CN101085014B - Traditional Chinese medicinal composition containing red sage root, notoginseng, safflower and borneol or storax and its preparation - Google Patents
Traditional Chinese medicinal composition containing red sage root, notoginseng, safflower and borneol or storax and its preparation Download PDFInfo
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- CN101085014B CN101085014B CN2006100142559A CN200610014255A CN101085014B CN 101085014 B CN101085014 B CN 101085014B CN 2006100142559 A CN2006100142559 A CN 2006100142559A CN 200610014255 A CN200610014255 A CN 200610014255A CN 101085014 B CN101085014 B CN 101085014B
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Landscapes
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Abstract
The invention discloses a Chinese medicinal composition for treating cardiovascular diseases, which is prepared from root of red rooted saliva, notoginseng, safflower and borneol or red sage root, notoginseng, safflower and liquidambar orientalis mill, and the preparation process comprises the steps of mixing red-rooted salvia, safflower and ginseng to obtain water extract or alcohol extract, subjecting the extract to preliminary settlement treatment, further subjecting the extract to ultrafiltration treatment, concentrating the ultrafiltrate to obtain concrete, mixing with baras camphor or liquidambar orientalis mill. The invention also discloses preparations using any one of the medicinal compositions as the effective constituents, preferably drop pills.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition and preparation thereof for the treatment of cardiovascular disease, particularly relating to a kind of is the pharmaceutical composition of the treatment cardiovascular disease made of raw material with the Chinese medicine medical material.
Background technology
Along with the rejuvenation of growth in the living standard, world population aging and morbidity colony, cardiovascular and cerebrovascular vessel patient increases year by year, has become the second largest disease of harm humans health.Angina pectoris is a kind of caused by the temporary transient ischemia of cardiac muscle, anoxia, serves as the clinical syndrome of main performance with ictal chest pain or chest discomfort.Angina pectoris is meant because coronary atherosclerosis or spasm cause myocardial ischemia, the caused angina pectoris of anoxia, accounts for 90% of patient with angina pectoris.Though the anginal Chinese patent medicine of many treatments is also arranged, wherein ball, loose, cream, pellet, decoction becomes old historical already, the modern seldom uses.There are preparations such as common compound Salviae Miltiorrhizae tablet and capsule to sell in the market, but conventional tablet, capsule manufacture technology are more backward, active constituent content is low, no quality control standard, need be oral through gastrointestinal absorption, go into blood at liver generation first pass effect post-absorption, bioavailability is low, absorb slowly, can not be fit to the need of angina pectoris patient's first aid.
Membrane separation technique (Membrane Separation Technique) is an emerging high efficient separation technology, by internationally recognized be a most rising great high production tech of mid-term 20 end of the centurys to 21 century.Ultrafiltration (Ultrafiltration, UF) technology is a kind of membrane separation technique, its ultimate principle is to utilize fenestra selectivity sieve performance, with separation, purification and condensed matter.Hyperfiltration process is that the anisotropic membrane (being asymmetric membrane) that utilizes macromolecular material to make is a filter medium, under normal temperature condition, relies on certain pressure and flow velocity, makes flow of solution through face, forces low molecular weight substance to see through film, and polymer substance is trapped.
Because hyperfiltration process is a physical method, do not have and must heat repeatedly, there be not " phase " to change, the probability of destroying effective ingredient is few than other universal method, characteristics such as technological process is short, thereby its be applied to extract in the research of pharmaceutically active ingredient become increasingly active, portioned product moves towards commercial production from laboratory research.Human ultrafiltrations such as 304 Wang Shiling of hospital of PLA are extracted effective ingredient baicalin in the Radix Scutellariae, the result shows that ultrafiltration is excellent than well-established law all aspect productive rate, purity, and a ultrafiltration can reach the injection requirement, do not need again row refining, technology is simple, and the production cycle can shorten 1～2 times of (Wang Shiling, Zheng Dianbao " ultrafiltration is extracted the preliminary investigation of baicalin ", Chinese patent medicine research, 1988 (3): 5).Wang Shiling etc. have also further studied the optimum process condition of ultrafiltration extraction baicalin, it is the key that improves baicalin yield and quality that the experimental result proof is selected the ultrafilter membrane in suitable aperture (molecular cut off is 6000～10000) for use, the fluid temperature that raises simultaneously or reduction concentration, strict control pH value (pH=1.5 during acidify, pH=7.0 when alkali is molten), can significantly improve ultrasiltrated rate, obtain best output effect (Wang Shiling, " ultrafiltration is once extracted the technical study of baicalin ", Chinese patent medicine, 1994,16 (3): 2).Xu Jinlin etc. are with ultrafiltration (polysulfone membrane, molecular cut off 6000) is used for the preparation of phytic acid, the phytic acid yield is 86.4%, and than the phytate method raising 12.6% of routine, and ultrafiltration gained phytic acid contains Phos hardly, appearance transparent is close to colourless (Xu Jinlin, Xu Jie, Wang Yuanjin " membrane separation technique prepares the research of phytic acid ", Chinese Journal of Pharmaceuticals, 1994,25 (4): 150).He Changsheng etc. use hyperfiltration technique separation and purification steviol glycosides, and adopting ultrathin plate-type hyperfiltration device and molecular cut off is that 10000 cellulose acetate membrane (CA film) purifies field experimentation to steviol glycosides, and its technological process is rationally feasible.The ultrafilter stable performance, the decoloration performance and the removal of impurity of film are respond well, bubble problem (He Changsheng in the time of can solving precipitation that steviol glycosides usually occurs in producing and embedding preferably, WangBing Nan, Zhu Shanshan " applied research of steviol glycosides ultrafiltration ", water technology, 1994,20 (2): 89).Huang is improved oneself and is adopted the refining sasanguasaponin of ultrafilter membrane (molecular cut off is 4000 and 10000 polysulfone membrane), compare with the domestic bleaching that mostly adopts, recrystallize method, the alcohol ether sedimentation method and the basic salt sedimentation method, the ultrafiltration flow process is simple, the efficient height, expense is low, to removing oils and fats, pigment, saccharide and the strong impurity of other hydrophilic in the thick sasanguasaponin, can both producing a desired effect, (Huang is improved oneself, " ultrafiltrationmembrane process is made with extra care the sasanguasaponin pre-test " water technology, 1995,21 (2): 99).Guo Li Wei of Nanjing University of Traditional Chinese Medicine etc. has relatively studied water alcohol method and ultrafiltration is clarified the influence of Fructus Corni preparation to its preparation ingredient, the result confirms that ultrafiltration is more effective to saccharide impurity in the removal medicinal liquid, molecular cut off is that 10000 ultrafilter membrane does not have obviously influence to meliatin (molecular weight is 384), but being 1000 film, molecular cut off makes meliatin loss about 50% (Guo Liwei, Peng Guoping, Pan Yang etc. " the refining comparative study that contains the Fructus Corni Chinese medicine preparation of water alcohol method and membrane separation process ", Chinese patent medicine, 1999,21 (2): 59).Wang Chengzhang etc. adopt ultrafiltration (polysulfone membrane; molecular cut off 30000) separates with the ethanol extract of polyamide absorb-elute method Folium Ginkgo; purification; detect through high performance liquid chromatography (HPLC); the ginkgetin salidroside content is about 45%; yield is 0.5%～0.7%; more conventional steam distillation; the organic solvent extraction method is excellent; and in ultrafiltration technology, can reduce discharge of wastewater, the protection environment reduces production costs; (Wang Chengzhang increases economic efficiency; Yu Qing, Tan Weihong etc. " application of ultrafiltration in purification Folium Ginkgo flavone glycoside ", forestry science and technology communication; 1997, (2): 21).
Though hyperfiltration technique is applied to the production of Chinese medicine preparation its unique advantage is arranged, its degree of applying is still very limited, traces it to its cause, and remains in following problem:
(1) medicinal herb components complexity, particularly many compound preparations, effective ingredient are also unclear fully, therefore need to carry out very deep research before hyperfiltration technique is applied to Chinese herbal and crude drugs preparations.For example because the complexity of composition, do not carry out a large amount of pharmacology and clinical research test fully estimate ultrafiltration to Chinese medicine preparation in before the drug effect influence degree of each composition, ultrafiltration can not be applied to the production of most of Chinese medicine preparation.
(2) kind of membrane material is few, and membrane aperture distributes wide, and performance is understable.Used ultrafilter membrane material has cellulose acetate, polyacrylonitrile, polysulfones, SPSF, polysulfonamides etc. in Chinese medicine preparation production.By its affinity classification, be broadly divided into two classes: hydrophobic film material and hydrophilic film material to water.Hydrophilic film such as cellulose acetate, SPSF material is few to solute absorption, and molecular cut off is less, but poor heat stability, mechanical strength, chemical proof, antibacterium erosiveness are not high usually; Hydrophobic film materials such as polysulfones, the mechanical strength height, high temperature resistant, anti-solvent, anti-biodegradation, but because of containing a large amount of hydrophobicity genes or chain link in the strand, and have more electrostatic charge, thereby the permeable speed of film is low, contamination resistance is lower.
(3) pollution problem of film is to hinder hyperfiltration technique is moved towards the commercial Application stage by laboratory research biggest obstacle.In the ultra-filtration process of Chinese medicine preparation, when not good as if the medicinal liquid pretreating effect, face easily pollutes, and fenestra stops up, and making permeation flux is that productivity ratio descends, even cisco unity malfunction, and production efficiency reduces, and cost rises, and causes the shortening in service life of film.
(4) system of selection of membrane module is not set up as yet, the optimization of still needing of ultrafiltration parameter.The factor that influences the ultrafiltration effect is a lot, comprises the selection of membrane module, the cleaning method after the definite and ultrafilter of technological parameter uses etc.Therefore be applicable to ultrafiltration apparatus and the operating procedure that the ultrafiltration of Chinese medicine system is used, remain further to be studied.
The relevant practical application that utilizes ultrafiltration to prepare compound red sage root preparation, the rare report of present document, particularly, utilize ultrafiltration to carry out suitability for industrialized production is a technical barrier in this area always.The inventor is through the effort of long-term and unremitting ground, by a large amount of experimental datas are analyzed, verified that ultrafiltration prepares the feasibility of compound red sage root preparation, and determined suitable process condition, for the suitability for industrialized production of utilizing ultrafiltration to carry out compound red sage root preparation provides concrete solution.
Drop pill then has the characteristics of quick acting, relatively is fit to the need of the first aid of coronary disease with angina pectoris.Although drop pill had had very big development on production equipment, preparation technology and types of drugs in recent years, go up slower development for the research and the application of drop pill new medium adjuvant.So far, most of drop pill substrate is selected Polyethylene Glycol for use, selects polyoxyethylene monostearate, gelatin, poloxamer, polyethers etc. individually for use.From the source, Polyethylene Glycol, polyoxyethylene monostearate, poloxamer, polyethers etc. all adopt making of synthetic, though gelatin from natural, it mainly comes from skin and the bone of animal.From safety perspective,, hemolytic is in various degree arranged all though that these chemical synthetic materials such as Polyethylene Glycol, polyoxyethylene monostearate, poloxamer, polyethers all can be done is medicinal; And in the chemosynthesis process, can mix unavoidably some to the chemical constituent of human body toxic side effect as oxirane, expoxy propane etc.; In addition, these synthetic materials and many medicines have incompatibility, as salicylic acid, diphenhydramine, potassium penicillin G, tetracycline etc., thereby have reduced the curative effect of these medicines.With regard to gelatin, the supplementary material of present many animal origins is carried out forbidding for avoiding zoonosis such as bovine spongiform encephalopathy, foot and mouth disease etc., and its purposes is limited.Therefore, in order to improve the product quality of drop pill, widen the application of drop pill in medical product, promote the development of drop pill dosage form, promote the internationalization of drop pill product, the drop pill new medium adjuvant of research, exploitation safety non-toxic has profound significance.But, because dropping pill formulation technology is very strict for the requirement of substrate adjuvant, often be difficult to prepare the drop pill that conforms to quality requirements after changing the substrate adjuvant, therefore, seek suitable substrate adjuvant and replace the direction that current Polyethylene Glycol becomes medical personnel effort always.
Summary of the invention
The purpose of this invention is to provide a kind of Chinese medicine composition and preparation thereof for the treatment of cardiovascular disease.
Medicine of the present invention is achieved through the following technical solutions:
The invention provides a kind of Chinese medicine composition for the treatment of cardiovascular disease, it is characterized in that it is to be prepared from by following materials of weight proportions medicine: Radix Salviae Miltiorrhizae 20～97, Radix Notoginseng 2～79, Borneolum Syntheticum or Styrax 0.2～3, Flos Carthami 10～40; Be preferably: Radix Salviae Miltiorrhizae 63.0～94.0, Radix Notoginseng 4.0～35.0, Borneolum Syntheticum or Styrax 0.5～2.0, Flos Carthami 15～30; More preferably: Radix Salviae Miltiorrhizae 75.2～90, Radix Notoginseng 9～23.5, Borneolum Syntheticum or Styrax 0.5～1.3, Flos Carthami 20～25.
Chinese medicine composition of the present invention, can adopt conventional method preparation, for example Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami can be mixed or make separately water extract or alcohol extract according to the Chinese medicine extraction method of routine, after the method for routine such as concentration such as rotary evaporation, concentrating under reduced pressure are made extractum, add Borneolum Syntheticum or Styrax and mix promptly then.Wherein can also comprise steps such as clarification.
Impurity is few in order to obtain, the Chinese medicine composition of the little above-mentioned treatment cardiovascular disease of loss of effective components, can be prepared according to the method that may further comprise the steps:
(1) Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami are mixed or make water extract or alcohol extract separately;
(2) described extracting solution being carried out predefecation handles;
(3) further described extracting solution is carried out hyperfiltration treatment;
(4) ultrafiltrate is concentrated make extractum, mix with Borneolum Syntheticum or Styrax.
In the above-mentioned steps (1), alcohol extraction can be adopted the lower alcohol of variable concentrations such as methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutanol etc. or its mixture, preferably uses ethanol extraction.Carrying out next step predefecation after water extract or alcohol extract can not concentrate or suitably concentrate handles.
In the above-mentioned above-mentioned steps (2), preliminary clarifying treatment can be with general material such as gauze, tiffany etc., the also available material such as the ceramic membrane of specialty, also can behind high speed centrifugation, divide and get supernatant, adsorption clarifications such as also available flocculating agent such as flocculate with chitosan clarifier, 101 fruit juice clarifiers, ZTC1+1 natural clarifying agent, Ovum Gallus domesticus album flocculating agent and remove particle bigger in the medicinal liquid, also available alcohol deposition method is removed most impurity.Both can singly use, but also use in conjunction.After can not concentrating or suitably concentrate, coarse filtration liquid carries out next step ultrafiltration; Preferably do not concentrate the ultrafiltration of promptly carrying out next step.
In the above-mentioned above-mentioned steps (3), the used ultrafilter membrane of ultrafiltration can be cellulose diacetate film (CA), three cellulose acetate membrane (CTA), cyanoethyl cellulose film (CN-CA), polysulfone membrane (PS), sulfonated polysulfone membrane (SPS), poly (ether sulfone) film (PES), sulfonated polyether sulfone film (SPES), polysulfonamides film (PSA), phenolphthalein side group polyarylsulfone (PAS) film (PDS), polyvinylidene fluoride film (PVDF), polyacrylonitrile film (PAN), polyimide film (N), cellulose membrane, methyl methacrylate-acrylonitrile copolymer film (MMA-AN), polyacrylonitrile/cellulose diacetate (PAN/CA) blend film, the dynamically ultrafilter membrane that forms, and the Modified Membrane of above-mentioned film.Be preferably cellulose diacetate film (CA), three cellulose acetate membrane (CTA), polysulfone membrane (PS), sulfonated polysulfone membrane (SPS), poly (ether sulfone) film (PES), sulfonated polyether sulfone film (SPES), polysulfonamides film (PSA), polyvinylidene fluoride film (PVDF), polyacrylonitrile film (PAN).The molecular cut off of ultrafilter membrane is generally 6000～80000, is preferably 10000～70000, and the best is 20000～50000.
The operating condition of described ultrafiltration technology is as follows:
(1) the inlet pressure of ultrafiltration is 0.1～0.5MPa, is preferably 0.1～0.35Mpa, and the best is 0.25～0.35Mpa; The liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.5～0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1～0.2Mpa.
(2) the feed liquid flow velocity is 1.0～4.0m/s, is preferably 2.0～3.0m/s.In the ultra-filtration process, adopt the fluctuation of periodicity flow so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 1.0～2.0m/s.
(3) feed high-pressure inert gas such as nitrogen in the ultrafiltration system discontinuous, form the gas-liquid stream of pulses, the cycle is that 0.5h～2h ventilates once, each 1 minute.
(4) feed temperature is 15～50 ℃, is preferably 20～40 ℃.
(5) when feed liquid stock solution is concentrated 1/15～1/5, add water or dilute alcohol solution ultrafiltration 1～2 time again; Be preferably when feed liquid stock solution is concentrated 1/12～1/8, add water or dilute alcohol solution ultrafiltration 1～2 time again.
(6) pH value of feed liquid is controlled at 5～9, is preferably 6.0～7.5;
(7) backwash condition: backwashing pressure is 0.15～2.5MPa, and backwashing period is that 0.5～1.5h, backwashing time are 1min～10min.When ultrafiltration module use in parallel is replaced the method for recoil, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, exchange is carried out behind the certain interval of time, generally is work 10～20min, recoil 30sec～3min.
(8) the Chemical cleaning cycle is 0.5 month～2 months, the Chemical cleaning medicament is generally diluted acid, diluted alkaline, surfactant, be preferably for example 0.5%～4.0% sodium hydroxide of diluted alkaline, the mixed solution of 1.5% sodium hydroxide and 2% sodium hypochlorite etc., pH value is 10～12, and cleaning pressure is 0.05～1.0MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
In ultra-filtration process, both periodic pressure oscillation or the fluctuation of periodicity flow or periodicity fed noble gas separately, also can unite use, be periodic pressure fluctuation and periodically flow fluctuation associating use, perhaps the periodic pressure fluctuation is with periodically feeding noble gas unites use, perhaps periodically the flow fluctuation is with periodically feeding noble gas unites use, and perhaps the three unites use together.
In the technology of the present invention step (4), ultrafiltrate is condensed into extractum after, mix with Borneolum Syntheticum or Styrax get final product Chinese medicine composition of the present invention.
The present invention also provides a kind of Chinese medicinal composition preparation for the treatment of angina pectoris, and said preparation is by above-mentioned any Chinese medicine composition and any or last made preparation of acceptable auxiliary of various medicaments.Adjuvant can be but is not limited on the pharmaceutics: starch, dextrin, lactose, microcrystalline Cellulose, hydroxypropyl methylcellulose, Polyethylene Glycol, magnesium stearate, micropowder silica gel, xylitol, lactose, glucose, glycine, mannitol, glycine etc. are mixed and made into tablet, capsule, granule, oral liquid, slow releasing preparation, controlled release preparation, gel, ointment, ointment, cream, suppository, injection, injectable powder, patch, drop pill, suspensoid, or the like.
The preferred drop pill of preparation of the present invention, this drop pill is prepared from as active component and adjuvant by above-mentioned any Chinese medicine composition, perhaps is prepared from as active component and substrate adjuvant and plasticity adjuvant by above-mentioned any Chinese medicine composition.
Described substrate adjuvant can be selected from drop pill substrate commonly used at present, and as Polyethylene Glycol-6000, Polyethylene Glycol-4000, Polyethylene Glycol-8000, sodium stearate, poloxamer, glyceryl monostearate etc., they can use or unite use separately.For example can select substrate Polyethylene Glycol-6000 commonly used for use, 53～58 ℃ of its condensation points.When adopting Polyethylene Glycol-6000 as substrate, its addition is 2～6 times of pharmaceutical composition of the present invention; Changing the material temperature is 60～100 ℃; The temperature of condensed fluid is 0～10 ℃ (the best is 5～10 ℃); Ball heavily is 5～50mg/ grain, diameter 1.95～4.29mm.Radix Salviae Miltiorrhizae of the present invention, Radix Notoginseng and Flos Carthami can be mixed or make separately water extract or alcohol extract, through predefecation, after ultrafiltrate is condensed into extractum, with Borneolum Syntheticum or Styrax and adjuvant mixed evenly after, add the transconversion into heat material, move into the jar that drips of drop pill machine, medicine liquid droplet is to condensed fluid such as liquid paraffin or methyl-silicone oil, remove condensed fluid, select ball.
But described substrate adjuvant is preferably from mainly from natural, the substrate adjuvant of plant origin particularly.
Specifically, the substrate adjuvant is selected from following one or more adjuvant: at least a substrate adjuvant in pharmaceutically useful monosaccharide, oligosaccharide, polysaccharide, sugar ester, sugar alcohol, fruit acid, advanced higher fatty acid derivative, high fatty alcohol, polyhydric alcohol, carbamide, the polyethylene oxide derivant.
In the above-mentioned substance, monosaccharide such as D-ribose, fructose, glucose, xylose; Oligosaccharide such as trehalose, Raffinose, maltose; Polysaccharide such as agarose; Sugar ester such as sucrose ester, D-ribonic acid-gamma lactone; Sugar alcohol such as erythritol, sorbitol, xylitol, arabitol, isomalt, lactose; Fruit acid such as malic acid, citric acid; Advanced higher fatty acid derivative such as sodium stearate, tristerin, tripalmitin, Lac; High fatty alcohol such as hexadecanol, octadecanol; Polyhydric alcohol such as phenylglycol; Polyethylene oxide derivant such as polyoxyethylene monostearate, polyoxyethylene alkyl ether, and above-claimed cpd contain water of crystallization chemical compound etc.In the above material, the natural adjuvant of plant origin such as D-ribose, fructose, glucose, xylose, trehalose, Raffinose, maltose, low melting-point agarose, sucrose ester, D-ribonic acid-gamma lactone, erythritol, sorbitol, xylitol, arabitol, isomalt, lactose, malic acid, citric acid, Lac etc., and they contain the water of crystallization chemical compound; Chemosynthesis adjuvant and animal origin adjuvant such as sodium stearate, tristerin, tripalmitin, hexadecanol, octadecanol, phenylglycol, Polyethylene Glycol, carbamide, polyoxyethylene monostearate, polyoxyethylene alkyl ether.In the above-mentioned substance, especially preferably from following one or more adjuvant: maltose, sucrose ester, sorbitol, xylitol, lactose, and they contain the water of crystallization chemical compound.
Above-mentioned substrate adjuvant is mainly the natural adjuvant of plant origin, is meant more than 50% of adjuvant of plant origin in adjuvant, and the content of chemosynthesis adjuvant and animal origin adjuvant is no more than the natural adjuvant of plant origin.Preferably, the substrate adjuvant of drop pill of the present invention only uses the natural adjuvant of plant origin, perhaps is mainly the natural adjuvant of plant origin and only contains a spot of chemosynthesis adjuvant and animal origin adjuvant, and its weight percentage is below 50%, preferred below 40%, more preferably below 30%.The natural adjuvant of above-described so-called plant origin is meant as adjuvant itself and extracts in plant cell or tissue, or by the material of plant extract through modifications such as derivatizations after the product of gained.So-called chemosynthesis adjuvant is meant synthetic micromolecule or the macromolecular compound that is obtained through chemical synthesis process by simple micromolecule.The natural adjuvant of so-called animal origin is meant as adjuvant itself and extracts in the animal cell or tissue, or the material that extracts by animal through modifications such as derivatizations after the product of gained.
The substrate adjuvant of above-mentioned plant origin, have now or in the future may have the synthetic product, if the synthetic product are identical or close with the character of the natural substrates adjuvant of original plant origin, characteristic with safety non-toxic, then the natural substrates adjuvant of alternative plant origin is used as the natural substrates adjuvant of above-mentioned plant origin.
For improving the formability of drop pill of the present invention, preferably also contain the plasticity adjuvant in the adjuvant of drop pill of the present invention.As this plasticity composition, for example can enumerate and be selected from following one or more composition: the natural adjuvant of plant origin such as starch and derivant, cellulose and derivant thereof, arabic gum, dextran, chitin, sesbania gum, carrageenan, Ficus elastica, Furcellaran, tragakanta, carrageenin, tamarind gum, pectin, xanthan gum, alginic acid and salt thereof, dextrin, cyclodextrin, agar, lactose; Chemosynthesis adjuvant and animal origin adjuvant such as polyvinylpyrrolidone, crospolyvinylpyrrolidone, carbomer, polyvinyl alcohol, acrylic resin, poloxamer, silicon dioxide, gelatin etc.
Above-mentioned starch and derivant thereof such as pregelatinized Starch, modified starch, hydroxypropyl starch, carboxymethyl starch etc.Described cellulose and derivant thereof such as methylcellulose, microcrystalline Cellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, cross-linking sodium carboxymethyl cellulose, hydroxyethylmethyl-cellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose.
In the plasticity composition, preferably from following one or more adjuvant: pregelatinized Starch, carboxymethyl starch, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, arabic gum, alginic acid, dextrin, cyclodextrin, agar, lactose.In addition, glyceryl monostearate, polyoxyethylene monostearate also can be used as the plasticity composition and other substrate supplementary product compatibility is used.
The composition of above-described so-called plant origin is meant as adjuvant itself and extracts in plant cell or tissue, or by the material of plant extract through modifications such as derivatizations after the product of gained.So-called chemosynthesis adjuvant is meant synthetic micromolecule or the macromolecular compound that is obtained through chemical synthesis process by simple micromolecule.The adjuvant of so-called animal origin is meant as adjuvant itself and extracts in the animal cell or tissue, or the material that extracts by animal through modifications such as derivatizations after the product of gained.
The plasticity composition of above-mentioned plant origin, have now or in the future may have the synthetic product, if the synthetic product are identical or close with the character of the natural plasticity composition of plant origin, characteristic with safety non-toxic, then the natural plasticity composition of alternative above-mentioned plant origin is used as the natural plasticity substrate adjuvant of above-mentioned plant origin.
The above-mentioned monosaccharide that is selected from, oligosaccharide, polysaccharide, sugar ester, sugar alcohol, fruit acid, advanced higher fatty acid derivative, high fatty alcohol, polyhydric alcohol, carbamide, the substrate adjuvant of polyethylene oxide derivant etc., the substrate adjuvant and the above-mentioned plasticity composition in preferred plant source are selected collocation according to medicinal property, it is preferably arranged in pairs or groups and is xylitol and starch, lactose and starch, xylitol and arabic gum, sucrose ester and glyceryl monostearate, sucrose ester and polyoxyethylene monostearate, sucrose ester and polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose, sucrose ester and polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose and silicon dioxide etc., but be not limited thereto.
Above-mentioned drop pill substrate adjuvant is 1: 0.1～1 with the ratio of the weight of pharmaceutical composition, be preferably 1: 0.1～and 0.6, the best is 1: 0.2～0.4.
The weight ratio of above-mentioned substrate adjuvant and plasticity composition is 1: 0～1.5, be preferably 1: 0.1～and 0.9, the best is 1: 0.1～0.5.
In the above-mentioned substrate adjuvant, xylitol is preferably 1: 0.2 with the ratio of the weight of starch～and 0.3;
In the above-mentioned substrate adjuvant, lactose is preferably 1: 0.2 with the ratio of the weight of starch～and 0.3;
In the above-mentioned substrate adjuvant, the ratio of the weight of xylitol and arabic gum is preferably 1: 0.2～and 0.4;
In the above-mentioned substrate adjuvant, the weight ratio of sucrose ester and glyceryl monostearate is 1: 0.1～1, and the best is 1: 0.5.
In the above-mentioned substrate adjuvant, the weight ratio of sucrose ester and polyoxyethylene monostearate is 1: 0.1～1, and the best is 1: 0.5.
In the above-mentioned substrate adjuvant, the weight ratio of sucrose ester and polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose is 1: (0.1～1): (0.1～1), the best are 1: 0.4: 0.6.
In the above-mentioned substrate adjuvant, the weight ratio of sucrose ester and polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose and silicon dioxide is 15: (7～15): (0.1～2): (0.1～2), the best are 15: 11: 1: 1.
Dropping pill formulation of the present invention adopts one or more aforesaid substrate adjuvants, and the substrate adjuvant meets aforementioned requirement with the ratio of the weight of medicine, and the substrate adjuvant also meets aforementioned requirement with the ratio of the weight of plasticity composition.The preparation of drop pill can be adopted following process conditions: medicine mixes mixing time with the substrate adjuvant be 10～30 minutes; A mixed heating and melting temperature of medicine and substrate adjuvant or a system temperature are 45～95 ℃, are preferably 60～95 ℃; Liquid coolant is liquid paraffin, methyl-silicone oil or vegetable oil such as Oleum Glycines, Semen Ricini wet goods, is preferably liquid paraffin, methyl-silicone oil; The temperature of liquid coolant is-20～30 ℃, is preferably 0～18 ℃; Dropper mouth internal diameter is 1.0～4.0mm, is preferably 1.2～2.5mm; The difference of dropper mouth external diameter and internal diameter is less for well.
Below by medicine of the present invention the experiment of the protective effect of Ischemia and Reperfusion in vivo in Rats myocardial damage is illustrated its beneficial effect.
1. animal model: Wistar strain male rat, open chest anesthetized is kept breathing, around left coronary artery, and carries out ligation between left auricle and pulmonary conus.
2. method: rat is divided into 4 groups at random: 1. sham operated rats (sham-operated contro1), normal saline is irritated stomach, 1ml/ days, totally 4 days; 2. myocardial ischemia-reperfusion group (M-IR), it is the same to irritate the stomach method; 3. FUFANG DANSHEN PIAN group (with reference to the preparation of the method for 2000 editions FUFANG DANSHEN PIAN of Chinese Pharmacopoeia) was dissolved in the 1ml normal saline with 2g crude drug/kg/ days, and it is the same to irritate the stomach method; 4. medicine group of the present invention (press embodiment six method preparation and extractum), be dissolved in the 1ml normal saline with 2g crude drug/kg/ days, it is the same to irritate the stomach method.
Not ligation of sham operated rats; Other group is in ligation perfusion again after 1 hour.Take out after injecting 1% her Wen orchid in the ligation left coronary artery once more before sacrifice of animal, ventricle, with the PBS rinsing, freezing 1 hour.After removing unnecessary tissue, 30 minutes (37 ℃) of dyeing in 1%TTC.With weight method calculating myocardium ischemia hazardous area (she does not dye the district by the Wen orchid), infarcted region (TTC does not dye the district).
3. the result of variations of myocardial infarct size
The myocardial infarction phenomenon was not seen in sham-operation in 7 hours; It is obvious that myocardial ischemia poured into after 6 hours myocardial infarction in 1 hour again; Medicine of the present invention can obviously dwindle the myocardial infarct size of myocardial reperfusion rat, shows that medicine of the present invention pours into the myocardium cell necrosis variation again to ischemic myocardial cells good protective action (seeing Table 1) is arranged.
Table 1 is respectively organized the variation of myocardial infarct size
Annotate: compare with the M-IR group,
*P＜0.05,
*P＜0.01; Compare with the FUFANG DANSHEN PIAN group,
△P＜0.05,
△ △P＜0.01.
The specific embodiment
The invention will be further elaborated below in conjunction with embodiment.These embodiment only are used to the purpose that exemplifies, rather than limit the present invention by any way.
Embodiment one
Crude drug adopts Radix Salviae Miltiorrhizae 375g, Radix Notoginseng 118g, Borneolum Syntheticum 4g, Flos Carthami 100g.
Obtain the ethanol extract of Radix Salviae Miltiorrhizae and Radix Notoginseng with ethanol extraction Radix Salviae Miltiorrhizae and Radix Notoginseng, with extracting liquid filtering, collect filtrate with gauze.Filtrate is that 6000 cellulose diacetate film carries out ultrafiltration with molecular cut off, and filter type adopts cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.5kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds the water ultrafiltration again 1 time, and the pH value of feed liquid is controlled at 5.Backwashing pressure is 0.15MPa, and backwashing period is that 0.5h, backwashing time are 1min.When with the in parallel method of using alternately recoil of ultrafiltration module, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, and exchange is carried out behind the certain interval of time, work 10min, recoil 30sec.The Chemical cleaning cycle is 0.5 month, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 0.05MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.35～1.39 (55 ℃).Flos Carthami powder is broken into fine powder, mixes all with above-mentioned extractum, drying is made granule.Borneolum Syntheticum and above-mentioned granule are mixed, are pressed into 1000, or sugar coating, promptly.
Embodiment two
Crude drug adopts Radix Salviae Miltiorrhizae 465g, Radix Notoginseng 30g, Borneolum Syntheticum 3.5g, Flos Carthami 85g.
Obtain the ethanol extract of Radix Salviae Miltiorrhizae and Radix Notoginseng with ethanol extraction Radix Salviae Miltiorrhizae and Radix Notoginseng, carry out microfiltration, collect filtrate with ceramic membrane.Filtrate is that 80000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and filter type adopts dead-end filtration.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.5Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 4.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 50 ℃, when feed liquid stock solution is concentrated 1/5, adds the dilute alcohol solution ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 9.Backwashing pressure is 2.5MPa, and backwashing period is that 1.5h, backwashing time are 10min.When with the in parallel method of using alternately recoil of ultrafiltration module, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, and exchange is carried out behind the certain interval of time, work 20min, recoil 3min.The Chemical cleaning cycle is 2 months, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 1.0MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.35～1.39 (55 ℃).Flos Carthami powder is broken into fine powder, mixes all, Borneolum Syntheticum and above-mentioned granule are mixed, add 3% polyvidone alcoholic solution system soft material, cross 18 mesh sieve system granules with above-mentioned extractum, 60 ℃ of dryings 30～45 minutes, granulate, the adding Pulvis Talci, mixing fills in capsule, promptly.
Embodiment three
Crude drug adopts Radix Salviae Miltiorrhizae 490g, Radix Notoginseng 84g, Borneolum Syntheticum 2.8g, Flos Carthami 60g.
Radix Salviae Miltiorrhizae, the Radix Notoginseng and Flos Carthami medical material of coarse pulverization are added in the extraction pot, add 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out the second time and extracts, and adds 4 times of water gagings, fries in shallow oil 1 hour, filters, and filtering residue discards, merging filtrate.Filtrate is that 6000 three cellulose acetate membrane carries out ultrafiltration with molecular cut off, and filter type adopts cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.5kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds the water ultrafiltration again 1 time, and the pH value of feed liquid is controlled at 5.Backwashing pressure is 0.15MPa, and backwashing period is that 0.5h, backwashing time are 1min.When with the in parallel method of using alternately recoil of ultrafiltration module, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, and exchange is carried out behind the certain interval of time, work 10min, recoil 30sec.The Chemical cleaning cycle is 0.5 month, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 0.05MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.32～1.40 (55 ℃), add Borneolum Syntheticum, mix homogeneously, with the lactose fluidisation, drying is made granule, promptly in the batch (-type) fluid bed.
Embodiment four
Crude drug adopts Radix Salviae Miltiorrhizae 242g, Radix Notoginseng 255g, Borneolum Syntheticum 2.6g, Flos Carthami 100g.
Radix Salviae Miltiorrhizae, the Radix Notoginseng and Flos Carthami medical material of coarse pulverization are added in the extraction pot, add 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out the second time and extracts, and adds 4 times of water gagings, fries in shallow oil 1 hour, filters, and filtering residue discards, merging filtrate.Filtrate is that 60000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and filter type adopts dead-end filtration.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.5Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 4.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 50 ℃, when feed liquid stock solution is concentrated 1/5, adds the dilute alcohol solution ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 9.Backwashing pressure is 2.5MPa, and backwashing period is that 1.5h, backwashing time are 10min.When with the in parallel method of using alternately recoil of ultrafiltration module, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, and exchange is carried out behind the certain interval of time, work 20min, recoil 3min.The Chemical cleaning cycle is 2 months, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 1.0MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.32～1.40 (55 ℃), add Borneolum Syntheticum, again with mannitol 30g, calcium disodium edetate 5g, distilled water 5ml, behind the said components mixing, lyophilization, packing, promptly.
Embodiment five
Crude drug adopts Radix Salviae Miltiorrhizae 26.0g, Radix Notoginseng 16.5g, Borneolum Syntheticum 0.35g, Flos Carthami 17.0g.
Obtain blended ethanol extract with 80% ethanol extraction Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami, get supernatant dividing behind this extracting solution high speed centrifugation.With this liquid molecular cut off is that 50000 sulfonated polysulfone membrane carries out ultrafiltration, and filter type adopts cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/8, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.Backwashing pressure is 2.5MPa, and backwashing period is that 1.5h, backwashing time are 10min.When with the in parallel method of using alternately recoil of ultrafiltration module, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, and exchange is carried out behind the certain interval of time, work 20min, recoil 3min.The Chemical cleaning cycle is 2 months, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 1.0MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.35～1.39 (55 ℃).Get extractum and Borneolum Syntheticum, evenly be heated to 60 ℃ of temperature, change material after 40 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃ with Polyethylene Glycol-600020g is mixed.In medicine liquid droplet to the 8 ℃ methyl-silicone oil, take out drop pill, oil removing, screen cloth selects ball, makes 1000 drop pill, promptly.
Embodiment six
Crude drug Radix Salviae Miltiorrhizae 29.0g, Radix Notoginseng 30.6g, Borneolum Syntheticum 0.6g, Flos Carthami 2.0g; Adjuvant lactose 18.0g, pregelatinized Starch 4.5g.
The Radix Salviae Miltiorrhizae of coarse pulverization, Radix Notoginseng and Flos Carthami medical material to extraction pot, are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill, and filters, and filtrate is concentrated to obtain the extractum that relative density is 1.32～1.40 (55 ℃).
Get above-mentioned extractum and Borneolum Syntheticum, evenly mixed with adjuvant lactose and pregelatinized Starch, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.
The drop pill (newly) that the new substrate adjuvant of above-mentioned usefulness is made with polyethylene glycol 6000 be the adjuvant dissolve scattered time limit of making drop pill (old), weight differential comparison (seeing the following form)
Above test data shows, the molten diffusing speed of the Chinese medicine dripping pills made from new substrate adjuvant of the present invention is faster, is more conducive to medicine and plays a role in the shortest time; The ball method of double differences is different all to be controlled in the pharmacopeia prescribed limit, and the alternative present chemosynthesis adjuvant of this natural substrates adjuvant is described, carries out suitability for industrialized production.
Embodiment seven
Crude drug Radix Salviae Miltiorrhizae 21.0g, Radix Notoginseng 38.0g, Borneolum Syntheticum 0.4g, Flos Carthami 3.0g; Adjuvant xylitol 15.0g, starch 5.0g.
Learn from else's experience the Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami medical material of coarse pulverization to extraction pot, add the 0.9g sodium bicarbonate, add 4 times of water gagings, decocted 2 hours, filter, filtering residue carries out extraction second time, adds 4 times of water gagings, decocted 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 75%, leaves standstill, and filters, and filtrate is concentrated to obtain the extractum that relative density is 1.32～1.40 (55 ℃).
Get above-mentioned extractum and Borneolum Syntheticum, evenly mixed with adjuvant xylitol and starch, be heated to 65 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 85 ℃.In medicine liquid droplet to the 8 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.65min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment eight
Crude drug Radix Salviae Miltiorrhizae 55.8g, Radix Notoginseng 3.4g, Borneolum Syntheticum 0.8g, Flos Carthami 7.2g; Adjuvant lactose 15.0g, arabic gum 3.0g.
With 30% ethanol extraction Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami, obtain the ethanol extract of Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami, with this extracting liquid filtering, collect filtrate with gauze.Filtrate is that 20000 cellulose diacetate film carries out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The condition of above-mentioned ultrafiltration is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/8, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Borneolum Syntheticum, evenly mixed with adjuvant lactose and arabic gum, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 85 ℃.In medicine liquid droplet to the 6 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.58min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment nine
Crude drug Radix Salviae Miltiorrhizae 59.3g, Radix Notoginseng 6.38g, Borneolum Syntheticum 0.34g, Flos Carthami 5.3g; Adjuvant xylitol 16.0g, tragakanta 5.0g.
The Radix Salviae Miltiorrhizae and the Radix Notoginseng of coarse pulverization are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out the second time and extracts, and adds 4 times of water gagings, fries in shallow oil 1 hour, filters, and filtering residue discards, and merging filtrate gets Radix Salviae Miltiorrhizae and Radix Notoginseng extracting solution.With 30% ethanol extraction Flos Carthami, get Flos Carthami extract.Above-mentioned Radix Salviae Miltiorrhizae and Radix Notoginseng extracting solution and Flos Carthami extracting solution are merged, leave standstill, filter.Filtrate is that 60000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/8, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Borneolum Syntheticum, evenly mixed with adjuvant xylitol and tragakanta, be heated to 60 ℃ of temperature, change material after 25 minutes, move in the dropping-pill machine jar that jar temperature remains on 89 ℃.In medicine liquid droplet to the 5 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.51min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment ten
Crude drug Radix Salviae Miltiorrhizae 36.0g, Radix Notoginseng 23.2g, Borneolum Syntheticum 0.8g, Flos Carthami 2.4g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 8.0g.
With 40% ethanol extraction Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami, obtain the ethanol extract of Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami, get supernatant with dividing behind this extracting solution high speed centrifugation.With this liquid molecular cut off is that 50000 sulfonated polysulfone membrane carries out ultrafiltration, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.5Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 4.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 50 ℃, when feed liquid stock solution is concentrated 1/5, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 9.
Get above-mentioned extractum and Borneolum Syntheticum, evenly mixed with adjuvant sucrose ester and polyoxyethylene monostearate, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 5 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.56min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 11
Crude drug Radix Salviae Miltiorrhizae 41.1g, Radix Notoginseng 8.0g, Borneolum Syntheticum 0.46g, Flos Carthami 5.0g; Adjuvant sucrose ester 15.0g, glyceryl monostearate 4.0g.
The Radix Salviae Miltiorrhizae of coarse pulverization, Radix Notoginseng and Flos Carthami medical material to extraction pot, are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate is that 60000 poly (ether sulfone) film carries out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/8, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Borneolum Syntheticum, evenly mixed with adjuvant sucrose ester and glyceryl monostearate, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 6 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.68min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 12
Crude drug Radix Salviae Miltiorrhizae 29.0g, Radix Notoginseng 30.6g, Borneolum Syntheticum 0.6g, Flos Carthami 3.5g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 2.0g, cross-linking sodium carboxymethyl cellulose 3.0g.
The Radix Salviae Miltiorrhizae of coarse pulverization, Radix Notoginseng and Flos Carthami medical material to extraction pot, are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate is that 60000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.5kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds water or dilute alcohol solution ultrafiltration 1 time again, and the pH value of feed liquid is controlled at 5.
Get above-mentioned extractum and Borneolum Syntheticum, evenly be heated to 65 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃ with adjuvant sucrose ester, polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose are mixed.In medicine liquid droplet to the 4 ℃ methyl-silicone oil, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.59min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 13
Crude drug Radix Salviae Miltiorrhizae 41.0g, Radix Notoginseng 18.0g, Borneolum Syntheticum 0.4g, Flos Carthami 6.5g; Adjuvant lactose 10.0g, carrageenan 8.0g, starch 2.0g.
Learn from else's experience the Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami medical material of coarse pulverization to extraction pot, add the 0.89g sodium bicarbonate, add 4 times of water gagings, decocted 2 hours, filter, filtering residue carries out extraction second time, adds 4 times of water gagings, decocted 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate is that 50000 polysulfonamides film carries out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.5Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 4.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 50 ℃, when feed liquid stock solution is concentrated 1/5, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 9.
Get above-mentioned extractum and Borneolum Syntheticum, evenly be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃ with adjuvant lactose, carrageenan and starch are mixed.In medicine liquid droplet to the 5 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.76min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 14
Crude drug Radix Salviae Miltiorrhizae 48.0g, Radix Notoginseng 11.0g, Borneolum Syntheticum 0.6g, Flos Carthami 4.6g; Adjuvant xylitol 10.0g, lactose 3.0g, arabic gum 5.0g.
The Radix Salviae Miltiorrhizae of coarse pulverization, Radix Notoginseng and Flos Carthami medical material to extraction pot, are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 75%, leaves standstill filtration.Filtrate is that 20000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds water or dilute alcohol solution ultrafiltration 1 time again, and the pH value of feed liquid is controlled at 6.
Get above-mentioned extractum and Borneolum Syntheticum, evenly be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 84 ℃ with adjuvant xylitol, lactose and arabic gum are mixed.In medicine liquid droplet to the 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.45min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 15
Crude drug Radix Salviae Miltiorrhizae 32.0g, Radix Notoginseng 25.0g, Borneolum Syntheticum 0.6g, Flos Carthami 3.7g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 6.0g, cross-linking sodium carboxymethyl cellulose 1.0g, silica 1 .0g.
The Radix Salviae Miltiorrhizae of coarse pulverization, Radix Notoginseng and Flos Carthami medical material to extraction pot, are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill filtration.Filtrate is that 20000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds water or dilute alcohol solution ultrafiltration 1 time again, and the pH value of feed liquid is controlled at 6.
Get above-mentioned extractum and Borneolum Syntheticum,, mixed evenly be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 84 ℃ with adjuvant sucrose ester, polyoxyethylene monostearate, cross-linking sodium carboxymethyl cellulose and silicon dioxide.In medicine liquid droplet to the 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.48min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 16
Crude drug Radix Salviae Miltiorrhizae 29.0g, Radix Notoginseng 32.0g, Borneolum Syntheticum 0.4g, Flos Carthami 6.0g; Adjuvant lactose 14.0g, tragakanta 5.0g.
Learn from else's experience the Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami medical material of coarse pulverization to extraction pot, add the 0.88g sodium bicarbonate, add 4 times of water gagings, decocted 2 hours, filter, filtering residue carries out extraction second time, adds 4 times of water gagings, decocted 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill filtration.Filtrate is that 20000 polyvinylidene fluoride film carries out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/9, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Borneolum Syntheticum, evenly mixed with adjuvant lactose and tragakanta, be heated to 65 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 85 ℃.In medicine liquid droplet to the 8 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.43min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 17
Crude drug Radix Salviae Miltiorrhizae 29.0g, Radix Notoginseng 30.6g, Styrax 0.6g, Flos Carthami 2.0g; Adjuvant lactose 18.0g, pregelatinized Starch 4.5g.
The Radix Salviae Miltiorrhizae of coarse pulverization, Radix Notoginseng and Flos Carthami medical material to extraction pot, are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill, and filters, and filtrate is concentrated to obtain the extractum that relative density is 1.32～1.40 (55 ℃).
Get above-mentioned extractum and Styrax, evenly mixed with adjuvant lactose and pregelatinized Starch, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.75min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 18
Crude drug Radix Salviae Miltiorrhizae 21.0g, Radix Notoginseng 38.0g, Styrax 0.4g, Flos Carthami 3.0g; Adjuvant xylitol 15.0g, starch 5.0g.
Learn from else's experience the Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami medical material of coarse pulverization to extraction pot, add the 0.9g sodium bicarbonate, add 4 times of water gagings, decocted 2 hours, filter, filtering residue carries out extraction second time, adds 4 times of water gagings, decocted 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 75%, leaves standstill, and filters, and filtrate is concentrated to obtain the extractum that relative density is 1.32～1.40 (55 ℃).
Get above-mentioned extractum and Styrax, evenly mixed with adjuvant xylitol and starch, be heated to 65 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 85 ℃.In medicine liquid droplet to the 8 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.67min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 19
Crude drug Radix Salviae Miltiorrhizae 55.8g, Radix Notoginseng 3.4g, Styrax 0.8g, Flos Carthami 7.2g; Adjuvant lactose 15.0g, arabic gum 3.0g.
With 30% ethanol extraction Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami, obtain the ethanol extract of Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami, with this extracting liquid filtering, collect filtrate with gauze.Filtrate is that 20000 cellulose diacetate film carries out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The condition of above-mentioned ultrafiltration is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/8, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Styrax, evenly mixed with adjuvant lactose and arabic gum, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 85 ℃.In medicine liquid droplet to the 6 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.61min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 20
Crude drug Radix Salviae Miltiorrhizae 59.3g, Radix Notoginseng 6.38g, Styrax 0.34g, Flos Carthami 5.3g; Adjuvant xylitol 16.0g, tragakanta 5.0g.
The Radix Salviae Miltiorrhizae and the Radix Notoginseng of coarse pulverization are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out the second time and extracts, and adds 4 times of water gagings, fries in shallow oil 1 hour, filters, and filtering residue discards, and merging filtrate gets Radix Salviae Miltiorrhizae and Radix Notoginseng extracting solution.With 30% ethanol extraction Flos Carthami, get Flos Carthami extract.Above-mentioned Radix Salviae Miltiorrhizae and Radix Notoginseng extracting solution and Flos Carthami extracting solution are merged, leave standstill, filter.Filtrate is that 60000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/8, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Styrax, evenly mixed with adjuvant xylitol and tragakanta, be heated to 60 ℃ of temperature, change material after 25 minutes, move in the dropping-pill machine jar that jar temperature remains on 89 ℃.In medicine liquid droplet to the 5 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.54min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 21
Crude drug Radix Salviae Miltiorrhizae 36.0g, Radix Notoginseng 23.2g, Styrax 0.8g, Flos Carthami 2.4g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 8.0g.
With 40% ethanol extraction Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami, obtain the ethanol extract of Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami, get supernatant with dividing behind this extracting solution high speed centrifugation.With this liquid molecular cut off is that 50000 sulfonated polysulfone membrane carries out ultrafiltration, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.5Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 4.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 50 ℃, when feed liquid stock solution is concentrated 1/5, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 9.
Get above-mentioned extractum and Styrax, evenly mixed with adjuvant sucrose ester and polyoxyethylene monostearate, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 5 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.54min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 22
Crude drug Radix Salviae Miltiorrhizae 41.1g, Radix Notoginseng 8.0g, Styrax 0.46g, Flos Carthami 5.0g; Adjuvant sucrose ester 15.0g, glyceryl monostearate 4.0g.
The Radix Salviae Miltiorrhizae of coarse pulverization, Radix Notoginseng and Flos Carthami medical material to extraction pot, are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate is that 60000 poly (ether sulfone) film carries out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/8, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Styrax, evenly mixed with adjuvant sucrose ester and glyceryl monostearate, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 6 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.65min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 23
Crude drug Radix Salviae Miltiorrhizae 29.0g, Radix Notoginseng 30.6g, Styrax 0.6g, Flos Carthami 3.5g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 2.0g, cross-linking sodium carboxymethyl cellulose 3.0g.
The Radix Salviae Miltiorrhizae of coarse pulverization, Radix Notoginseng and Flos Carthami medical material to extraction pot, are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate is that 60000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.5kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds water or dilute alcohol solution ultrafiltration 1 time again, and the pH value of feed liquid is controlled at 5.
Get above-mentioned extractum and Styrax, evenly be heated to 65 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃ with adjuvant sucrose ester, polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose are mixed.In medicine liquid droplet to the 4 ℃ methyl-silicone oil, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.57min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 24
Crude drug Radix Salviae Miltiorrhizae 41.0g, Radix Notoginseng 18.0g, Styrax 0.4g, Flos Carthami 6.5g; Adjuvant lactose 10.0g, carrageenan 8.0g, starch 2.0g.
Learn from else's experience the Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami medical material of coarse pulverization to extraction pot, add the 0.89g sodium bicarbonate, add 4 times of water gagings, decocted 2 hours, filter, filtering residue carries out extraction second time, adds 4 times of water gagings, decocted 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate is that 50000 polysulfonamides film carries out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.5Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 4.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 50 ℃, when feed liquid stock solution is concentrated 1/5, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 9.
Get above-mentioned extractum and Styrax, evenly be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃ with adjuvant lactose, carrageenan and starch are mixed.In medicine liquid droplet to the 5 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.78min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 25
Crude drug Radix Salviae Miltiorrhizae 48.0g, Radix Notoginseng 11.0g, Styrax 0.6g, Flos Carthami 4.6g; Adjuvant xylitol 10.0g, lactose 3.0g, arabic gum 5.0g.
The Radix Salviae Miltiorrhizae of coarse pulverization, Radix Notoginseng and Flos Carthami medical material to extraction pot, are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 75%, leaves standstill filtration.Filtrate is that 20000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds water or dilute alcohol solution ultrafiltration 1 time again, and the pH value of feed liquid is controlled at 6.
Get above-mentioned extractum and Styrax, evenly be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 84 ℃ with adjuvant xylitol, lactose and arabic gum are mixed.In medicine liquid droplet to the 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.47min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 26
Crude drug Radix Salviae Miltiorrhizae 32.0g, Radix Notoginseng 25.0g, Styrax 0.6g, Flos Carthami 3.7g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 6.0g, cross-linking sodium carboxymethyl cellulose 1.0g, silica 1 .0g.
The Radix Salviae Miltiorrhizae of coarse pulverization, Radix Notoginseng and Flos Carthami medical material to extraction pot, are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill filtration.Filtrate is that 20000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds water or dilute alcohol solution ultrafiltration 1 time again, and the pH value of feed liquid is controlled at 6.
Get above-mentioned extractum and Styrax,, mixed evenly be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 84 ℃ with adjuvant sucrose ester, polyoxyethylene monostearate, cross-linking sodium carboxymethyl cellulose and silicon dioxide.In medicine liquid droplet to the 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.48min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 27
Crude drug Radix Salviae Miltiorrhizae 29.0g, Radix Notoginseng 32.0g, Styrax 0.4g, Flos Carthami 6.0g; Adjuvant lactose 14.0g, tragakanta 5.0g.
Learn from else's experience the Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami medical material of coarse pulverization to extraction pot, add the 0.88g sodium bicarbonate, add 4 times of water gagings, decocted 2 hours, filter, filtering residue carries out extraction second time, adds 4 times of water gagings, decocted 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill filtration.Filtrate is that 20000 polyvinylidene fluoride film carries out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃).The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/9, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Styrax, evenly mixed with adjuvant lactose and tragakanta, be heated to 65 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 85 ℃.In medicine liquid droplet to the 8 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.45min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Claims (10)
1. Chinese medicine composition for the treatment of the myocardial infarction that myocardial ischemia causes is characterized in that it is to be prepared from by following materials of weight proportions medicine:
Radix Salviae Miltiorrhizae 20～97
Radix Notoginseng 2～79
Flos Carthami 10～40
Borneolum Syntheticum or Styrax 0.2～3.
2. Chinese medicine composition as claimed in claim 1 is characterized in that the weight proportion of described raw material is:
Radix Salviae Miltiorrhizae 63.0～94
Radix Notoginseng 4.0～35
Flos Carthami 15～30
Borneolum Syntheticum or Styrax 0.5～2.0.
3. Chinese medicine composition as claimed in claim 2 is characterized in that the weight proportion of described raw material is:
Radix Salviae Miltiorrhizae 75.2～90
Radix Notoginseng 9～23.5
Flos Carthami 20～25
Borneolum Syntheticum or Styrax 0.5～1.3.
4. as the described arbitrary Chinese medicine composition of claim 1～3, it is characterized in that its preparation comprises the steps:
(a) Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami are mixed or make water extract or alcohol extract separately;
(b) described extracting solution being carried out predefecation handles;
(c) further described extracting solution is carried out hyperfiltration treatment;
(d) ultrafiltrate is concentrated make extractum, mix with Borneolum Syntheticum or Styrax.
5. Chinese medicine composition as claimed in claim 4 is characterized in that the alcohol extraction employing of described step a is selected from following lower alcohol or its mixture: methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutanol; And/or
Described predefecation is treated to coarse filtration-adsorption clarification, adsorption clarification-high speed centrifugation, coarse filtration-microfiltration or coarse filtration-precipitate with ethanol; And/or
The used ultrafilter membrane of described hyperfiltration treatment is selected from: cellulose diacetate film, three cellulose acetate membrane, cyanoethyl cellulose film, polysulfone membrane, sulfonated polysulfone membrane, poly (ether sulfone) film, sulfonated polyether sulfone film, polysulfonamides film, phenolphthalein side group polyarylsulfone (PAS) film, polyvinylidene fluoride film, polyacrylonitrile film, polyimide film, cellulose membrane, methyl methacrylate-acrylonitrile copolymer film, polyacrylonitrile/cellulose diacetate blend film, the dynamically ultrafilter membrane that forms, and the Modified Membrane of above-mentioned film; The molecular cut off of its ultrafilter membrane is 6000～80000; And/or
The operating procedure condition of described hyperfiltration treatment is as follows: the inlet pressure of ultrafiltration is 0.1～0.5MPa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25～0.5kPa; Feed temperature is 15～50 ℃; The pH value of feed liquid is controlled at 5～9; When feed liquid stock solution is concentrated 1/15～1/5, add water or dilute alcohol solution ultrafiltration 1～2 time again; And/or
In the process of described ultrafiltration separately or unite the following method that adopts: periodic pressure fluctuation, periodically flow fluctuation, feed noble gas off and on; Wherein the pressure wave moment of periodic pressure fluctuation is 0.1～0.2Mpa, and periodically the flow speed wave moment of flow fluctuation is 1.0～2.0 meter per seconds, feeds noble gas off and on and be ventilation in 0.5 hour～2 hours once, each 1 minute.
6. Chinese medicinal composition preparation for the treatment of the myocardial infarction that myocardial ischemia causes, said preparation is gone up acceptable auxiliary by any Chinese medicine composition of claim 1-5 and any or various medicaments and is made.
7. preparation as claimed in claim 6, said preparation is a drop pill, described drop pill, any Chinese medicine composition and substrate adjuvant by claim 1-5 are prepared from, perhaps be prepared from by any Chinese medicine composition of claim 1-5 and substrate adjuvant and plasticity adjuvant, wherein said substrate adjuvant is selected from least a in pharmaceutically useful monosaccharide, oligosaccharide, polysaccharide, sugar ester, sugar alcohol, fruit acid, advanced higher fatty acid derivative, high fatty alcohol, polyhydric alcohol, carbamide, the polyethylene oxide derivant; Described plasticity substrate adjuvant is selected from starch and derivant, arabic gum, dextran, chitin, sesbania gum, carrageenan, Ficus elastica, Furcellaran, tragakanta, carrageenin, tamarind gum, pectin, xanthan gum, alginic acid and salt thereof, dextrin, cyclodextrin, agar, lactose; Polyvinylpyrrolidone, crospolyvinylpyrrolidone, carbomer, polyvinyl alcohol, acrylic resin, poloxamer, silicon dioxide, gelatin, glyceryl monostearate, polyoxyethylene monostearate.
8. preparation according to claim 7 is characterized in that, described substrate adjuvant is selected from sorbitol, xylitol, lactose, maltose, sucrose ester, and they contain in the water of crystallization chemical compound one or more; Described plasticity substrate adjuvant is selected from one or more in pregelatinized Starch, carboxymethyl starch, arabic gum, alginic acid, agar, lactose, glyceryl monostearate, polyoxyethylene monostearate, cross-linking sodium carboxymethyl cellulose, the silicon dioxide.
9. preparation according to claim 8, wherein said adjuvant is selected from a kind of of following combination: lactose and starch, xylitol and arabic gum, sucrose ester and glyceryl monostearate, sucrose ester and polyoxyethylene monostearate, sucrose ester, polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose, or sucrose ester, polyoxyethylene monostearate, cross-linking sodium carboxymethyl cellulose and silicon dioxide.
10. preparation as claimed in claim 9 is characterized in that the wherein said substrate adjuvant and the ratio of the weight of medicine are 1: 0.1～1; And/or the weight ratio of described substrate adjuvant and plasticity composition is 1: 0～1.5.
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