CN101195000B - Mailuoning dropping pills and method for preparing the same - Google Patents
Mailuoning dropping pills and method for preparing the same Download PDFInfo
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- CN101195000B CN101195000B CN2006101299463A CN200610129946A CN101195000B CN 101195000 B CN101195000 B CN 101195000B CN 2006101299463 A CN2006101299463 A CN 2006101299463A CN 200610129946 A CN200610129946 A CN 200610129946A CN 101195000 B CN101195000 B CN 101195000B
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- mailuoning
- drop pill
- ethyl acetate
- polyethylene glycol
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- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention provides an MLN dropping pill and process for preparation. The preparation method of the medicament of the invention comprises extracting percolation dendrobium, achyranthes root, radix scrophulariae and honeysuckle flower after adding ethanol, precipitating water, purifying with ethyl acetate, and obtaining extracts, taking proper polyethylene glycol to heat, adding the extracts after melting, stirring uniformly, dropping the liquor into condensate with a proper speed, and then forming dropping pill. The dropping pill has rapid releasing speed in bodies, high bioavailability and small volume, which is carried conveniently.
Description
Technical field
The present invention relates to dropping pill formulation, specifically a kind of Mailuoning dropping pills and preparation method thereof with the Chinese medicine extract preparation.
Background technology
MAILUONING ZHUSHEYE is the Chinese medicine compound injection that on the basis of famous hospital " SIMIAOYONGAN TANG ", develops; Form by Radix Achyranthis Bidentatae, Radix Scrophulariae, Herba Dendrobii, Flos Lonicerae four flavor Chinese medicines, be widely used in thromboangiitis obliterans, arteriosclerosis obliterans, cerebral thrombosis and sequela, multiple takayasu arteritis, acute limb Arteriae embolization, diabetic gangrene, venous thrombosis and thrombophlebitis etc.Chinese patent CN1557398A discloses it also to have prevention and treats anginal effect.But the preparation technology of existing MAILUONING ZHUSHEYE adopts decoction and alcohol sedimentation technique that four kinds of medical materials are extracted simultaneously; And then get effective ingredient with ethyl acetate extraction and (see " process of MAILUONING ZHUSHEYE "; Publication number CN1078148A); Yet contain chlorogenic acid etc. to illumination and air unstability composition in the side, in storage process, occur phenomenons such as the variation of injection color and luster, active constituent content reduction easily, have compositions such as organic acid and alkaloid in the while side; Flocculation sediment very easily takes place in these compositions under the liquid drugs injection state, badly influences the safety and the effectiveness of MAILUONING ZHUSHEYE clinical practice.
Chinese patent CN1682928A discloses a kind of new method for preparing MAILUONING ZHUSHEYE, and this method is with Radix Achyranthis Bidentatae and Radix Scrophulariae alcohol extraction, and Herba Dendrobii soaks with pure, reflux, extract,, and the two extract merges the back and goes up macroporous adsorbent resin, gets extract X; Go up the D101 macroporous adsorbent resin after the Flos Lonicerae water supersound extraction, the ultrafilter membrane ultrafiltration of the centrifugal back of water lotion gets extract Y; Perhaps NKA-II type macroporous adsorbent resin still after the water supersound extraction is collected alcohol eluen, extract Y; X and Y are merged, process preparation.Although this technology is more abundant to the extraction of effective ingredient, very loaded down with trivial details, supersound process wherein is difficult to use in commercial production, and macroporous adsorbent resin is handled deficiencies such as then there being long processing period.
So, press for a kind of determined curative effect, rapid-action, taking convenience, low-cost 'Mailuoning ' on the market.
Summary of the invention
One of the object of the invention provides a kind of determined curative effect, rapid-action, taking convenience, low-cost Mailuoning dropping pills;
Another object of the present invention provides the method for preparing of this Mailuoning dropping pills.
The object of the invention is achieved through following technical scheme.
Medicine of the present invention is the drop pill of being processed by following bulk drugs, adjuvant:
The extract of Herba Dendrobii, Radix Achyranthis Bidentatae, Radix Scrophulariae, Flos Lonicerae is an active component, and wherein the weight ratio of active constituents of medicine and adjuvant Polyethylene Glycol is 1: 1～10; Preferred weight ratio is 1: 1～6; Optimum weight ratio is 1: 1.5.
The present invention prepares active component raw material medicine weight proportion: 1～4 part of 1～4 portion of Radix Scrophulariae of 1～4 part of Radix Achyranthis Bidentatae of 1～4 portion of Flos Lonicerae of Herba Dendrobii.
Preferred preparation active component raw material medicine weight proportion is:
1 part of 1 portion of Radix Scrophulariae of 1 part of Radix Achyranthis Bidentatae of 1 portion of Flos Lonicerae of Herba Dendrobii.
Drop pill of the present invention adopts following method preparation: get 1～4 part of ethanol percolate extraction of 1～4 portion of Radix Scrophulariae of 1～4 part of Radix Achyranthis Bidentatae of 1～4 portion of Flos Lonicerae of Herba Dendrobii, percolate is condensed into extractum, and is centrifugal; Add water, leave standstill, filter; Filtrate decompression is condensed into extractum, filters, and filtrating is regulated pH value; Ethyl acetate extraction reclaims the ethyl acetate after drying and gets extract; Get the Polyethylene Glycol that 1-10 doubly measures and be heated to 60～95 ℃, add extract after the fusion, stir, move in the drop pill machine, keeping the fused solution temperature is 40 ℃～105 ℃, from top to bottom, drips moderate the splashing in 0 ℃～15 ℃ condensed fluid of speed, processes drop pill.
Preferred method for preparing of the present invention is:
Get 1～4 part of pulverizing of 1～4 portion of Radix Scrophulariae of 1～4 part of Radix Achyranthis Bidentatae of 1～4 portion of Flos Lonicerae of Herba Dendrobii, with 50～90% ethanol percolate extraction, collect the percolate of 8～16 times of crude drug amounts, low-temperature reduced-pressure reclaims ethanol; Concentrating under reduced pressure becomes extractum, and centrifugal removal insoluble impurities adds 2～8 times of water gagings, fully stirs; Hold over night is filtered, and filtrate decompression is condensed into extractum, filters; Regulate pH value to 1～6, ethyl acetate extraction 2～8 times, combining extraction liquid reclaims the dry extract that gets of ethyl acetate final vacuum; Get the Polyethylene Glycol that 1-6 doubly measures and be heated to 65 ℃～90 ℃, add extract after the fusion, stir, move in the drop pill machine, keeping the fused solution temperature is 50 ℃～95 ℃, from top to bottom, drips moderate the splashing in 5 ℃～15 ℃ condensed fluid of speed, processes drop pill.
Best method for preparing of the present invention is:
Get 1 portion of Radix Scrophulariae of 1 part of Radix Achyranthis Bidentatae of 1 portion of Flos Lonicerae of Herba Dendrobii and be ground into coarse powder for 1 part, extract with 100～300ml/min speed percolation with 50～90% ethanol, collect the percolate of 10～14 times of crude drug amounts, low-temperature reduced-pressure reclaims ethanol; Be evaporated to 50 ℃ of following relative densities and be 1.0～1.3 extractum, centrifugal removal insoluble impurities adds 4～8 times of water gagings, fully stirs; Hold over night is filtered, and it is 1.0～1.3 extractum that filtrate decompression is concentrated into 50 ℃ of following relative densities, filters; Remove deposition, regulate pH value to 1～4, equal-volume ethyl acetate extraction 4～8 times; Combining extraction liquid reclaims ethyl acetate, and 50～80 ℃ of vacuum dryings get extract; The Polyethylene Glycol-4000 of getting 1.5 times of amounts is heated to 70～90 ℃, adds extract after the fusion, stirs; Move in the drop pill machine, keeping the fused solution temperature is 70 ℃～80 ℃, from top to bottom; Drip moderate the splashing in 10 ℃～15 ℃ methyl-silicone oils of speed, process 1000 of drop pills.
Said Polyethylene Glycol is selected from Polyethylene Glycol-1000, Polyethylene Glycol-1500, Polyethylene Glycol-4000, Polyethylene Glycol-6000, Polyethylene Glycol-8000 or their mixture.The Polyethylene Glycol quality standard meets regulation under two each Polyethylene Glycol items of Chinese Pharmacopoeia version in 2000; Adjuvant is preferably Polyethylene Glycol-4000, Polyethylene Glycol-6000 and both mixture thereof; The best is a Polyethylene Glycol-4000.Wherein can contain other does not influence Polyethylene Glycol on a small quantity and returns other solid-state adjuvants at normal temperatures yet, these adjuvants should be in prescription, have favourable or help the pharmaceutic adjuvant of clinical efficacy to stablizing of medicine.
The heating-up temperature of Polyethylene Glycol is 60 ℃～95 ℃, and preferred heating-up temperature is 65 ℃～90 ℃, and optimum heating temperature is 70 ℃～90 ℃; The fused solution holding temperature is 40 ℃～105 ℃, and preferred molten liquid holding temperature is 50 ℃～95 ℃, and best fused solution holding temperature is 70 ℃～80 ℃; Condensed fluid is liquid Paraffin, methyl-silicone oil, kerosene, glycerol or their mixture, and preferred condensed fluid is liquid Paraffin, methyl-silicone oil or their mixture, and best condensed fluid is a methyl-silicone oil; The temperature of condensed fluid is 0 ℃～15 ℃, and the temperature of preferred condensed fluid is 5 ℃～15 ℃, and the temperature of best condensed fluid is 10 ℃～15 ℃.
Polymeric solid dispersion method principle has been adopted in the making of these article, medicine is dissolved in the carrier under the situation of heating for dissolving, and splashes into immediately in the inconsistent liquid and cool off, owing to capillary existence between medicine and the coolant is shunk and is condensed into sphere.
On the basis of lot of experiments, the present invention finally selects the substrate of Polyethylene Glycol-4000 (PEG 4000) as drop pill, and methyl-silicone oil is a condensing agent.PEG4000 is water-soluble base commonly used, and stable in properties not with principal agent generation chemical reaction, can be melted into liquid under 60～95 ℃, and the solid that can congeal into again after the quenching keeps solid-state and harmless at normal temperatures; With substrate PEG 4000 the fusion effect does not take place, specific gravity range is suitable, and when the drop bottle bore was 2.0/6.2, the pill falling speed was moderate.
Drop pill of the present invention has following characteristics: 1. specific surface area is big, and rate of release is fast in the body, and bioavailability is high; 2. because drops itself is the solid dispersion that medicine and substrate are processed through heating and melting; Drug molecule is dispersed directly in the substrate; So drug molecule can absorb directly into blood through sublingual vein; Avoid the first pass effect that produces because of gastrointestinal absorption, guaranteed the abundant absorption of effective ingredient; 3. volume is little, is convenient for carrying, and taking dose is easy to grasp; 4. production equipment is simple, and is with low cost, and profit is high.
In order to understand the present invention better, below with dissolve scattered time limit, the weight differential description of test advantage of the present invention of Mailuoning dropping pills.
Experimental example 1: Mailuoning dropping pills dissolve scattered time limit embodiment
According to the Mailuoning dropping pills of the present invention of embodiment 5 methods preparation,, investigate its good releasing effect through indexs such as mensuration dissolve scattered time limits.Through weight differential, whether indexs such as drop pill character are investigated its preparation technology ripe, whether is fit to suitability for industrialized production.
1. experimental drug: Mailuoning dropping pills of the present invention.
2. method and result:
Dissolve scattered time limit: by " method is measured under this item of Chinese pharmacopoeia; The ball method of double differences is different: by " method is measured under this item of Chinese pharmacopoeia.Experimental result is seen table 1.
The dissolve scattered time limit of three batches of Mailuoning dropping pills of the present invention of table 1, weight differential are relatively
Experimental data shows, the dissolve scattered time limit of Mailuoning dropping pills of the present invention, the ball method of double differences is different all is controlled in the pharmacopeia prescribed limit.The molten speed of loosing of Mailuoning dropping pills of the present invention is fast, and help medicine and play a role in the shortest time, and suitable suitability for industrialized production.
Experimental example 2: Mailuoning dropping pills soft durometer of the present invention, the sticking ball comparative observation of drop pill
1. reagent: Mailuoning dropping pills of the present invention.
2. method and result: get according to three batches of the medicines of the present invention of embodiment 5 preparations, be loaded in the porcelain vase respectively, and use the bottle stopper good seal.Putting it into the bottom has in the exsiccator of saturated Nacl (humidity 75%) solution, again exsiccator is put into 40 ℃ of drying baker of constant temperature, and timing sampling is observed situation such as drop pill soft durometer, the sticking ball of drop pill, and the result sees table 2.
Three batches of Mailuoning dropping pills reserved sample observings of the present invention of table 2 relatively
Experimental result shows that Mailuoning dropping pills soft durometer of the present invention is stable, and sticking ball situation is rare, is fit to suitability for industrialized production.
Pharmacodynamic experiment through Mailuoning dropping pills further sets forth beneficial effect of the present invention below, but is not construed as limiting the invention.The medicine that this experimental example adopts is made by embodiment 5.
Experimental example 3: the pharmacodynamic experiment of Mailuoning dropping pills
Pharmacodynamics test
1. experiment material
1.1 medicine
Receive the reagent thing: medicine of the present invention is provided specification by Tianjin Tasly Pharmaceutical Co., Ltd: 8.2g crude drug/kg, product batch number: 051103.
Positive control drug: MAILUONING ZHUSHEYE, Jinling Pharmaceutical Co., Ltd., Jinling Pharmaceutical Factory's product, product batch number: 200312072, national accurate word Z32021102.
Negative control: sodium chloride injection, by Jiangxi Pharmaceutical Co. Ltd.'s product, lot number: 030710-1.
1.2 an animal cleaning level Kunming mouse, body weight 18-22g, male and female half and half, the quality certification number: 2001A030; A cleaning level SD rat, male body weight 240-280g, the quality certification number: 2001A029; New zealand white rabbit, body weight 1.5-2.5kg, male and female are not limit, the quality certification number: 2001A033; More than by Zhongshan University's Experimental Animal Center product.
To draw 14.6g crude drug/kg be preferable effective dose to the prerun that influences of mice GBI anoxia (mice broken end breathing time and number of times) and clotting time 1.3 the dosage setting is through medicine of the present invention; Get it 1/2 for low dosage; 2 times is high dose, and basic, normal, high dosage is respectively 7.3,14.6,29.2g crude drug/kg.Convert through body surface area, rat basic, normal, high dosage is respectively 5.0,10.0,20.0g crude drug/kg.
MAILUONING ZHUSHEYE, people's consumption are 15ml/ days, convert through body surface area, and mice is about 1.95ml/kg, and rat is about 1.35ml/kg.
Drug dilution method, route of administration and volume: drop pill grinds before using, and crosses 100 mesh sieves, is made into the test solution of variable concentrations with distilled water; MAILUONING ZHUSHEYE is prepared with normal saline, prepares existing usefulness every day at present.Route of administration: intravenous injection or lumbar injection.Various units administration volume is respectively: mice is the 0.15ml/10g body weight; Rat is the 0.4ml/100g body weight.
1.4 date processing
All experimental datas are represented with
.Continuous data carries out check between variance analysis and group by the SPSS11.0 statistical software.
2. method and result
2.1 Mailuoning dropping pills is to the influence of chmice acute cerebral anoxia
70 of Kunming mouses, body weight 18-22g is divided into 7 groups at random, 10 every group.Receive the reagent group to be respectively Mailuoning dropping pills 7.3g/kg, 14.6g/kg, 29.2g/kg, the 58.4g/kg group; Positive control drug MAILUONING ZHUSHEYE 1.95ml/kg; Negative control group (waiting the normal saline of capacity).Intraperitoneal injection, totally 3 times, every day 1 time, 15min by only breaking end, to dehisce breathes dwell time and dehisce number of times as anoxia enduring index after breaking end by stopwatch record mice immediately with mice after the last administration.
The result shows, all can obviously prolong dehisce number of times and panting the time of mice broken end behind Mailuoning dropping pills 14.6g/kg, 29.2g/kg, 58.4g/kg group and the MAILUONING ZHUSHEYE intravenously administrable, relatively is remarkable difference (P＜0.05 or P＜0.01) with matched group.See table 3 for details.
Table 3 Mailuoning dropping pills is to the influence
of chmice acute cerebral anoxia
Compare with the normal saline group,
*P＜0.05,
2.2 Mailuoning dropping pills is to clotting time and thrombotic influence
2.2.1 influence to clotting time of mice
84 of Kunming mouses, body weight 18-22g, the male and female dual-purpose is divided into 12 groups at random by body weight and sex, and the administration volume is the 0.15ml/10g body weight.Give the intravenous injection normal saline solution respectively, Mailuoning dropping pills 7.3g/kg, 14.6g/kg, 29.2g/kg, 58.4g/kg, MAILUONING ZHUSHEYE 1.95ml/kg.15min after the administration, eyeball is got blood, and slide method is measured clotting time.
Visible by table 4, Mailuoning dropping pills 14.6g/kg, 29.2g/kg, 58.4g/kg all have the effect (p＜0.05 or P＜0.01) of tangible prolongation clotting time of mice.MAILUONING ZHUSHEYE group clotting time obviously prolongs (p＜0.05).
Table 4 Mailuoning dropping pills is to the influence
of clotting time of mice
2.2.2 to the thrombotic influence of rat artery-vein bypass
50 of SD rats are divided into 5 groups at random, and 10 every group, the anesthesia of 10% chloral hydrate 3.5ml/kg lumbar injection (ip) is fixing, gives Mailuoning dropping pills 5.0g/kg, 10.0g/kg, 20.0g/kg from sublingual vein respectively, MAILUONING ZHUSHEYE 1.95ml/kg group; Matched group gives isometric normal saline.20min after administration separates right carotid and left side external jugular vein.Put into No. 4 silk threads of a long 6cm in the polyethylene tube stage casing, (50 μ l/ml) is full of polyethylene tube with heparin-saline solution.After an end of polyethylene tube inserted left external jugular vein, other end plastic tube injected heparin (50 μ l/m) 0.2ml anticoagulant, and then this end is inserted right carotid.Open bulldog clamp, let blood in the right carotid inflow pipe, return the left side external jugular vein, behind the open blood 15min, middle Herba Clinopodii, the thrombosis that takes out rapidly in the polyethylene tube is weighed on analytical balance, obtains the thrombosis suppression ratio.
Thrombosis suppression ratio=[(matched group wet weight of thrombus-administration group wet weight of thrombus) * 100%]/matched group wet weight of thrombus
Visible by following table 5, Mailuoning dropping pills 10.0g/kg, 20.0g/kg group more all can obviously suppress rat suppository with model group and form (P＜0.05 or P＜0.01), and MAILUONING ZHUSHEYE and 5.0g/kg group have certain inhibitory action, but do not have significant difference.
The total artery and vein of table 5 pair rat neck is put up a bridge and is formed thrombosis influence
Compare with model group
*P＜0.05,
*P＜0.01
Conclusion: Mailuoning dropping pills can effectively prolong the time that the mice broken end is breathed, and increases the number of times of breathing; Anticoagulant prolongs clotting time, rat suppository is formed have the obvious suppression effect; Show that Mailuoning dropping pills has tangible preventive and therapeutic effect to apoplexy.
The specific embodiment
Come further to explain the present invention through the specific embodiment below, but method of the present invention is not limited to following embodiment.
The preparation of embodiment 1 extract
Get 5000g Herba Dendrobii, 5000g Radix Scrophulariae, 5000g Radix Achyranthis Bidentatae, 5000g Flos Lonicerae powder and be broken into coarse powder, extract with 100ml/min speed percolation with 70% ethanol, collect the percolate of 12 times of crude drug amounts, low-temperature reduced-pressure reclaims ethanol; Be evaporated to 50 ℃ of following relative densities and be 1.20 extractum, centrifugal removal insoluble impurities adds 6 times of water gagings, fully stirs; Hold over night is filtered, and it is 1.20 extractum that filtrate decompression is concentrated into 50 ℃ of following relative densities, filters; Remove deposition, regulate pH value to 1～2, equal-volume ethyl acetate extraction 6 times; Combining extraction liquid reclaims ethyl acetate, and 60 ℃ of vacuum dryings get extract 345g.
The preparation of embodiment 2 Mailuoning dropping pills
Get 1000g Polyethylene Glycol-6000 and be heated to 60 ℃, add the extract 100g among the embodiment 1 after the fusion, stir; Move in the drop pill machine, keep 40 ℃ of fused solution temperature, from top to bottom; The speed of dripping with 20 droplets/minute at the uniform velocity splashes in 0 ℃ of paraffin, processes drop pill 1500g.
The preparation of embodiment 3 Mailuoning dropping pills
Get 1000g Polyethylene Glycol-4000 and be heated to 90 ℃, add the extract 150g among the embodiment 1 after the fusion, stir; Move in the drop pill machine, keep 80 ℃ of fused solution temperature, from top to bottom; The speed of dripping with 30 droplets/minute at the uniform velocity splashes in 0 ℃ of paraffin, processes drop pill 1500g.
The preparation of embodiment 4 Mailuoning dropping pills
Get 1000g Polyethylene Glycol-6000 and be heated to 70 ℃, add the extract 200g among the embodiment 1 after the fusion, stir; Move in the drop pill machine, keep 70 ℃ of fused solution temperature, from top to bottom; The speed of dripping with 30 droplets/minute at the uniform velocity splashes in 0 ℃ of methyl-silicone oil, processes drop pill 1500g.
The preparation of embodiment 5 Mailuoning dropping pills
Get 300g Polyethylene Glycol-4000 and be heated to 80 ℃, add the extract 200g among the embodiment 1 after the fusion, stir; Move in the drop pill machine, keep 80 ℃ of fused solution temperature, from top to bottom; The speed of dripping with 30 droplets/minute at the uniform velocity splashes in 12 ℃ of methyl-silicone oils, processes drop pill 600g.
The preparation of embodiment 6 Mailuoning dropping pills
Get 900g Polyethylene Glycol-4000 and be heated to 95 ℃, add the extract 150g among the embodiment 1 after the fusion, stir; Move in the drop pill machine, keep 105 ℃ of fused solution temperature, from top to bottom; The speed of dripping with 40 droplets/minute at the uniform velocity splashes in 12 ℃ of methyl-silicone oils, processes drop pill 1200g.
The preparation of embodiment 7 Mailuoning dropping pills
Get 150g Polyethylene Glycol-4000 and be heated to 60 ℃, add the extract 100g among the embodiment 1 after the fusion, stir; Move in the drop pill machine, keep 40 ℃ of fused solution temperature, from top to bottom; The speed of dripping with 20 droplets/minute at the uniform velocity splashes in 15 ℃ of liquid paraffin, processes drop pill 300g.
The preparation of embodiment 8 Mailuoning dropping pills
Get 800g Polyethylene Glycol-1500 and be heated to 85 ℃, add the extract 100g among the embodiment 1 after the fusion, stir; Move in the drop pill machine, keep 95 ℃ of fused solution temperature, from top to bottom; The speed of dripping with 30 droplets/minute at the uniform velocity splashes in 15 ℃ of methyl-silicone oils, processes drop pill 1000g.
The preparation of embodiment 9 Mailuoning dropping pills
Get 600g Polyethylene Glycol-4000 and be heated to 65 ℃, add the extract 150g among the embodiment 1 after the fusion, stir; Move in the drop pill machine, keep 50 ℃ of fused solution temperature, from top to bottom; The speed of dripping with 30 droplets/minute at the uniform velocity splashes in 12 ℃ of methyl-silicone oils, processes drop pill 900g.
The preparation of embodiment 10 Mailuoning dropping pills
Get 900g Polyethylene Glycol-8000 and be heated to 80 ℃, add the extract 150g among the embodiment 1 after the fusion, stir; Move in the drop pill machine, keep 95 ℃ of fused solution temperature, from top to bottom; The speed of dripping with 40 droplets/minute at the uniform velocity splashes in 10 ℃ of methyl-silicone oils, processes drop pill 1200g.
The preparation of embodiment 11 Mailuoning dropping pills
Get 25g Herba Dendrobii, 50g Radix Scrophulariae, 75g Radix Achyranthis Bidentatae, 50g Flos Lonicerae powder and be broken into coarse powder, extract with 250ml/min speed percolation with 60% ethanol, collect the percolate of 8 times of crude drug amounts, low-temperature reduced-pressure reclaims ethanol; Be evaporated to 50 ℃ of following relative densities and be 1.10 extractum, centrifugal removal insoluble impurities adds 8 times of water gagings, fully stirs; Hold over night is filtered, and it is 1.05 extractum that filtrate decompression is concentrated into 50 ℃ of following relative densities, filters; Remove deposition, regulate pH value to 3～4, equal-volume ethyl acetate extraction 8 times; Combining extraction liquid reclaims ethyl acetate, and 60 ℃ of vacuum dryings get extract.Get an amount of Polyethylene Glycol-4000 and be heated to 65 ℃, add extract after the fusion, stir, move in the drop pill machine, keep 70 ℃ of fused solution temperature, from top to bottom, drip moderate the splashing in 5 ℃ of paraffin of speed, process 1000 of drop pill.
The preparation of embodiment 12 Mailuoning dropping pills
Get 25g Herba Dendrobii, 60g Radix Scrophulariae, 55g Radix Achyranthis Bidentatae, 60g Flos Lonicerae powder and be broken into coarse powder, extract with 200ml/min speed percolation with 90% ethanol, collect the percolate of 12 times of crude drug amounts, low-temperature reduced-pressure reclaims ethanol; Be evaporated to 50 ℃ of following relative densities and be 1.20 extractum, centrifugal removal insoluble impurities adds 8 times of water gagings, fully stirs; Hold over night is filtered, and it is 1.20 extractum that filtrate decompression is concentrated into 50 ℃ of following relative densities, filters; Remove deposition, regulate pH value to 3～4, equal-volume ethyl acetate extraction 6 times; Combining extraction liquid reclaims ethyl acetate, and 50 ℃ of vacuum dryings get extract.Get an amount of Polyethylene Glycol-6000 and be heated to 90 ℃, add medicated powder and volatile oil clathrate compound after the fusion, move in the drop pill machine, keep 105 ℃ of fused solution temperature, from top to bottom, drip moderate the splashing in 10 ℃ of paraffin of speed, process 1000 of drop pill.
The preparation of embodiment 13 Mailuoning dropping pills
Get 45g Herba Dendrobii, 55g Radix Scrophulariae, 80g Radix Achyranthis Bidentatae, 20g Flos Lonicerae powder and be broken into coarse powder, extract with 200ml/min speed percolation with 55% ethanol, collect the percolate of 14 times of crude drug amounts, low-temperature reduced-pressure reclaims ethanol; Be evaporated to 50 ℃ of following relative densities and be 1.35 extractum, centrifugal removal insoluble impurities adds 4 times of water gagings, fully stirs; Hold over night is filtered, and it is 1.20 extractum that filtrate decompression is concentrated into 50 ℃ of following relative densities, filters; Remove deposition, regulate pH value to 1～2, equal-volume ethyl acetate extraction 6 times; Combining extraction liquid reclaims ethyl acetate, and 70 ℃ of vacuum dryings get extract.Get an amount of Polyethylene Glycol-6000 and be heated to 70 ℃, add extract after the fusion, stir, move in the drop pill machine, keep 60 ℃ of fused solution temperature, from top to bottom, drip moderate the splashing in 15 ℃ of methyl-silicone oils of speed, process 1000 of drop pill.
The preparation of embodiment 14 Mailuoning dropping pills
Get 30g Herba Dendrobii, 80g Radix Scrophulariae, 45g Radix Achyranthis Bidentatae, 45g Flos Lonicerae powder and be broken into coarse powder, extract with 150ml/min speed percolation with 70% ethanol, collect the percolate of 16 times of crude drug amounts, low-temperature reduced-pressure reclaims ethanol; Be evaporated to 50 ℃ of following relative densities and be 1.25 extractum, centrifugal removal insoluble impurities adds 8 times of water gagings, fully stirs; Hold over night is filtered, and it is 1.05 extractum that filtrate decompression is concentrated into 50 ℃ of following relative densities, filters; Remove deposition, regulate pH value to 1～2, equal-volume ethyl acetate extraction 6 times; Combining extraction liquid reclaims ethyl acetate, and 50 ℃ of vacuum dryings get extract.Get an amount of Polyethylene Glycol-6000 and be heated to 80 ℃, add extract after the fusion, move in the drop pill machine, keep 80 ℃ of fused solution temperature, from top to bottom, drip moderate the splashing in 8 ℃ of methyl-silicone oils of speed, process 1000 of drop pill.
The preparation of embodiment 15 Mailuoning dropping pills
Get 50g Herba Dendrobii, 50g Radix Scrophulariae, 50g Radix Achyranthis Bidentatae, 50g Flos Lonicerae powder and be broken into coarse powder, extract with 300ml/min speed percolation with 70% ethanol, collect the percolate of 10 times of crude drug amounts, low-temperature reduced-pressure reclaims ethanol; Be evaporated to 50 ℃ of following relative densities and be 1.15 extractum, centrifugal removal insoluble impurities adds 8 times of water gagings, fully stirs; Hold over night is filtered, and it is 1.15 extractum that filtrate decompression is concentrated into 50 ℃ of following relative densities, filters; Remove deposition, regulate pH value to 5～6, equal-volume ethyl acetate extraction 8 times; Combining extraction liquid reclaims ethyl acetate, and 50 ℃ of vacuum dryings get extract.Get an amount of Polyethylene Glycol-4000 and be heated to 90 ℃, add extract after the fusion, stir, move in the drop pill machine, keep 80 ℃ of fused solution temperature, from top to bottom, drip moderate the splashing in 10 ℃ of methyl-silicone oils of speed, process 1000 of drop pill.
The preparation of embodiment 16 Mailuoning dropping pills
Get 80g Herba Dendrobii, 20g Radix Scrophulariae, 40g Radix Achyranthis Bidentatae, 60g Flos Lonicerae powder and be broken into coarse powder, extract with 200ml/min speed percolation with 80% ethanol, collect the percolate of 12 times of crude drug amounts, low-temperature reduced-pressure reclaims ethanol; Be evaporated to 50 ℃ of following relative densities and be 1.20 extractum, centrifugal removal insoluble impurities adds 8 times of water gagings, fully stirs; Hold over night is filtered, and it is 1.15 extractum that filtrate decompression is concentrated into 50 ℃ of following relative densities, filters; Remove deposition, regulate pH value to 1～2, equal-volume ethyl acetate extraction 10 times; Combining extraction liquid reclaims ethyl acetate, and 50 ℃ of vacuum dryings get extract.Get an amount of Polyethylene Glycol-8000 and be heated to 75 ℃, add extract after the fusion, stir, move in the drop pill machine, keep 90 ℃ of fused solution temperature, from top to bottom, drip moderate the splashing in 10 ℃ of glycerol of speed, process 1000 of drop pill.
The preparation of embodiment 17 Mailuoning dropping pills
Get 25g Herba Dendrobii, 60g Radix Scrophulariae, 55g Radix Achyranthis Bidentatae, 60g Flos Lonicerae powder and be broken into coarse powder, extract with 200ml/min speed percolation with 90% ethanol, collect the percolate of 12 times of crude drug amounts, low-temperature reduced-pressure reclaims ethanol; Be evaporated to 50 ℃ of following relative densities and be 1.20 extractum, centrifugal removal insoluble impurities adds 8 times of water gagings, fully stirs; Hold over night is filtered, and it is 1.20 extractum that filtrate decompression is concentrated into 50 ℃ of following relative densities, filters; Remove deposition, regulate pH value to 3～4, equal-volume ethyl acetate extraction 6 times; Combining extraction liquid reclaims ethyl acetate, and 50 ℃ of vacuum dryings get extract.Get an amount of Polyethylene Glycol-1500 and be heated to 95 ℃, add extract after the fusion, stir, move in the drop pill machine, keep 100 ℃ of fused solution temperature, from top to bottom, drip moderate the splashing in 10 ℃ of methyl-silicone oils of speed, process 1000 of drop pill.
The preparation of embodiment 18 Mailuoning dropping pills
Get 50g Herba Dendrobii, 50g Radix Scrophulariae, 50g Radix Achyranthis Bidentatae, 50g Flos Lonicerae powder and be broken into coarse powder, extract with 100ml/min speed percolation with 70% ethanol, collect the percolate of 12 times of crude drug amounts, low-temperature reduced-pressure reclaims ethanol; Be evaporated to 50 ℃ of following relative densities and be 1.20 extractum, centrifugal removal insoluble impurities adds 6 times of water gagings, fully stirs; Hold over night is filtered, and it is 1.20 extractum that filtrate decompression is concentrated into 50 ℃ of following relative densities, filters; Remove deposition, regulate pH value to 1～2, equal-volume ethyl acetate extraction 6 times; Combining extraction liquid reclaims ethyl acetate, and 60 ℃ of vacuum dryings get extract.The mixture (weight ratio is 1: 8) of getting an amount of Polyethylene Glycol-4000 and Polyethylene Glycol-6000 is heated to 75 ℃, adds extract after the fusion, stirs; Move in the drop pill machine, keep 50 ℃ of fused solution temperature, from top to bottom; Drip moderate the splashing in 6 ℃ of kerosene of speed, process 1000 of drop pill.
The preparation of embodiment 19 Mailuoning dropping pills
Get 35g Herba Dendrobii, 40g Radix Scrophulariae, 65g Radix Achyranthis Bidentatae, 60g Flos Lonicerae powder and be broken into coarse powder, extract with 250ml/min speed percolation with 80% ethanol, collect the percolate of 16 times of crude drug amounts, low-temperature reduced-pressure reclaims ethanol; Be evaporated to 50 ℃ of following relative densities and be 1.30 extractum, centrifugal removal insoluble impurities adds 6 times of water gagings, fully stirs; Hold over night is filtered, and it is 1.20 extractum that filtrate decompression is concentrated into 50 ℃ of following relative densities, filters; Remove deposition, regulate pH value to 1～2, equal-volume ethyl acetate extraction 8 times; Combining extraction liquid reclaims ethyl acetate, and 50 ℃ of vacuum dryings get extract.The mixture (weight ratio 1: 6) of getting an amount of Polyethylene Glycol-1500 and Polyethylene Glycol-4000 is heated to 60 ℃, adds extract after the fusion, stirs; Move in the drop pill machine, keep 40 ℃ of fused solution temperature, from top to bottom; Drip moderate the splashing in 0 ℃ of liquid paraffin of speed, process 1000 of drop pill.
The preparation of embodiment 20 Mailuoning dropping pills
Get 45g Herba Dendrobii, 55g Radix Scrophulariae, 80g Radix Achyranthis Bidentatae, 20g Flos Lonicerae powder and be broken into coarse powder, extract with 200ml/min speed percolation with 55% ethanol, collect the percolate of 14 times of crude drug amounts, low-temperature reduced-pressure reclaims ethanol; Be evaporated to 50 ℃ of following relative densities and be 1.35 extractum, centrifugal removal insoluble impurities adds 4 times of water gagings, fully stirs; Hold over night is filtered, and it is 1.20 extractum that filtrate decompression is concentrated into 50 ℃ of following relative densities, filters; Remove deposition, regulate pH value to 1～2, equal-volume ethyl acetate extraction 6 times; Combining extraction liquid reclaims ethyl acetate, and 70 ℃ of vacuum dryings get extract.The mixture (weight ratio 1: 3) of getting an amount of Polyethylene Glycol-4000 and Polyethylene Glycol-6000 is heated to 95 ℃, adds extract after the fusion, stirs; Move in the drop pill machine, keep 100 ℃ of fused solution temperature, from top to bottom; Drip moderate the splashing in 6 ℃ of methyl-silicone oils of speed, process 1000 of drop pill.
The preparation of embodiment 21 Mailuoning dropping pills
Get 40g Herba Dendrobii, 80g Radix Scrophulariae, 30g Radix Achyranthis Bidentatae, 50g Flos Lonicerae powder and be broken into coarse powder, extract with 200ml/min speed percolation with 60% ethanol, collect the percolate of 12 times of crude drug amounts, low-temperature reduced-pressure reclaims ethanol; Be evaporated to 50 ℃ of following relative densities and be 1.35 extractum, centrifugal removal insoluble impurities adds 8 times of water gagings, fully stirs; Hold over night is filtered, and it is 1.05 extractum that filtrate decompression is concentrated into 50 ℃ of following relative densities, filters; Remove deposition, regulate pH value to 1～2, equal-volume ethyl acetate extraction 4 times; Combining extraction liquid reclaims ethyl acetate, and 60 ℃ of vacuum dryings get extract.Get an amount of Polyethylene Glycol-4000 and be heated to 85 ℃, add extract after the fusion, stir, move in the drop pill machine, keep 95 ℃ of fused solution temperature, from top to bottom, drip moderate the splashing in 8 ℃ of methyl-silicone oils of speed, process 1000 of drop pill.
The preparation of embodiment 22 Mailuoning dropping pills
Get 30g Herba Dendrobii, 60g Radix Scrophulariae, 60g Radix Achyranthis Bidentatae, 50g Flos Lonicerae powder and be broken into coarse powder, extract with 300ml/min speed percolation with 70% ethanol, collect the percolate of 12 times of crude drug amounts, low-temperature reduced-pressure reclaims ethanol; Be evaporated to 50 ℃ of following relative densities and be 1.20 extractum, centrifugal removal insoluble impurities adds 8 times of water gagings, fully stirs; Hold over night is filtered, and it is 1.15 extractum that filtrate decompression is concentrated into 50 ℃ of following relative densities, filters; Remove deposition, regulate pH value to 1～2, equal-volume ethyl acetate extraction 8 times; Combining extraction liquid reclaims ethyl acetate, and 50 ℃ of vacuum dryings get extract.Get an amount of Polyethylene Glycol-4000 and be heated to 80 ℃, add extract after the fusion, stir, move in the drop pill machine, keep 60 ℃ of fused solution temperature, from top to bottom, drip moderate the splashing in 10 ℃ of methyl-silicone oils of speed, process 1000 of drop pill.
The preparation of embodiment 23 Mailuoning dropping pills
Get 3000g Herba Dendrobii, 8000g Radix Scrophulariae, 4500g Radix Achyranthis Bidentatae, 4500g Flos Lonicerae powder and be broken into coarse powder, extract with 150ml/min speed percolation with 70% ethanol, collect the percolate of 16 times of crude drug amounts, low-temperature reduced-pressure reclaims ethanol; Be evaporated to 50 ℃ of following relative densities and be 1.25 extractum, centrifugal removal insoluble impurities adds 8 times of water gagings, fully stirs; Hold over night is filtered, and it is 1.05 extractum that filtrate decompression is concentrated into 50 ℃ of following relative densities, filters; Remove deposition, regulate pH value to 1～2, equal-volume ethyl acetate extraction 6 times; Combining extraction liquid reclaims ethyl acetate, and 50 ℃ of vacuum dryings get extract.Get an amount of Polyethylene Glycol-6000 and be heated to 95 ℃, add extract after the fusion, stir, move in the drop pill machine, keep 75 ℃ of fused solution temperature, from top to bottom, drip moderate the splashing in 15 ℃ of liquid paraffin of speed, process 1000 of drop pill.
Above embodiment and non exhaustive one of ordinary skill in the art will appreciate that, any equal substitute or change what the present invention carried out, like the variation of conventional parameter in the technology, as required with the specifications vary of preparation etc. all within protection scope of the present invention.
Claims (1)
1. a Mailuoning dropping pills is characterized in that, is processed into by following composition process:
Get 5000g Herba Dendrobii, 5000g Radix Scrophulariae, 5000g Radix Achyranthis Bidentatae, 5000g Flos Lonicerae powder and be broken into coarse powder, extract with 100ml/min speed percolation with 70% ethanol, collect the percolate of 12 times of crude drug amounts, low-temperature reduced-pressure reclaims ethanol; Be evaporated to 50 ℃ of following relative densities and be 1.20 extractum, centrifugal removal insoluble impurities adds 6 times of water gagings, fully stirs; Hold over night is filtered, and it is 1.20 extractum that filtrate decompression is concentrated into 50 ℃ of following relative densities, filters; Remove deposition, regulate pH value to 1～2, equal-volume ethyl acetate extraction 6 times, combining extraction liquid; Reclaim ethyl acetate, 60 ℃ of vacuum dryings get extract 345g
Get 300g Polyethylene Glycol-4000 and be heated to 80 ℃, add after the fusion and go up the extract 200g that step obtains, stir; Move in the drop pill machine, keep 80 ℃ of fused solution temperature, from top to bottom; The speed of dripping with 30 droplets/minute evenly splashes in 12 ℃ of methyl-silicone oils, processes drop pill 600g.
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| CN1491689A (en) * | 2003-07-25 | 2004-04-28 | 金陵药业股份有限公司 | Process for preparing Chinese medicinal dripping pills for treating and preventing ischemic cardio-cerebral vascular diseases |
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