CN1778326B - Medicine for treating cardiovascular disease - Google Patents
Medicine for treating cardiovascular disease Download PDFInfo
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- CN1778326B CN1778326B CN 200410072937 CN200410072937A CN1778326B CN 1778326 B CN1778326 B CN 1778326B CN 200410072937 CN200410072937 CN 200410072937 CN 200410072937 A CN200410072937 A CN 200410072937A CN 1778326 B CN1778326 B CN 1778326B
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- ultrafiltration
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- membrane
- heart disease
- coronary heart
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- 238000001256 steam distillation Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
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Abstract
A Chinese medicine for treating coronary heart disease is prepared from Chuan-xiong rhizome, notoginseng and dalbergia wood oil or storax is prepared through extracting the liquid extract from Chuan-xiong rhizome and notoginseng in water or alcohol, clarifying, ultrafiltering, concentrating, adding dalbergia wood oil or storax and shaping.
Description
Technical field
The present invention relates to a kind of Chinese medicine of using the ultrafiltration technology preparation.Particularly, the present invention relates to a kind of treat cardiovascular disease Chinese medicine composition.
Background technology
Membrane separation technique (Membrane Separation Technique) is an emerging high efficient separation technology, by internationally recognized be a most rising great high production tech of mid-term 20 end of the centurys to 21 century.Ultrafiltration (Ultrafiltration, UF) technology is a kind of membrane separation technique, its ultimate principle is to utilize fenestra selectivity sieve performance, with separation, purification and condensed matter.Hyperfiltration process is that the anisotropic membrane (being asymmetric membrane) that utilizes macromolecular material to make is a filter medium, under normal temperature condition, relies on certain pressure and flow velocity, makes flow of solution through face, forces low molecular weight substance to see through film, and polymer substance is trapped.
Because hyperfiltration process is a physical method, do not have and must heat repeatedly, there be not " phase " to change, the probability of destroying effective ingredient is few than other universal method, characteristics such as technological process is short, thereby its be applied to extract in the research of pharmaceutically active ingredient become increasingly active, portioned product moves towards commercial production from laboratory research.Human ultrafiltrations such as 304 Wang Shiling of hospital of PLA are extracted effective ingredient baicalin in the Radix Scutellariae, the result shows that ultrafiltration is excellent than well-established law all aspect productive rate, purity, and a ultrafiltration can reach the injection requirement, do not need again row refining, technology is simple, and the production cycle can shorten 1～2 times of (Wang Shiling, Zheng Dianbao " ultrafiltration is extracted the preliminary investigation of baicalin ", Chinese patent medicine research, 1988 (3): 5).Wang Shiling etc. have also further studied the optimum process condition of ultrafiltration extraction baicalin, it is the key that improves baicalin yield and quality that the experimental result proof is selected the ultrafilter membrane in suitable aperture (molecular cut off is 6000～10000) for use, the fluid temperature that raises simultaneously or reduction concentration, strict control pH value (pH=1.5 during acidify, pH=7.0 when alkali is molten), can significantly improve ultrasiltrated rate, obtain best output effect (Wang Shiling, " ultrafiltration is once extracted the technical study of baicalin ", Chinese patent medicine, 1994,16 (3): 2).Xu Jinlin etc. are with ultrafiltration (polysulfone membrane, molecular cut off 6000) is used for the preparation of phytic acid, the phytic acid yield is 86.4%, and than the phytate method raising 12.6% of routine, and ultrafiltration gained phytic acid contains Phos hardly, appearance transparent is close to colourless (Xu Jinlin, Xu Jie, Wang Yuanjin " membrane separation technique prepares the research of phytic acid ", Chinese Journal of Pharmaceuticals, 1994,25 (4): 150).He Changsheng etc. use hyperfiltration technique separation and purification steviol glycosides, and adopting ultrathin plate-type hyperfiltration device and molecular cut off is that 10000 cellulose acetate membrane (CA film) purifies field experimentation to steviol glycosides, and its technological process is rationally feasible.The ultrafilter stable performance, the decoloration performance and the removal of impurity of film are respond well, bubble problem (He Changsheng in the time of can solving precipitation that steviol glycosides usually occurs in producing and embedding preferably, WangBing Nan, Zhu Shanshan " applied research of steviol glycosides ultrafiltration ", water technology, 1994,20 (2): 89).Huang is improved oneself and is adopted the refining sasanguasaponin of ultrafilter membrane (molecular cut off is 4000 and 10000 polysulfone membrane), compare with the domestic bleaching that mostly adopts, recrystallize method, the alcohol ether sedimentation method and the basic salt sedimentation method, the ultrafiltration flow process is simple, the efficient height, expense is low, to removing oils and fats, pigment, saccharide and the strong impurity of other hydrophilic in the thick sasanguasaponin, can both producing a desired effect, (Huang is improved oneself, " ultrafiltrationmembrane process is made with extra care the sasanguasaponin pre-test " water technology, 1995,21 (2): 99).Guo Li Wei of Nanjing University of Traditional Chinese Medicine etc. has relatively studied water alcohol method and ultrafiltration is clarified the influence of Fructus Corni preparation to its preparation ingredient, the result confirms that ultrafiltration is more effective to saccharide impurity in the removal medicinal liquid, molecular cut off is that 10000 ultrafilter membrane does not have obviously influence to meliatin (molecular weight is 384), but being 1000 film, molecular cut off makes meliatin loss about 50% (Guo Liwei, Peng Guoping, Pan Yang etc. " the refining comparative study that contains the Fructus Corni Chinese medicine preparation of water alcohol method and membrane separation process ", Chinese patent medicine, 1999,21 (2): 59).Wang Chengzhang etc. adopt ultrafiltration (polysulfone membrane; molecular cut off 30000) separates with the ethanol extract of polyamide absorb-elute method Folium Ginkgo; purification; detect through high performance liquid chromatography (HPLC); the ginkgetin salidroside content is about 45%; yield is 0.5%～0.7%; more conventional steam distillation; the organic solvent extraction method is excellent; and in ultrafiltration technology, can reduce discharge of wastewater, the protection environment reduces production costs; (Wang Chengzhang increases economic efficiency; Yu Qing, Tan Weihong etc. " application of ultrafiltration in purification Folium Ginkgo flavone glycoside ", forestry science and technology communication; 1997, (2): 21).
Though hyperfiltration technique is applied to the production of Chinese medicine preparation its unique advantage is arranged, its degree of applying is still very limited, traces it to its cause, and remains in following problem:
(1) medicinal herb components complexity, particularly many compound preparations, effective ingredient are also unclear fully, therefore need to carry out very deep research before hyperfiltration technique is applied to Chinese herbal and crude drugs preparations.For example because the complexity of composition, do not carry out a large amount of pharmacology and clinical research test fully estimate ultrafiltration to Chinese medicine preparation in before the drug effect influence degree of each composition, ultrafiltration can not be applied to the production of most of Chinese medicine preparation.
(2) kind of membrane material is few, and membrane aperture distributes wide, and performance is understable.Used ultrafilter membrane material has cellulose acetate, polyacrylonitrile, polysulfones, SPSF, polysulfonamides etc. in Chinese medicine preparation production.By its affinity classification, be broadly divided into two classes: hydrophobic film material and hydrophilic film material to water.Hydrophilic film such as cellulose acetate, SPSF material is few to solute absorption, and molecular cut off is less, but poor heat stability, mechanical strength, chemical proof, antibacterium erosiveness are not high usually; Hydrophobic film materials such as polysulfones, the mechanical strength height, high temperature resistant, anti-solvent, anti-biodegradation, but because of containing a large amount of hydrophobicity genes or chain link in the strand, and have more electrostatic charge, thereby the permeable speed of film is low, contamination resistance is lower.
(3) pollution problem of film is to hinder hyperfiltration technique is moved towards the commercial Application stage by laboratory research biggest obstacle.In the ultra-filtration process of Chinese medicine preparation, when not good as if the medicinal liquid pretreating effect, face easily pollutes, and fenestra stops up, and making permeation flux is that productivity ratio descends, even cisco unity malfunction, and production efficiency reduces, and cost rises, and causes the shortening in service life of film.
(4) system of selection of membrane module is not set up as yet, the optimization of still needing of ultrafiltration parameter.The factor that influences the ultrafiltration effect is a lot, comprises the selection of membrane module, the cleaning method after the definite and ultrafilter of technological parameter uses etc.Therefore be applicable to ultrafiltration apparatus and the operating procedure that the ultrafiltration of Chinese medicine system is used, remain further to be studied.
The inventor by a large amount of experimental datas are analyzed, has determined suitable process condition, for the suitability for industrialized production of utilizing ultrafiltration to carry out medicine of the present invention provides concrete solution through the effort of long-term and unremitting ground.
Summary of the invention
The purpose of this invention is to provide the Chinese medicine of the treatment cardiovascular disease that a kind of impurity is few, loss of effective components is little, it has overcome the deficiencies in the prior art, has solved the difficult problem of suitability for industrialized production ultrafiltration technology condition operability.
The present invention realizes by following technical step: with Rhizoma Chuanxiong, Radix Notoginseng and Lignum Dalbergiae Odoriferae oil is crude drug, is prepared according to following steps:
(1) with Rhizoma Chuanxiong, panax mixed or make water extract or alcohol extract separately;
(2) described extracting solution being carried out predefecation handles;
(3) further described extracting solution is carried out hyperfiltration treatment;
(4) ultrafiltrate is concentrated, add Lignum Dalbergiae Odoriferae oil, make preparation according to a conventional method.
The percentage by weight of above-mentioned raw materials medicine is: Rhizoma Chuanxiong 20%～97%, Radix Notoginseng 2%～79%, Lignum Dalbergiae Odoriferae oil 0.2%～3%; Be preferably Rhizoma Chuanxiong 63.0%%～94%, Radix Notoginseng 4.0%～35.0%, Lignum Dalbergiae Odoriferae oil 0.5%～2.0%; More preferably Rhizoma Chuanxiong 75.2%～90%, Radix Notoginseng 9%～23.5%, Lignum Dalbergiae Odoriferae oil 0.5%～1.3%.The percentage by weight sum of Rhizoma Chuanxiong, Radix Notoginseng, Lignum Dalbergiae Odoriferae oil is 100%.
The above-mentioned raw materials Lignum Dalbergiae Odoriferae can be replaced with Styrax, and promptly the above-mentioned raw materials medicine can be Rhizoma Chuanxiong 20%～97%, Radix Notoginseng 2%～79%, Styrax 0.2%～3%; Be preferably Rhizoma Chuanxiong 63.0%%～94%, Radix Notoginseng 4.0%～35.0%, Styrax 0.5%～2.0%; More preferably Rhizoma Chuanxiong 75.2%～90%, Radix Notoginseng 9%～23.5%, Styrax 0.5%～1.3%.The percentage by weight sum of Rhizoma Chuanxiong, Radix Notoginseng, Styrax is 100%.
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 angina pectoris of the present invention
1 data and method
1.1 case is selected: 124 routine patients all meet the diagnostic criteria of the middle angina pectoris of Ministry of Public Health bureau of drug administration " Clinical Researches of New Drugs guideline " in 1993, and meet the diagnostic criteria for coronary heart disease of WHO formulation in 1979.All cases are the coronary heart disease stable type fatigue patient with angina pectoris that shows effect weekly more than 2 times.Get rid of unstable angina pectoris, myocardial infarction, other heart disease, merge the above hypertension of moderate [blood pressure＞24/14kPa (1kPa=7.5mmHg)] cardio-pulmonary function serious hindrance, severe arrhythmia, severe neurosis, climacteric syndrome and gestation, women breast-feeding their children.
124 routine patients are in hospital and the outpatient for the Supreme People's Court and the Supreme People's Procuratorate, be in hospital and the out-patient than being 3:2.All cases are divided into 2 groups at random.84 examples are organized in treatment, male 52 examples, women 32 examples, 43 years old～78 years old age, average 63 ± 12 years old; The course of disease 1 year～12 years, average 4.3 ± 1.2 years.Matched group 40 examples, male 24 examples, women 16 examples, 39 years old～76 years old age, average 61 ± 11 years old; The course of disease 1 year～15 years, average 4.6 ± 1.6 years.Data such as 2 groups of patient's age, sex, the course of disease there are no significant difference (P all＞0.05) has comparability.
1.2 Therapeutic Method: oral medicine of the present invention is organized in treatment, each 3, and every day 3 times; The oral DIAOXINXUE KANG of matched group, each 0.2g, every day 3 times.Be for 4 weeks 2 groups of courses of treatment.All withdraw 1 week of other cardiovascular drugs (comprise expand the blood vessel medicine, anti-blood is pulled medicines such as medicine and blood fat reducing for a short time) before 2 groups of patient treatments; Angina pectoris takes place during the treatment can obey nitroglycerin and carry out dosage and the record of number of times.
1.3 observation item
1.3.1 the frequency of itemized record patient's angina pectoris attacks, position, degree, persistent period, nitroglycerin consumption, heart rate and blood pressure.
1.3.2 do conventional 12 lead electrocardiogram before and after the medication, force down scope and the degree that summation (∑ ST) is represented myocardial ischemia with descend lead number (NST) and ST section of ST section, representing the degree of myocardial oxygen consumption with heart rate (HR), 2 products of systolic pressure (SBP) (RPP) is the myocardial oxygen consumption index.
Abdomen venous blood detects hemorheology index (project comprises whole blood viscosity, hematocrit value and erythrocyte aggregation index), serum total cholesterol (TC), triglyceride (TG), HDL-C (HDLC), apolipoprotein (ApoA1, ApoB) 1.3.3 find time before and after the treatment, does liver function, renal function, blood, urine routine test simultaneously.
1.4 curative effect mark Huaihe River
1.4.1 curative effect to treat angina pectoris: produce effects: the angina pectoris attacks number of times reduces more than 80%, and the nitroglycerin consumption reduces more than 80% or equal tired degree does not cause angina pectoris; Effectively: angina pectoris attacks number of times and nitroglycerin consumption all reduce 50%～80%; Invalid: angina pectoris attacks number of times and nitroglycerin consumption reduce less than 50%; Increase the weight of: angina pectoris attacks number of times, degree and persistent period, nitroglycerin consumption increase.
1.4.2 ECG curative effect: produce effects: resting electrocardiogram recovers normal; Effectively: the resting electrocardiogram ischemic ST moves down more than the treatment back rise 1.5mm or the T ripple inversion of mainly leading shoals reaches more than 50%, or the smooth commentaries on classics of T popin is upright; Invalid: resting electrocardiogram is preceding basic identical with treatment; Increase the weight of: resting electrocardiogram ST section is the preceding decline 〉=0.5mm of treatment, and main T ripple intensification 〉=50% or upright T ripple become smooth, or smooth T ripple transfers inversion to.
1.5 statistical procedures: (x ± s) expression adopts the t check to measurement data with mean ± standard deviation; Enumeration data x
2Check, there is significance P＜0.05 for difference.
2 results
2.1 curative effect to treat angina pectoris
2.1.12 the curative effect of angina pectoris symptom relatively sees Table 1 behind the group patient treatment
The curative effect of angina pectoris symptom relatively behind 2 groups of patient treatments of table 1
2.1.22 angina pectoris attacks frequency, persistent period and nitroglycerin consumption relatively sees Table 2 before and after the group patient treatment.
The comparison of rap pain seizure frequency persistent period and nitroglycerin consumption behind 2 groups of patient treatment bacterium of table 2 (x ± s)
Annotate: compare 1 with the treatment of this group is preceding) P＜0.05,2) P＜0.01,3) P＜0.001; With after the treatment of control group relatively: 4) P＜0.01
2.2 ECG curative effect
2.2.12 the electrocardio curative effect relatively sees Table 3 behind the group patient treatment.
The electrocardio curative effect relatively behind 2 groups of patient treatments of table 3
2.2.22 electrocardiogram ∑ ST before and after the group patient treatment, NST, HR, SBP, RPP relatively see Table 4.
2.32 the variation of hemorheology index relatively sees Table 5 before and after the group patient treatment
2.42 the variation of blood fat relatively sees Table 6 before and after the group patient treatment
∑ ST behind 2 groups of patient treatments of table 4, NST, HR, the comparison of SBP and RPP (x ± s)
Annotate: relatively preceding with the treatment of this group: 1) P＜0.05,2) P＜0.01; With after the treatment of control group relatively: 3) P＜0.05,4) P＜0.01
Hemorheology index variation comparison before and after 2 groups of patient treatments of table 5 (x ± s)
Annotate: relatively preceding with the treatment of this group: 1) P＜0.05,2) P＜0.01; With after the treatment of control group relatively: 3) P＜0.05,4) P＜0.01
The variation comparison of blood fat before and after 2 groups of patient treatments of table 6 (x ± s)
Annotate: relatively preceding with the treatment of this group: 1) P＜0.05,2) P＜0.01; With after the treatment of control group relatively: 3) P＜0.05,4) P＜0.01
The specific embodiment
The invention will be further elaborated below in conjunction with embodiment.These embodiment only are used to the purpose that exemplifies, rather than limit the present invention by any way.
Embodiment one
Crude drug adopts Rhizoma Chuanxiong 450g, Radix Notoginseng 141g, Lignum Dalbergiae Odoriferae oil 8g.
Obtain the ethanol extract of Rhizoma Chuanxiong with the ethanol extraction Rhizoma Chuanxiong, 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 Rhizoma Chuanxiong extractum that relative density is 1.35～1.39 (55 ℃).Radix Notoginseng powder is broken into fine powder, mixes all with Rhizoma Chuanxiong extractum, drying is made granule, sprays into Lignum Dalbergiae Odoriferae oil, is mixed with above-mentioned granule, is pressed into 1000, sugar coating, promptly.
Embodiment two
Crude drug adopts Rhizoma Chuanxiong 558g, Radix Notoginseng 34g, Lignum Dalbergiae Odoriferae oil 8g.
With 70% ethanol extraction Rhizoma Chuanxiong, obtain the Rhizoma Chuanxiong extracting solution, carry out microfiltration with ceramic membrane, collect filtrate.Filtrate is that 80000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and filter type adopts dead-end filtration.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.5Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 4.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 50 ℃, when feed liquid stock solution is concentrated 1/5, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 9.Backwashing pressure is 2.5MPa, and backwashing period is that 1.5h, backwashing time are 10min.When with the in parallel method of using alternately recoil of ultrafiltration module, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, and exchange is carried out behind the certain interval of time, work 20min, recoil 3min.The Chemical cleaning cycle is 2 months, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 1.0MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the Rhizoma Chuanxiong extractum that relative density is 1.35～1.39 (55 ℃).Radix Notoginseng powder is broken into fine powder, mixes all with Rhizoma Chuanxiong extractum, drying is made granule, sprays into Lignum Dalbergiae Odoriferae oil; be mixed with above-mentioned granule, add 3% polyvidone alcoholic solution system soft material, cross 18 mesh sieve system granules, 60 ℃ of dryings 30～45 minutes, granulate; add Pulvis Talci, mixing fills in capsule, promptly.
Embodiment three
Crude drug adopts Rhizoma Chuanxiong 360g, Radix Notoginseng 232g, Lignum Dalbergiae Odoriferae oil 8g.
Obtain the ethanol extract of Rhizoma Chuanxiong with the ethanol extraction Rhizoma Chuanxiong, 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 Rhizoma Chuanxiong extractum that relative density is 1.35～1.39 (55 ℃).Radix Notoginseng powder is broken into fine powder, mixes all with Rhizoma Chuanxiong extractum, drying is made granule, sprays into Lignum Dalbergiae Odoriferae oil, is mixed with above-mentioned granule, is pressed into 1000, or sugar coating, promptly.
Embodiment four
Crude drug adopts Rhizoma Chuanxiong 500 grams, Radix Notoginseng 94 grams, Lignum Dalbergiae Odoriferae oil 6 grams.
The Rhizoma Chuanxiong of coarse pulverization, pseudo-ginseng to extraction pot, are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate is that 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 ℃), spray into Lignum Dalbergiae Odoriferae oil, mix homogeneously, with the lactose fluidisation, drying is made granule, promptly in the batch (-type) fluid bed.
Embodiment five
Crude drug adopts Rhizoma Chuanxiong 290 grams, Radix Notoginseng 306 grams, Lignum Dalbergiae Odoriferae oil 6 grams.
The Rhizoma Chuanxiong of coarse pulverization, pseudo-ginseng to extraction pot, are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate is that 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 ℃), with this extractum and an amount of magnesium stearate mix homogeneously, spray into Lignum Dalbergiae Odoriferae oil, be mixed with above-mentioned granule, compacting is wrapped film-coat in flakes.
Embodiment six
Crude drug adopts Rhizoma Chuanxiong 210 grams, Radix Notoginseng 380 grams, Lignum Dalbergiae Odoriferae oil 4 grams.
The Rhizoma Chuanxiong of coarse pulverization, pseudo-ginseng to extraction pot, are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate is that 50000 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 ℃),, spray into Lignum Dalbergiae Odoriferae oil, be mixed, be pressed into tablet with above-mentioned granule with this extractum and an amount of magnesium stearate mix homogeneously.
Embodiment seven
Crude drug adopts Rhizoma Chuanxiong 450g, Radix Notoginseng 141g, Styrax 8g.
Obtain the ethanol extract of Rhizoma Chuanxiong with the ethanol extraction Rhizoma Chuanxiong, 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 Rhizoma Chuanxiong extractum that relative density is 1.35～1.39 (55 ℃).Radix Notoginseng powder is broken into fine powder, mixes all with Rhizoma Chuanxiong extractum, drying is made granule, adds Styrax, is mixed, and is pressed into 1000, sugar coating, promptly.
Embodiment eight
Crude drug adopts Rhizoma Chuanxiong 558g, Radix Notoginseng 34g, Styrax 8g.
Obtain the ethanol extract of Rhizoma Chuanxiong with the ethanol extraction Rhizoma Chuanxiong, 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 Rhizoma Chuanxiong 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 Styrax porphyrize with Rhizoma Chuanxiong extractum, 60 ℃ of dryings 30～45 minutes, granulate, the adding Pulvis Talci, mixing fills in capsule, promptly.
Embodiment nine
Crude drug adopts Rhizoma Chuanxiong 360g, Radix Notoginseng 232g, Styrax 8g.
Obtain the ethanol extract of Rhizoma Chuanxiong with the ethanol extraction Rhizoma Chuanxiong, 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 Rhizoma Chuanxiong extractum that relative density is 1.35～1.39 (55 ℃).Radix Notoginseng powder is broken into fine powder, mixes all with Rhizoma Chuanxiong extractum, drying is made granule, adds Styrax, is mixed, and is pressed into 1000, or sugar coating, promptly.
Embodiment ten
Crude drug adopts Rhizoma Chuanxiong 500 grams, Radix Notoginseng 94. grams, Styrax 6 grams.
The Rhizoma Chuanxiong of coarse pulverization, pseudo-ginseng to extraction pot, are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate is that 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 Styrax, mix homogeneously, with the lactose fluidisation, drying is made granule, promptly in the batch (-type) fluid bed.
Embodiment 11
Crude drug adopts Radix Salviae Miltiorrhizae 290 grams, Radix Notoginseng 306 grams, Styrax 6 grams.
The Rhizoma Chuanxiong of coarse pulverization, pseudo-ginseng to extraction pot, are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate is that 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 Styrax, again with mannitol 30g, calcium disodium edetate 5g, distilled water 5ml, behind the said components mixing, lyophilization, packing, promptly.
Embodiment 12
Crude drug adopts Rhizoma Chuanxiong 210 grams, Radix Notoginseng 380 grams, Styrax 4 grams.
The Rhizoma Chuanxiong of coarse pulverization, pseudo-ginseng to extraction pot, are added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out second time and extracts, and adds 4 times of water gagings, fried in shallow oil 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate is that 50000 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 ℃), with this extractum and an amount of magnesium stearate mix homogeneously, the adding Styrax is mixed, and is pressed into tablet.
Claims (11)
1. treatment coronary heart disease and anginal medicine is characterized in that it is to be prepared from by following raw materials by weight percent: Rhizoma Chuanxiong 20%～97%, Radix Notoginseng 2%～79%, Lignum Dalbergiae Odoriferae oil or Styrax 0.2%～3%;
Its preparation method is as follows:
(a) with Rhizoma Chuanxiong, panax mixed or make water extract or alcohol extract separately;
(b) described extracting solution being carried out predefecation handles;
(c) further described extracting solution is carried out hyperfiltration treatment;
(d) ultrafiltrate is concentrated, add Lignum Dalbergiae Odoriferae oil or Styrax, 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.
2. treatment coronary heart disease as claimed in claim 1 and anginal medicine is characterized in that, the percentage by weight of described raw material is:
Rhizoma Chuanxiong 63.0%～94%,
Radix Notoginseng 4.0%～35.0%,
Lignum Dalbergiae Odoriferae oil or Styrax 0.5%～2.0%.
3. treatment coronary heart disease as claimed in claim 2 and anginal medicine is characterized in that, the percentage by weight of described raw material is:
Rhizoma Chuanxiong 75.2%～90%,
Radix Notoginseng 9%～23.5%,
Lignum Dalbergiae Odoriferae oil or Styrax 0.5%～1.3%.
4. treatment coronary heart disease as claimed in claim 1 and anginal medicine 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. treatment coronary heart disease as claimed in claim 4 and anginal medicine is characterized in that, described alcohol extract is an ethanol extract.
6. treatment coronary heart disease as claimed in claim 1 and anginal medicine is characterized in that, what described step (a) obtained is the aqueous extract that Rhizoma Chuanxiong and panax mixed are made.
7. treatment coronary heart disease as claimed in claim 1 and anginal medicine 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.
8. treatment coronary heart disease as claimed in claim 1 and anginal medicine, 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 molecular cut off of its ultrafilter membrane is 6000～80000.
9. treatment coronary heart disease as claimed in claim 8 and anginal medicine, 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.
10. treatment coronary heart disease as claimed in claim 1 and anginal medicine is characterized in that, 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.
11. treatment coronary heart disease as claimed in claim 1 and anginal medicine, 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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| CN1362084A (en) * | 2001-01-08 | 2002-08-07 | 杨孟君 | Nano coronary heart disease treating red sage medicine and its preparation |
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