CN1778342B - Chinese medicine composition for treating coronary heart disease - Google Patents
Chinese medicine composition for treating coronary heart disease Download PDFInfo
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- CN1778342B CN1778342B CN 200410072947 CN200410072947A CN1778342B CN 1778342 B CN1778342 B CN 1778342B CN 200410072947 CN200410072947 CN 200410072947 CN 200410072947 A CN200410072947 A CN 200410072947A CN 1778342 B CN1778342 B CN 1778342B
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Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
Abstract
A Chinese medicine for treating coronary heart disease and angina pectoris is prepared from red sage root, notoginseng, boreol and safflower through extracting the liquid extract from red sage root, notogingseng and safflower in water or alcohol, clarifying, ultrafiltering, concentrating, adding borneol and shaping.
Description
Technical field
The present invention relates to a kind of Chinese medicine composition of using the ultrafiltration technology preparation.Particularly, the present invention relates to a kind of Chinese medicine composition of using the treatment coronary heart disease of ultrafiltration technology preparation.
Background technology
FUFANG DANSHEN PIAN is that Chinese Pharmacopoeia is gone through the kind recorded of version, has the effect of blood circulation promoting and blood stasis dispelling, regulating QI to relieve pain, be used for feeling oppressed in the heart, angina pectoris, and be medicine commonly used clinically at present.Its traditional handicraft is: gets Radix Salviae Miltiorrhizae and extracts 3 times, added alcohol reflux 1.5 hours the 1st time, filter, and filtrate recycling ethanol, being concentrated into relative density is 1.30 (55～60 ℃); Add 50% alcohol reflux 1.5 hours the 2nd time, filter.Add water for the 3rd time and refluxed 2 hours, filter, merge filtrate the 2nd time, the 3rd time, reclaim ethanol, being concentrated into relative density is 1.40 (55～60 ℃), and with the 1st time concentrated solution merging, mixing, making relative density is the extractum of 1.35～1.39 (55 ℃).Radix Notoginseng powder is broken into fine powder, mixes all with Radix Salviae Miltiorrhizae extractum, drying is made granule.With the Borneolum Syntheticum porphyrize, be mixed with above-mentioned granule, be pressed into 1000, or sugar coating, promptly.
Though above-mentioned technology can make most effective ingredient be kept, also can remove the impurity of a great deal of, this technology is adopted in discovering in recent years, makes much relevant with immunity polysaccharose substance and many trace element that very big loss be arranged; And the production cycle of this production technology is long, complex process, and the production cost height, finished product stability is poor, easily produces environmental pollution.
Membrane separation technique (Membrane Separation Technique) is an emerging high efficient separation technology, by internationally recognized be a most rising great high production tech of mid-term 20 end of the centurys to 21 century.Ultrafiltration (Ultrafiltration, UF) technology is a kind of membrane separation technique, its ultimate principle is to utilize fenestra selectivity sieve performance, with separation, purification and condensed matter.Hyperfiltration process is that the anisotropic membrane (being asymmetric membrane) that utilizes macromolecular material to make is a filter medium, under normal temperature condition, relies on certain pressure and flow velocity, makes flow of solution through face, forces low molecular weight substance to see through film, and polymer substance is trapped.
Because hyperfiltration process is a physical method, do not have and must heat repeatedly, there be not " phase " to change, the probability of destroying effective ingredient is few than other universal method, characteristics such as technological process is short, thereby its be applied to extract in the research of pharmaceutically active ingredient become increasingly active, portioned product moves towards commercial production from laboratory research.Human ultrafiltrations such as 304 Wang Shiling of hospital of PLA are extracted effective ingredient baicalin in the Radix Scutellariae, the result shows that ultrafiltration is excellent than well-established law all aspect productive rate, purity, and a ultrafiltration can reach the injection requirement, do not need again row refining, technology is simple, and the production cycle can shorten 1～2 times of (Wang Shiling, Zheng Dianbao " ultrafiltration is extracted the preliminary investigation of baicalin ", Chinese patent medicine research, 1988 (3): 5).Wang Shiling etc. have also further studied the optimum process condition of ultrafiltration extraction baicalin, it is the key that improves baicalin yield and quality that the experimental result proof is selected the ultrafilter membrane in suitable aperture (molecular cut off is 6000～10000) for use, the fluid temperature that raises simultaneously or reduction concentration, strict control pH value (pH=1.5 during acidify, pH=7.0 when alkali is molten), can significantly improve ultrasiltrated rate, obtain best output effect (Wang Shiling, " ultrafiltration is once extracted the technical study of baicalin ", Chinese patent medicine, 1994,16 (3): 2).Xu Jinlin etc. are with ultrafiltration (polysulfone membrane, molecular cut off 6000) is used for the preparation of phytic acid, the phytic acid yield is 86.4%, and than the phytate method raising 12.6% of routine, and ultrafiltration gained phytic acid contains Phos hardly, appearance transparent is close to colourless (Xu Jinlin, Xu Jie, Wang Yuanjin " membrane separation technique prepares the research of phytic acid ", Chinese Journal of Pharmaceuticals, 1994,25 (4): 150).He Changsheng etc. use hyperfiltration technique separation and purification steviol glycosides, and adopting ultrathin plate-type hyperfiltration device and molecular cut off is that 10000 cellulose acetate membrane (CA film) purifies field experimentation to steviol glycosides, and its technological process is rationally feasible.The ultrafilter stable performance, the decoloration performance and the removal of impurity of film are respond well, bubble problem (He Changsheng in the time of can solving precipitation that steviol glycosides usually occurs in producing and embedding preferably, WangBing Nan, Zhu Shanshan " applied research of steviol glycosides ultrafiltration ", water technology, 1994,20 (2): 89).Huang is improved oneself and is adopted the refining sasanguasaponin of ultrafilter membrane (molecular cut off is 4000 and 10000 polysulfone membrane), compare with the domestic bleaching that mostly adopts, recrystallize method, the alcohol ether sedimentation method and the basic salt sedimentation method, the ultrafiltration flow process is simple, the efficient height, expense is low, to removing oils and fats, pigment, saccharide and the strong impurity of other hydrophilic in the thick sasanguasaponin, can both producing a desired effect, (Huang is improved oneself, " ultrafiltrationmembrane process is made with extra care the sasanguasaponin pre-test " water technology, 1995,21 (2): 99).Guo Li Wei of Nanjing University of Traditional Chinese Medicine etc. has relatively studied water alcohol method and ultrafiltration is clarified the influence of Fructus Corni preparation to its preparation ingredient, the result confirms that ultrafiltration is more effective to saccharide impurity in the removal medicinal liquid, molecular cut off is that 10000 ultrafilter membrane does not have obviously influence to meliatin (molecular weight is 384), but being 1000 film, molecular cut off makes meliatin loss about 50% (Guo Liwei, Peng Guoping, Pan Yang etc. " the refining comparative study that contains the Fructus Corni Chinese medicine preparation of water alcohol method and membrane separation process ", Chinese patent medicine, 1999,21 (2): 59).Wang Chengzhang etc. adopt ultrafiltration (polysulfone membrane; molecular cut off 30000) separates with the ethanol extract of polyamide absorb-elute method Folium Ginkgo; purification; detect through high performance liquid chromatography (HPLC); the ginkgetin salidroside content is about 45%; yield is 0.5%～0.7%; more conventional steam distillation; the organic solvent extraction method is excellent; and in ultrafiltration technology, can reduce discharge of wastewater, the protection environment reduces production costs; (Wang Chengzhang increases economic efficiency; Yu Qing, Tan Weihong etc. " application of ultrafiltration in purification Folium Ginkgo flavone glycoside ", forestry science and technology communication; 1997, (2): 21).
Though hyperfiltration technique is applied to the production of Chinese medicine preparation its unique advantage is arranged, its degree of applying is still very limited, traces it to its cause, and remains in following problem:
(1) medicinal herb components complexity, particularly many compound preparations, effective ingredient are also unclear fully, therefore need to carry out very deep research before hyperfiltration technique is applied to Chinese herbal and crude drugs preparations.For example because the complexity of composition, do not carry out a large amount of pharmacology and clinical research test fully estimate ultrafiltration to Chinese medicine preparation in before the drug effect influence degree of each composition, ultrafiltration can not be applied to the production of most of Chinese medicine preparation.
(2) kind of membrane material is few, and membrane aperture distributes wide, and performance is understable.Used ultrafilter membrane material has cellulose acetate, polyacrylonitrile, polysulfones, SPSF, polysulfonamides etc. in Chinese medicine preparation production.By its affinity classification, be broadly divided into two classes: hydrophobic film material and hydrophilic film material to water.Hydrophilic film such as cellulose acetate, SPSF material is few to solute absorption, and molecular cut off is less, but poor heat stability, mechanical strength, chemical proof, antibacterium erosiveness are not high usually; Hydrophobic film materials such as polysulfones, the mechanical strength height, high temperature resistant, anti-solvent, anti-biodegradation, but because of containing a large amount of hydrophobicity genes or chain link in the strand, and have more electrostatic charge, thereby the permeable speed of film is low, contamination resistance is lower.
(3) pollution problem of film is to hinder hyperfiltration technique is moved towards the commercial Application stage by laboratory research biggest obstacle.In the ultra-filtration process of Chinese medicine preparation, when not good as if the medicinal liquid pretreating effect, face easily pollutes, and fenestra stops up, and making permeation flux is that productivity ratio descends, even cisco unity malfunction, and production efficiency reduces, and cost rises, and causes the shortening in service life of film.
(4) system of selection of membrane module is not set up as yet, the optimization of still needing of ultrafiltration parameter.The factor that influences the ultrafiltration effect is a lot, comprises the selection of membrane module, the cleaning method after the definite and ultrafilter of technological parameter uses etc.Therefore be applicable to ultrafiltration apparatus and the operating procedure that the ultrafiltration of Chinese medicine system is used, remain further to be studied.
The relevant practical application that utilizes ultrafiltration to prepare FUFANG DANSHEN PIAN, present document does not have any report as yet.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 medicine of the present invention, and determined suitable process condition, for the suitability for industrialized production of utilizing ultrafiltration to carry out medicine of the present invention provides concrete solution.
Summary of the invention
The Chinese medicine that the purpose of this invention is to provide the treatment coronary heart disease of ultrafiltration preparation technology's preparation that a kind of impurity is few, loss of effective components is little, cost is low, it has overcome the deficiencies in the prior art, solve the difficult problem of suitability for industrialized production ultrafiltration technology condition operability, and on prescription, increased the cardiac stimulant effect of QI invigorating.
The present invention realizes by following technical step: with Radix Salviae Miltiorrhizae, Radix Notoginseng, Borneolum Syntheticum and Flos Carthami is crude drug, is prepared according to following steps:
(1) Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami are mixed or make water extract or alcohol extract separately;
(2) described extracting solution being carried out predefecation handles;
(3) further described extracting solution is carried out hyperfiltration treatment;
(4) ultrafiltrate is concentrated, add Borneolum Syntheticum, make preparation according to a conventional method.
The proportioning of above-mentioned raw materials medicine is counted by weight: Radix Salviae Miltiorrhizae 20～97, Radix Notoginseng 2～79, Borneolum Syntheticum 0.2～3, Flos Carthami 3～15; Be preferably: Radix Salviae Miltiorrhizae 63.0～94.0, Radix Notoginseng 4.0～35.0, Borneolum Syntheticum 0.5～2.0, Flos Carthami 4～10; More preferably: Radix Salviae Miltiorrhizae 75.2～90, Radix Notoginseng 9～23.5, Borneolum Syntheticum 0.5～1.3, Flos Carthami 5～8.
In the technology of the present invention step (1), alcohol extract can be the extracting solution of the lower alcohol of variable concentrations such as methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutanol etc. or the extracting solution of its mixture.Carrying out next step predefecation after alcohol extract can not concentrate or suitably concentrate handles.
In the technology of the present invention step (2), preliminary clarifying treatment can be carried out coarse filtration with general material such as gauze, tiffany etc., the also available material such as the ceramic membrane of specialty carry out microfiltration, also can behind high speed centrifugation, divide and get supernatant, adsorption clarifications such as also available flocculating agent such as flocculate with chitosan clarifier, 101 fruit juice clarifiers, ZTC1+1 natural clarifying agent, Ovum Gallus domesticus album flocculating agent and remove particle bigger in the medicinal liquid, also available alcohol deposition method is removed most impurity.Both can singly use above-mentioned defecation method, but also use in conjunction, coarse filtration-adsorption clarification for example, adsorption clarification-high speed centrifugation, coarse filtration-microfiltration, coarse filtration-precipitate with ethanol etc.After can not concentrating or suitably concentrate, the solution that predefecation is handled carries out next step ultrafiltration; Preferably do not concentrate the ultrafiltration of promptly carrying out next step.
In the technology of the present invention step (3), the used ultrafilter membrane of ultrafiltration can be cellulose diacetate film (CA), three cellulose acetate membrane (CTA), cyanoethyl cellulose film (CN-CA), polysulfone membrane (PS), sulfonated polysulfone membrane (SPS), poly (ether sulfone) film (PES), sulfonated polyether sulfone film (SPES), polysulfonamides film (PSA), phenolphthalein side group polyarylsulfone (PAS) film (PDS), polyvinylidene fluoride film (PVDF), polyacrylonitrile film (PAN), polyimide film (N), cellulose membrane, methyl methacrylate-acrylonitrile copolymer film (MMA-AN), polyacrylonitrile/cellulose diacetate (PAN/CA) blend film, the dynamically ultrafilter membrane that forms, and the Modified Membrane of above-mentioned film.Be preferably cellulose diacetate film (CA), three cellulose acetate membrane (CTA), polysulfone membrane (PS), sulfonated polysulfone membrane (SPS), poly (ether sulfone) film (PES), sulfonated polyether sulfone film (SPES), polysulfonamides film (PSA), polyvinylidene fluoride film (PVDF), polyacrylonitrile film (PAN).
The molecular cut off of above-mentioned ultrafilter membrane is generally 6000～80000, is preferably 10000～70000, and the best is 20000～50000.
Ultrafiltration both can be adopted cross flow filter, also can adopt dead-end filtration, but preferred cross flow filter.
The operating condition of ultrafiltration technology is as follows:
(1) the inlet pressure of ultrafiltration is 0.1～0.5MPa, is preferably 0.1～0.35Mpa, and the best is 0.25～0.35Mpa; The liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.5～0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1～0.2Mpa.
(2) the feed liquid flow velocity is 1.0～4.0m/s, is preferably 2.0～3.0m/s.In the ultra-filtration process, adopt the fluctuation of periodicity flow so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 1.0～2.0m/s.
(3) feed high-pressure inert gas such as nitrogen in the ultrafiltration system discontinuous, form the gas-liquid stream of pulses, the cycle is that 0.5h～2h ventilates once, each 1 minute.
(3) feed temperature is 15～50 ℃, is preferably 20～40 ℃.
(4) when feed liquid stock solution is concentrated 1/15～1/5, add water or dilute alcohol solution ultrafiltration 1～2 time again; Be preferably when feed liquid stock solution is concentrated 1/12～1/8, add water or dilute alcohol solution ultrafiltration 1～2 time again.
(5) pH value of feed liquid is controlled at 5～9, is preferably 6.0～7.5;
(6) backwash condition: backwashing pressure is 0.15～2.5MPa, and backwashing period is that 0.5～1.5h, backwashing time are 1min～10min.When ultrafiltration module use in parallel is replaced the method for recoil, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, exchange is carried out behind the certain interval of time, generally is work 10～20min, recoil 30sec～3min.
(7) the Chemical cleaning cycle is 0.5 month～February, the Chemical cleaning medicament is generally diluted acid, diluted alkaline, surfactant, be preferably diluted alkaline, 0.5%～4.0% sodium hydroxide for example, the mixed solution of 1.5% sodium hydroxide and 2% sodium hypochlorite etc., pH value is 10～12, and cleaning pressure is 0.05～1.0MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
In ultra-filtration process, both periodic pressure oscillation or the fluctuation of periodicity flow or periodicity fed noble gas separately, also can unite use, be periodic pressure fluctuation and periodically flow fluctuation associating use, perhaps the periodic pressure fluctuation is with periodically feeding noble gas unites use, perhaps periodically the flow fluctuation is with periodically feeding noble gas unites use, and perhaps the three unites use together.
In the technology of the present invention step (4), ultrafiltrate is condensed into extractum after, make preparation more according to a conventional method.For example, can be mixed and made into tablet, capsule, granule, oral liquid, slow releasing preparation, controlled release preparation, gel, ointment, ointment, cream, suppository, injection, injectable powder, patch, drop pill, suspensoid or the like with adjuvant on any or more than one pharmaceuticss such as starch, dextrin, lactose, microcrystalline Cellulose, hydroxypropyl methylcellulose, Polyethylene Glycol, magnesium stearate, micropowder silica gel, xylitol, lactose, glucose, glycine, mannitol, glycine etc.
The clinical observation of experimental example Drug therapy coronary heart disease of the present invention
1 clinical data
Patient who finds when 1.1 the object of observation is health check-up and the patient who originally just suffers from coronary heart disease, age is 42～84 years old, mean age is 61.4 years old, adopt the random packet method that 184 routine coronary disease patients are divided into 2 groups, medicine group of the present invention (for the treatment group) 88 examples, wherein male's 48 examples, women's 40 examples, 42～78 years old age, 58.6 years old mean age, the course of disease 4～25a.Sorbitrate group (being matched group) 96 examples, male's 52 examples, women's 44 examples, 46～84 years old age, 63.8 years old mean age. the course of disease 3～27a.Coronary heart disease diagnosis meets The World Health Organization's diagnostic criteria.
1.2 oral new compound Radix Salviae Miltiorrhizae Tabellae is organized in the observational technique treatment, each 3, every day 3 times, obeys for 12 weeks altogether: the oral sorbitrate of matched group, each 5mg, obeyed for 12 weeks altogether at every day 3 times.Measuring blood pressure, blood glucose, blood fat and Electrocardioscopy before the treatment.Inactive all other myocardial ischemic antagonists during the treatment, during the medication if any angina pectoris attacks, interim buccal nitroglycerin has hypertension, diabetics to continue to take depressor and antidiabetic drug, and per 2 weeks follow up a case by regular visits to 1 time, inquiry clinical symptoms and untoward reaction, record angina pectoris attacks number of times, pain condition, buccal nitroglycerin number of times, and simultaneously recorded heart rate, blood pressure etc., treatment finishes back check blood fat, blood glucose and Electrocardioscopy.
1.3 therapeutic evaluation standard
1.3.1 the angina pectoris symptom produce effects: angina pectoris disappears substantially, without nitroglycerin; Effectively: angina pectoris attacks number of times and nitroglycerin consumption reduce by half; Invalid: angina pectoris does not alleviate substantially or attack times reduces less than half; Increase the weight of: angina pectoris attacks number of times and nitroglycerin consumption increase.
1.3.2 electrocardiogram produce effects: treatment back tranquillization ischemic electrocardiogram recovers normally or is roughly normal: effectively: about ST section rise 0.5mv; The T ripple is inverted to shoal and is reached more than 50% or smooth transferring to uprightly; Invalid: ST-T changes not have and improves; Increase the weight of: ST-T changes and increases the weight of.
2 results
2.1 improving, angina pectoris sees Table 1
Table 1 liang group patient with angina pectoris therapeutic effect
Annotate: numeral is percentage rate (%) in ().
As seen from Table 1: after the treatment, measure two groups of patient's tranquillization ischemic electrocardiograms, treatment group total effective rate (produce effects adds effectively) is 93.18%, and matched group is 66.67%.μ=4.44, P＜0.01 liang group therapeutic scheme difference has highly significant.
2.2 improving, electrocardiogram sees Table 2
Table 2 patient with angina pectoris tranquillization ischemic ECG curative effect relatively
Annotate: numeral is percentage rate (%) in ()
As seen from Table 2: treatment group total effective rate (produce effects adds effectively) is 92.05%.Matched group is 62.50%.μ=4.73, P＜0.01, difference has highly significant..
2.3 the variation to blood pressure and heart rate relatively sees Table 3
Heart rate, blood pressure are relatively before and after the table 3 liang group medication
Annotate: compare P＜0.01 before * and the medication
As seen from Table 3: the heart rate of treatment group and blood pressure are being treated the forward and backward significant change that all has; And the matched group variation is not obvious.
2.4 the influence to blood fat sees Table 4
Table 4 liang group patient different pharmaceutical treatment is to blood fat influence (mmol/L)
As seen from Table 4: the medication of treatment group still has effect for reducing blood fat, and matched group is not obvious with the sorbitrate effect for reducing blood fat.
88 routine patients with coronary heart disease adopt new compound Radix Salviae Miltiorrhizae Tabellae therapeutic outcome to show that this medicine obviously is better than sorbitrate to the improvement of angina pectoris and myocardial ischemia, blood pressure and heart rate are descended, thereby play a part certain to the improvement that promotes myocardial ischemia.
The specific embodiment
The invention will be further elaborated below in conjunction with embodiment.These embodiment only are used to the purpose that exemplifies, rather than limit the present invention by any way.
Embodiment one
Crude drug adopts Radix Salviae Miltiorrhizae 450g, Radix Notoginseng 141g, Borneolum Syntheticum 8g, Flos Carthami 50g.
Obtain the ethanol extract of Radix Salviae Miltiorrhizae and Flos Carthami with ethanol extraction Radix Salviae Miltiorrhizae and Flos Carthami, with this extracting liquid filtering, collect filtrate with gauze.Filtrate is that 6000 cellulose diacetate film carries out ultrafiltration with molecular cut off, and filter type adopts cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.5kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds water or dilute alcohol solution ultrafiltration 1 time again, and the pH value of feed liquid is controlled at 5.Backwashing pressure is 0.15MPa, and backwashing period is that 0.5h, backwashing time are 1min.When with the in parallel method of using alternately recoil of ultrafiltration module, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, and exchange is carried out behind the certain interval of time, work 10min, recoil 30sec.The Chemical cleaning cycle is 0.5 month, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 0.05MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.35～1.39 (55 ℃).Radix Notoginseng powder is broken into fine powder, mixes all with above-mentioned extractum, drying is made granule.With the Borneolum Syntheticum porphyrize, be mixed with above-mentioned granule, be pressed into 1000, or sugar coating, promptly.
Embodiment two
Crude drug adopts Radix Salviae Miltiorrhizae 558g, Radix Notoginseng 34g, Borneolum Syntheticum 8g, Flos Carthami 72g.
Obtain the ethanol extract of Radix Salviae Miltiorrhizae and Flos Carthami with ethanol extraction Radix Salviae Miltiorrhizae and Flos Carthami, carry out microfiltration, collect filtrate with ceramic membrane.Filtrate is that 80000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and filter type adopts dead-end filtration.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.5Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 4.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 50 ℃, when feed liquid stock solution is concentrated 1/5, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 9.Backwashing pressure is 2.5MPa, and backwashing period is that 1.5h, backwashing time are 10min.When with the in parallel method of using alternately recoil of ultrafiltration module, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, and exchange is carried out behind the certain interval of time, work 20min, recoil 3min.The Chemical cleaning cycle is 2 months, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 1.0MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.35～1.39 (55 ℃).Radix Notoginseng powder is broken into fine powder, mixes all,, be mixed, add 3% polyvidone alcoholic solution system soft material, cross 18 mesh sieve system granules with above-mentioned granule with the Borneolum Syntheticum porphyrize with above-mentioned extractum, 60 ℃ of dryings 30～45 minutes, granulate, the adding Pulvis Talci, mixing fills in capsule, promptly.
Embodiment three
Crude drug adopts Radix Salviae Miltiorrhizae 360g, Radix Notoginseng 232g, Borneolum Syntheticum 8g, Flos Carthami 24g.
Obtain blended ethanol extract with ethanol extraction Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami, get supernatant dividing behind this extracting solution high speed centrifugation.With this liquid molecular cut off is that 50000 polysulfone membrane is carried out ultrafiltration, and filter type adopts cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/8, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.Backwashing pressure is 2.5MPa, and backwashing period is that 1.5h, backwashing time are 10min.When with the in parallel method of using alternately recoil of ultrafiltration module, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, and exchange is carried out behind the certain interval of time, work 20min, recoil 3min.The Chemical cleaning cycle is 2 months, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 1.0MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.35～1.39 (55 ℃).Drying is made granule.With the Borneolum Syntheticum porphyrize, be mixed with above-mentioned granule, add an amount of magnesium stearate mix homogeneously, be pressed into 1000, or sugar coating, promptly.
Embodiment four
Crude drug adopts Radix Salviae Miltiorrhizae 500 grams, Radix Notoginseng 94 grams, Borneolum Syntheticum 6 grams, Flos Carthami 42g.
Radix Salviae Miltiorrhizae, the Radix Notoginseng and Flos Carthami medical material of coarse pulverization are added in the extraction pot, add 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out the second time and extracts, and adds 4 times of water gagings, fries in shallow oil 1 hour, filters, and filtering residue discards, merging filtrate.Filtrate is that 6000 cellulose diacetate film carries out ultrafiltration with molecular cut off, and filter type adopts cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.5kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds water or dilute alcohol solution ultrafiltration 1 time again, and the pH value of feed liquid is controlled at 5.Backwashing pressure is 0.15MPa, and backwashing period is that 0.5h, backwashing time are 1min.When with the in parallel method of using alternately recoil of ultrafiltration module, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, and exchange is carried out behind the certain interval of time, work 10min, recoil 30sec.The Chemical cleaning cycle is 0.5 month, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 0.05MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.32～1.40 (55 ℃), add Borneolum Syntheticum, mix homogeneously, with the lactose fluidisation, drying is made granule, promptly in the batch (-type) fluid bed.
Embodiment five
Crude drug adopts Radix Salviae Miltiorrhizae 290 grams, Radix Notoginseng 306 grams, Borneolum Syntheticum 6 grams, Flos Carthami 20g.
Radix Salviae Miltiorrhizae, the Radix Notoginseng and Flos Carthami medical material of coarse pulverization are added in the extraction pot, add 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out the second time and extracts, and adds 4 times of water gagings, fries in shallow oil 1 hour, filters, and filtering residue discards, merging filtrate.Filtrate is that 80000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and filter type adopts dead-end filtration.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.5Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 4.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 50 ℃, when feed liquid stock solution is concentrated 1/5, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 9.Backwashing pressure is 2.5MPa, and backwashing period is that 1.5h, backwashing time are 10min.When with the in parallel method of using alternately recoil of ultrafiltration module, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, and exchange is carried out behind the certain interval of time, work 20min, recoil 3min.The Chemical cleaning cycle is 2 months, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 1.0MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.32～1.40 (55 ℃), add Borneolum Syntheticum, again with mannitol 30g, calcium disodium edetate 5g, distilled water 5ml, behind the said components mixing, lyophilization, 1000 of packing.
Embodiment six
Crude drug adopts Radix Salviae Miltiorrhizae 210 grams, Radix Notoginseng 380 grams, Borneolum Syntheticum 4 grams, Flos Carthami 30g.
Radix Salviae Miltiorrhizae, the Radix Notoginseng and Flos Carthami medical material of coarse pulverization are added in the extraction pot, add 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out the second time and extracts, and adds 4 times of water gagings, fries in shallow oil 1 hour, filters, and filtering residue discards, merging filtrate.Filtrate is that 50000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and filter type adopts cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/8, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.Backwashing pressure is 2.5MPa, and backwashing period is that 1.5h, backwashing time are 10min.When with the in parallel method of using alternately recoil of ultrafiltration module, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, and exchange is carried out behind the certain interval of time, work 20min, recoil 3min.The Chemical cleaning cycle is 2 months, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 1.0MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.32～1.40 (55 ℃),, be pressed into tablet this extractum and Borneolum Syntheticum and an amount of magnesium stearate mix homogeneously.
Claims (11)
1. a Chinese medicine composition for the treatment of coronary heart disease is characterized in that, it is to be prepared from by following raw materials in weight portion: Radix Salviae Miltiorrhizae 20～97, Radix Notoginseng 2～79, Borneolum Syntheticum 0.2～3, Flos Carthami 3～15; Described preparation method is:
(a) Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong are mixed or make water extract or alcohol extract separately;
(b) described extracting solution being carried out predefecation handles;
(c) further described extracting solution is carried out hyperfiltration treatment;
(d) ultrafiltrate is concentrated, add Borneolum Syntheticum, make preparation according to a conventional method;
The operating procedure condition of described hyperfiltration treatment is as follows:
The inlet pressure of ultrafiltration is 0.1～0.5MPa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25～0.5kPa; Feed temperature is 15～50 ℃; The pH value of feed liquid is controlled at 5～9; When feed liquid stock solution is concentrated 1/15～1/5, add water or dilute alcohol solution ultrafiltration 1～2 time again;
In the process of described ultrafiltration separately or unite the following method that adopts: periodic pressure fluctuation, periodically flow fluctuation, feed noble gas off and on; Wherein the pressure wave moment of periodic pressure fluctuation is 0.1～0.2Mpa, and periodically the flow speed wave moment of flow fluctuation is 1.0～2.0 meter per seconds, feeds noble gas off and on and be ventilation in 0.5 hour～2 hours once, each 1 minute.
2. Chinese medicine composition as claimed in claim 1 is characterized in that, the weight portion proportioning of described raw material is:
Radix Salviae Miltiorrhizae 63.0～94.0,
Radix Notoginseng 4.0～35.0,
Borneolum Syntheticum 0.5～2.0,
Flos Carthami 4～10.
3. Chinese medicine composition as claimed in claim 2 is characterized in that, the weight portion proportioning of described raw material is:
Radix Salviae Miltiorrhizae 75.2～90,
Radix Notoginseng 9～23.5,
Borneolum Syntheticum 0.5～1.3,
Flos Carthami 5～8.
4. Chinese medicine composition as claimed in claim 1 is characterized in that, described alcohol extract is to be selected from the following lower alcohol or the extracting solution of its mixture: methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutanol.
5. Chinese medicine composition as claimed in claim 1 is characterized in that, described alcohol extract is an ethanol extract.
6. Chinese medicine composition as claimed in claim 1 is characterized in that, what described step (a) obtained is the ethanol extract of Radix Salviae Miltiorrhizae and Flos Carthami.
7. Chinese medicine composition as claimed in claim 1 is characterized in that, what described step (a) obtained is the aqueous extract that Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami are mixed and made into.
8. Chinese medicine composition as claimed in claim 1 is characterized in that described predefecation is treated to coarse filtration-adsorption clarification, adsorption clarification-high speed centrifugation, coarse filtration-microfiltration or coarse filtration-precipitate with ethanol.
9. Chinese medicine composition as claimed in claim 1, it is characterized in that, the used ultrafilter membrane of described hyperfiltration treatment is selected from: cellulose diacetate film, three cellulose acetate membrane, cyanoethyl cellulose film, polysulfone membrane, sulfonated polysulfone membrane, poly (ether sulfone) film, sulfonated polyether sulfone film, polysulfonamides film, phenolphthalein side group polyarylsulfone (PAS) film, polyvinylidene fluoride film, polyacrylonitrile film, polyimide film, cellulose membrane, methyl methacrylate-acrylonitrile copolymer film, polyacrylonitrile/cellulose diacetate blend film, the dynamically ultrafilter membrane that forms, and the Modified Membrane of above-mentioned film; The molecular cut off of its ultrafilter membrane is 6000～80000.
10. Chinese medicine composition as claimed in claim 9, it is characterized in that, described ultrafilter membrane is selected from: cellulose diacetate film, three cellulose acetate membrane, polysulfone membrane, sulfonated polysulfone membrane, poly (ether sulfone) film, sulfonated polyether sulfone film, polysulfonamides film, polyvinylidene fluoride film, polyacrylonitrile film; The molecular cut off of its ultrafilter membrane is 10000～70000.
11. Chinese medicine composition as claimed in claim 4, it is characterized in that described preparation contains any or more than one are selected from following pharmaceutics adjuvant: starch, dextrin, lactose, microcrystalline Cellulose, hydroxypropyl methylcellulose, Polyethylene Glycol, magnesium stearate, micropowder silica gel, xylitol, lactose, glucose, glycine, mannitol.
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| CN1348815A (en) * | 2001-11-09 | 2002-05-15 | 天津天士力制药股份有限公司 | Medicine for preventing and treating coronary heart disease and angina pectoris and its prepn and other use |
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| CN1348815A (en) * | 2001-11-09 | 2002-05-15 | 天津天士力制药股份有限公司 | Medicine for preventing and treating coronary heart disease and angina pectoris and its prepn and other use |
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| Title |
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| 中华人民共和国药典.化学工业出版社,2000,518. * |
| 中华人民共和国药典2000年版.化学工业出版社,2000,518. * |
| 殷士海等.中药澄清分离技术的应用与发展.中国药业8 11.1999,8(11),56-57. |
| 殷士海等.中药澄清分离技术的应用与发展.中国药业8 11.1999,8(11),56-57. * |
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