CN1778354B - Chinese medicine dropping ball for coronary heart disease and angina cordis - Google Patents
Chinese medicine dropping ball for coronary heart disease and angina cordis Download PDFInfo
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- CN1778354B CN1778354B CN 200410072936 CN200410072936A CN1778354B CN 1778354 B CN1778354 B CN 1778354B CN 200410072936 CN200410072936 CN 200410072936 CN 200410072936 A CN200410072936 A CN 200410072936A CN 1778354 B CN1778354 B CN 1778354B
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- 206010002383 Angina Pectoris Diseases 0.000 title claims abstract description 13
- 208000029078 coronary artery disease Diseases 0.000 title abstract description 4
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- 239000006187 pill Substances 0.000 claims abstract description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 34
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- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 claims abstract description 27
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Landscapes
- Separation Using Semi-Permeable Membranes (AREA)
- Medicines Containing Plant Substances (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, Chuang-xiong rhizome and borneol through extracting the liquid extract from red sage root and Chuan-xiong rhizome in water or alcohol, clarifying, ultrafiltering, concentrating, adding borneol and preparing dripping pills.
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 reduces production costs; (Wang Chengzhang increases economic efficiency; Yu Qing, Tan Weihong etc. " application of ultrafiltration in purification Folium Ginkgo flavone glycoside ", forestry science and technology communication; 1997, (2): 21).
Though hyperfiltration technique is applied to the production of Chinese medicine preparation its unique advantage is arranged, its degree of applying is still very limited, traces it to its cause, and remains in following problem:
(1) medicinal herb components complexity, particularly many compound preparations, effective ingredient are also unclear fully, therefore need to carry out very deep research before hyperfiltration technique is applied to Chinese herbal and crude drugs preparations.For example because the complexity of composition, do not carry out a large amount of pharmacology and clinical research test fully estimate ultrafiltration to Chinese medicine preparation in before the drug effect influence degree of each composition, ultrafiltration can not be applied to the production of most of Chinese medicine preparation.
(2) kind of membrane material is few, and membrane aperture distributes wide, and performance is understable.Used ultrafilter membrane material has cellulose acetate, polyacrylonitrile, polysulfones, SPSF, polysulfonamides etc. in Chinese medicine preparation production.By its affinity classification, be broadly divided into two classes: hydrophobic film material and hydrophilic film material to water.Hydrophilic film such as cellulose acetate, SPSF material is few to solute absorption, and molecular cut off is less, but poor heat stability, mechanical strength, chemical proof, antibacterium erosiveness are not high usually; Hydrophobic film materials such as polysulfones, the mechanical strength height, high temperature resistant, anti-solvent, anti-biodegradation, but because of containing a large amount of hydrophobicity genes or chain link in the strand, and have more electrostatic charge, thereby the permeable speed of film is low, contamination resistance is lower.
(3) pollution problem of film is to hinder hyperfiltration technique is moved towards the commercial Application stage by laboratory research biggest obstacle.In the ultra-filtration process of Chinese medicine preparation, when not good as if the medicinal liquid pretreating effect, face easily pollutes, and fenestra stops up, and making permeation flux is that productivity ratio descends, even cisco unity malfunction, and production efficiency reduces, and cost rises, and causes the shortening in service life of film.
(4) system of selection of membrane module is not set up as yet, the optimization of still needing of ultrafiltration parameter.The factor that influences the ultrafiltration effect is a lot, comprises the selection of membrane module, the cleaning method after the definite and ultrafilter of technological parameter uses etc.Therefore be applicable to ultrafiltration apparatus and the operating procedure that the ultrafiltration of Chinese medicine system is used, remain further to be studied.
The relevant so far application of ultrafiltration technology in (compound recipe) red sage formulation, only limit to report that it is used to prepare Radix Salviae Miltiorrhizae Injection, for example officina of Beijing Hospital of the Air Force of Chinese People's Liberation Army has reported that the ultrafiltration preparation comprises the plurality of Chinese injection (officina of Beijing Hospital of the Air Force of Chinese People's Liberation Army of FUFANG DANSHEN ZHUSHEYE, " ultrafiltration prepares the experimentation of herbal mixture injection ", Chinese herbal medicine, 1981,12 (12): 8～12).Yaan, the Sichuan Hao Li of pharmaceutical factory prepares Radix Salviae Miltiorrhizae Injection (Hao Li, " ultrafiltration prepares the process modification of Radix Salviae Miltiorrhizae Injection ", Chengdu University of Traditional Chinese Medicine's journal, 1996,27 (8): 7) with ultrafiltration (ultrafilter membrane of molecular cut off 20000).People such as wangdan report utilizes the micelle ultrafiltration to prepare Radix Salviae Miltiorrhizae Injection (wangdan, " the micelle ultrafiltration prepares Radix Salviae Miltiorrhizae Injection ", Chinese patent medicine, 2003,25 (6): 441～443).But these reports all derive from laboratory research, do not propose the feasibility of suitability for industrialized production and concrete process condition thereof.
The present inventor, has verified that ultrafiltration prepares the feasibility of medicine of the present invention, and has determined suitable process condition by a large amount of experimental datas are analyzed through the effort of long-term and unremitting ground.
Summary of the invention
The treatment treating coronary heart disease and angina pectoris that the purpose of this invention is to provide ultrafiltration preparation technology's preparation that a kind of impurity is few, loss of effective components is little, cost is low, it has overcome the deficiencies in the prior art, has solved the difficult problem of suitability for industrialized production ultrafiltration technology condition operability.
The present invention realizes by following technical step: with Radix Salviae Miltiorrhizae, Radix Paeoniae Rubra and Borneolum Syntheticum is crude drug, is prepared according to following steps:
(1) Radix Salviae Miltiorrhizae, Radix Paeoniae Rubra are mixed or make water extract or alcohol extract respectively 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 percentage by weight of above-mentioned raw materials medicine is: Radix Salviae Miltiorrhizae 20%～97%, Radix Paeoniae Rubra 2%～79%, Borneolum Syntheticum 0.2%～3%; Be preferably Radix Salviae Miltiorrhizae 63.0%～94%, Radix Paeoniae Rubra 4.0%～35.0%, Borneolum Syntheticum 0.5%～2.0%; More preferably Radix Salviae Miltiorrhizae 75.2%～90%, Radix Paeoniae Rubra 9%～23.5%, Borneolum Syntheticum 0.5%～1.3%.The percentage by weight sum of Radix Salviae Miltiorrhizae, Radix Paeoniae Rubra, Borneolum Syntheticum is 100%.
Described step (1) is: the Radix Salviae Miltiorrhizae of the coarse pulverization of learning from else's experience, Radix Paeoniae Rubra medical material add an amount of sodium bicarbonate to extraction pot, decoct with water secondary, filter, and filtering residue discards, and merging filtrate gets extracting solution.
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.
Utilize the drop pill of prepared of the present invention, be used for the treatment of angina pectoris and have the good curing effect.
The clinical observation of experimental example Drug therapy angina pectoris of the present invention
1 data and method
1.1 case is selected among the 100 routine angina pectoris patients, male 65 examples, and women 35 examples, 35～55 years old 32 age example, 56～70 years old 68 example, 50.2 years old mean age, the course of disease 2.6 years, wherein with hyperpietic's 43 examples, type ii diabetes 7 examples.All patients all meet name and the standard of WTO about the ischemic heart desease diagnosis, wherein stable angina pectoris 48 row, unstable angina 52 examples.Be divided into treatment group and matched group at random, every group 50 example, two groups of sexes, medical history, age no significant difference.
1.2 removing, knot prescription method is associated with protopathy (hypertension, the conventional depressor of using), diabetes (routine is kept on a diet and used antidiabetic drug).Other treatment medicaments for coronary disease in principle requires to stop using during all MethodsThe cases enrolled treatments.The treatment group gives oral medicine of the present invention, and each 10, every day 3 times, sublingual administration nitroglycerin in case of necessity.Matched group gives FUFANG DANSHEN PIAN, and each 3, every day 3 times, sublingual administration nitroglycerin in case of necessity.4 weeks of the course of treatment.
1.3 observed content is inquired clinical symptoms and untoward reaction before and after taking medicine of the present invention.Recording blood pressure is done conventional 12 lead electrocardiogram and blood, routine urinalysis, hepatic and renal function detection.
1.4 efficacy assessment standard is evaluated according to bureau of drug administration of Ministry of Health of the People's Republic of China specified " cardiovascular medicament clinical research guideline ".The symptom efficacy assessment standard: produce effects, equal work capacity do not cause that angina pectoris attacks or attack times reduce more than 70%, and general activity does not have symptom uncomfortable in chest; Effectively, angina pectoris attacks number of times, sx uncomfortable in chest 50%～70%; Invalid, above situation does not have significant change after the medication.The ECG curative effect evaluation criteria: produce effects, the performance of resting electrocardiogram ischemia recovers normal; Effectively, the resting electrocardiogram ischemic ST descends, and more than the treatment back rise 1mm, but abnormal, lower wall and left chest lead negative T wave shoal and reach more than the 1mm; Invalid, resting electrocardiogram is preceding basic identical with treatment.
2 results
2.1 treatment group and matched group curative effect relatively see Table 1, table 2.
Table 1 Drug therapy angina pectoris symptom of the present invention curative effect and matched group are relatively
Table 2 Drug therapy angina pectoris of the present invention ECG curative effect and matched group are relatively
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 Paeoniae Rubra 3.4g, Borneolum Syntheticum 0.8g.
With ethanol extraction Radix Salviae Miltiorrhizae and Radix Paeoniae Rubra, obtain the ethanol extract of Radix Salviae Miltiorrhizae and Radix Paeoniae Rubra, 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 Paeoniae Rubra 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 Paeoniae Rubra, get the Radix Paeoniae Rubra extracting solution.Above-mentioned Radix Salviae Miltiorrhizae extract and Radix Paeoniae Rubra 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 Paeoniae Rubra 23.2g, Borneolum Syntheticum 0.8g.
With 80% ethanol extraction Radix Salviae Miltiorrhizae and Radix Paeoniae Rubra, obtain the ethanol extract of Radix Salviae Miltiorrhizae and Radix Paeoniae Rubra, 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-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 41.1g, Radix Paeoniae Rubra 8.0g, Borneolum Syntheticum 0.46g.
The Radix Salviae Miltiorrhizae of coarse pulverization, Radix Paeoniae Rubra medical material 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 Paeoniae Rubra 30.6g, Borneolum Syntheticum 0.6g.
The Radix Salviae Miltiorrhizae of coarse pulverization, Radix Paeoniae Rubra medical material 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 Paeoniae Rubra 38.0g, Borneolum Syntheticum 0.4g.
Learn from else's experience the Radix Salviae Miltiorrhizae, Radix Paeoniae Rubra medical material 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 (12)
1. Chinese medicine dripping pills for the treatment of angina pectoris, it is that crude drug is made with Radix Salviae Miltiorrhizae, Radix Paeoniae Rubra and Borneolum Syntheticum, it is characterized in that the weight percent proportioning of described crude drug is: Radix Salviae Miltiorrhizae 20%～97%, Radix Paeoniae Rubra 2%～79%, Borneolum Syntheticum 0.2%～3%;
The processing step of its preparation is:
(1) Radix Salviae Miltiorrhizae, Radix Paeoniae Rubra 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; The operating procedure condition of described hyperfiltration treatment is as follows:
The inlet pressure of ultrafiltration is 0.1～0.5MPa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25～0.5kPa;
Feed temperature is 15～50 ℃; The pH value of feed liquid is controlled at 5～9; When feed liquid stock solution is concentrated 1/15～1/5, add water or dilute alcohol solution ultrafiltration 1～2 time again.
2. Chinese medicine dripping pills according to claim 1 is characterized in that, the percentage by weight of described raw material is:
Radix Salviae Miltiorrhizae 63.0%～94%,
Radix Paeoniae Rubra 4.0%～35.0%,
Borneolum Syntheticum 0.5%～2.0%.
3. Chinese medicine dripping pills according to claim 2 is characterized in that, the percentage by weight of described raw material is:
Radix Salviae Miltiorrhizae 75.2%～90%,
Radix Paeoniae Rubra 9%～23.5%,
Borneolum Syntheticum 0.5%～1.3%.
4. Chinese medicine dripping pills according to claim 1 is characterized in that, described alcohol extract is to be selected from the following lower alcohol or the extracting solution of its mixture: methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutanol.
5. Chinese medicine dripping pills according to claim 4, its feature is an ethanol extract at described alcohol extract.
6. what Chinese medicine dripping pills according to claim 1, its feature obtained in described step (1) is the ethanol extract that Radix Salviae Miltiorrhizae and Radix Paeoniae Rubra are mixed and made into.
7. Chinese medicine dripping pills according to claim 1 is characterized in that, what described step (1) obtained is the aqueous extract that Radix Salviae Miltiorrhizae and Radix Paeoniae Rubra are mixed and made into.
8. Chinese medicine dripping pills according to claim 1 is characterized in that, described step (1) is: the Radix Salviae Miltiorrhizae of the coarse pulverization of learning from else's experience, Radix Paeoniae Rubra medical material add an amount of sodium bicarbonate to extraction pot, decoct with water secondary, filter, and filtering residue discards, and merging filtrate gets extracting solution.
9. Chinese medicine dripping pills according to claim 1 is characterized in that described predefecation is treated to coarse filtration-adsorption clarification, adsorption clarification-high speed centrifugation, coarse filtration-microfiltration or coarse filtration-precipitate with ethanol.
10. Chinese medicine dripping pills according to claim 1, it is characterized in that, the used ultrafilter membrane of described hyperfiltration treatment is selected from: cellulose diacetate film, three cellulose acetate membrane, cyanoethyl cellulose film, polysulfone membrane, sulfonated polysulfone membrane, poly (ether sulfone) film, sulfonated polyether sulfone film, polysulfonamides film, phenolphthalein side group polyarylsulfone (PAS) film, polyvinylidene fluoride film, polyacrylonitrile film, polyimide film, cellulose membrane, methyl methacrylate-acrylonitrile copolymer film, polyacrylonitrile/cellulose diacetate blend film, the dynamically ultrafilter membrane that forms, and the Modified Membrane of above-mentioned film; The molecular cut off of its ultrafilter membrane is 6000～80000.
11. Chinese medicine dripping pills 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.
12. Chinese medicine dripping pills according to claim 1 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.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410072936 CN1778354B (en) | 2004-11-26 | 2004-11-26 | Chinese medicine dropping ball for coronary heart disease and angina cordis |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410072936 CN1778354B (en) | 2004-11-26 | 2004-11-26 | Chinese medicine dropping ball for coronary heart disease and angina cordis |
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| CN1778354A CN1778354A (en) | 2006-05-31 |
| CN1778354B true CN1778354B (en) | 2010-11-10 |
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| CN101085057B (en) * | 2006-06-08 | 2011-09-21 | 天津天士力制药股份有限公司 | Traditional Chinese medicinal composition containing red sage root, and radix paeoniae rubrathe and its preparation |
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