CN101085070B - Traditional Chinese medicinal composition containing notoginseng and haw and its preparation - Google Patents

Abstract

The invention discloses a Chinese medicinal composition for treating cardiovascular diseases, which is prepared mainly from notoginseng, haw thorn, Chinese angelica root, motherwort, astragalus root, ginseng or Codonopsis pilosula, any one of the compositions may also comprise baras camphor, rosewood oil, liquidambar orientalis mill, musk or musk ketone. The invention also discloses preparations using any one of the medicinal compositions as the effective constituents, preferably drop pills. The auxiliary materials of the drop pill substrate can be polyethylene glycol or natural materials, especially those of plant sources. The medicament has quick effect and good therapeutic action for coronary disease and angina pectoris.

Description

The Chinese medicine composition and the preparation thereof that contain Radix Notoginseng, Fructus Crataegi

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

According to China's Epidemiological study, though over nearly 50 years in the rural area or the city, the M ﹠ M of cardiovascular and cerebrovascular disease is all in rising trend.50-60 age China population cause of death central vessel disease and cerebrovascular occupy the five or six respectively, then rise to the two or three respectively later in 1970, and cardiovascular and cerebrovascular disease death person has accounted for first of whole disease cause of the death.China accounts for part proportioning of total dead population because of cardiovascular and cerebrovascular disease death person, rise to 42.6% of calendar year 2001 by 12.07% of nineteen fifty-seven, the person reaches 2,000,000 to die from the cardiovascular and cerebrovascular disease every year, though other has the part patient to survive through rescue, but majority stays deformity, can't take care of oneself, cause serious burden to relatives and society.Cardiovascular and cerebrovascular disease also is western countries crowd main causes of death.Infer that according to present existing epidemiologic data advancing of disease trend is: to the year two thousand twenty, the human diseases cause of the death puts in order will have great change, but coronary heart disease and apoplexy will be first and second of the human cause of the death.Till that time, estimate that global coronary heart disease death number will increase to 1,100 ten thousand from 6,300,000 of nineteen ninety; Apoplexy increases to 7,700,000 from 4,400,000.Blood circulation cause of the death formation will increase 59.6% in 30 years, and coronary heart disease and apoplexy increase 74.6% and 75% respectively.These data prove absolutely that cardiovascular and cerebrovascular disease is not only the principal disease of harm humans health, especially human " the No.1 killer " who causes death, disables at present and in following 20 years.

In the medicine of cardiovascular and cerebrovascular disease, the application of Chinese medicine and western medicine emphasizes particularly on different fields, and Chinese medicine also occupies the bigger market share with the little advantage of its side effect.For example: the benefiting QI for activating blood circulation side [Zhu Weifeng, Shandong College of Traditional Chinese Medicine's journal, 1994,18 (5)] that forms by Radix Ginseng, Radix Codonopsis, Radix Angelicae Sinensis, Radix Salviae Miltiorrhizae, Flos Carthami; Add the red stilbene SHENGMAI YIN that Radix Salviae Miltiorrhizae, Radix Ginseng, Radix Notoginseng, Flos Carthami, Rhizoma Corydalis, Fructus Crataegi are formed, [Chen Yuchun, the bright traditional Chinese medical science, 1999,14 (5)] by SHENGMAI YIN; The coronary heart disease of being made up of Radix Ginseng, Radix Codonopsis, Radix Ophiopogonis, Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Lignum Dalbergiae Odoriferae is square [Wang Jinrong etc., Liaoning Journal of Traditional Chinese Medicine, 2001,28 (8)] substantially; By Radix Salviae Miltiorrhizae, Rhizoma Corydalis, Radix Ginseng, Radix Paeoniae Rubra, Rhizoma Chuanxiong, when the Shuxintongmai sheet that is grouped into [Wang Xiue etc., Shandong journal of Chinese medicine, 1997,16 (8)]; Or the like.But above clinical prescription and Chinese patent medicine all have certain weak point, or are partial to QI invigorating, or relatively activate yang, or relatively invigorate blood circulation, and do not obtain clinically popularizing in an all-round way.And dosage form mostly is traditional conventional tablet, capsule etc., production technology is more backward, and active constituent content is low, no quality control standard, therefore, utilize the new treatment cardiovascular disease of new technology development particularly the Chinese medicine of coronary heart disease be the target that vast medical worker makes great efforts.

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.

The relevant practical application that utilizes ultrafiltration to prepare notoginseng preparations, 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 notoginseng preparations, and determined suitable process condition, for the suitability for industrialized production of utilizing ultrafiltration to carry out notoginseng preparations 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

One of purpose of the present invention is to overcome the deficiencies in the prior art, and a kind of compositions for the treatment of cardiovascular disease is provided.

It is the preparation of effective ingredient that another object of the present invention provides with the said composition.

The present invention is implemented by the following technical programs:

Compositions of the present invention is mainly made by following raw materials in weight portion medicine: Radix Notoginseng 20～97, Fructus Crataegi 2～79; Also can add Radix Angelicae Sinensis or Herba Leonuri in the crude drug, its weight portion proportioning is a Radix Notoginseng 20～97, Fructus Crataegi 2～79, Radix Angelicae Sinensis or Herba Leonuri 5～25; Perhaps add the Radix Astragali or Radix Ginseng or Radix Codonopsis, its weight portion proportioning is a Radix Notoginseng 20～97, Fructus Crataegi 2～79, the Radix Astragali or Radix Ginseng or Radix Codonopsis 10～40; Further, in above-mentioned arbitrary prescription, also can add Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil or Styrax or Moschus or muscone in the crude drug, its weight portion proportioning is a Radix Notoginseng 20～97, Fructus Crataegi 2～79, Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil or Styrax or Moschus or muscone 0.2～3; Radix Notoginseng 20～97, Fructus Crataegi 2～79, Radix Angelicae Sinensis or Herba Leonuri 5～25, Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil or Styrax or Moschus or muscone 0.2～3; Radix Notoginseng 20～97, Fructus Crataegi 2～79, the Radix Astragali or Radix Ginseng or Radix Codonopsis 10～40, Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil or Styrax or Moschus or muscone 0.2～3.

But above-mentioned raw materials medicine both medication powder directly is mixed with compositions, also can will make preparation again behind whole crude drug or the part material medicine extraction extractum.Available decoction and alcohol sedimentation technique obtains extractum; Also available alcohol or water alcohol extracting method obtain extractum, and wherein alcohol is lower alcohol such as methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutanol etc.; Further coarse filtration, ultrafiltration of the extracting solution that decoction and alcohol sedimentation technique or alcohol extracting method or water alcohol extracting method obtain, the ultrafiltrate reconcentration becomes extractum.The preferred for preparation method may further comprise the steps:

(a) with Radix Notoginseng, Fructus Crataegi, perhaps Radix Notoginseng, Fructus Crataegi, Radix Angelicae Sinensis or Herba Leonuri, perhaps Radix Notoginseng, Fructus Crataegi, the Radix Astragali or Radix Ginseng or Radix Codonopsis are separately or be mixed and made into water extract or alcohol extract;

(b) described extracting solution being carried out predefecation handles;

(c) further described extracting solution is carried out hyperfiltration treatment;

(d) ultrafiltrate is condensed into extractum, or adds Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil or Styrax or Moschus or muscone again, promptly.

Wherein in the step (a), 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 step (b), 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 step (c), 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～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 step (d), ultrafiltrate is condensed into extractum, or mixes, promptly get Chinese medicine composition of the present invention with Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil or Styrax or Moschus or muscone.

The present invention also provides a kind of preparation for the treatment of cardiovascular disease, said preparation is made by the adjuvant of accepting on above-mentioned any Chinese medicine composition and any or more than one pharmaceuticss, wherein preparation can be but be not limited to 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; Be preferably tablet, capsule, granule, injection, drop pill; The best is a drop pill.

Drop pill of the present invention is prepared from as effective ingredient and adjuvant by above-mentioned any Chinese medicine composition, perhaps is prepared from as effective ingredient and substrate adjuvant and plasticity adjuvant by above-mentioned any 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 Chinese medicine composition weight, preferred 2～6 times.

The preferred for preparation method is: with the Chinese medicine composition in the step (d) and adjuvant mixed evenly after, add the transconversion into heat material, move into dripping jar of drop pill machine, medicine liquid droplet is removed condensed fluid to condensed fluid such as liquid paraffin or methyl-silicone oil, select ball.

Wherein: adjuvant is a Polyethylene Glycol-6000,53～58 ℃ of its condensation points, and 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 Chinese medicine composition of the present invention, 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: Chinese medicine composition of the present invention mixes mixing time with the substrate adjuvant be 10～30 minutes; A mixed heating and melting temperature of Chinese medicine composition 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 SANQI PIAN group (with reference to the preparation of the method for 2000 editions FUFANG SANQI 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 6 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 * P＜0.05, * * P＜0.01 with the M-IR group; Compare with the FUFANG SANQI 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 1

Crude drug adopts Radix Notoginseng 375g, Fructus Crataegi 118g, Lignum Dalbergiae Odoriferae oil 4.5g, Radix Ginseng 80g

Radix Notoginseng, Fructus Crataegi and people participate in 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 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 ℃).Add Lignum Dalbergiae Odoriferae oil, drying is made granule, and compacting is in blocks, or sugar coating, promptly.

Embodiment 2

Radix Notoginseng 465g, Fructus Crataegi 30g.

Fructus Crataegi is used 70% ethanol extraction, and extracting solution carries out microfiltration with ceramic membrane, collects filtrate; The filtrate ultrafiltration, the operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, 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.

Ultrafiltrate concentrates and obtains the extractum that relative density is 1.35～1.39 (55 ℃), adds the Radix Notoginseng of pulverizing, and adds 3% polyvidone alcoholic solution system soft material, crosses 18 mesh sieve system granules, 60 ℃ of dryings 30～45 minutes, granulate adds Pulvis Talci, mixing fills in capsule, promptly.

Embodiment 3

Crude drug Radix Notoginseng 485g, Fructus Crataegi 30g, Radix Angelicae Sinensis 100g, Borneolum Syntheticum 2.2g.

Fructus Crataegi and Radix Angelicae Sinensis 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 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 ℃).With the Radix Notoginseng of pulverizing, extractum and Borneolum Syntheticum in the batch (-type) fluid bed with the lactose fluidisation, drying is made granule, promptly.

Embodiment 4

Crude drug Radix Notoginseng 485g, Fructus Crataegi 70g, muscone 2.2g, Radix Codonopsis 50g.

Radix Notoginseng, Fructus Crataegi and Radix Codonopsis 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 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 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 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.

Ultrafiltrate concentrates and obtains the extractum that relative density is 1.32～1.40 (55 ℃), adds muscone, and mix homogeneously adds mannitol 30g, calcium disodium edetate 5g, distilled water 5ml, behind the said components mixing, and lyophilization, packing, promptly.

Embodiment 5

Crude drug Radix Notoginseng 180g, Fructus Crataegi 50g, Styrax 4g.

Radix Notoginseng and Fructus Crataegi 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 decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 1.1～1.2, 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 that extractum, Styrax and Polyethylene Glycol-600018g are mixed evenly to be heated to 85 ℃ 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 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, makes 1000 drop pill, promptly.

Embodiment 6

Crude drug Radix Notoginseng 12.5g, Fructus Crataegi 3.5g.

Radix Notoginseng adds 5 times of water gagings, decocts 2 hours, filters, 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.Fructus Crataegi is used 70% ethanol extraction, and merging filtrate and extracting solution are that 50000 sulfonated polysulfone 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 0.35Mpa, 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 that extractum and Polyethylene Glycol-600020g 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 7

Crude drug Radix Notoginseng 15g, Fructus Crataegi 4.5g, Lignum Dalbergiae Odoriferae oil 0.25g.Adjuvant lactose 18.0g, pregelatinized Starch 4.5g.

The Radix Notoginseng of coarse pulverization, Fructus Crataegi 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 Lignum Dalbergiae Odoriferae oil, 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 8

Crude drug Radix Notoginseng 24.2g, Fructus Crataegi 25.5g, Moschus 0.35g, Herba Leonuri 10.0g; Adjuvant xylitol 15.0g, starch 5.0g.

Learn from else's experience Radix Notoginseng, Fructus Crataegi and the Herba Leonuri 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 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 9

Crude drug Radix Notoginseng 16.2g, Fructus Crataegi 29.5g, Styrax 0.31g, Radix Astragali 13.8g; Adjuvant lactose 15.0g, arabic gum 3.0g.

With 80% ethanol extraction Radix Notoginseng, Fructus Crataegi and Milkvetch Root, obtain Radix Notoginseng, Fructus Crataegi and Radix Astragali ethanol extract, 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 the water ultrafiltration again 2 times, 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 10

Crude drug Radix Notoginseng 46.5g, Fructus Crataegi 5.0g, Borneolum Syntheticum 0.57g, Radix Ginseng 5.5g; Adjuvant xylitol 16.0g, tragakanta 5.0g.

Radix Notoginseng, Fructus Crataegi and the people of coarse pulverization are participated in 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 Notoginseng, Fructus Crataegi and Radix Ginseng extractive solution, leaves standstill, and filters.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 the dilute alcohol solution ultrafiltration again 2 times, 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 2.62min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 11

Crude drug Radix Notoginseng 46.5g, Fructus Crataegi 3.0g, Radix Ginseng 8.5g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 8.0g.

With 80% ethanol extraction Radix Notoginseng, Fructus Crataegi and Radix Ginseng, obtain the ethanol extract of Radix Notoginseng, Fructus Crataegi and Radix Ginseng, 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 the water ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 9.

Get that above-mentioned extractum and adjuvant sucrose ester and polyoxyethylene monostearate are mixed evenly to 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 2.64min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 12

Crude drug Radix Notoginseng 49.0g, Fructus Crataegi 16.5g, Radix Angelicae Sinensis 6.0g; Adjuvant sucrose ester 15.0g, glyceryl monostearate 4.0g.

Radix Notoginseng, Fructus Crataegi and the Radix Angelicae Sinensis medical material of coarse pulverization to extraction pot, 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 the water ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 7.5.

Get that above-mentioned extractum and adjuvant sucrose ester and glyceryl monostearate are mixed evenly to 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 2.67min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 13

Crude drug Radix Notoginseng 47.0g, Fructus Crataegi 8.6g, Borneolum Syntheticum 0.40g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 2.0g, cross-linking sodium carboxymethyl cellulose 3.0g.

The pseudo-ginseng of coarse pulverization to extraction pot, is 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.Fructus Crataegi is used 80% ethanol extraction, and merging filtrate and extracting solution are 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 the water ultrafiltration again 1 time, 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 2.66min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 14

Crude drug Radix Notoginseng 47.0g, Fructus Crataegi 18.0g, Radix Codonopsis 12.5g; Adjuvant lactose 10.0g, carrageenan 8.0g, starch 2.0g.

Learn from else's experience the Fructus Crataegi of coarse pulverization and codonopsis pilosula 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 the dilute alcohol solution ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 9.

Get above-mentioned extractum, the Radix Notoginseng of pulverizing and adjuvant lactose, carrageenan and starch 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 2.77min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 15

Crude drug Radix Notoginseng 48.0g, Fructus Crataegi 30.0, Borneolum Syntheticum 0.19g, Radix Ginseng 25.6g; Adjuvant xylitol 10.0g, lactose 3.0g, arabic gum 5.0g.

Radix Notoginseng, Fructus Crataegi and the ginseng crude drug of coarse pulverization to extraction pot, 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 the water ultrafiltration again 1 time, 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 2.55min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 16

Crude drug Radix Notoginseng 18.0g, Fructus Crataegi 20.0g, Borneolum Syntheticum 0.26g, Herba Leonuri 7.5g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 6.0g, cross-linking sodium carboxymethyl cellulose 1.0g, silica 1 .0g.

Radix Notoginseng, Fructus Crataegi and the Herba Leonuri medical material of coarse pulverization to extraction pot, 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 the dilute alcohol solution ultrafiltration again 1 time, 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 2.57min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 17

Crude drug Radix Notoginseng 23.0g, Fructus Crataegi 7.8g, Lignum Dalbergiae Odoriferae oil 0.21g, Radix Astragali 27.0g; Adjuvant lactose 14.0g, tragakanta 5.0g.

Learn from else's experience Radix Notoginseng, Fructus Crataegi and the Milkvetch Root 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 the water ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 7.5.

Get above-mentioned extractum and Lignum Dalbergiae Odoriferae oil, 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 2.49min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 18

Crude drug Radix Notoginseng 24.2g, Fructus Crataegi 25.0g, Radix Codonopsis 10.0g; Adjuvant lactose 18.0g, pregelatinized Starch 4.5g.

The Fructus Crataegi of coarse pulverization and codonopsis pilosula 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, the Radix Notoginseng of pulverizing and adjuvant lactose and pregelatinized Starch 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 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 2.81min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 19

Crude drug Radix Notoginseng 26.2g, Fructus Crataegi 7.0g, Radix Angelicae Sinensis 10.8g; Adjuvant xylitol 15.0g, starch 5.0g.

Learn from else's experience Radix Notoginseng, Fructus Crataegi and the Radix Angelicae Sinensis 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 that above-mentioned extractum and adjuvant xylitol and starch are mixed evenly to 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 2.73min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 20

Crude drug Radix Notoginseng 30.8g, Fructus Crataegi 15.2g, Lignum Dalbergiae Odoriferae oil 0.25g, Herba Leonuri 8.0g; Adjuvant lactose 15.0g, arabic gum 3.0g.

With 70% ethanol extraction Radix Notoginseng, Fructus Crataegi medical material, obtain Radix Notoginseng and Fructus Crataegi ethanol extract, with this extracting liquid filtering, collect filtrate with gauze.Herba Leonuri 70% ethanol extraction, merging filtrate and extracting solution are that 20000 cellulose diacetate film carries out ultrafiltration with molecular cut off, 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 the dilute alcohol solution ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 7.5.

Get above-mentioned extractum and Lignum Dalbergiae Odoriferae oil, 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 2.60min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 21

Crude drug Radix Notoginseng 46.5g, Fructus Crataegi 5.5g; Adjuvant xylitol 16.0g, tragakanta 5.0g.

The Radix Notoginseng and the Fructus Crataegi 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 Notoginseng and Radix Ginseng extractive solution, leaves standstill, and filters.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 the water ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 7.5.

Get that above-mentioned extractum and adjuvant xylitol and tragakanta are mixed evenly to 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 2.59min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 22

Crude drug Radix Notoginseng 26.0g, Fructus Crataegi 3.0g, Borneolum Syntheticum 0.21g, Radix Angelicae Sinensis 10.0g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 8.0g.

With 80% ethanol extraction Fructus Crataegi and Radix Angelicae Sinensis, obtain Fructus Crataegi and Radix Angelicae Sinensis ethanol extract, get supernatant with dividing behind this extracting solution high speed centrifugation.Radix Notoginseng is used 70% ethanol extraction, merges supernatant and extracting solution, is that 50000 sulfonated polysulfone membrane carries out ultrafiltration with this liquid molecular cut off, and ultrafiltrate is concentrated to obtain 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 the dilute alcohol solution ultrafiltration again 2 times, 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 2.61min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 23

Crude drug Radix Notoginseng 49.0g, Fructus Crataegi 12.5g, Borneolum Syntheticum 0.20g, Radix Ginseng 6.0g; Adjuvant sucrose ester 15.0g, glyceryl monostearate 4.0g.

Radix Notoginseng, Fructus Crataegi and the ginseng crude drug of coarse pulverization to extraction pot, 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 the water ultrafiltration again 2 times, 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 2.62min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 24

Crude drug Radix Notoginseng 21.0g, Fructus Crataegi 8.5g, Styrax 0.20g, Radix Angelicae Sinensis 9.0g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 2.0g, cross-linking sodium carboxymethyl cellulose 3.0g.

Radix Notoginseng, Fructus Crataegi and the Radix Angelicae Sinensis medical material of coarse pulverization to extraction pot, 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 the water ultrafiltration again 1 time, 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 2.62min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 25

Crude drug Radix Notoginseng 31.0g, Fructus Crataegi 31.5g, muscone 0.18g, Radix Codonopsis 12.5g; Adjuvant lactose 10.0g, carrageenan 8.0g, starch 2.0g.

Learn from else's experience Radix Notoginseng, Fructus Crataegi and the codonopsis pilosula 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 the dilute alcohol solution ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 9.

Get above-mentioned extractum and muscone, 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 2.74min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 26

Crude drug Radix Notoginseng 28.0g, Fructus Crataegi 16.6g, Lignum Dalbergiae Odoriferae oil 0.20g, Radix Angelicae Sinensis 8.0g; Adjuvant xylitol 10.0g, lactose 3.0g, arabic gum 5.0g.

Radix Notoginseng, Fructus Crataegi and the Radix Angelicae Sinensis medical material of coarse pulverization to extraction pot, 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 the dilute alcohol solution ultrafiltration again 1 time, and the pH value of feed liquid is controlled at 6.

Get above-mentioned extractum and Lignum Dalbergiae Odoriferae oil, 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 2.57min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 27

Crude drug Radix Notoginseng 28.0g, Fructus Crataegi 18.0g, Moschus 0.21g, Radix Ginseng 18.7g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 6.0g, cross-linking sodium carboxymethyl cellulose 1.0g, silica 1 .0g.

Radix Notoginseng, Fructus Crataegi and the ginseng crude drug of coarse pulverization to extraction pot, 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 the dilute alcohol solution ultrafiltration again 1 time, and the pH value of feed liquid is controlled at 6.

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

Embodiment 28

Crude drug Radix Notoginseng 23.0g, Fructus Crataegi 7.8g, Radix Ginseng 15.0g; Adjuvant lactose 14.0g, tragakanta 5.0g.

Learn from else's experience Radix Notoginseng, Fructus Crataegi and the ginseng crude drug 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 the water ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 7.5.

Get that above-mentioned extractum and adjuvant lactose and tragakanta are mixed evenly to 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 2.44min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 29

Crude drug Radix Notoginseng 26.0g, Fructus Crataegi 25.5g; Adjuvant sucrose ester 10.0g.

With 80% ethanol extraction Radix Notoginseng and Fructus Crataegi, obtain Radix Notoginseng and Fructus Crataegi ethanol extract, 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 the water ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 9.

Get that above-mentioned extractum and adjuvant sucrose ester and polyoxyethylene monostearate are mixed evenly to 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 2.64min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Embodiment 30

Crude drug Radix Notoginseng 49.0g, Fructus Crataegi 12.0g, Styrax 0.27g; Adjuvant sucrose ester 8.0g, polyoxyethylene monostearate 12.0g.

The Radix Notoginseng of coarse pulverization and Fructus Crataegi 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 the water ultrafiltration again 2 times, 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 2.67min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.

Claims (1)

1. Chinese medicine composition for the treatment of angina pectoris, it is made by crude drug Radix Notoginseng 12.5g, Fructus Crataegi 3.5g, and it is prepared from by the following method:

(1) Radix Notoginseng adds 5 times of water gagings, decocts 2 hours, filters, 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; Fructus Crataegi is used 70% ethanol extraction, and merging filtrate and extracting solution are that 50000 sulfonated polysulfone membrane carries out ultrafiltration with molecular cut off, and filter type adopts cross flow filter, wherein

The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa, the ultrafiltration initial stage is adopted lower pressure, slowly boost then, in ultra-filtration process, the fluctuation of employing periodic pressure, the pressure wave moment is 0.2Mpa, and the feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopt periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow, 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 1.5h, and backwashing time is 10min;

(2) described ultrafiltrate being concentrated relative density when obtaining 55 ℃ is 1.35～1.39 extractum, and it is evenly mixed to get extractum and Polyethylene Glycol-6000 20g, is heated to 60 ℃ of temperature, changes material after 40 minutes, moves to jar warm remaining in 90 ℃ the dropping-pill machine jar;

(3) 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.