CN1778336B - Preparation of compound Danshen Root dropping ball - Google Patents
Preparation of compound Danshen Root dropping ball Download PDFInfo
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- CN1778336B CN1778336B CN 200410072941 CN200410072941A CN1778336B CN 1778336 B CN1778336 B CN 1778336B CN 200410072941 CN200410072941 CN 200410072941 CN 200410072941 A CN200410072941 A CN 200410072941A CN 1778336 B CN1778336 B CN 1778336B
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- 244000132619 red sage Species 0.000 title abstract 3
- 150000001875 compounds Chemical class 0.000 title description 4
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- 239000007788 liquid Substances 0.000 claims abstract description 41
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
A composite Danshen dripping pill is prepared from red sage root, notoginseng and borneol through extracting the liquid extract from red sage root and notoginseng in water or alcohol, clarifying, ultrafiltering, concentrating, adding borneol and preparing dripping pills.
Description
Technical field
The present invention relates to a kind of preparation method for the treatment of the medicaments compound Radix Salviae Miltiorrhizae drop pill of coronary heart disease, belong to the field of Chinese medicines.
Background technology
Along with the rejuvenation of growth in the living standard, world population aging and morbidity colony, cardiovascular and cerebrovascular vessel patient increases year by year, has become the second largest disease of harm humans health.Angina pectoris is a kind of caused by the temporary transient ischemia of cardiac muscle, anoxia, serves as the clinical syndrome of main performance with ictal chest pain or chest discomfort.Angina pectoris is meant because coronary atherosclerosis or spasm cause myocardial ischemia, the caused angina pectoris of anoxia, accounts for 90% of patient with angina pectoris.
The anginal method of treatment is based on blood vessel dilating, reduction blood viscosity, antiplatelet aggregation, anticoagulation at present.Traditional Western medicine of using is nitrate, nitrous acid ester, beta-receptor resistance preparation, calcium antagonist etc., but all has bigger toxic and side effects, should not take for a long time, mostly is symptomatic treatment and course of disease progress is not had bigger effect.For example take and occur jumping pain, palpitating speed in feeling of fullness in the head, the head behind the nitroglycerin sometimes, even faint and [, find again in recent years to cause severe hypotension [referring to contemporary Chinese medical journal 1997 referring to new pharmacology [the 14th edition) 264 page]; 7 (4): 42; Shaanxi medical journal 1996; 25 (5): 315], easily produce toleration [referring to southern nursing magazine 1996; 3 (5): 7～9] etc. problem has hindered its application clinically.
Though the anginal Chinese patent medicine of many treatments is also arranged, wherein ball, loose, cream, pellet, decoction becomes old historical already, the modern seldom uses.There are preparations such as common compound Salviae Miltiorrhizae tablet and capsule to sell in the market, but conventional tablet, capsule manufacture technology are more backward, active constituent content is low, no quality control standard, need be oral through gastrointestinal absorption, go into blood at liver generation first pass effect post-absorption, bioavailability is low, absorb slowly, can not be fit to the need of angina pectoris patient's first aid.
FUFANG DANSHEN DIWAN is a kind of rapid-action, eutherapeutic therapeutic drug of coronary heart disease, is subjected to patient's welcome clinically deeply.In order to improve the preparation technology of FUFANG DANSHEN DIWAN, the inventor furthers investigate from the extraction process aspect, has finished the present invention.
Summary of the invention
The object of the present invention is to provide a kind of preparation technology of new FUFANG DANSHEN DIWAN.
The present invention is implemented by following scheme:
The present invention realizes by following technical step: with Radix Salviae Miltiorrhizae, Radix Notoginseng and Borneolum Syntheticum is crude drug, is prepared according to following steps:
(1) with Radix Salviae Miltiorrhizae, 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 condensed into extractum, with gained extractum and Borneolum Syntheticum and adjuvant mixed evenly after, make drop pill.
The percentage by weight of above-mentioned raw materials medicine is Radix Salviae Miltiorrhizae 20%～97%, Radix Notoginseng 2%～79%, Borneolum Syntheticum 0.2%～3%; Be preferably Radix Salviae Miltiorrhizae 63.0%～94%, Radix Notoginseng 4.0%～35.0%, Borneolum Syntheticum 0.5%～2.0%; More preferably Radix Salviae Miltiorrhizae 75.2%～90%, Radix Notoginseng 9%～23.5%, Borneolum Syntheticum 0.5%～1.3%; The best is Radix Salviae Miltiorrhizae 82.87%, Radix Notoginseng 16.21%, Borneolum Syntheticum 0.92%.The percentage by weight sum of Radix Salviae Miltiorrhizae, Radix Notoginseng, Borneolum Syntheticum 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～2 months, the Chemical cleaning medicament is generally diluted acid, diluted alkaline, surfactant, be preferably for example 0.5%～4.0% sodium hydroxide of diluted alkaline, the mixed solution of 1.5% sodium hydroxide and 2% sodium hypochlorite etc., pH value is 10～12, and cleaning pressure is 0.05～1.0MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
In ultra-filtration process, both periodic pressure oscillation or the fluctuation of periodicity flow or periodicity fed noble gas separately, also can unite use, be periodic pressure fluctuation and periodically flow fluctuation associating use, perhaps the periodic pressure fluctuation is with periodically feeding noble gas unites use, perhaps periodically the flow fluctuation is with periodically feeding noble gas unites use, and perhaps the three unites use together.
In the technology of the present invention step (4), ultrafiltrate is condensed into extractum after, with Borneolum Syntheticum and adjuvant mixed evenly after, add the transconversion into heat material, move into dripping jar of drop pill machine, medicine liquid droplet is removed liquid paraffin to cryogenic liquid paraffin, select ball.
Wherein: adjuvant is a Polyethylene Glycol-6000, and 53～58 ℃ of its condensation points, addition are extractum and Borneolum Syntheticum weight 2～6 times; Changing the material temperature is 60～100 ℃; The temperature of liquid paraffin is 0～10 ℃ (the best is 5～10 ℃); Ball heavily is 5～50mg/ grain, diameter 1.95～4.29mm.
The composite salvia dropping pill for curing angina pectoris curative effect of the inventive method preparation is outstanding.
Experimental example composite salvia dropping pill for curing angina pectoris clinical observation on the therapeutic effect
1 clinical data
1.1 case selects whole cases all to diagnose by the standard of national prevention and treatment in Chinese and western angina pectoris forum in 1979 revision, and carries out angina pectoris by " ischemic heart desease nomenclature " that International Society of Cardiology in 1979 and association and World Health Organization's clinical name standardization associating special topic group are worked out and classify.102 routine angina pectoriss are shown effect weekly, and the patient is divided into treatment group and matched group at random more than 5 times.51 examples are organized in treatment, male 30 examples, women 21 examples; 39～76 years old age; The course of disease 1～20 year; Stablize angina of effort 41 examples, unstable angina pectoris 10 examples (comprising postinfarction angina pectoris 1 example); With hypertension 15 examples, diabetes 2 examples, old myocardial infarction 1 example.Matched group 51 examples, male 29 examples, women 22 examples; 40～75 years old age; The course of disease 1～20 year; Stablize angina of effort 42 examples, unstable angina pectoris 9 examples (comprising postinfarction angina pectoris 1 example); With hypertension 14 examples, diabetes 2 examples, old myocardial infarction 1 example.Aspects such as two groups of patient ages, sex, the course of disease, the state of an illness all have comparability (P＞0.05).
1.2 the Therapeutic Method patient withdraws anti-anginal drug in treatment in preceding 1 week, but if angina pectoris attacks buccal nitroglycerine tablets, and the record consumption.The treatment group is taken FUFANG DANSHEN DIWAN, and 3 times/day, each 10; Matched group is taken sorbitrate, and 3 times/day, each 10mg.Be for 4 weeks the course of treatment.During the treatment, suck the nitroglycerine tablets other anti-anginal drugs of stopping using during except that angina pectoris attacks.
1.3 observational technique writes down angina pectoris attacks number of times, pain degree, persistent period, sucks nitroglycerin tablet amounts and heart rate, blood pressure and the inspection of having an electro-cardiogram before treatment.After taking medicine, do 1 routine electrocardiogram inspection weekly, and write down above-mentioned every index.Before and after treatment, do blood, routine urinalysis, chest x-ray, liver, kidney function test, blood examination, cardiac ultrasonic.
1.4 the efficacy assessment standard efficacy assessment standard is with reference to " the medicine for cardiovascular system clinical research guideline draft " of Ministry of Public Health formulation in 1987.
1.4.1 clinical efficacy evaluation criteria produce effects: equal tired degree does not cause that angina pectoris attacks or attack times reduce more than 80%, and the nitroglycerin consumption reduces more than 80%.Effectively: angina pectoris attacks number of times and nitroglycerin consumption reduce 50%～80%.Invalid: angina pectoris attacks number of times and nitroglycerin consumption reduce less than 50%.Increase the weight of: the angina pectoris attacks increased frequency, degree increases the weight of, the persistent period lengthening, the nitroglycerin consumption increases.Produce effects adds effective calculating total effective rate.
1.4.2 ECG curative effect evaluation criteria produce effects: resting electrocardiogram recovers normal, and the exercise test of limiting the quantity of transfers feminine gender to by the positive or exercise tolerance rises more than 2 grades.Effectively: the resting electrocardiogram ischemic ST descends and replys below the 0.15mV, and the T ripple is inverted to shoal and is reached more than 50%, or exercise tolerance rises 1 grade.Invalid: resting electrocardiogram and the preceding no change of treatment.Increase the weight of: resting electrocardiogram ST section is forced down, declines＞0.05mV before the treatment, and the T ripple is inverted intensification＞50%, or the T ripple is smooth by uprightly becoming, or becomes inversion by smooth.Produce effects adds effective calculating total effective rate.
1.5 the statistical procedures data are represented with x ± s, adopt t check and Ridit to analyze and carry out date processing.
2 results
2.1 the angina pectoris symptom curative effect is analyzed through Ridit, two groups have significant differences, show evident in efficacy the be better than sorbitrate of FUFANG DANSHEN DIWAN to angina pectoris symptom, see Table 1.
The comparison of table 1 liang group aspect the angina pectoris treatment effect
Annotate: 1. compare, analyze U=3.039, P＜0.01 through Radit with matched group.
2.2 ECG curative effect is analyzed through Radit, FUFANG DANSHEN DIWAN significantly is better than sorbitrate to Electrocardiographic improvement, sees Table 2.
The comparison of table 2 liang group aspect ECG curative effect
Annotate: 1. compare, analyze U=2.685, P＜0.01 through Rtdit with matched group.
2.3 hemorheology index changes, and treatment organizes that 4 all height are cut, lowly cut, blood plasma viscosity, erythrocyte aggregation index all have obvious reduction before the treatment; , reduces the matched group above-mentioned parameter not statistically significant (P＜0.05) though having to a certain degree.Compare between two groups: the Composite Salvia Dropping Pill group sorbitrate group that is higher than evident in efficacy, P＜0.01 or P＜0.05.See Table 3.
Hemorheology index variation before and after the table 3 liang group treatment (x ± s)
2.4 left chamber contractile function influenced the FUFANG DANSHEN DIWAN treatment check ultrasonic cardiography diagram after 1 month of hanging oneself: left chamber contractile function, visible SV, CO, EF and FS all have increase, difference significance (P＜0.05), and matched group does not have obviously change before and after medication, see Table 4.
Table 4 liang group medication left ventricular contractile function comparison (x ± s)
Annotate: 1. compare P＞0.05 before and after the medication; 2. compare P＜0.05 before and after the medication.
By clinical research to FUFANG DANSHEN DIWAN, think that FUFANG DANSHEN DIWAN can coronary artery dilating, improve coronary flow, increase the blood oxygen supply of cardiac muscle, ST-T is changed and myocardial ischemia that Q-T prolongs damages and myocardium multipole is bad improves or recover normal condition, make cardiac dysfunction symptoms such as cardiopalmus that myocardial ischemia causes, uncomfortable in chest and precordialgia be eased (total effective rate is more than 90%).Behind the oral administered compound Radix Salviae Miltiorrhizae drop pill, not only rapid-action (how be onset at 4～5min), and the persistent period reach 2～3h, longer than nitroglycerin.Therefore has the clinical value of protecting the heart and rescuing the heart.
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 55.8g, Radix Notoginseng 3.4g, Borneolum Syntheticum 0.8g.
With ethanol extraction Radix Salviae Miltiorrhizae and Radix Notoginseng, obtain the ethanol extract of Radix Salviae Miltiorrhizae and Radix Notoginseng, 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 ℃).Get extractum and Borneolum Syntheticum, evenly be heated to 85 ℃ of temperature, change material after 20～120 minutes, move in the dropping-pill machine jar that jar temperature remains on 85～90 ℃ with Polyethylene Glycol-6000 18g is mixed.In ℃ liquid paraffin of medicine liquid droplet to 7～8, take out drop pill, oil removing, screen cloth selects ball, makes 1000 drop pill, promptly.
Embodiment two
Crude drug adopts Radix Salviae Miltiorrhizae 59.3g, Radix Notoginseng 6.38g, Borneolum Syntheticum 0.34g.
The Radix Salviae Miltiorrhizae of coarse pulverization is added 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out the second time and extracts, and adds 4 times of water gagings, fries in shallow oil 1 hour, filters, and filtering residue discards, and merging filtrate gets Radix Salviae Miltiorrhizae extract.With 70% ethanol extraction Radix Notoginseng, get the Radix Notoginseng extracting solution.Above-mentioned Radix Salviae Miltiorrhizae extract and Radix Notoginseng extracting solution are merged, leave standstill, filter.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 ℃).Get extractum and Borneolum Syntheticum, evenly be heated to 85 ℃ of temperature, change material after 20～120 minutes, move in the dropping-pill machine jar that jar temperature remains on 85～90 ℃ with Polyethylene Glycol-6000 20g is mixed.In ℃ liquid paraffin of medicine liquid droplet to 7～8, take out drop pill, oil removing, screen cloth selects ball, makes 1000 drop pill, promptly.
Embodiment three
Crude drug adopts Radix Salviae Miltiorrhizae 36.0g, Radix Notoginseng 23.2g, Borneolum Syntheticum 0.8g.
With 80% ethanol extraction Radix Salviae Miltiorrhizae and Radix Notoginseng, obtain the ethanol extract of Radix Salviae Miltiorrhizae and Radix Notoginseng, get supernatant with 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 ℃).Get extractum and Borneolum Syntheticum, evenly be heated to 60 ℃ of temperature, change material after 20～120 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃ with Polyethylene Glycol-600020g is mixed.In ℃ methyl-silicone oil of medicine liquid droplet to 7～8, take out drop pill, oil removing, screen cloth selects ball, makes 1000 drop pill, promptly.
Embodiment four
Crude drug adopts Radix Salviae Miltiorrhizae 41.1g, Radix Notoginseng 8.0g, Borneolum Syntheticum 0.46g.
The Radix Salviae Miltiorrhizae 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 1.35～1.39 (55 ℃).Get extractum and Borneolum Syntheticum, evenly be heated to 60 ℃ of temperature, change material after 20～120 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃ with polyethylene glycol 6000 21g is mixed.In ℃ liquid paraffin of medicine liquid droplet to 7～8, take out drop pill, oil removing, screen cloth selects ball, makes 1000 drop pill, promptly.
Embodiment five
Crude drug adopts Radix Salviae Miltiorrhizae 29.0g, Radix Notoginseng 30.6g, Borneolum Syntheticum 0.6g.
The Radix Salviae Miltiorrhizae 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 ℃), get extractum and Borneolum Syntheticum, evenly mixed with Polyethylene Glycol-6000 20g, be heated to 60 ℃ of temperature, change material after 20～120 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In ℃ liquid paraffin of medicine liquid droplet to 7～8, take out drop pill, oil removing, screen cloth selects ball, makes 1000 drop pill, promptly.
Embodiment six
Crude drug adopts Radix Salviae Miltiorrhizae 21.0g, Radix Notoginseng 38.0g, Borneolum Syntheticum 0.4g.
Learn from else's experience the Radix Salviae Miltiorrhizae, pseudo-ginseng of coarse pulverization to extraction pot, add the 0.89g sodium bicarbonate, add 4 times of water gagings, decocted 2 hours, filter, filtering residue carries out extraction second time, adds 4 times of water gagings, decocted 1 hour, and filtration, filtering residue discards, merging filtrate.Filtrate is that 50000 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 ℃), get extractum and Borneolum Syntheticum, evenly mixed with Polyethylene Glycol-6000 18g, be heated to 85 ℃ of temperature, change material after 20～120 minutes, move in the dropping-pill machine jar that jar temperature remains on 85～90 ℃.In ℃ liquid paraffin of medicine liquid droplet to 7～8, take out drop pill, oil removing, screen cloth selects ball, makes 1000 drop pill, promptly.
Claims (11)
1. the preparation method of a FUFANG DANSHEN DIWAN is that crude drug is made with Radix Salviae Miltiorrhizae, Radix Notoginseng and Borneolum Syntheticum, it is characterized in that the weight percent proportioning of described crude drug is: Radix Salviae Miltiorrhizae 20%～97%, Radix Notoginseng 2%～79%, Borneolum Syntheticum 0.2%～3%;
The processing step of its preparation is:
(1) with Radix Salviae Miltiorrhizae, 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, with gained extractum and Borneolum Syntheticum and adjuvant mixed even after, make drop pill; 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. the preparation method of FUFANG DANSHEN DIWAN according to claim 1 is characterized in that, the percentage by weight of described raw material is: Radix Salviae Miltiorrhizae 63.0%～94%, Radix Notoginseng 4.0%～35.0%, Borneolum Syntheticum 0.5%～2.0%.
3. the preparation method of FUFANG DANSHEN DIWAN according to claim 2 is characterized in that, the percentage by weight of described raw material is: Radix Salviae Miltiorrhizae 75.2%～90%, Radix Notoginseng 9%～23.5%, Borneolum Syntheticum 0.5%～1.3%.
4. according to the preparation method of the arbitrary described FUFANG DANSHEN DIWAN of claim 1～3, it 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. according to the preparation method of the arbitrary described FUFANG DANSHEN DIWAN of claim 1～3, it is characterized in that described alcohol extract is an ethanol extract.
6. according to the preparation method of the arbitrary described FUFANG DANSHEN DIWAN of claim 1～3, it is characterized in that what described step (1) obtained is the ethanol extract that Radix Salviae Miltiorrhizae and panax mixed are made.
7. according to the preparation method of the arbitrary described FUFANG DANSHEN DIWAN of claim 1～3, it is characterized in that what described step (1) obtained is the aqueous extract that Radix Salviae Miltiorrhizae and panax mixed are made.
8. according to the preparation method of the arbitrary described FUFANG DANSHEN DIWAN of claim 1～3, it is characterized in that described step (1) is: the Radix Salviae Miltiorrhizae of the coarse pulverization of learning from else's experience, pseudo-ginseng are to extraction pot, add an amount of sodium bicarbonate, decoct with water secondary, filter, filtering residue discards, and merging filtrate gets extracting solution.
9. according to the preparation method of the arbitrary described FUFANG DANSHEN DIWAN of claim 1～3, it 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.
10. according to the preparation method of the arbitrary described FUFANG DANSHEN DIWAN of claim 1～3, it is characterized in that, the used ultrafilter membrane of described hyperfiltration treatment is selected from: the cellulose diacetate film, three cellulose acetate membrane, the cyanoethyl cellulose film, polysulfone membrane, sulfonated polysulfone membrane, poly (ether sulfone) film, the sulfonated polyether sulfone film, the 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.
11. the preparation method of FUFANG DANSHEN DIWAN according to claim 10, 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.
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