CN101084961B

CN101084961B - Medicinal composition containing ligusticum wallichii and musk, preparation method and preparation

Info

Publication number: CN101084961B
Application number: CN200610014278XA
Authority: CN
Inventors: 李旭; 郑永锋; 范立君
Original assignee: Tianjin Tasly Pharmaceutical Co Ltd
Current assignee: Tasly Pharmaceutical Group Co Ltd
Priority date: 2006-06-08
Filing date: 2006-06-08
Publication date: 2011-10-05
Anticipated expiration: 2026-06-08
Also published as: CN101084961A

Abstract

The invention discloses a Chinese medicinal composition for treating cardiovascular diseases, wherein the composition is prepared from Chuanxiong rhizome, pseudo-ginseng, musk and musk ketone as the raw materials, and the preparation process comprises the steps of mixing Chuanxiong rhizome with pseudo-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, charging musk or musk ketone, and producing preparation through the conventional process.

Description

A kind of pharmaceutical composition, preparation method and preparation that contains Rhizoma Chuanxiong and Moschus

Technical field

The present invention relates to a kind of Chinese medicine composition of using the ultrafiltration technology preparation.Particularly, the present invention relates to a kind of Chinese medicine composition for the treatment of cardiovascular disease.

Background technology

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 the compound rhizome of Sichuan lovage 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 rhizome of Sichuan lovage preparation, and determined suitable process condition, for the suitability for industrialized production of utilizing ultrafiltration to carry out the compound rhizome of Sichuan lovage preparation provides concrete solution.

Summary of the invention

The purpose of this invention is to provide the Chinese medicine composition of the treatment cardiovascular disease that a kind of impurity is few, loss of effective components is little, it has overcome the deficiencies in the prior art, has solved the difficult problem of suitability for industrialized production ultrafiltration technology condition operability.

Another object of the present invention is to provide a kind of preparation by the above-mentioned composition preparation.

Another purpose of the present invention is to provide a kind of dropping pill formulation by the above-mentioned composition preparation.

The present invention realizes by following technical step: with Rhizoma Chuanxiong, Radix Notoginseng and Moschus or Rhizoma Chuanxiong, Radix Notoginseng and muscone is crude drug, is prepared according to following steps:

(1) with Rhizoma Chuanxiong, panax 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, add Moschus or muscone, make preparation according to a conventional method.

The weight portion of above-mentioned raw materials medicine is: 20～97 parts of Rhizoma Chuanxiongs, 2～79 parts of Radix Notoginseng, 0.2～3 part of Moschus or muscone; Preferred weight part is: 63.0～94 parts of Rhizoma Chuanxiongs, 4.0～35.0 parts of Radix Notoginseng, 0.5～2.0 part of Moschus or muscone; More preferably: 75.2～90 parts of Rhizoma Chuanxiongs, 9～23.5 parts of Radix Notoginseng, 0.5～1.3 part of Moschus or muscone.

In the technology of the present invention step (1), alcohol extract can be the extracting solution of the lower alcohol of variable concentrations such as methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutanol etc. or the extracting solution of its mixture.Carrying out next step predefecation after alcohol extract can not concentrate or suitably concentrate handles.

In the technology of the present invention step (2), preliminary clarifying treatment can be carried out coarse filtration with general material such as gauze, tiffany etc., the also available material such as the ceramic membrane of specialty carry out microfiltration, 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 above-mentioned defecation method, but also use in conjunction, coarse filtration-adsorption clarification for example, adsorption clarification-high speed centrifugation, coarse filtration-microfiltration, coarse filtration-precipitate with ethanol etc.After can not concentrating or suitably concentrate, the solution that predefecation is handled carries out next step ultrafiltration; Preferably do not concentrate the ultrafiltration of promptly carrying out next step.

In the technology of the present invention step (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 above-mentioned ultrafilter membrane is generally 6000～80000, is preferably 10000～70000, and the best is 20000～50000.

Ultrafiltration both can be adopted cross flow filter, also can adopt dead-end filtration, but preferred cross flow filter.

The operating condition of 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.

(3) feed temperature is 15～50 ℃, is preferably 20～40 ℃.

(4) 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.

(5) pH value of feed liquid is controlled at 5～9, is preferably 6.0～7.5;

(6) 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.

(7) the Chemical cleaning cycle is 0.5 month～February, the Chemical cleaning medicament is generally diluted acid, diluted alkaline, surfactant, be preferably diluted alkaline, 0.5%～4.0% sodium hydroxide for example, 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, make preparation more according to a conventional method.For example, can be 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 etc. with adjuvant on any or more than one pharmaceuticss such as starch, dextrin, lactose, microcrystalline Cellulose, hydroxypropyl methylcellulose, Polyethylene Glycol, magnesium stearate, micropowder silica gel, xylitol, lactose, glucose, glycine, mannitol, glycine etc., preferred drop pill.

Drop pill of the present invention is prepared from as active component and adjuvant by above-mentioned Chinese medicine composition, perhaps is prepared from as active component and substrate adjuvant and plasticity adjuvant by above-mentioned Chinese medicine composition.

The substrate adjuvant of drop pill can be used Polyethylene Glycol, can be one or more the mixture in cetomacrogol 1000, polyethylene glycol 1500, Macrogol 4000, the polyethylene glycol 6000; Preferred Macrogol 4000, polyethylene glycol 6000; The best is a polyethylene glycol 6000; Addition is 2～10 times of extractum weight.

The preferred for preparation method is: after step (d) ultrafiltrate is condensed into extractum, directly with adjuvant or with Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil or Styrax or Moschus or muscone and adjuvant mixed even 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.

Wherein: adjuvant is a Polyethylene Glycol-6000, and 53～58 ℃ of its condensation points, addition are extractum or extractum and Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil or Styrax or Moschus or muscone weight 2～6 times; Changing the material temperature is 60～100 ℃; The temperature of condensed fluid is 0～10 ℃, and the best is 5～10 ℃; Ball heavily is 5～50mg/ grain, diameter 1.95～4.29mm.

The substrate adjuvant of drop pill preferably from natural, the substrate adjuvant of plant origin particularly, also can contain the plasticity composition in this substrate adjuvant.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 erythritol, sorbitol, fructose, D-ribonic acid-gamma lactone, arabitol, trehalose, D-ribose, low melting-point agarose, Lac, xylitol, Raffinose, glucose, malic acid, citric acid, isomalt, lactose, maltose, xylose, sucrose ester etc., and they contain the water of crystallization chemical compound; Chemosynthesis adjuvant and animal origin adjuvant such as phenylglycol, Polyethylene Glycol, hexadecanol, octadecanol, sodium stearate, tristerin, tripalmitin, carbamide, polyoxyethylene monostearate, polyoxyethylene alkyl ether.In the above-mentioned substance, especially preferably from following one or more adjuvant: sorbitol, xylitol, lactose, maltose, sucrose ester, and they contain the water of crystallization chemical compound.

Above-mentioned substrate adjuvant is mainly the natural adjuvant of plant origin, and the content that is meant the adjuvant of plant origin in adjuvant is more than 50 weight %, 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 content is below 50 weight %, below the preferred 40 weight %, more preferably below the 30 weight %.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 composition 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.

The weight ratio of above-mentioned substrate adjuvant and plasticity composition is 1: 0～1: 1.5, is preferably 1: 0.1～1: 0.9, and the best is 1: 0.1～1: 0.5.

In the above-mentioned substrate adjuvant, xylitol is preferably 1: 0.2 with the ratio of the weight of starch～and 1: 0.3;

In the above-mentioned substrate adjuvant, lactose is preferably 1: 0.2 with the ratio of the weight of starch～and 1: 0.3;

In the above-mentioned substrate adjuvant, the ratio of the weight of xylitol and arabic gum is preferably 1: 0.2～and 1: 0.4;

In the above-mentioned substrate adjuvant, the weight ratio of sucrose ester and glyceryl monostearate is 1: 0.1～1: 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 to 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.

Above-mentioned drop pill substrate adjuvant is 1: 0.1～1: 1 with the ratio of the weight of extractum, is preferably 1: 0.1～1: 0.6, and the best is 1: 0.2～1: 0.4.

The preferred for preparation process conditions are: extractum mixes mixing time with the substrate adjuvant be 10～30 minutes; A mixed heating and melting temperature of extractum 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 (Oleum Glycines, Semen Ricini wet goods) etc., 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 control), 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 was dissolved in the 1ml normal saline with 2g crude drug/kg/ days, and 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＜005, ^*P＜001; Compare with the FUFANG DANSHEN PIAN group, ^△P＜0.05, ^{△ △}P＜001.

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 Rhizoma Chuanxiong 450g, Radix Notoginseng 76g, Moschus 8g.

Obtain the ethanol extract of Rhizoma Chuanxiong with the ethanol extraction Rhizoma Chuanxiong, 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 water or dilute alcohol solution ultrafiltration 1 time again, 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 Rhizoma Chuanxiong extractum that relative density is 1.35～1.39 (55 ℃).Radix Notoginseng powder is broken into fine powder, mixes all with Rhizoma Chuanxiong extractum, drying is made granule.Moschus and above-mentioned granule are mixed, are pressed into 1000, or sugar coating, promptly.

Embodiment two

Crude drug adopts Rhizoma Chuanxiong 558g, Radix Notoginseng 34g, Moschus 8g.

With 70% ethanol extraction Rhizoma Chuanxiong and Radix Notoginseng, obtain the ethanol extract of Rhizoma Chuanxiong and Radix Notoginseng, carry out microfiltration with ceramic membrane, collect filtrate.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 water or dilute alcohol solution ultrafiltration 2 times again, 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 ℃), add Moschus, be mixed, add 3% polyvidone alcoholic solution system soft material with above-mentioned extractum, cross 18 mesh sieve system granules, 60 ℃ of dryings 30～45 minutes, granulate adds Pulvis Talci, mixing fills in capsule, promptly.

Embodiment three

Crude drug adopts Rhizoma Chuanxiong 360g, Radix Notoginseng 232g, Moschus 8g.

Obtain Rhizoma Chuanxiong and Radix Notoginseng extracting solution with 80% ethanol extraction Rhizoma Chuanxiong and Radix Notoginseng, 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 ℃), add Moschus, be mixed, be pressed into 1000 with above-mentioned granule, or sugar coating, promptly.

Embodiment four

Crude drug adopts Rhizoma Chuanxiong 500g, Radix Notoginseng 94g, Moschus 8g.

Rhizoma Chuanxiong extracts volatile oil, adds 0.5% HP-aqueous solution in the Rhizoma Chuanxiong volatile oil, and stirring and dissolving filters, and makes inclusion complex in solution, and is standby; Residue and Radix Notoginseng that Rhizoma Chuanxiong extracts behind the volatile oil add 5 times of water gagings, decoct 2 hours, filter, and 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 and inclusion complex in solution merge, and are that 6000 three cellulose acetate membrane carries out ultrafiltration, filter type employing cross flow filter with molecular cut off.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.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 Moschus, mix homogeneously, with the lactose fluidisation, drying is made granule, promptly in the batch (-type) fluid bed.

Embodiment five

Crude drug adopts Rhizoma Chuanxiong 290g, Radix Notoginseng 306g, Moschus 6g.

Rhizoma Chuanxiong extracts volatile oil, adds 0.5% HP-aqueous solution in the Rhizoma Chuanxiong volatile oil, and stirring and dissolving filters, and makes inclusion complex in solution, and is standby; Residue and Radix Notoginseng that Rhizoma Chuanxiong extracts behind the volatile oil add 5 times of water gagings, decoct 2 hours, filter, and 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 and inclusion complex in solution merge, and are that 80000 polysulfone membrane is carried out ultrafiltration, filter type employing dead-end filtration with molecular cut off.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.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 Moschus, again with mannitol 30g, calcium disodium edetate 5g, distilled water 5ml, behind the said components mixing, lyophilization, packing, promptly.

Embodiment six

Crude drug adopts Rhizoma Chuanxiong 210g, Radix Notoginseng 380g, Moschus 4g.

Rhizoma Chuanxiong extracts volatile oil, adds 0.5% HP-aqueous solution in the Rhizoma Chuanxiong volatile oil, and stirring and dissolving filters, and makes inclusion complex in solution, and is standby; Residue and Radix Notoginseng that Rhizoma Chuanxiong extracts behind the volatile oil add 5 times of water gagings, decoct 2 hours, filter, and 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 and inclusion complex in solution merge, and are that 50000 poly (ether sulfone) film carries out ultrafiltration, filter type employing cross flow filter with molecular cut off.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 1.32～1.40 (55 ℃),, be pressed into tablet this extractum and Moschus and an amount of magnesium stearate mix homogeneously.

Embodiment seven

Crude drug adopts Rhizoma Chuanxiong 450g, Radix Notoginseng 76g, muscone 4.5g.

Described ultrafiltrate concentrated obtain the Rhizoma Chuanxiong extractum that relative density is 1.35～1.39 (55 ℃).Radix Notoginseng powder is broken into fine powder, mixes all with Rhizoma Chuanxiong extractum, drying is made granule.Muscone and above-mentioned granule are mixed, are pressed into 1000, or sugar coating, promptly.

Embodiment eight

Crude drug adopts Rhizoma Chuanxiong 558g, Radix Notoginseng 34g, muscone 3.5g.

Described ultrafiltrate concentrated obtain the extractum that relative density is 1.35～1.39 (55 ℃), add muscone, be mixed with above-mentioned extractum, add 3% polyvidone alcoholic solution system soft material, cross 18 mesh sieve system granules, 60 ℃ of dryings 30～45 minutes, granulate adds Pulvis Talci, mixing, fill in capsule, promptly.

Embodiment nine

Crude drug adopts Rhizoma Chuanxiong 360g, Radix Notoginseng 232g, muscone 5g.

Described ultrafiltrate concentrated obtain the extractum that relative density is 1.35～1.39 (55 ℃), add muscone, be mixed, be pressed into 1000 with above-mentioned granule, or sugar coating, promptly.

Embodiment ten

Crude drug adopts Rhizoma Chuanxiong 500g, Radix Notoginseng 94g, muscone 3.8g.

Described ultrafiltrate concentrated obtain the extractum that relative density is 1.32～1.40 (55 ℃), add muscone, mix homogeneously, with the lactose fluidisation, drying is made granule, promptly in the batch (-type) fluid bed.

Embodiment 11

Crude drug adopts Rhizoma Chuanxiong 290g, Radix Notoginseng 306g, muscone 3.5g.

Described ultrafiltrate concentrated obtain the extractum that relative density is 1.32～1.40 (55 ℃), add muscone, again with mannitol 30g, calcium disodium edetate 5g, distilled water 5ml, behind the said components mixing, lyophilization, packing, promptly.

Embodiment 12

Crude drug adopts Rhizoma Chuanxiong 210g, Radix Notoginseng 380g, muscone 3g.

The Rhizoma Chuanxiong of coarse pulverization, pseudo-ginseng 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 50000 poly (ether sulfone) 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 0.35Mpa, 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 1.32～1.40 (55 ℃),, be pressed into tablet this extractum and muscone and an amount of magnesium stearate mix homogeneously.

Embodiment 13

Crude drug adopts Rhizoma Chuanxiong 210g, Radix Notoginseng 380g, muscone 3g.

Described extract concentrated obtain the extractum that relative density is 1.35～1.39 (55 ℃).Get that extractum and muscone and Polyethylene Glycol-6000 20g are mixed evenly to be heated to 60 ℃ of temperature, change material after 40 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.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 14

Crude drug adopts Rhizoma Chuanxiong 360g, Radix Notoginseng 232g, Moschus 8g, adjuvant xylitol 15.0g, starch 5.0g.

Get above-mentioned extractum and Moschus, 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 2.78min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 15

Crude drug adopts Rhizoma Chuanxiong 210g, Radix Notoginseng 380g, Moschus 4g, adjuvant lactose 15.0g, arabic gum 3.0g.

Rhizoma Chuanxiong extracts volatile oil, adds 0.5% HP-aqueous solution in the Rhizoma Chuanxiong volatile oil, and stirring and dissolving filters, and makes inclusion complex in solution, and is standby; Residue and Radix Notoginseng that Rhizoma Chuanxiong extracts behind the volatile oil add 5 times of water gagings, decoct 2 hours, filter, and 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 and inclusion complex in solution merge, and are that 50000 poly (ether sulfone) film carries out ultrafiltration, filter type employing cross flow filter with molecular cut off.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 20mi n, 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.

Get above-mentioned extractum and Moschus, 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 16

Crude drug adopts Rhizoma Chuanxiong 210g, Radix Notoginseng 380g, muscone 3g, adjuvant xylitol 16.0g, tragakanta 5.0g.

Get above-mentioned extractum and muscone, 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 2.62min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 17

Crude drug adopts Rhizoma Chuanxiong 450g, Radix Notoginseng 76g, Moschus 8g, sucrose ester 10.0g, polyoxyethylene monostearate 8.0g.

Get above-mentioned extractum, Moschus and adjuvant sucrose ester and polyoxyethylene monostearate are mixed evenly to be heated to 60 ℃ of temperature, changes material after 30 minutes, moves 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 2.64min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Claims

1. Chinese medicine composition for the treatment of angina pectoris is characterized in that it is prepared from by following raw materials in weight portion medicine:

Rhizoma Chuanxiong 20～97,

Radix Notoginseng 2～79,

Muscone 0.2～3.

2. Chinese medicine composition as claimed in claim 1 is characterized in that the weight portion proportioning of described raw material is:

Rhizoma Chuanxiong 63.0～94,

Radix Notoginseng 4.0～35.0,

Muscone 0.5～2.0.

3. Chinese medicine composition as claimed in claim 2 is characterized in that the weight portion proportioning of described raw material is:

Radix Salviae Miltiorrhizae 75.2～90,

Rhizoma Chuanxiong 9～23.5,

Muscone 0.5～1.3.

4. as the arbitrary described Chinese medicine composition of claim 1～3, it is characterized in that it is prepared from by following steps:

(a) with Rhizoma Chuanxiong, panax 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, add muscone, promptly.

5. Chinese medicine composition as claimed in claim 4 is characterized in that described alcohol extract is to be selected from the following lower alcohol or the extracting solution of its mixture: methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutanol; And/or

Described alcohol extract is an ethanol extract; And/or

What described step (a) obtained is the ethanol extract of Rhizoma Chuanxiong; And/or

What described step (a) obtained is the aqueous extract that Rhizoma Chuanxiong and panax mixed are made; 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.

6. preparation, said preparation is gone up acceptable auxiliary by each described 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, wherein said drop pill is prepared from by any Chinese medicine composition of claim 1-5 and substrate adjuvant and plasticity adjuvant, and 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, the luxuriant glue of Calculus Bovis from Northwest of China, 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 as claimed in 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 as claimed in claim 7, it is characterized in that described adjuvant is 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, a kind of combination in sucrose ester, polyoxyethylene monostearate, cross-linking sodium carboxymethyl cellulose and the 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.