Summary of the invention
The object of the present invention is to provide a kind of Chinese medicine dripping pills for the treatment of angina pectoris.
The present invention realizes by following technical step: with Radix Salviae Miltiorrhizae, Radix Notoginseng and Lignum Dalbergiae Odoriferae oil 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, adds Lignum Dalbergiae Odoriferae oil, with adjuvant mixed evenly after, make dropping pill formulation.
The percentage by weight of above-mentioned raw materials medicine is: Radix Salviae Miltiorrhizae 20%~97%, Radix Notoginseng 2%~79%, Lignum Dalbergiae Odoriferae oil 0.2%~3%; Be preferably Radix Salviae Miltiorrhizae 63.0%%~94%, Radix Notoginseng 4.0%~35.0%, Lignum Dalbergiae Odoriferae oil 0.5%~2.0%; More preferably Radix Salviae Miltiorrhizae 75.2%~90%, Radix Notoginseng 9%~23.5%, Lignum Dalbergiae Odoriferae oil 0.5%~1.3%.The percentage by weight sum of Radix Salviae Miltiorrhizae, Radix Notoginseng, Lignum Dalbergiae Odoriferae oil is 100%.
The above-mentioned raw materials Lignum Dalbergiae Odoriferae oil can be replaced with Styrax, and promptly the above-mentioned raw materials medicine can be Radix Salviae Miltiorrhizae 20%~97%, Radix Notoginseng 2%~79%, Styrax 0.2%~3%; Be preferably Radix Salviae Miltiorrhizae 63.0%%~94%, Radix Notoginseng 4.0%~35.0%, Styrax 0.5%~2.0%; More preferably Radix Salviae Miltiorrhizae 75.2%~90%, Radix Notoginseng 9%~23.5%, and the percentage by weight sum of Styrax 0.5%~1.3%. Radix Salviae Miltiorrhizae, 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, backwashing period is that 0.5~1.5h, backwashing time are that 1min~10min. is when replacing the method for recoil with ultrafiltration module use in parallel, 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 be 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 Lignum Dalbergiae Odoriferae oil or Styrax 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 Lignum Dalbergiae Odoriferae oil or Styrax 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 clinical observation of experimental example Drug therapy angina pectoris of the present invention
1 clinical data
1.1 case is selected: 46 examples are the out-patient, wherein use 36 examples, women 10 examples; 60~85 years old age, average 67.2 years old; The course of disease 10~30 years; Stable type 40 examples wherein, instability mode 6 examples; With hypertension 15 examples, diabetes 10 examples, hyperlipemia 21 examples.All patients all meet " ischemic heart desease " diagnostic criteria that World Health Organization (WHO) works out.
1.2 therapeutic scheme: the antianginal drug of stopping using in preceding 1 week of patient treatment (if angina pectoris attacks containing nitroglycerin temporarily, and record consumption), diabetes, hyperlipidemia can be constant.Take medicine of the present invention, 3 times/day, each 10, one after each meal, 8 weeks of the course of treatment.
1.3 observational technique: observe angina pectoris attacks number of times, pain degree, persistent period, application nitroglycerin dosage and heart rate, blood pressure situation before the treatment, and have an electro-cardiogram.1 Electrocardioscopy weekly after taking medicine is done blood, urine, just conventional, the hepatic and renal function inspection before the treatment.
1.4 efficacy assessment standard: press " medicine for cardiovascular system clinical research guideline " that Ministry of Public Health is worked out.1. clinical efficacy.Produce effects: the angina pectoris attacks number of times reduces more than 80%; Effectively: attack times reduces 50%~80%; Invalid: attack times reduces less than 50%.2. ECG curative effect.Produce effects: resting electrocardiogram recovers normal; Effectively: the resting electrocardiogram ischemic ST descends and replys more than the 1.5mm, and the T ripple is inverted and is shoaled; Invalid: no change before and after the electrocardiogram treatment.
2 results
2.1 clinical efficacy: produce effects 24 examples (52.9%), effective 15 examples (32.8%), invalid 7 examples (15.1%), total effective rate 85.9%.
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 45.0g, Radix Notoginseng 14.0g, Lignum Dalbergiae Odoriferae oil 0.8g.
With ethanol extraction Radix Salviae Miltiorrhizae and Radix Notoginseng, obtain the ethanol extract of Radix Salviae Miltiorrhizae and Radix Notoginseng, with gauze with this extracting liquid filtering, collect filtrate. filtrate is that 6000 cellulose diacetate film carries out ultrafiltration with molecular cut off, filter type adopts cross flow filter. and the operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1Mpa, the low 0.5kPa. ultrafiltration initial stage of the liquid outlet pressure ratio inlet pressure of ultrafiltration is adopted lower pressure, slowly boosts then; In ultra-filtration process, the fluctuation of employing periodic pressure, the pressure wave moment is that 0.1Mpa. feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopt periodically flow fluctuation so that in membrane channels, produce pulsating flow or non-stationary flow, the flow speed wave moment is 1.0m/s, feed nitrogen in the ultrafiltration system discontinuous, form 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, add water or dilute alcohol solution ultrafiltration 1 time again, it is 0.15MPa that the pH value of feed liquid is controlled at 5. backwashing pressures, backwashing period is 0.5h, backwashing time is that 1min. is when replacing the method for recoil with ultrafiltration module use in parallel, 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, work 10min, the recoil 30sec. Chemical cleaning cycle is 0.5 month, the Chemical cleaning medicament is 0.5%~4.0% sodium hydroxide, the mixed solution of 1.5% sodium hydroxide and 2% sodium hypochlorite, pH value is 10~12, and cleaning pressure is 0.05MPa. after cleaning with chemical, and 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, add Lignum Dalbergiae Odoriferae oil, 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.
Embodiment two
Crude drug adopts Radix Salviae Miltiorrhizae 55.8g, Radix Notoginseng 3.4g, Lignum Dalbergiae Odoriferae oil 0.8g.
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, add Lignum Dalbergiae Odoriferae oil, evenly mixed with Polyethylene Glycol-6000 20g, 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.
Embodiment three
Crude drug adopts Radix Salviae Miltiorrhizae 36.0g, Radix Notoginseng 23.2g, Lignum Dalbergiae Odoriferae oil 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, add Lignum Dalbergiae Odoriferae oil, 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 ℃ 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 50.0 grams, Radix Notoginseng 9.4 grams, Lignum Dalbergiae Odoriferae oil 0.6 gram.
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 1.32~1.40 (55 ℃).Get extractum, add Lignum Dalbergiae Odoriferae oil, evenly mixed with Polyethylene Glycol-6000 21g, 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 five
Crude drug adopts Radix Salviae Miltiorrhizae 29.0 grams, Radix Notoginseng 30.6 grams, Lignum Dalbergiae Odoriferae oil 0.6 gram.
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, add Lignum Dalbergiae Odoriferae oil, 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 21.0 grams, Radix Notoginseng 38.0 grams, Lignum Dalbergiae Odoriferae oil 0.4 gram.
The Radix Salviae Miltiorrhizae of coarse pulverization, pseudo-ginseng to extraction pot, are added the 0.89g sodium bicarbonate, add 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out extraction second time, 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 ℃).Get extractum, add Lignum Dalbergiae Odoriferae oil, 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.
Embodiment seven
Crude drug adopts Radix Salviae Miltiorrhizae 55.8g, Radix Notoginseng 3.4g, Styrax 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 Styrax, 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 eight
Crude drug adopts Radix Salviae Miltiorrhizae 59.3g, Radix Notoginseng 6.38g, Styrax 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, carry out microfiltration, collect filtrate with ceramic membrane.Filtrate is that 80000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and filter type adopts dead-end filtration.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.5Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 4.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 50 ℃, when feed liquid stock solution is concentrated 1/5, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 9.Backwashing pressure is 2.5MPa, and backwashing period is that 1.5h, backwashing time are 10min.When with the in parallel method of using alternately recoil of ultrafiltration module, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, and exchange is carried out behind the certain interval of time, work 20min, recoil 3min.The Chemical cleaning cycle is 2 months, and the Chemical cleaning medicament is the mixed solution of 0.5%~4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10~12, and cleaning pressure is 1.0MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.35~1.39 (55 ℃).Get extractum and Styrax, 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 nine
Crude drug adopts Radix Salviae Miltiorrhizae 36.0g, Radix Notoginseng 23.2g, Styrax 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 Styrax, 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 20g 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 ten
Crude drug adopts Radix Salviae Miltiorrhizae 41.1 grams, Radix Notoginseng 8.0 grams, Styrax 0.46 gram.
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 Styrax, 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 11
Crude drug adopts Radix Salviae Miltiorrhizae 29.0 grams, Radix Notoginseng 30.6 grams, Styrax 0.6 gram.
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 Styrax, 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 12
Crude drug adopts Radix Salviae Miltiorrhizae 21.0 grams, Radix Notoginseng 38.0 grams, Styrax 0.4 gram.
The Radix Salviae Miltiorrhizae of coarse pulverization, pseudo-ginseng to extraction pot, are added the 0.89g sodium bicarbonate, add 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out extraction second time, 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 ℃), get extractum and Styrax, evenly mixed with Polyethylene Glycol-6000 18g, be heated to 85 ℃ of temperature, change material after 20~120 minutes, move to jar in the dropping-pill machine jar that 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, make 1000 drop pill, promptly.