution an amount of of the present invention of 20ug/mL, is equivalent to 6 respectively, 12, the medicament sustained-release tablets of the present invention of 20ug is handled by above-mentioned blood sample preprocess method, and measure with the HPLC method, average recovery sees Table 17.
The test of table 17 average recovery
| The blood plasma Chinese medicine amount addition amount of recording response rate average recovery rate RSD% (ug) is (ug) (%) (%) (ug) |
| 8.5 4 12.7 105 8.5 4 12.4 97.5 8.5 5 13.3 96 8.5 5 13.7 104 101.3 3.63 8.5 6 14.6 101.7 8.5 6 14.7 103.3 |
2.6 pharmacokinetics in medicament sustained-release tablets of the present invention and ordinary tablet animal (dog) body
2.6.1 animal subject: select the more approaching dog of digestive system and people as study subject.
2.6.2 medication
Adopt self intersection single oral dose administration, directly tablet is sent into dog throat, 50mL simultaneously feeds water; Dosage 3.75 grams/only, respectively at timing is from the about 2.5mL of hind leg venous blood collection before the administration and after the administration, separated plasma is standby immediately; Fasting 12h before the administration, and fasting to sampling finishes; Dosing interval: 1 week; Plasma sample is used with method and is handled and measure.
Adopt the pharmacokinetic parameter and the statistical result of two kinds of preparations of 3P87 program calculating to see Table 18.
The statistical result of the main pharmacokinetic parameter of two kinds of preparations of table 18
| Cmax (ug/mL) Tmax (min) AUC[ug/ (mL min) slow releasing tablet ordinary tablet slow releasing tablet ordinary tablet slow releasing tablet ordinary tablet |
| 131.75 82.36 287.83 202.25 343.8 222.5 P value P〉0.05 P＜0.01 P＜0.05 |
3, conclusion and discussion
Pharmacokinetic parameters statistical result shows: there is significant differences in the peak time of two kinds of preparations, and the slow releasing tablet peak time significantly improves, and the indication slow releasing tablet can be brought into play drug effect soon; The difference of the peak value blood drug level of two kinds of preparations does not have significance, but there is significant difference in the area under the drug-time curve of the two (AUC), illustrate that slow releasing tablet can keep higher haemoconcentration for more time than ordinary tablet, this is very important to keeping of the performance of drug effect and drug effect; AUC with ordinary tablet is a reference, and the relative bioavailability of slow releasing tablet is 152%, illustrates that slow releasing tablet absorbs fully than ordinary tablet.
Below by clinical trial beneficial effect of the present invention is described.
As follows according to 370 routine Clinical results:
Therapeutic outcome:
One, expectorant heat syndrome [phlegm-heat cough (acute episode of chronic bronchitis)]
Total obvious effective rate of 1, treatment group Succus Bambusae capsule (Succus Bambusae granule, bamboo drop plate, medicine dispersible tablet of the present invention, Succus Bambusae buccal tablet, medicament sustained-release tablets of the present invention) treatment phlegm-heat cough (acute episode of chronic bronchitis) is 55%, effective percentage is 31%, and total effective rate is 86%.Main symptom to phlegm-heat cough is coughed, is coughed up phlegm, before the tight improvement uncomfortable in chest of gas and the treatment relatively, significant difference is arranged, P＜0.05.
Total obvious effective rate of matched group 1 fresh Succus Bambusae water treatment phlegm-heat cough (acute episode of chronic bronchitis) is 51.67%, and effective percentage is 35%, and total effective rate is 86.67%.Main symptom to phlegm-heat cough is coughed, is coughed up phlegm, before the tight improvement uncomfortable in chest of gas and the treatment relatively, significant difference is arranged, P＜0.05.
Total obvious effective rate of matched group 11 pioneer 1V capsule for treating phlegm-heat coughs (acute episode of chronic bronchitis) is 23.33%, and effective percentage is 51.67%, and total effective rate is 75%.Main symptom to phlegm-heat cough is coughed, is coughed up phlegm, before the tight improvement uncomfortable in chest of gas and the treatment relatively, significant difference is arranged, P＜0.05.
Illustrate: the main symptom before each group treatment back of phlegm-heat cough (acute episode of chronic bronchitis) and the treatment cough, coughed up phlegm, gas is tightly uncomfortable in chest more all significant difference, P＜0.05.
Total effects compares: there is significant difference Ridit:X=12.9997 P＜0.01.
2, the main symptom behind treatment group Succus Bambusae capsule (Succus Bambusae granule, bamboo drop plate, medicine dispersible tablet of the present invention, Succus Bambusae buccal tablet, medicament sustained-release tablets of the present invention) and the matched group 1 fresh Succus Bambusae water treatment phlegm-heat cough (acute episode of chronic bronchitis) cough, is coughed up phlegm, tightly comparison uncomfortable in chest of gas, difference does not have significantly, P〉0.05.
Main symptom cough behind treatment group Succus Bambusae capsule (Succus Bambusae granule, bamboo drop plate, medicine dispersible tablet of the present invention, Succus Bambusae buccal tablet, medicament sustained-release tablets of the present invention) and the matched group 11 pioneer 1V capsule for treating phlegm-heat coughs (acute episode of chronic bronchitis), the comparison of coughing up phlegm, significant difference is arranged, P＜0.05; The tight comparing difference uncomfortable in chest of gas does not have significantly P〉0.05.
Main symptom cough behind matched group 1 fresh Succus Bambusae water and the matched group 11 pioneer 1V capsule for treating phlegm-heat coughs (acute episode of chronic bronchitis), the comparison of coughing up phlegm have significant difference, P＜0.05; The tight comparing difference uncomfortable in chest of gas does not have significantly P〉0.05.
Illustrate: Succus Bambusae capsule (Succus Bambusae granule, bamboo drop plate, medicine dispersible tablet of the present invention, Succus Bambusae buccal tablet, medicament sustained-release tablets of the present invention) and fresh Succus Bambusae water treatment phlegm-heat cough (acute episode of chronic bronchitis) to main symptom cough, cough up phlegm, tightly improvement uncomfortable in chest of gas, the curative effect there was no significant difference has the effect of same removing heat-phlegm.
3, three groups control phlegm-heat cough (acute episode of chronic bronchitis) to before pulmonary sign treatment back and the treatment relatively, difference that there are no significant, P〉0.05.
Control phlegm-heat cough (acute episode of chronic bronchitis) for three groups and compare with age and curative effect, Ridit:X is followed successively by 30.44,13.06,25.66, and P all＜0.05 has significant difference, illustrates that young person's curative effect is good relatively.
The three groups of course of disease and therapies of controlling phlegm-heat cough (acute episode of chronic bronchitis) are imitated relatively, and Ridit:X is followed successively by 81.20,29.34,26.17, and P all＜0.05 has significant difference, illustrate that disease time is short, and curative effect is good relatively.
4,220 routine patients have all done blood, urine, the stool routine examination inspection before and after the treatment, wherein have 140 routine patients to make liver function ALT, A/G, none example of kidney merit BUN, Cr unusually.
5, do not find adverse effect.
Two, expectorant heat syndrome [apoplexy apoplex involving the channels and collaterals: real, the syndrome of wind-phlegm invading upward (acute period of cerebral infarction) of the hot internal organs of expectorant]
1, the main effect of fresh Succus Bambusae water: removing heat-phlegm.Succus Bambusae capsule (Succus Bambusae granule, bamboo drop plate, medicine dispersible tablet of the present invention, Succus Bambusae buccal tablet, medicament sustained-release tablets of the present invention) is the dosage form transformation of the way of fresh Succus Bambusae water.The patient of the apoplexy-apoplex involving the channels and collaterals of, syndrome of wind-phlegm invading upward (acute period of cerebral infarction) real to the hot internal organs of expectorant only does the observation of accumulation and obstruction of sputum, two symptoms of stiff tongue.
2, the hot internal organs of treatment group Succus Bambusae capsule (Succus Bambusae granule, bamboo drop plate, medicine dispersible tablet of the present invention, Succus Bambusae buccal tablet, medicament sustained-release tablets of the present invention) treatment expectorant is real, the patient of the apoplexy-apoplex involving the channels and collaterals of syndrome of wind-phlegm invading upward (acute period of cerebral infarction) only does to compare with treatment is preceding behind accumulation and obstruction of sputum, the stiff tongue, obvious effective rate is 46.67%, effective percentage is 48.33%, and total effective rate is 85%.Accumulation and obstruction of sputum, has significant difference at t=2.63, P＜0.05; Stiff tongue, t=0.89, P〉0.05, difference do not have significance.
The hot internal organs of matched group 1 fresh Succus Bambusae water treatment expectorant is real, behind the patient's accumulation and obstruction of sputum of the apoplexy-apoplex involving the channels and collaterals of syndrome of wind-phlegm invading upward (acute period of cerebral infarction), stiff tongue with treatment before relatively, obvious effective rate is 43.33%, effective percentage is 50%, total effective rate is 93.33%.Accumulation and obstruction of sputum, has significant difference at t=2.25, P＜0.05; Stiff tongue, t=0.63, P〉0.05, difference do not have significance.
The hot internal organs of matched group 11 conventional therapy expectorant is real, behind the patient's accumulation and obstruction of sputum of the apoplexy-apoplex involving the channels and collaterals of syndrome of wind-phlegm invading upward (acute period of cerebral infarction), stiff tongue with treatment before relatively, obvious effective rate is 26.67%, effective percentage is 36.67%, total effective rate is 63.34%.Accumulation and obstruction of sputum, has significant difference at t=1.49, P＜0.05; Stiff tongue, t=1.13, P〉0.05, difference do not have significance.
Illustrate: the hot internal organs of each group treatment expectorant is real, patient's accumulation and obstruction of sputum of the apoplexy-apoplex involving the channels and collaterals of wind-heat troubling card (acute period of cerebral infarction) is all effective, and stiff tongue improves not obvious.
Total effects compares, and there is significant difference Ridit:X=6.455 P＜0.05.
3, treatment group Succus Bambusae capsule (Succus Bambusae granule, bamboo drop plate, medicine dispersible tablet of the present invention, Succus Bambusae buccal tablet, medicament sustained-release tablets of the present invention) is real with the hot internal organs of matched group 1 fresh Succus Bambusae water expectorant, the comparison of patient's accumulation and obstruction of sputum of the apoplexy-apoplex involving the channels and collaterals of wind-heat troubling card (acute period of cerebral infarction), difference does not have significance, P〉0.05.
Treatment group Succus Bambusae capsule (Succus Bambusae granule, bamboo drop plate, medicine dispersible tablet of the present invention, Succus Bambusae buccal tablet, medicament sustained-release tablets of the present invention) is real with the hot internal organs of matched group 11 fresh Succus Bambusae water expectorant, the comparison of patient's accumulation and obstruction of sputum of the apoplexy-apoplex involving the channels and collaterals of wind-heat troubling card (acute period of cerebral infarction), significant difference is arranged, P＜0.05.The hot internal organs of matched group 1 fresh Succus Bambusae water and matched group 11 conventional therapy expectorant is real, the comparison of patient's accumulation and obstruction of sputum of the apoplexy-apoplex involving the channels and collaterals of wind-heat troubling card (acute period of cerebral infarction), significant difference is arranged, P＜0.05.
Illustrate: Succus Bambusae capsule (Succus Bambusae granule, bamboo drop plate, medicine dispersible tablet of the present invention, Succus Bambusae buccal tablet, medicament sustained-release tablets of the present invention) is real with the hot internal organs of fresh Succus Bambusae water treatment expectorant, the comparison of patient's accumulation and obstruction of sputum of the apoplexy-apoplex involving the channels and collaterals of wind-heat troubling card (acute period of cerebral infarction), the curative effect there was no significant difference, P〉0.05, two group have the effect of same removing heat-phlegm.
By 370 routine expectorant heat syndromes [phlegm-heat cough (acute episode of chronic bronchitis)] [apoplexy-apoplex involving the channels and collaterals: real, the wind-heat troubling (acute period of cerebral infarction) of the hot internal organs of expectorant] are compared: drug therapy expectorant heat syndrome of the present invention [phlegm-heat cough (acute episode of chronic bronchitis)], its total effects and matched group relatively (X=12.99997 P＜0.01) have significant difference.Accumulation and obstruction of sputum, its total effects of stiff tongue symptom and the matched group of treatment expectorant heat syndrome [apoplexy-apoplex involving the channels and collaterals: real, the syndrome of wind-phlegm invading upward (acute period of cerebral infarction) of the hot internal organs of expectorant] relatively (X=6.455 P＜0.05) has significant difference.Has the removing heat-phlegm effect equally with fresh Succus Bambusae water treatment phlegm-heat cough.
By above-mentioned pharmacodynamics test, adopt traditional bake fresh Succus Bambusae contrast, raw extract adopts extract at low temperature to concentrate, can to greatest extent effective ingredient be kept, and increased activity, bioavailability improves, and have analgesic, cough-relieving, eliminate the phlegm, relieving asthma, antiphlogistic effect, and refrigeration function is apparently higher than the fresh Succus Bambusae of the traditional bake of tradition; Medicine material extract of the present invention is prepared into various solid-liquid body preparations, comprise common oral preparation, buccal lozenge, dispersible tablet, slow releasing preparation, the absorption approach is many, the bioavailability height, and steady quality, controllability is strong, and use is carried, be beneficial to and take and take care of, provide new medication to select for clinical.
Claims (4)
1, a kind of pharmaceutical composition of removing heat-phlegm is characterized in that: it is prepared by following method:
A, get the bright stalk 100g of grass phyllostachys glauca Mcclure, cut into 2-5cm, put in the 1000ml beaker, add the water of 6 times of amounts, temperature is controlled at 100 ℃, decocts to extract 1.5 hours, decoction liquor is filtered, filtering residue adds the water of 4 times of amounts, and 100 ℃ of temperature decocted 1.0 hours, filter, merge filtrate twice, adding distil water is to the 1000ml standardize solution, and every ml is equivalent to crude drug 0.1g;
B, the temperature of A step is carried out triple effect less than 80 ℃, proportion greater than 1.01 bamboo extract concentrate: one to imitate temperature be 75～85 ℃, and vacuum is 0.020～0.040MPa; Two effect temperature are 65～75 ℃, and vacuum is 0.040～0.060MPa; The triple effect temperature is 55～65 ℃, and vacuum is 0.060～0.080MPa; Receipts cream proportion is 1.10～1.35 when being 40～80 ℃;
C, airpillow-dry;
D, be active component, add the preparation that acceptable accessories is prepared from dried bamboo extract.
2, the pharmaceutical composition of removing heat-phlegm according to claim 1 is characterized in that: described preparation is conventional tablet, dispersible tablet, capsule, granule, buccal tablet or slow releasing preparation.
3, a kind of method for preparing the pharmaceutical composition of the described removing heat-phlegm of claim 1, it comprises the steps:
A, get the bright stalk 100g of grass phyllostachys glauca Mcclure, cut into 2-5cm, put in the 1000ml beaker, add the water of 6 times of amounts, temperature is controlled at 100 ℃, decocts to extract 1.5 hours, decoction liquor is filtered, filtering residue adds the water of 4 times of amounts, and 100 ℃ of temperature decocted 1.0 hours, filter, merge filtrate twice, adding distil water is to the 1000ml standardize solution, and every ml is equivalent to crude drug 0.1g;
B, the temperature of A step is carried out triple effect less than 80 ℃, proportion greater than 1.01 bamboo extract concentrate: one to imitate temperature be 75～85 ℃, and vacuum is 0.020～0.040MPa; Two effect temperature are 65～75 ℃, and vacuum is 0.040～0.060MPa; The triple effect temperature is 55～65 ℃, and vacuum is 0.060～0.080MPa; Receipts cream proportion is 1.10～1.35 when being 40～80 ℃;
C, airpillow-dry.
4, the preparation of drug combination method of removing heat-phlegm according to claim 3, it is characterized in that: with dried bamboo extract is active component, adds the preparation that acceptable accessories is prepared from.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1057196A (en) * | 1990-06-13 | 1991-12-25 | 成都中医学院 | A kind of preparation method of Chinese medicine fresh Succus Bambusae |
| CN1151883A (en) * | 1996-07-17 | 1997-06-18 | 蒋道友 | Method for extracting succus Bambusae |
| CN1517118A (en) * | 2003-01-14 | 2004-08-04 | 莫尚武 | Bamboo extract and its preparation method and application |
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2005
- 2005-01-21 CN CNB2005100202235A patent/CN100473408C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1057196A (en) * | 1990-06-13 | 1991-12-25 | 成都中医学院 | A kind of preparation method of Chinese medicine fresh Succus Bambusae |
| CN1151883A (en) * | 1996-07-17 | 1997-06-18 | 蒋道友 | Method for extracting succus Bambusae |
| CN1517118A (en) * | 2003-01-14 | 2004-08-04 | 莫尚武 | Bamboo extract and its preparation method and application |
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