CN1778343A - Medicine dropping ball for treating coronary heart disease - Google Patents
Medicine dropping ball for treating coronary heart disease Download PDFInfo
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- CN1778343A CN1778343A CN 200410072948 CN200410072948A CN1778343A CN 1778343 A CN1778343 A CN 1778343A CN 200410072948 CN200410072948 CN 200410072948 CN 200410072948 A CN200410072948 A CN 200410072948A CN 1778343 A CN1778343 A CN 1778343A
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- film
- chinese medicine
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- membrane
- dripping pills
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Landscapes
- Medicines Containing Plant Substances (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
Abstract
A Chinese medicine in the form of dripping pill for treating coronary heart disease and angina pectoris is prepared from red sage root, notoginseng, boreol and safflower through extracting the liquid extract from red sage root, notogingseng and safflower in water or alcohol, clarifying, ultrafiltering, concentrating, adding borneol and shaping.
Description
Technical field
The present invention relates to a kind of Chinese medicine of using the ultrafiltration technology preparation.Particularly, the present invention relates to a kind of Chinese medicine dripping pills of using the ultrafiltration technology preparation.
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; reduce production costs increase economic efficiency (Wang Chengzhang 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 object of the present invention is to provide a kind of Chinese medicine dripping pills for the treatment of coronary heart disease.
The present invention is implemented by following scheme:
The present invention realizes by following technical step: with Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and Borneolum Syntheticum is crude drug, is prepared according to following steps:
(1) Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami are mixed or make water extract or alcohol extract separately;
(2) described extracting solution being carried out predefecation handles;
(3) further described extracting solution is carried out hyperfiltration treatment;
(4) ultrafiltrate is condensed into extractum, with gained extractum and Borneolum Syntheticum and adjuvant mixed evenly after, make dropping pill formulation.
The proportioning of above-mentioned raw materials medicine is counted by weight: Radix Salviae Miltiorrhizae 20～97, Radix Notoginseng 2～79, Borneolum Syntheticum 0.2～3, Flos Carthami 3～15; Be preferably: Radix Salviae Miltiorrhizae 63.0～94.0, Radix Notoginseng 4.0～35.0, Borneolum Syntheticum 0.5～2.0, Flos Carthami 4～10; More preferably: Radix Salviae Miltiorrhizae 75.2～90, Radix Notoginseng 9～23.5, Borneolum Syntheticum 0.5～1.3, Flos Carthami 5～8.
In the technology of the present invention step (1), alcohol extract can be the extracting solution of the lower alcohol of variable concentrations such as methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutanol etc. or the extracting solution of its mixture.Carrying out next step predefecation after alcohol extract can not concentrate or suitably concentrate handles.
In the technology of the present invention step (2), preliminary clarifying treatment can be carried out coarse filtration with general material such as gauze, tiffany etc., the also available material such as the ceramic membrane of specialty carry out microfiltration, also can behind high speed centrifugation, divide and get supernatant, adsorption clarifications such as also available flocculating agent such as flocculate with chitosan clarifier, 101 fruit juice clarifiers, ZTC1+1 natural clarifying agent, Ovum Gallus domesticus album flocculating agent and remove particle bigger in the medicinal liquid, also available alcohol deposition method is removed most impurity.Both can singly use above-mentioned defecation method, but also use in conjunction, coarse filtration-adsorption clarification for example, adsorption clarification-high speed centrifugation, coarse filtration-microfiltration, coarse filtration-precipitate with ethanol etc.After can not concentrating or suitably concentrate, the solution that predefecation is handled carries out next step ultrafiltration; Preferably do not concentrate the ultrafiltration of promptly carrying out next step.
In the technology of the present invention step (3), the used ultrafilter membrane of ultrafiltration can be cellulose diacetate film (CA), three cellulose acetate membrane (CTA), cyanoethyl cellulose film (CN-CA), polysulfone membrane (PS), sulfonated polysulfone membrane (SPS), poly (ether sulfone) film (PES), sulfonated polyether sulfone film (SPES), polysulfonamides film (PSA), phenolphthalein side group polyarylsulfone (PAS) film (PDS), polyvinylidene fluoride film (PVDF), polyacrylonitrile film (PAN), polyimide film (N), cellulose membrane, methyl methacrylate-acrylonitrile copolymer film (MMA-AN), polyacrylonitrile/cellulose diacetate (PAN/CA) blend film, the dynamically ultrafilter membrane that forms, and the Modified Membrane of above-mentioned film.Be preferably cellulose diacetate film (CA), three cellulose acetate membrane (CTA), polysulfone membrane (PS), sulfonated polysulfone membrane (SPS), poly (ether sulfone) film (PES), sulfonated polyether sulfone film (SPES), polysulfonamides film (PSA), polyvinylidene fluoride film (PVDF), polyacrylonitrile film (PAN).
The molecular cut off of above-mentioned ultrafilter membrane is generally 6000～80000, is preferably 10000～70000, and the best is 20000～50000.
Ultrafiltration both can be adopted cross flow filter, also can adopt dead-end filtration, but preferred cross flow filter.
The operating condition of ultrafiltration technology is as follows:
(1) the inlet pressure of ultrafiltration is 0.1～0.5MPa, is preferably 0.1～0.35Mpa, and the best is 0.25～0.35Mpa; The liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.5～0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1～0.2Mpa.
(2) the feed liquid flow velocity is 1.0～4.0m/s, is preferably 2.0～3.0m/s.In the ultra-filtration process, adopt the fluctuation of periodicity flow so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 1.0～2.0m/s.
(3) feed high-pressure inert gas such as nitrogen in the ultrafiltration system discontinuous, form the gas-liquid stream of pulses, the cycle is that 0.5h～2h ventilates once, each 1 minute.
(3) feed temperature is 15～50 ℃, is preferably 20～40 ℃.
(4) when feed liquid stock solution is concentrated 1/15～1/5, add water or dilute alcohol solution ultrafiltration 1～2 time again; Be preferably when feed liquid stock solution is concentrated 1/12～1/8, add water or dilute alcohol solution ultrafiltration 1～2 time again.
(5) pH value of feed liquid is controlled at 5～9, is preferably 6.0～7.5;
(6) backwash condition: backwashing pressure is 0.15～2.5MPa, and backwashing period is that 0.5～1.5h, backwashing time are 1min～10min.When ultrafiltration module use in parallel is replaced the method for recoil, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, exchange is carried out behind the certain interval of time, generally is work 10～20min, recoil 30sec～3min.
(7) the Chemical cleaning cycle is 0.5 month～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.
Experimental example Drug therapy angina pectoris of the present invention clinical observation on the therapeutic effect
1. data and method
1.1 physical data pushes away according to WHO diagnosis of coronary heart disease in 1979 mark, selects coronary heart disease 52 examples at random, male 35 examples, women 17 examples, 44～72 years old age, average 56.4 years old, stable angina pectoris 30 examples wherein, instability mode heart system Bears 13 examples, angina pectoris 8 examples after the myocardial infarction.All the case electrocardiograms all have myocardial ischemia sexually revise the T ripple low flat, be inverted and or the ST section force down 〉=1mv.Selecting 40 routine patient with angina pectoris else is matched group, male 25 examples, women 15 examples, 45～74 years old age, 58.2 years old mean age.
1.2 administrated method treatment group adopts medicine of the present invention, each 10, oral 3 times of every day, 2 months courses of treatment.Matched group gives sorbitrate, each 10mg, every day 3 times, 2 months courses of treatment.Withdraw other anti-anginal drug before the treatment.All patients before treatment, treatment January and the course of treatment do hematuria routine, blood fat, liver function, renal function, serum potassium, uranium, chlorine, blood glucose, Electrocardioscopy after the end.Period in a medicine is observed the angina pectoris attacks number of times, detects blood pressure, heart rate and inquiry untoward reaction.
1.3 curative effect is declared standard: it is produce effects that (1) angina pectoris symptom angina pectoris attacks number of times reduces by 80% above person, it is effective reducing by 50% above person, less than 50% is invalid, and angina pectoris attacks number of times degree and persistent period or nitroglycerin consumption all are worse than in the past for increasing the weight of; (2) recovery of ECG curative effect resting electrocardiogram is a produce effects normally, the ST section is recovered or the T ripple that mainly leads shoals more than 50% for effective, it is invalid that the ECG change end reaches above-mentioned standard person, and the ECG ST section preceding decline＞0.5mv of treatment, T ripple is inverted intensification＞50% and is inverted to increasing the weight of by upright change.
2. result
2.1 the curative effect of angina pectoris symptom (seeing Table 1)
Table 1 liang group curative effect to treat angina pectoris relatively
| Group | The example number | Produce effects (%) | Effectively (%) | Invalid (%) | Total effective rate (%) |
| Treatment group matched group | 52 40 | 38(73) 21(52.5) | 11(21.5) 12(30) | 3(5.8) 7(17.5) | 49(94.2) 33(82.5) |
Treatment group total effective rate 94.2%, 82.5%, two group of comparing difference of sorbitrate group total effective rate be remarkable (P＞0.05) not.But treatment group obvious effective rate 73%, 52.5%, two group there were significant differences (P＜0.05) for the sorbitrate group.Show that Drug therapy obvious effective rate of the present invention aspect is better than sorbitrate.
2.2 the curative effect that electrocardiogram improves
52 examples are organized in treatment, effective 37 examples, effective percentage 71.1%, invalid 15 examples, inefficiency 28.9%; Sorbitrate group 40 examples, effective 16 examples, effective percentage 40%, invalid 24 examples, inefficiency 60% is significant difference (P＜0.01).Show that medicine of the present invention improves myocardial ischemia and be better than sorbitrate aspect ECG change.
2.3 the curative effect of hyperlipidemia
Blood Lipid before and after table 2 treatment
| Blood fat before the treatment | Treatment back blood fat | |||
| TC(mmol/L) | TG(mmol/L) | TC(mmol/L) | TG(mmol/L) | |
| Treatment group (n=30) matched group (n=30) t value P value | 6.88±1.31 6.70±1.11 1.70 ＞0.05 | 2.74±1.10 2.90±1.03 1.83 ＞0.05 | 5.70±1.21 6.30±0.95 3.02 ＜0.01 | 1.90±0.83 2.50±1.13 2.81 ＜0.01 |
The treatment group has 30 routine hyperlipemias, and the sorbitrate group has 26 routine hyperlipemias, and show through treating two months results: treatment group rate and blood-lipid decreased is obvious, and sorbitrate group blood fat changes does not have obviously treatment meaning.
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 14.1g, Borneolum Syntheticum 0.8g, Flos Carthami 5.0g.
With ethanol extraction Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami, obtain the ethanol extract of Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami, with this extracting liquid filtering, collect filtrate with gauze.Filtrate is that 6000 cellulose diacetate film carries out ultrafiltration with molecular cut off, and filter type adopts cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.5kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds water or dilute alcohol solution ultrafiltration 1 time again, and the pH value of feed liquid is controlled at 5.Backwashing pressure is 0.15MPa, and backwashing period is that 0.5h, backwashing time are 1min.When with the in parallel method of using alternately recoil of ultrafiltration module, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, and exchange is carried out behind the certain interval of time, work 10min, recoil 30sec.The Chemical cleaning cycle is 0.5 month, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 0.05MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.35～1.39 (55 ℃).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 55.8g, Radix Notoginseng 3.4g, Borneolum Syntheticum 0.8g, Flos Carthami 7.2g.
With the Radix Salviae Miltiorrhizae and the Radix Notoginseng of coarse pulverization, add 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out the second time and extracts, and adds 4 times of water gagings, fries in shallow oil 1 hour, filters, and filtering residue discards, and merging filtrate gets Radix Salviae Miltiorrhizae and Radix Notoginseng extracting solution.With 70% ethanol extraction Flos Carthami, get Flos Carthami extract.Above-mentioned Radix Salviae Miltiorrhizae and Radix Notoginseng extracting solution, Flos Carthami extract 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 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, Flos Carthami 2.4g.
Obtain blended ethanol extract with 80% ethanol extraction Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami, get supernatant dividing behind this extracting solution high speed centrifugation.With this liquid molecular cut off is that 50000 polysulfone membrane is carried out ultrafiltration, and filter type adopts cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/8, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.Backwashing pressure is 2.5MPa, and backwashing period is that 1.5h, backwashing time are 10min.When with the in parallel method of using alternately recoil of ultrafiltration module, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, and exchange is carried out behind the certain interval of time, work 20min, recoil 3min.The Chemical cleaning cycle is 2 months, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 1.0MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.35～1.39 (55 ℃).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 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 four
Crude drug adopts Radix Salviae Miltiorrhizae 50.0 grams, Radix Notoginseng 9.4 grams, Borneolum Syntheticum 0.6 gram, Flos Carthami 4.2g.
Radix Salviae Miltiorrhizae, the Radix Notoginseng and Flos Carthami medical material of coarse pulverization are added in the extraction pot, add 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out the second time and extracts, and adds 4 times of water gagings, fries in shallow oil 1 hour, filters, and filtering residue discards, merging filtrate.Filtrate is that 6000 cellulose diacetate film carries out ultrafiltration with molecular cut off, and filter type adopts cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.1Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.5kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.1Mpa.The feed liquid flow velocity is 1.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 1.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 0.5h ventilates once each 1 minute.Feed temperature is 15 ℃, when feed liquid stock solution is concentrated 1/15, adds water or dilute alcohol solution ultrafiltration 1 time again, and the pH value of feed liquid is controlled at 5.Backwashing pressure is 0.15MPa, and backwashing period is that 0.5h, backwashing time are 1min.When with the in parallel method of using alternately recoil of ultrafiltration module, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, and exchange is carried out behind the certain interval of time, work 10min, recoil 30sec.The Chemical cleaning cycle is 0.5 month, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 0.05MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.35～1.39 (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 29.0 grams, Radix Notoginseng 30.6 grams, Borneolum Syntheticum 0.6 gram, Flos Carthami 2.0g.
Radix Salviae Miltiorrhizae, the Radix Notoginseng and Flos Carthami medical material of coarse pulverization are added in the extraction pot, add 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out the second time and extracts, and adds 4 times of water gagings, fries in shallow oil 1 hour, filters, and filtering residue discards, merging filtrate.Filtrate is that 80000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and filter type adopts dead-end filtration.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.5Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 4.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 50 ℃, when feed liquid stock solution is concentrated 1/5, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 9.Backwashing pressure is 2.5MPa, and backwashing period is that 1.5h, backwashing time are 10min.When with the in parallel method of using alternately recoil of ultrafiltration module, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, and exchange is carried out behind the certain interval of time, work 20min, recoil 3min.The Chemical cleaning cycle is 2 months, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 1.0MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.32～1.40 (55 ℃), 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 21.0 grams, Radix Notoginseng 38.0 grams, Borneolum Syntheticum 0.4 gram, Flos Carthami 3.0g.
Radix Salviae Miltiorrhizae, the Radix Notoginseng and Flos Carthami medical material of coarse pulverization are added in the extraction pot, add the 0.89g sodium bicarbonate, add 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out the second time and extracts, and adds 4 times of water gagings, fries in shallow oil 1 hour, filters, and filtering residue discards, merging filtrate.Filtrate is that 50000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and filter type adopts cross flow filter.The operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.20kPa.The ultrafiltration initial stage is adopted lower pressure, slowly boosts then; In ultra-filtration process, adopt the periodic pressure fluctuation, the pressure wave moment is 0.2Mpa.The feed liquid flow velocity is 3.0m/s, in the ultra-filtration process, adopts periodically flow fluctuation so that produce pulsating flow or non-stationary flow in membrane channels, the flow speed wave moment is 2.0m/s, feeds nitrogen in the ultrafiltration system discontinuous, forms the gas-liquid stream of pulses, cycle is that 2h ventilates once each 1 minute.Feed temperature is 40 ℃, when feed liquid stock solution is concentrated 1/8, adds water or dilute alcohol solution ultrafiltration 2 times again, and the pH value of feed liquid is controlled at 7.5.Backwashing pressure is 2.5MPa, and backwashing period is that 1.5h, backwashing time are 10min.When with the in parallel method of using alternately recoil of ultrafiltration module, wherein a cover or a few cover carry out normal ultrafiltration and distribute the recoil ultrafilter membrane of another set of or several grip assemblies of a part of filtrate, and exchange is carried out behind the certain interval of time, work 20min, recoil 3min.The Chemical cleaning cycle is 2 months, and the Chemical cleaning medicament is the mixed solution of 0.5%～4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, and pH value is 10～12, and cleaning pressure is 1.0MPa.After cleaning with chemical, the flushing of reuse water is near neutral.
Described ultrafiltrate concentrated obtain the extractum that relative density is 1.32～1.40 (55 ℃), 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 (14)
1. Chinese medicine dripping pills for the treatment of angina pectoris, it is that crude drug is made with Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and Borneolum Syntheticum, it is characterized in that the processing step of its preparation is:
(1) Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami are mixed or make water extract or alcohol extract separately;
(2) described extracting solution being carried out predefecation handles;
(3) further described extracting solution is carried out hyperfiltration treatment;
(4) ultrafiltrate is concentrated, with gained extractum and Borneolum Syntheticum and adjuvant mixed even after, make drop pill.
2. Chinese medicine dripping pills according to claim 1 is characterized in that the weight proportion of described crude drug is:
Radix Salviae Miltiorrhizae 20～97,
Radix Notoginseng 2～79,
Borneolum Syntheticum 0.2～3,
Flos Carthami 3～15.
3. Chinese medicine dripping pills according to claim 2 is characterized in that the weight proportion of described raw material is:
Radix Salviae Miltiorrhizae 63.0～94.0,
Radix Notoginseng 4.0～35.0,
Borneolum Syntheticum 0.5～2.0,
Flos Carthami 4～10.
4. Chinese medicine dripping pills according to claim 3 is characterized in that the weight proportion of described raw material is:
Radix Salviae Miltiorrhizae 75.2～90,
Radix Notoginseng 9～23.5,
Borneolum Syntheticum 0.5～1.3,
Flos Carthami 5～8.
5. according to the described Chinese medicine dripping pills of claim 1～4, 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.
6. according to the described Chinese medicine dripping pills of claim 1～4, its feature is an ethanol extract at described alcohol extract.
7. according to the described Chinese medicine dripping pills of claim 1～4, what its feature obtained in described step (a) is the ethanol extract that Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami are mixed and made into.
8. according to the described Chinese medicine dripping pills of claim 1～4, what its feature obtained in described step (a) is the aqueous extract that Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami are mixed and made into.
9. according to the described Chinese medicine dripping pills of claim 1～4, its feature in described step (a) is: the Radix Salviae Miltiorrhizae of the coarse pulverization of learning from else's experience, Radix Notoginseng and Flos Carthami medical material add an amount of sodium bicarbonate to extraction pot, decoct with water secondary, filter, filtering residue discards, merging filtrate gets extracting solution.
10. according to the described Chinese medicine dripping pills of claim 1～4, 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.
11. according to the described Chinese medicine dripping pills of claim 1～4, it is characterized in that the used ultrafilter membrane of described hyperfiltration treatment is selected from: cellulose diacetate film, three cellulose acetate membrane, cyanoethyl cellulose film, polysulfone membrane, sulfonated polysulfone membrane, poly (ether sulfone) film, sulfonated polyether sulfone film, polysulfonamides film, phenolphthalein side group polyarylsulfone (PAS) film, polyvinylidene fluoride film, polyacrylonitrile film, polyimide film, cellulose membrane, methyl methacrylate-acrylonitrile copolymer film, polyacrylonitrile/cellulose diacetate blend film, the dynamically ultrafilter membrane that forms, and the Modified Membrane of above-mentioned film; The molecular cut off of its ultrafilter membrane is 6000～80000.
12. Chinese medicine dripping pills according to claim 11, 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.
13. according to the described Chinese medicine dripping pills of claim 1～4, it is characterized in that the operating procedure condition of described hyperfiltration treatment is as follows: the inlet pressure of ultrafiltration is 0.1～0.5MPa, 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.
14. Chinese medicine dripping pills according to claim 13 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.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101085022B (en) * | 2006-06-08 | 2011-09-21 | 天津天士力制药股份有限公司 | Medicinal composition containing safflower and musk, preparation method and preparation |
| CN101085019B (en) * | 2006-06-08 | 2012-07-18 | 天津天士力制药股份有限公司 | Traditional Chinese medicinal composition containing red sage root, notoginseng, safflower and musk or muscone and its preparation |
| CN108379510A (en) * | 2018-04-18 | 2018-08-10 | 张凯 | A kind of Chinese medicine composition for treating angiocardiopathy |
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2004
- 2004-11-26 CN CN 200410072948 patent/CN1778343B/en active Active
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101085022B (en) * | 2006-06-08 | 2011-09-21 | 天津天士力制药股份有限公司 | Medicinal composition containing safflower and musk, preparation method and preparation |
| CN101085019B (en) * | 2006-06-08 | 2012-07-18 | 天津天士力制药股份有限公司 | Traditional Chinese medicinal composition containing red sage root, notoginseng, safflower and musk or muscone and its preparation |
| CN108379510A (en) * | 2018-04-18 | 2018-08-10 | 张凯 | A kind of Chinese medicine composition for treating angiocardiopathy |
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| CN1778343B (en) | 2010-05-12 |
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