Summary of the invention
One of purpose of the present invention is to overcome the deficiencies in the prior art, and a kind of compositions for the treatment of cardiovascular disease is provided.
It is the preparation of effective ingredient that another object of the present invention provides with the said composition.
The present invention is implemented by the following technical programs:
Compositions of the present invention is mainly made by following raw materials in weight portion medicine: Radix Salviae Miltiorrhizae 20~97, Radix Notoginseng 2~79, Flos Carthami 3~35; Also can add Radix Angelicae Sinensis or Herba Leonuri in the crude drug, its weight portion proportioning is a Radix Salviae Miltiorrhizae 20~97, Radix Notoginseng 2~79, Flos Carthami 3~35, Radix Angelicae Sinensis or Herba Leonuri 5~25; Perhaps add the Radix Astragali or Radix Ginseng or Radix Codonopsis, its weight portion proportioning is a Radix Salviae Miltiorrhizae 20~97, Radix Notoginseng 2~79, Flos Carthami 3~35, the Radix Astragali or Radix Ginseng or Radix Codonopsis 10~40; Further, in above-mentioned arbitrary prescription, also can add Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil or Styrax or Moschus or muscone in the crude drug, its weight portion proportioning is a Radix Salviae Miltiorrhizae 20~97, Radix Notoginseng 2~79, Flos Carthami 3~35, Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil or Styrax or Moschus or muscone 0.2~3; Radix Salviae Miltiorrhizae 20~97, Radix Notoginseng 2~79, Flos Carthami 3~35, Radix Angelicae Sinensis or Herba Leonuri 5~25, Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil or Styrax or Moschus or muscone 0.2~3; Radix Salviae Miltiorrhizae 20~97, Radix Notoginseng 2~79, Flos Carthami 3~35, the Radix Astragali or Radix Ginseng or Radix Codonopsis 10~40, Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil or Styrax or Moschus or muscone 0.2~3.
But above-mentioned raw materials medicine both medication powder directly is mixed with compositions, also can will make preparation again behind whole crude drug or the part material medicine extraction extractum.Available decoction and alcohol sedimentation technique obtains extractum; Also available alcohol or water alcohol extracting method obtain extractum, and wherein alcohol is lower alcohol such as methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutanol etc.; Further coarse filtration, ultrafiltration of the extracting solution that decoction and alcohol sedimentation technique or alcohol extracting method or water alcohol extracting method obtain, the ultrafiltrate reconcentration becomes extractum.The preferred for preparation method may further comprise the steps:
(a) with Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami, perhaps Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami, Radix Angelicae Sinensis or Herba Leonuri, perhaps Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami, the Radix Astragali or Radix Ginseng or Radix Codonopsis are separately or be mixed and made into water extract or alcohol extract;
(b) described extracting solution being carried out predefecation handles;
(c) further described extracting solution is carried out hyperfiltration treatment;
(d) ultrafiltrate is condensed into extractum, or adds Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil or Styrax or Moschus or muscone again, promptly.
Wherein in the step (a), 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 step (b), 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, ZTCl+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 step (c), 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 step (d), with ultrafiltrate be condensed into behind the extractum directly with any or more than one pharmaceuticss on the adjuvant accepted mixed evenly after, or with Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil or Styrax or Moschus or muscone and any or more than one pharmaceuticss on the adjuvant accepted is mixed can be made into tablet, capsule, granule, oral liquid, slow releasing preparation, controlled release preparation, gel, ointment, ointment, cream, suppository, injection, injectable powder, patch, drop pill, suspensoid after evenly, or the like; Be preferably tablet, capsule, granule, injection, drop pill; The best is a drop pill.
Drop pill of the present invention is prepared from as active component and adjuvant by above-mentioned Chinese medicine composition, perhaps is prepared from as active component and substrate adjuvant and plasticity adjuvant by above-mentioned Chinese medicine composition.
The substrate adjuvant of drop pill can be used Polyethylene Glycol, can be one or more the mixture in cetomacrogol 1000, polyethylene glycol 1500, Macrogol 4000, the polyethylene glycol 6000; Preferred Macrogol 4000, polyethylene glycol 6000; The best is a polyethylene glycol 6000; Addition is 2~10 times of extractum weight.
The preferred for preparation method is: after step (d) ultrafiltrate is condensed into extractum, directly with adjuvant or with Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil or Styrax or Moschus or muscone and adjuvant mixed even after, add the transconversion into heat material, move into the jar that drips of drop pill machine, medicine liquid droplet is to condensed fluid such as liquid paraffin or methyl-silicone oil, remove condensed fluid, select ball.
Wherein: adjuvant is a Polyethylene Glycol-6000, and 53~58 ℃ of its condensation points, addition are extractum or extractum and Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil or Styrax or Moschus or muscone weight 2~6 times; Changing the material temperature is 60~100 ℃; The temperature of condensed fluid is 0~10 ℃, and the best is 5~10 ℃; Ball heavily is 5~50mg/ grain, diameter 1.95~4.29mm.
The substrate adjuvant of drop pill preferably from natural, the substrate adjuvant of plant origin particularly, also can contain the plasticity composition in this substrate adjuvant.Specifically, the substrate adjuvant is selected from following one or more adjuvant: at least a substrate adjuvant in pharmaceutically useful monosaccharide, oligosaccharide, polysaccharide, sugar ester, sugar alcohol, fruit acid, advanced higher fatty acid derivative, high fatty alcohol, polyhydric alcohol, carbamide, the polyethylene oxide derivant.
In the above-mentioned substance, monosaccharide such as D-ribose, fructose, glucose, xylose; Oligosaccharide such as trehalose, Raffinose, maltose; Polysaccharide such as agarose; Sugar ester such as sucrose ester, D-ribonic acid-gamma lactone; Sugar alcohol such as erythritol, sorbitol, xylitol, arabitol, isomalt, lactose; Fruit acid such as malic acid, citric acid; Advanced higher fatty acid derivative such as sodium stearate, tristerin, tripalmitin, Lac; High fatty alcohol such as hexadecanol, octadecanol; Polyhydric alcohol such as phenylglycol; Polyethylene oxide derivant such as polyoxyethylene monostearate, polyoxyethylene alkyl ether, and above-claimed cpd contain water of crystallization chemical compound etc.In the above material, the natural adjuvant of plant origin such as erythritol, sorbitol, fructose, D-ribonic acid-gamma lactone, arabitol, trehalose, D-ribose, low melting-point agarose, Lac, xylitol, Raffinose, glucose, malic acid, citric acid, isomalt, lactose, maltose, xylose, sucrose ester etc., and they contain the water of crystallization chemical compound; Chemosynthesis adjuvant and animal origin adjuvant such as phenylglycol, Polyethylene Glycol, hexadecanol, octadecanol, sodium stearate, tristerin, tripalmitin, carbamide, polyoxyethylene monostearate, polyoxyethylene alkyl ether.In the above-mentioned substance, especially preferably from following one or more adjuvant: sorbitol, xylitol, lactose, maltose, sucrose ester, and they contain the water of crystallization chemical compound.
Above-mentioned substrate adjuvant is mainly the natural adjuvant of plant origin, and the content that is meant the adjuvant of plant origin in adjuvant is more than 50 weight %, and the content of chemosynthesis adjuvant and animal origin adjuvant is no more than the natural adjuvant of plant origin.Preferably, the substrate adjuvant of drop pill of the present invention only uses the natural adjuvant of plant origin, perhaps is mainly the natural adjuvant of plant origin and only contains a spot of chemosynthesis adjuvant and animal origin adjuvant, and its content is below 50 weight %, below the preferred 40 weight %, more preferably below the 30 weight %.The natural adjuvant of above-described so-called plant origin is meant as adjuvant itself and extracts in plant cell or tissue, or by the material of plant extract through modifications such as derivatizations after the product of gained.So-called chemosynthesis adjuvant is meant synthetic micromolecule or the macromolecular compound that is obtained through chemical synthesis process by simple micromolecule.The natural adjuvant of so-called animal origin is meant as adjuvant itself and extracts in the animal cell or tissue, or the material that extracts by animal through modifications such as derivatizations after the product of gained.
The substrate adjuvant of above-mentioned plant origin, have now or in the future may have the synthetic product, if the synthetic product are identical or close with the character of the natural substrates adjuvant of original plant origin, characteristic with safety non-toxic, then the natural substrates adjuvant of alternative plant origin is used as the natural substrates adjuvant of above-mentioned plant origin.
For improving the formability of drop pill of the present invention, preferably also contain the plasticity composition in the adjuvant of drop pill of the present invention.As this plasticity composition, for example can enumerate and be selected from following one or more composition: the natural adjuvant of plant origin such as starch and derivant, cellulose and derivant thereof, arabic gum, dextran, chitin, sesbania gum, carrageenan, Ficus elastica, Furcellaran, tragakanta, carrageenin, tamarind gum, pectin, xanthan gum, alginic acid and salt thereof, dextrin, cyclodextrin, agar, lactose; Chemosynthesis adjuvant and animal origin adjuvant such as polyvinylpyrrolidone, crospolyvinylpyrrolidone, carbomer, polyvinyl alcohol, acrylic resin, poloxamer, silicon dioxide, gelatin etc.
Above-mentioned starch and derivant thereof such as pregelatinized Starch, modified starch, hydroxypropyl starch, carboxymethyl starch etc.Described cellulose and derivant thereof such as methylcellulose, microcrystalline Cellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, cross-linking sodium carboxymethyl cellulose, hydroxyethylmethyl-cellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose.
In the plasticity composition, preferably from following one or more adjuvant: pregelatinized Starch, carboxymethyl starch, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, arabic gum, alginic acid, dextrin, cyclodextrin, agar, lactose.In addition, glyceryl monostearate, polyoxyethylene monostearate also can be used as the plasticity composition and other substrate supplementary product compatibility is used.
The composition of above-described so-called plant origin is meant as adjuvant itself and extracts in plant cell or tissue, or by the material of plant extract through modifications such as derivatizations after the product of gained.So-called chemosynthesis adjuvant is meant synthetic micromolecule or the macromolecular compound that is obtained through chemical synthesis process by simple micromolecule.The adjuvant of so-called animal origin is meant as adjuvant itself and extracts in the animal cell or tissue, or the material that extracts by animal through modifications such as derivatizations after the product of gained.
The plasticity composition of above-mentioned plant origin, have now or in the future may have the synthetic product, if the synthetic product are identical or close with the character of the natural plasticity composition of plant origin, characteristic with safety non-toxic, then the natural plasticity composition of alternative above-mentioned plant origin is used as the natural plasticity substrate adjuvant of above-mentioned plant origin.
The above-mentioned monosaccharide that is selected from, oligosaccharide, polysaccharide, sugar ester, sugar alcohol, fruit acid, advanced higher fatty acid derivative, high fatty alcohol, polyhydric alcohol, carbamide, the substrate adjuvant of polyethylene oxide derivant etc., the substrate adjuvant and the above-mentioned plasticity composition in preferred plant source are selected collocation according to medicinal property, it is preferably arranged in pairs or groups and is xylitol and starch, lactose and starch, xylitol and arabic gum, sucrose ester and glyceryl monostearate, sucrose ester and polyoxyethylene monostearate, sucrose ester and polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose, sucrose ester and polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose and silicon dioxide etc., but be not limited thereto.
The weight ratio of above-mentioned substrate adjuvant and plasticity composition is 1: 0~1: 1.5, is preferably 1: 0.1~1: 0.9, and the best is 1: 0.1~1: 0.5.
In the above-mentioned substrate adjuvant, xylitol is preferably 1: 0.2 with the ratio of the weight of starch~and 1: 0.3;
In the above-mentioned substrate adjuvant, lactose is preferably 1: 0.2 with the ratio of the weight of starch~and 1: 0.3;
In the above-mentioned substrate adjuvant, the ratio of the weight of xylitol and arabic gum is preferably 1: 0.2~and 1: 0.4;
In the above-mentioned substrate adjuvant, the weight ratio of sucrose ester and glyceryl monostearate is 1: 0.1~1: 1, and the best is 1: 0.5.
In the above-mentioned substrate adjuvant, the weight ratio of sucrose ester and polyoxyethylene monostearate is 1: 0.1 to 1: 1, and the best is 1: 0.5.
In the above-mentioned substrate adjuvant, the weight ratio of sucrose ester and polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose is 1: (0.1~1): (0.1~1), the best are 1: 0.4: 0.6.
In the above-mentioned substrate adjuvant, the weight ratio of sucrose ester and polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose and silicon dioxide is 15: (7~15): (0.1~2): (0.1~2), the best are 15: 11: 1: 1.
Above-mentioned drop pill substrate adjuvant is 1: 0.1~1: 1 with the ratio of the weight of extractum, is preferably 1: 0.1~1: 0.6, and the best is 1: 0.2~1: 0.4.
The preferred for preparation process conditions are: extractum mixes mixing time with the substrate adjuvant be 10~30 minutes; A mixed heating and melting temperature of extractum and substrate adjuvant or a system temperature are 45~95 ℃, are preferably 60~95 ℃; Liquid coolant is liquid paraffin, methyl-silicone oil or vegetable oil (Oleum Glycines, Semen Ricini wet goods) etc., is preferably liquid paraffin, methyl-silicone oil; The temperature of liquid coolant is-20~30 ℃, is preferably 0~18 ℃; Dropper mouth internal diameter is 1.0~4.0mm, is preferably 1.2~2.5mm; The difference of dropper mouth external diameter and internal diameter is less for well.
Below by medicine of the present invention the experiment of the protective effect of Ischemia and Reperfusion in vivo in Rats myocardial damage is illustrated its beneficial effect.
1. animal model: Wistar strain male rat, open chest anesthetized is kept breathing, around left coronary artery, and carries out ligation between left auricle and pulmonary conus.
2. method: rat is divided into 4 groups at random: 1. sham operated rats (sham-operated control), normal saline is irritated stomach, 1ml/ days, totally 4 days; 2. myocardial ischemia-reperfusion group (M-IR), it is the same to irritate the stomach method; 3. FUFANG DANSHEN PIAN group (with reference to the preparation of the method for 2000 editions FUFANG DANSHEN PIAN of Chinese Pharmacopoeia) was dissolved in the 1ml normal saline with 2g crude drug/kg/ days, and it is the same to irritate the stomach method; 4. medicine group of the present invention (press embodiment 6 method preparation and extractum), be dissolved in the 1ml normal saline with 2g crude drug/kg/ days, it is the same to irritate the stomach method.Not ligation of sham operated rats; Other group is in ligation perfusion again after 1 hour.Take out after injecting 1% her Wen orchid in the ligation left coronary artery once more before sacrifice of animal, ventricle, with the PBS rinsing, freezing 1 hour.After removing unnecessary tissue, 30 minutes (37 ℃) of dyeing in 1%TTC.With weight method calculating myocardium ischemia hazardous area (she does not dye the district by the Wen orchid), infarcted region (TTC does not dye the district).
3. the result of variations of myocardial infarct size
The myocardial infarction phenomenon was not seen in sham-operation in 7 hours; It is obvious that myocardial ischemia poured into after 6 hours myocardial infarction in 1 hour again; Medicine of the present invention can obviously dwindle the myocardial infarct size of myocardial reperfusion rat, shows that medicine of the present invention pours into the myocardium cell necrosis variation again to ischemic myocardial cells good protective action (seeing Table 1) is arranged.
Table 1 is respectively organized the variation of myocardial infarct size
Group |
Example number (n) |
Infarcted region weight/left ventricular mass (%) |
Infarcted region weight/hazardous area weight (%) |
Sham-control group M-IR group FUFANG DANSHEN PIAN group medicine group of the present invention |
10 10 10 10 |
0 41.3±7.6 34.6±7.0* 27.5±6.7** |
0 63.4±8.3 53.4±7.6* 45.4±8.3**
Δ |
Annotate: compare * P<0.05, * * P<0.01 with the M-IR group; Compare with the FUFANG DANSHEN PIAN group,
ΔP<0.05,
The Δ ΔP<0.01.
The specific embodiment
The invention will be further elaborated below in conjunction with embodiment.These embodiment only are used to the purpose that exemplifies, rather than limit the present invention by any way.
Embodiment 1
Crude drug adopts Radix Salviae Miltiorrhizae 97g, Radix Notoginseng 79g, Flos Carthami 35g, Lignum Dalbergiae Odoriferae oil 3g, Radix Ginseng 40g
Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and people participate in 5 times of water gagings, decoct 2 hours, filter, and 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 decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9~1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill, and filters, and filtrate is concentrated to obtain the extractum that relative density is 1.32~1.40 (55 ℃).Add Lignum Dalbergiae Odoriferae oil, drying is made granule, and compacting is in blocks, or sugar coating, promptly.
Embodiment 2
Radix Salviae Miltiorrhizae 100g, Radix Notoginseng 10g, Flos Carthami 15g;
Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami 70% ethanol extraction, extracting solution carries out microfiltration with ceramic membrane, collects filtrate; The filtrate ultrafiltration, the operating condition of ultrafiltration technology is: the inlet pressure of ultrafiltration is 0.35Mpa, 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.
Ultrafiltrate concentrates and to obtain the extractum that relative density is 1.35~1.39 (55 ℃), adds 3% polyvidone alcoholic solution system soft material, crosses 18 mesh sieve system granules, 60 ℃ of dryings 30~45 minutes, and granulate, the adding Pulvis Talci, mixing fills in capsule, promptly.
Embodiment 3
Crude drug Radix Salviae Miltiorrhizae 20g, Radix Notoginseng 2g, Flos Carthami 10g, Radix Angelicae Sinensis 100g, Borneolum Syntheticum 2.2g.
Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and Radix Angelicae Sinensis add 5 times of water gagings, decoct 2 hours, filter, and 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 decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9~1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill, and filters, and filtrate is concentrated to obtain the extractum that relative density is 1.32~1.40 (55 ℃).With extractum and Borneolum Syntheticum in the batch (-type) fluid bed with the lactose fluidisation, drying is made granule, promptly.
Embodiment 4
Crude drug Radix Salviae Miltiorrhizae 485g, Radix Notoginseng 70g, Flos Carthami 150g, muscone 2.2g, Radix Codonopsis 50g.
Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and Radix Codonopsis add 5 times of water gagings, decoct 2 hours, filter, and 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 decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9~1.1, adds ethanol and makes medicinal liquid contain determining alcohol 75%, leaves standstill filtration; Filtrate is that 6000 three cellulose acetate membrane 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.
Ultrafiltrate concentrates and obtains the extractum that relative density is 1.32~1.40 (55 ℃), adds muscone, and mix homogeneously adds mannitol 30g, calcium disodium edetate 5g, distilled water 5ml, behind the said components mixing, and lyophilization, packing, promptly.Embodiment 5
Crude drug Radix Salviae Miltiorrhizae 180g, Radix Notoginseng 50g, Flos Carthami 50g, Styrax 4g.
Radix Salviae Miltiorrhizae, Radix Notoginseng and Flos Carthami add 5 times of water gagings, decoct 2 hours, filter, and 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 decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 1.1~1.2, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill, and filters, and filtrate is concentrated to obtain the extractum that relative density is 1.32~1.40 (55 ℃).Get that extractum, Styrax and Polyethylene Glycol-6000 18g are mixed evenly to be heated to 85 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 85 ℃; In medicine liquid droplet to the 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, makes 1000 drop pill, promptly.
Embodiment 6
Crude drug Radix Salviae Miltiorrhizae 97g, Radix Notoginseng 79g, Flos Carthami 35g.
Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami add 5 times of water gagings, decoct 2 hours, filter, and 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.Is that 50000 sulfonated polysulfone membrane carries out ultrafiltration with filtrate 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 1.35~1.39 (55 ℃).Get that extractum and Polyethylene Glycol-6000 20g are mixed evenly to be heated to 60 ℃ of temperature, change material after 40 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 8 ℃ methyl-silicone oil, take out drop pill, oil removing, screen cloth selects ball, makes 1000 drop pill, promptly.Embodiment 7
Crude drug Radix Salviae Miltiorrhizae 15g, Radix Notoginseng 4.5g, Flos Carthami 2g, Lignum Dalbergiae Odoriferae oil 0.25g, adjuvant lactose 18.0g, pregelatinized Starch 4.5g.
The Radix Salviae Miltiorrhizae of coarse pulverization, Radix Notoginseng, flos carthami 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 decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9~1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill, and filters, and filtrate is concentrated to obtain the extractum that relative density is 1.32~1.40 (55 ℃).
Get above-mentioned extractum and Lignum Dalbergiae Odoriferae oil, evenly mixed with adjuvant lactose and pregelatinized Starch, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.
The drop pill (newly) that the new substrate adjuvant of above-mentioned usefulness is made with polyethylene glycol 6000 be the adjuvant dissolve scattered time limit of making drop pill (embodiment 6), weight differential comparison (seeing the following form)
|
0 month |
January |
February |
March |
June |
December |
18 months |
|
Criterion |
The result |
1 batch |
Weight differential (± 15%) |
New and old |
All in 10% |
All in 10% |
All in 10% |
All in 10% |
All in 10% |
All in 10% |
All in 10% |
Dissolve scattered time limit (30 minutes) |
New and old |
2′83″ 4′52″ |
2′83″ 4′52″ |
2′83″ 4′52″ |
2′83″ 4′53″ |
2′85″ 4′53″ |
2′87″ 4′55″ |
2′89″ 4′56″ |
2 batches |
Weight differential (± 15%) |
New and old |
All in 10% |
All in 10% |
All in 10% |
All in 10% |
All in 10% |
All in 10% |
All in 10% |
Dissolve scattered time limit (30 minutes) |
New and old |
2′84″ 4′53″ |
2′84″ 4′53″ |
2′84″ 4′53″ |
2′85″ 4′54″ |
2′85″ 4′54″ |
2′86″ 4′55″ |
2′87″ 4′57″ |
3 batches |
Weight differential (± 15%) |
New and old |
All in 10% |
All in 10% |
All in 10% |
All in 10% |
All in 10% |
All in 10% |
All in 10% |
Dissolve scattered time limit (30 minutes) |
New and old |
2′85″ 4′53″ |
2′85″ 4′53″ |
2′85″ 4′53″ |
2′86″ 4′54″ |
2′86″ 4′55″ |
2′87″ 4′57″ |
2′88″ 4′58″ |
Above test data shows, the molten diffusing speed of the Chinese medicine dripping pills made from new substrate adjuvant of the present invention is faster, is more conducive to medicine and plays a role in the shortest time; The ball method of double differences is different all to be controlled in the pharmacopeia prescribed limit, and the alternative present chemosynthesis adjuvant of this natural substrates adjuvant is described, carries out suitability for industrialized production.
Embodiment 8
Crude drug Radix Salviae Miltiorrhizae 24.2g, Radix Notoginseng 25.5g, Flos Carthami 25.4g, Moschus 0.35g, Herba Leonuri 10.0g; Adjuvant xylitol 15.0g, starch 5.0g.
Learn from else's experience Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and the Herba Leonuri medical material of coarse pulverization to extraction pot, add the 0.9g 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 decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9~1.1, adds ethanol and makes medicinal liquid contain determining alcohol 75%, leaves standstill, and filters, and filtrate is concentrated to obtain the extractum that relative density is 1.32~1.40 (55 ℃).
Get above-mentioned extractum and Moschus, evenly mixed with adjuvant xylitol and starch, be heated to 65 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 85 ℃.In medicine liquid droplet to the 8 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.78min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 9
Crude drug Radix Salviae Miltiorrhizae 16.2g, Radix Notoginseng 29.5g, Flos Carthami 20.5g, Styrax 0.31g, Radix Astragali 13.8g; Adjuvant lactose 15.0g, arabic gum 3.0g.
With ethanol extraction Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and Milkvetch Root, obtain Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and Radix Astragali ethanol extract, with this extracting liquid filtering, collect filtrate with gauze.Filtrate is that 20000 cellulose diacetate film carries out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).The condition of above-mentioned ultrafiltration 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 the water ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Styrax, evenly mixed with adjuvant lactose and arabic gum, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 85 ℃.In medicine liquid droplet to the 6 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.61min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 10
Crude drug Radix Salviae Miltiorrhizae 46.5g, Radix Notoginseng 5.0g, Flos Carthami 10.5g, Borneolum Syntheticum 0.57g, Radix Ginseng 5.5g; Adjuvant xylitol 16.0g, tragakanta 5.0g.
Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and the people of coarse pulverization are participated in 5 times of water gagings, decocted 2 hours, filter, filtering residue carries out the second time and extracts, add 4 times of water gagings, fried in shallow oil 1 hour, filter, filtering residue discards, merging filtrate gets Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and Radix Ginseng extractive solution, leaves standstill, and filters.Filtrate is that 60000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).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 the dilute alcohol solution ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Borneolum Syntheticum, evenly mixed with adjuvant xylitol and tragakanta, be heated to 60 ℃ of temperature, change material after 25 minutes, move in the dropping-pill machine jar that jar temperature remains on 89 ℃.In medicine liquid droplet to the 5 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.62min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 11
Crude drug Radix Salviae Miltiorrhizae 46.5g, Radix Notoginseng 3.0g, Flos Carthami 3.0g, Radix Ginseng 8.5g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 8.0g.
With 80% ethanol extraction Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and Radix Ginseng, obtain the ethanol extract of Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and Radix Ginseng, get supernatant with dividing behind this extracting solution high speed centrifugation.With this liquid molecular cut off is that 50000 sulfonated polysulfone membrane carries out ultrafiltration, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).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 the water ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 9.
Get that above-mentioned extractum and adjuvant sucrose ester and polyoxyethylene monostearate are mixed evenly to be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 5 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.64min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 12
Crude drug Radix Salviae Miltiorrhizae 49.0g, Radix Notoginseng 16.5g, Flos Carthami 17.5g, Radix Angelicae Sinensis 6.0g; Adjuvant sucrose ester 15.0g, glyceryl monostearate 4.0g.
Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and the Radix Angelicae Sinensis medical material of coarse pulverization to extraction pot, 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 60000 poly (ether sulfone) film carries out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).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 the water ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 7.5.
Get that above-mentioned extractum and adjuvant sucrose ester and glyceryl monostearate are mixed evenly to be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 6 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.67min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 13
Crude drug Radix Salviae Miltiorrhizae 47.0g, Radix Notoginseng 8.6g, Flos Carthami 2g, Borneolum Syntheticum 0.40g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 2.0g, cross-linking sodium carboxymethyl cellulose 3.0g.
The Radix Salviae Miltiorrhizae of coarse pulverization, pseudo-ginseng and Flos Carthami 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 60000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).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 the water ultrafiltration again 1 time, and the pH value of feed liquid is controlled at 5.
Get above-mentioned extractum and Borneolum Syntheticum, evenly be heated to 65 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃ with adjuvant sucrose ester, polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose are mixed.In medicine liquid droplet to the 4 ℃ methyl-silicone oil, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.66min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 14
Crude drug Radix Salviae Miltiorrhizae 97.0g, Radix Notoginseng 79.0g, Flos Carthami 35g, Radix Codonopsis 40g; Adjuvant lactose 40.0g, carrageenan 18.0g, starch 15.0g.
Learn from else's experience Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and the codonopsis pilosula 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 polysulfonamides film carries out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).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 the dilute alcohol solution ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 9.
Get that above-mentioned extractum and adjuvant lactose, carrageenan and starch are mixed evenly to be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 5 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.77min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 15
Crude drug Radix Salviae Miltiorrhizae 20.0g, Radix Notoginseng 2.0, Flos Carthami 3.0g, Borneolum Syntheticum 0.2g, Radix Ginseng 10.0g; Adjuvant xylitol 5.0g, lactose 2.0g, arabic gum 2.0g.
Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and the ginseng crude drug of coarse pulverization to extraction pot, 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 decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9~1.1, adds ethanol and makes medicinal liquid contain determining alcohol 75%, leaves standstill filtration.Filtrate is that 20000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).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 the water ultrafiltration again 1 time, and the pH value of feed liquid is controlled at 6.
Get above-mentioned extractum and Borneolum Syntheticum, evenly be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 84 ℃ with adjuvant xylitol, lactose and arabic gum are mixed.In medicine liquid droplet to the 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.55min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 16
Crude drug Radix Salviae Miltiorrhizae 18.0g, Radix Notoginseng 20.0g, Flos Carthami 15.5g, Borneolum Syntheticum 0.26g, Herba Leonuri 7.5g; Adjuvant sucrose ester 10.0g, polyoxyethylene monostearate 6.0g, cross-linking sodium carboxymethyl cellulose 1.0g, silica 1 .0g.
Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and the Herba Leonuri medical material of coarse pulverization to extraction pot, 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 decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9~1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill filtration.Filtrate is that 20000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).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 the dilute alcohol solution ultrafiltration again 1 time, and the pH value of feed liquid is controlled at 6.
Get above-mentioned extractum and Borneolum Syntheticum,, mixed evenly be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 84 ℃ with adjuvant sucrose ester, polyoxyethylene monostearate, cross-linking sodium carboxymethyl cellulose and silicon dioxide.In medicine liquid droplet to the 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.57min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 17
Crude drug Radix Salviae Miltiorrhizae 23.0g, Radix Notoginseng 7.8g, Flos Carthami 35g, Lignum Dalbergiae Odoriferae oil 0.21g, Radix Astragali 27.0g; Adjuvant lactose 14.0g, tragakanta 5.0g.
Learn from else's experience Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and the Milkvetch Root of coarse pulverization to extraction pot, add the 0.88g 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 decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9~1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill filtration.Filtrate is that 20000 polyvinylidene fluoride film carries out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).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 1/9, adds the water ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Lignum Dalbergiae Odoriferae oil, evenly mixed with adjuvant lactose and tragakanta, be heated to 65 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 85 ℃.In medicine liquid droplet to the 8 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.49min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 18
Crude drug Radix Salviae Miltiorrhizae 24.2g, Radix Notoginseng 25.0g, Flos Carthami 5g, Radix Codonopsis 10.0g; Adjuvant lactose 18.0g, pregelatinized Starch 4.5g.
Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and the codonopsis pilosula of coarse pulverization to extraction pot, 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 decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9~1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill, and filters, and filtrate is concentrated to obtain the extractum that relative density is 1.32~1.40 (55 ℃).
Get that above-mentioned extractum and adjuvant lactose and pregelatinized Starch are mixed evenly to be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.81min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 19
Crude drug Radix Salviae Miltiorrhizae 26.2g, Radix Notoginseng 7.0g, Flos Carthami 6g, Radix Angelicae Sinensis 10.8g; Adjuvant xylitol 15.0g, starch 5.0g.
Learn from else's experience Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and the Radix Angelicae Sinensis medical material of coarse pulverization to extraction pot, add the 0.9g 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 decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9~1.1, adds ethanol and makes medicinal liquid contain determining alcohol 75%, leaves standstill, and filters, and filtrate is concentrated to obtain the extractum that relative density is 1.32~1.40 (55 ℃).
Get that above-mentioned extractum and adjuvant xylitol and starch are mixed evenly to be heated to 65 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 85 ℃.In medicine liquid droplet to the 8 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.73min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 20
Crude drug Radix Salviae Miltiorrhizae 30.8g, Radix Notoginseng 15.2g, Flos Carthami 16.2g, Lignum Dalbergiae Odoriferae oil 0.25g, Herba Leonuri 8.0g; Adjuvant lactose 18.0g, arabic gum 4.0g.
With ethanol extraction Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and Herba Leonuri medical material, obtain Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and Herba Leonuri ethanol extract, with this extracting liquid filtering, collect filtrate with gauze.Filtrate is that 20000 cellulose diacetate film carries out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).The condition of above-mentioned ultrafiltration 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 the dilute alcohol solution ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Lignum Dalbergiae Odoriferae oil, evenly mixed with adjuvant lactose and arabic gum, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 85 ℃.In medicine liquid droplet to the 6 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.60min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 21
Crude drug Radix Salviae Miltiorrhizae 48.5g, Radix Notoginseng 39.5g, Flos Carthami 17.5; Adjuvant xylitol 26.0g, tragakanta 8.0g.
The Radix Salviae Miltiorrhizae and the Radix Notoginseng of coarse pulverization are 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 and Radix Ginseng extractive solution, leaves standstill, and filters.Filtrate is that 60000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).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 the water ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 7.5.
Get that above-mentioned extractum and adjuvant xylitol and tragakanta are mixed evenly to be heated to 60 ℃ of temperature, change material after 25 minutes, move in the dropping-pill machine jar that jar temperature remains on 89 ℃.In medicine liquid droplet to the 5 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.59min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 22
Crude drug Radix Salviae Miltiorrhizae 26.0g, Radix Notoginseng 3.0g, Flos Carthami 12g, Borneolum Syntheticum 0.21g, Radix Angelicae Sinensis 10.0g; Adjuvant sucrose ester 13.0g, polyoxyethylene monostearate 8.0g.
With 80% ethanol extraction Radix Salviae Miltiorrhizae and Radix Angelicae Sinensis, obtain Radix Salviae Miltiorrhizae and Radix Angelicae Sinensis ethanol extract, get supernatant with dividing behind this extracting solution high speed centrifugation.With this liquid molecular cut off is that 50000 sulfonated polysulfone membrane carries out ultrafiltration, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).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 the dilute alcohol solution ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 9.
Get above-mentioned extractum and Borneolum Syntheticum, evenly mixed with adjuvant sucrose ester and polyoxyethylene monostearate, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 5 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.61min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 23
Crude drug Radix Salviae Miltiorrhizae 49.0g, Radix Notoginseng 12.5g, Flos Carthami 3g, Borneolum Syntheticum 0.20g, Radix Ginseng 6.0g; Adjuvant sucrose ester 15.0g, glyceryl monostearate 4.0g.
Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and the ginseng crude drug of coarse pulverization to extraction pot, 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 60000 poly (ether sulfone) film carries out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).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 the water ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Borneolum Syntheticum, evenly mixed with adjuvant sucrose ester and glyceryl monostearate, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 6 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.62min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 24
Crude drug Radix Salviae Miltiorrhizae 21.0g, Radix Notoginseng 8.5g, Flos Carthami 13.5g, Styrax 0.20g, Radix Angelicae Sinensis 9.0g; Adjuvant sucrose ester 13.0g, polyoxyethylene monostearate 2.0g, cross-linking sodium carboxymethyl cellulose 3.0g.
Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and the Radix Angelicae Sinensis medical material of coarse pulverization to extraction pot, 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 60000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).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 the water ultrafiltration again 1 time, and the pH value of feed liquid is controlled at 5.
Get above-mentioned extractum and Styrax, evenly be heated to 65 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃ with adjuvant sucrose ester, polyoxyethylene monostearate and cross-linking sodium carboxymethyl cellulose are mixed.In medicine liquid droplet to the 4 ℃ methyl-silicone oil, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.62min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 25
Crude drug Radix Salviae Miltiorrhizae 31.0g, Radix Notoginseng 31.5g, Flos Carthami 45g, muscone 0.18g, Radix Codonopsis 12.5g; Adjuvant lactose 18.0g, carrageenan 8.0g, starch 2.0g.
Learn from else's experience Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and the codonopsis pilosula 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 polysulfonamides film carries out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).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 the dilute alcohol solution ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 9.
Get above-mentioned extractum and muscone, evenly be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃ with adjuvant lactose, carrageenan and starch are mixed.In medicine liquid droplet to the 5 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.74min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 26
Crude drug Radix Salviae Miltiorrhizae 28.0g, Radix Notoginseng 16.6g, Flos Carthami 9.5g, Lignum Dalbergiae Odoriferae oil 0.20g, Radix Angelicae Sinensis 8.0g; Adjuvant xylitol 10.0g, lactose 3.0g, arabic gum 5.0g.
Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and the Radix Angelicae Sinensis medical material of coarse pulverization to extraction pot, 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 decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9~1.1, adds ethanol and makes medicinal liquid contain determining alcohol 75%, leaves standstill filtration.Filtrate is that 20000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).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 the dilute alcohol solution ultrafiltration again 1 time, and the pH value of feed liquid is controlled at 6.
Get above-mentioned extractum and Lignum Dalbergiae Odoriferae oil, evenly be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 84 ℃ with adjuvant xylitol, lactose and arabic gum are mixed.In medicine liquid droplet to the 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.57min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 27
Crude drug Radix Salviae Miltiorrhizae 28.0g, Radix Notoginseng 18.0g, Flos Carthami 14.5g, Moschus 0.21g, Radix Ginseng 18.7g; Adjuvant sucrose ester 14.0g, polyoxyethylene monostearate 6.0g, cross-linking sodium carboxymethyl cellulose 1.0g, silica 1 .0g.
Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and the ginseng crude drug of coarse pulverization to extraction pot, 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 decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9~1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill filtration.Filtrate is that 20000 polysulfone membrane is carried out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).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 the dilute alcohol solution ultrafiltration again 1 time, and the pH value of feed liquid is controlled at 6.
Get above-mentioned extractum and Moschus,, mixed evenly be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 84 ℃ with adjuvant sucrose ester, polyoxyethylene monostearate, cross-linking sodium carboxymethyl cellulose and silicon dioxide.In medicine liquid droplet to the 7 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.62min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 28
Crude drug Radix Salviae Miltiorrhizae 23.0g, Radix Notoginseng 7.8g, Flos Carthami 22g, Radix Ginseng 15.0g; Adjuvant lactose 18.0g, tragakanta 5.0g.
Learn from else's experience Radix Salviae Miltiorrhizae, Radix Notoginseng, Flos Carthami and the ginseng crude drug of coarse pulverization to extraction pot, add the 0.88g 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 decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9~1.1, adds ethanol and makes medicinal liquid contain determining alcohol 70%, leaves standstill filtration.Filtrate is that 20000 polyvinylidene fluoride film carries out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).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 1/9, adds the water ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 7.5.
Get that above-mentioned extractum and adjuvant lactose and tragakanta are mixed evenly to be heated to 65 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 85 ℃.In medicine liquid droplet to the 8 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.44min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 29
Crude drug Radix Salviae Miltiorrhizae 26.0g, Radix Notoginseng 25.5g, Flos Carthami 25.5g; Adjuvant sucrose ester 15.0g.
With 80% ethanol extraction Radix Salviae Miltiorrhizae, Flos Carthami and Radix Notoginseng, obtain Radix Salviae Miltiorrhizae and Radix Notoginseng ethanol extract, get supernatant with dividing behind this extracting solution high speed centrifugation.With this liquid molecular cut off is that 50000 sulfonated polysulfone membrane carries out ultrafiltration, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).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 the water ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 9.
Get that above-mentioned extractum and adjuvant sucrose ester and polyoxyethylene monostearate are mixed evenly to be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 5 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.64min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.
Embodiment 30
Crude drug Radix Salviae Miltiorrhizae 49.0g, Radix Notoginseng 12.0g, Flos Carthami 17.0g, Styrax 0.27g; Adjuvant sucrose ester 11.0g, polyoxyethylene monostearate 12.0g.
Radix Salviae Miltiorrhizae, Flos Carthami and the pseudo-ginseng of coarse pulverization to extraction pot, 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 60000 poly (ether sulfone) film carries out ultrafiltration with molecular cut off, and ultrafiltrate concentrates and obtains the extractum that relative density is 1.35~1.39 (55 ℃).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 the water ultrafiltration again 2 times, and the pH value of feed liquid is controlled at 7.5.
Get above-mentioned extractum and Styrax, evenly mixed with adjuvant sucrose ester and glyceryl monostearate, be heated to 60 ℃ of temperature, change material after 30 minutes, move in the dropping-pill machine jar that jar temperature remains on 90 ℃.In medicine liquid droplet to the 6 ℃ liquid paraffin, take out drop pill, oil removing, screen cloth selects ball, promptly.The result shows, prepared drop pill rounding, even, consistent, the no adhesion phenomenon of color and luster of size.By measuring under Chinese Pharmacopoeia version in 2000 the method disintegration item, the result does not add the average 2.67min of baffle plate by screen cloth, meets the pharmacopeia regulation this disintegration.