CN1785253B - Micro-balls of compound red-rooted salvia injection, and its preparation method - Google Patents
Micro-balls of compound red-rooted salvia injection, and its preparation method Download PDFInfo
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- CN1785253B CN1785253B CN 200410093890 CN200410093890A CN1785253B CN 1785253 B CN1785253 B CN 1785253B CN 200410093890 CN200410093890 CN 200410093890 CN 200410093890 A CN200410093890 A CN 200410093890A CN 1785253 B CN1785253 B CN 1785253B
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- Prior art keywords
- salviae miltiorrhizae
- radix salviae
- microsphere
- borneolum syntheticum
- radix notoginseng
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- 238000002347 injection Methods 0.000 title abstract description 7
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- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
A microball used for compound red sage root injection contains the active components (the extracts of red sage root and notoginseng, and borneol), and biodegradable medicinal high-molecular auxiliary. Its preparing process is also disclosed.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to a kind of compound slow-releasing red-rooted salvia injection microsphere and preparation method thereof.
Background technology
The compound Salviae Miltiorrhizae prescription has blood circulation promoting and blood stasis dispelling, the effect of regulating QI to relieve pain.Be used for the treatment of in the heart and feel oppressed, angina pectoris, it mainly consists of Radix Salviae Miltiorrhizae, Radix Notoginseng and Borneolum Syntheticum.Through clinical practice for many years, people recognize gradually that except that above-mentioned effect compound Salviae Miltiorrhizae also has the blood fat of accent, atherosclerosis (AS); Effects such as treatment cerebral infarction.Since coming out from the seventies in last century, it has been subjected to the favorable comment of extensive patients.
The oral formulations of compound Salviae Miltiorrhizae is a tablet all the time, continuous development along with pharmaceutics, the research of relevant compound red sage root preparation is also more and more, as compound Salviae Miltiorrhizae granule, compound Salviae Miltiorrhizae oral liquid, compound Salviae Miltiorrhizae soft gelatin capsule, FUFANG DANSHEN JIAONANG, compound Salviae Miltiorrhizae aerosol and FUFANG DANSHEN DIWAN etc.But owing to the intravital half-life of water-soluble active ingredient in the Radix Salviae Miltiorrhizae is shorter, make common oral formulations be faced with a series of problem, frequent as the clinical administration number of times, use inconvenience, patient's compliance (compliance) difference etc.
Inventor's process years of researches find that Radix Salviae Miltiorrhizae, pseudo-ginseng are extracted the back makes microsphere with suitable adjuvant, can reach non-lentamente constant release, reduce and take number of times, improve the purpose of patient's compliance.
Summary of the invention
The object of the invention has been to provide a kind of brand-new slow release, the micro-balls of compounding red-rooted salvia injection of high bioavailability.
Another object of the present invention is to provide the preparation method of this micro-balls of compounding red-rooted salvia injection.
Compound Salviae Miltiorrhizae prescription of the present invention is (in a weight percentage):
Radix Salviae Miltiorrhizae 48%～97%
Radix Notoginseng 2%～50%
Borneolum Syntheticum 0.2%～3%
The optimizing prescriptions proportioning is (in a weight percentage):
Radix Salviae Miltiorrhizae 63.0%～94%
Radix Notoginseng 4.0%～35.0%
Borneolum Syntheticum 0.5%～2.0%
Further the optimizing prescriptions proportioning is (in a weight percentage):
Radix Salviae Miltiorrhizae 75.2%～90%
Radix Notoginseng 9%～23.5%
Borneolum Syntheticum 0.5%～1.3%
The best prescription proportioning is (in a weight percentage):
Radix Salviae Miltiorrhizae 82.87%
Radix Notoginseng 16.21%
Borneolum Syntheticum 0.92%
Said medicine prescription proportioning is the weight proportion of institute's uses crude drug, if it is need be to described Radix Salviae Miltiorrhizae, Radix Notoginseng further independent or mixed extraction is processed into extract and suitable adjuvant is made gel matrix tablet to be made into preparation.Extracting method wherein is selected from (but being not limited to this): decoction and alcohol sedimentation technique, percolation, column chromatography method etc.
For the ease of understanding, the existing extracting method in present technique field is described below for example, but is not limited to this.
The Radix Salviae Miltiorrhizae water extraction: get red rooted salvia, 20 mesh sieves are pulverized, extracting in water 2 times, the water logging bubble that adds for the first time 9～10 times of amounts, heating extraction 1.5 hours adds 5～7 times of water gagings, heating extraction 1 hour for the second time, merge extractive liquid,, suitably concentrate, add 95% ethanol, make to contain alcohol amount arrival 50%～70%, concentrate and reclaim ethanol, get Radix Salviae Miltiorrhizae extract.
The tanshinol extraction method: get red rooted salvia, 20 mesh sieves are pulverized, and 7～9 times of amount 70% alcohol heating reflux extract 2 times, each 1 hour, merge extractive liquid,, concentrate Radix Salviae Miltiorrhizae extract.
The extraction of active component of red sage root: get red rooted salvia, 20 mesh sieves are pulverized, water or ethanol extraction concentrate, and add ethanol precipitation, be dissolved in water after reclaiming ethanol, last macroporous resin chromatography separates, after water elution is removed impurity, ethanol elution to effective ingredient fully till, reclaim ethanol, get exsiccant Radix Salviae Miltiorrhizae extract.
The ethanol extraction of Radix Notoginseng: add the ethanol extraction 3 times of 10 times of amount 10%～30% concentration, reflux 8 hours, merge extractive liquid, concentrates and reclaims ethanol, Radix Notoginseng extract.
Radix Notoginseng column chromatography method: get Radix Notoginseng, suitably pulverize, add ethanol and divide 2 extractions, filter, merge filtering, decompression recycling ethanol is to a certain amount of, add suitable quantity of water, continuing to be recycled to does not have the alcohol flavor, and it is past that medicinal liquid is crossed pretreated macroporous adsorbent resin, and it is colourless to be washed to filter liquor, continue to use 50% ethanol elution, collect eluent, concentrate, get Radix Notoginseng extract.
Except that the independent extraction of above-mentioned medical material, described Radix Salviae Miltiorrhizae, all right mixed extraction of Radix Notoginseng are mainly: Radix Salviae Miltiorrhizae, the pseudo-ginseng of learning from else's experience and pulverizing, and boiling water boils to be carried, filter, merging filtrate, and filtrate is suitably concentrated; Add ethanol and carry out precipitate with ethanol in concentrated solution, leave standstill, supernatant reclaims ethanol, is condensed into extractum, gets medicinal substances extract.
Be used as medicine after described Borneolum Syntheticum is directly pulverized and get final product.
Micro-balls of compounding red-rooted salvia injection diameter of the present invention is 1～250 μ m, is made up of at 5000～1000000 daltonian biodegradable medical high-molecular additives the active component of microsphere gross weight 0.2%～50% (w/w) and the molecular weight of derivant and microsphere gross weight 50～99.8% (w/w) thereof.Wherein said biodegradable medical high-molecular additive is selected from polylactide. Acetic acid, hydroxy-, bimol. cyclic ester, polylactic acid, polyglycolic acid, poly--the 3-butyric ester, polylactic acid-polyglycolic acid, polylactic acid. and glycolic, poly-adjacent ester, polylactone, polyanhydride, poly butyric ester-hydroxyl pentanoate copolymer, polyglycolic acid, polypropylene glucosan, hydroxyacetic acid, polylactic acid-polyglycol, polyglycolic acid. wherein a kind of of Polyethylene Glycol; Preferred polylactide-co-glycolide, polylactic acid, polylactic acid. polyglycolic acid, polylactic acid. glycolic, poly butyric ester-hydroxyl pentanoate copolymer, the best is a polylactide. Acetic acid, hydroxy-, bimol. cyclic ester, molecular weight are 12000～15000 dalton; The polymerization ratio of lactide-Acetic acid, hydroxy-, bimol. cyclic ester is 40: 60-60: 40.
Microsphere of the present invention can adopt the conventional preparation method of microsphere to make, as adopting emulsifying dispersion method, spray drying method and solvent evaporation method, preferably spray drying method.When preparing microsphere of the present invention with the emulsifying dispersion method, with dichloromethane, chloroform, ethyl acetate, dioxane, ether, acetone, oxolane, glacial acetic acid and by the mixed acid that they are formed huperzine A or derivatives thereof and the dissolving of biodegradable pharmaceutic adjuvant are mixed with organic facies, wherein the bulking value percent of pharmaceutic adjuvant in organic solvent is 1～30%, the emulsifying agent that organic facies adopts is the nonionic emulsifier of HBL=4.5～6.0, and consumption is the 0.01-12% of organic facies; Prepare continuous water with polyvinyl alcohol, polyvinyl pyrrolidone, sodium polymethacrylate, sodium polyacrylate, sodium carboxymethyl cellulose solution in addition, wherein they are 0.01～10.0% in the percetage by weight of aqueous phase, the emulsifying agent of aqueous phase is the nonionic emulsifier of HLB=14.0～15.5, and consumption is 0.01～12% of a water; The volume ratio of organic facies and water is 1: 4～100; Organic facies slowly is injected in the continuous phase by tubule, fully emulsified after, the formed microsphere of sieving separating is drying to obtain.When adopting solvent evaporation method, be decentralized photo slowly be injected into by tubule in the continuous phase fully emulsified after, the decompression solvent flashing, centrifugalize obtains formed microsphere, is drying to obtain.
When adopting the attached side's Radix Salviae Miltiorrhizae of spray drying method for preparation microsphere, to be the mixed acid formed with dichloromethane, chloroform, ethyl acetate, dioxane, ether, acetone, oxolane, glacial acetic acid and by them compound Salviae Miltiorrhizae and biodegradable pharmaceutic adjuvant fully dissolve is mixed with organic solution; Filter, spray drying is made microsphere.
Compound Salviae Miltiorrhizae microsphere of the present invention be will make microsphere sterilized powder suspendible in aseptic 0.9% normal saline solvent earlier, evenly the back intramuscular injection comes administration.
In motherland's medical science to record that pill has " the ball person is slow also, releives and controls it ... " (Li Gao, 1180-1251).As seen Ancient Times in China medicine man early has recognized that and has used practice of pharmacy, reaches the purpose of steadily lasting curative effect.
Conventional dosage forms, most drug release process is all undertaken by first order kinetics, and the blood drug level of its medicine might be lower than minimum effective blood drug concentration and hold time short shortcoming in treatment concentration.For reaching therapeutic purposes and reducing side effect and often take repeatedly medicining mode, the compliance that makes the patient take medicine like this descends.Slow releasing preparation has overcome the deficiency of conventional formulation just, and steady, persistent blood drug level is provided.
Compound Salviae Miltiorrhizae microsphere of the present invention has adopted the design principle of Western medicine slow releasing preparation to obtain achievement at aspects such as adjuvant selection, quality evaluations, for the research of Chinese medicine slow releasing preparation is used for reference.
Below beneficial effect by extracorporeal releasing test explanation compound Salviae Miltiorrhizae microsphere
Laboratory sample: according to the microsphere of the embodiment of the invention 1,2,3 described method preparations.
Experiment reagent: the buffer solution (4.0,5.5) of certain pH value.
Experimental apparatus: constant temperature oscillator, centrifuge.
Experiment condition: temperature: 37 ± 10 ℃; Rotating speed: 30rp/ minute.
Experimental technique: precision takes by weighing the about 10mg of laboratory sample, and to place volume be the tool lid plastic centrifuge tube of 15ml, adds 5ml release medium (PH=4.0 and 5.5 phosphate buffer solutions) and place constant temperature oscillator, keeps certain temperature and rotating speed to take a sample on time.
Sampling method: centrifugal 50min under the 3600 commentaries on classics conditions, essence is got 3ml solution, adds the release medium of 3ml again, takes out liquid and detects with HPLC.Concrete detection index is a danshensu, detects wavelength: 281nm.
Sampling time point (my god): 0,1,2,4,6,8,10,12,14,16,18,20.
Result of the test: the external release test of huperzine A control-release microsphere is table 1 as a result.
Danshensu release in vitro result in table 1, the compound Salviae Miltiorrhizae control-release microsphere
The specific embodiment
The present invention is further illustrated below in conjunction with embodiment, and following this embodiment only is used to the present invention is described and to the present invention without limits.
Embodiment 1
Take off and state medical material: Radix Salviae Miltiorrhizae 41.06g Radix Notoginseng 8.03g Borneolum Syntheticum 0.46g;
The extraction of Salvia miltiorrhiza and Panax notoginseng medical material: the Radix Salviae Miltiorrhizae of the coarse pulverization of learning from else's experience, pseudo-ginseng add 5 times of water gagings to extraction pot, decoct 2 hours, filter, and filtering residue carries out the second time and extracts, and adds 4 times of water gagings, decocts 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, slowly adds 95% ethanol, makes medicinal liquid contain determining alcohol 69～71%, leaves standstill 12 hours.Get the supernatant of medicinal liquid behind the precipitate with ethanol, filter, filtrate recycling ethanol is condensed into extractum.
The preparation of microsphere: above-mentioned 100mg medicinal substances extract, 200mg polylactide-co-glycolide are dissolved in the 3ml dichloromethane, with syringe under high degree of agitation with it to being equipped with in the three-necked bottle of 10%PVA that 300ml includes the 3.5Ghlb=14 emulsifying agent, after fully emulsified 1 hour, under the pressure of 30 ℃ of 0.03MPa, solvent flashing 1.5 hours, centrifugalize, wash reactant three times with distillation, in 30 ℃ of vacuum drying ovens, dry, sterilized 48 hours at 30 ℃ with oxirane, guarantee residual ethylene oxide content below 5ppm, fill.
Embodiment 2
Take off and state medical material: Radix Salviae Miltiorrhizae 31.12g Radix Notoginseng 9.21g Borneolum Syntheticum 0.50g
The extraction of Salvia miltiorrhiza and Panax notoginseng medical material: the Radix Salviae Miltiorrhizae of the coarse pulverization of learning from else's experience, pseudo-ginseng add 5 times of water gagings to extraction pot, decoct 2 hours, filter, and filtering residue carries out the second time and extracts, and adds 4 times of water gagings, decocts 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, slowly adds 95% ethanol, makes medicinal liquid contain determining alcohol 69～71%, leaves standstill 12 hours.Get the supernatant of medicinal liquid behind the precipitate with ethanol, filter, filtrate recycling ethanol is condensed into extractum.
The preparation of microsphere: above-mentioned 100mg medicinal substances extract, 200mg polylactide-co-glycolide are dissolved in the 3ml dichloromethane, with syringe under high degree of agitation with it to being equipped with in the three-necked bottle of 10%PVA that 300ml includes the 3.5Ghlb=14 emulsifying agent, after fully emulsified 1 hour, under the pressure of 30 ℃ of 0.03MPa, solvent flashing 1.5 hours, centrifugalize, wash reactant three times with distillation, in 30 ℃ of vacuum drying ovens, dry, sterilized 48 hours at 30 ℃ with oxirane, guarantee residual ethylene oxide content below 5ppm, fill.
Embodiment 3
The material of getting it filled: Radix Salviae Miltiorrhizae 41.06g Radix Notoginseng 8.03g Borneolum Syntheticum 0.46g;
The extraction of Salvia miltiorrhiza and Panax notoginseng medical material: the Radix Salviae Miltiorrhizae of the coarse pulverization of learning from else's experience, pseudo-ginseng add 5 times of water gagings to extraction pot, decoct 2 hours, filter, and filtering residue carries out the second time and extracts, and adds 4 times of water gagings, decocts 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, slowly adds 95% ethanol, makes medicinal liquid contain determining alcohol 69～71%, leaves standstill 12 hours.Get the supernatant of medicinal liquid behind the precipitate with ethanol, filter, filtrate recycling ethanol is condensed into extractum.
The preparation of microsphere: take by weighing the above-mentioned Radix Salviae Miltiorrhizae that obtains, pseudo-ginseng extract 100mg, polylactide-co-glycolide (lactide: Acetic acid, hydroxy-, bimol. cyclic ester=50: 50), 2.0g in small beaker, the 31.5ml that adds methylene chloride, electromagnetic agitation is used filtering with microporous membrane to fully dissolving, adopt the spray drying method for preparation microsphere, record particle diameter 5～80gm, sterilization, packing.
Embodiment 4
Take off and state medical material: Radix Salviae Miltiorrhizae 41.06g Radix Notoginseng 8.03g Borneolum Syntheticum 0.46g;
The extraction of red rooted salvia: get above-mentioned Radix Salviae Miltiorrhizae 41.06g, 20 mesh sieves are pulverized, extracting in water 2 times, the water logging bubble that adds for the first time 9～10 times of amounts, heating extraction 1.5 hours adds 5～7 times of water gagings, heating extraction 1 hour for the second time, merge extractive liquid,, suitably concentrate, add 95% ethanol, make to contain alcohol amount arrival 60%, concentrate and reclaim ethanol, get Radix Salviae Miltiorrhizae extract.
The extraction of pseudo-ginseng: get the 8.03g Radix Notoginseng, add 10 times of amount ethanol extractions of 20% 3 times, reflux 8 hours, merge extractive liquid, concentrates and reclaims ethanol, Radix Notoginseng extract.
The preparation of microsphere: take by weighing and get above-mentioned Radix Salviae Miltiorrhizae extract and the common 100mg (ratio is 1: 1) of Radix Notoginseng extract, polylactide-co-glycolide (lactide: Acetic acid, hydroxy-, bimol. cyclic ester=60: 40), 4.0g in small beaker, the 41ml that adds methylene chloride, electromagnetic agitation adopts the spray drying method for preparation microsphere to fully dissolving, record particle diameter 1～50 μ m, mean diameter 13.26 μ m, sterilization, packing.
Embodiment 5
Take off and state medical material: Radix Salviae Miltiorrhizae 41.06g Radix Notoginseng 8.03g Borneolum Syntheticum 0.46g;
The extraction of red rooted salvia: get above-mentioned Radix Salviae Miltiorrhizae 41.06g, 20 mesh sieves are pulverized, extracting in water 2 times, the water logging bubble that adds for the first time 9～10 times of amounts, heating extraction 1.5 hours adds 5～7 times of water gagings, heating extraction 1 hour for the second time, merge extractive liquid,, suitably concentrate, add 95% ethanol, make to contain alcohol amount arrival 60%, concentrate and reclaim ethanol, get Radix Salviae Miltiorrhizae extract.
The extraction of pseudo-ginseng: get the 8.03g Radix Notoginseng, add 10 times of amount ethanol extractions of 20% 3 times, reflux 8 hours, merge extractive liquid, concentrates and reclaims ethanol, Radix Notoginseng extract.
The preparation of microsphere: with medicinal substances extract 100mg, (lactide: Acetic acid, hydroxy-, bimol. cyclic ester=50: 50) 1.0g places small beaker to polylactide-co-glycolide altogether, adds glacial acetic acid 22ml, electromagnetic agitation adopts the spray drying method for preparation microsphere to fully dissolving, records particle diameter 1～100 μ m, sterilization, packing.
Embodiment 6
Take off and state medical material: Radix Salviae Miltiorrhizae 59.36g Radix Notoginseng 6.38g Borneolum Syntheticum 0.34g
The extraction of Salvia miltiorrhiza and Panax notoginseng medical material: the Radix Salviae Miltiorrhizae of the coarse pulverization of learning from else's experience, pseudo-ginseng add 5 times of water gagings to extraction pot, decoct 2 hours, filter, and filtering residue carries out the second time and extracts, and adds 4 times of water gagings, decocts 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, slowly adds 95% ethanol, makes medicinal liquid contain determining alcohol 69～71%, leaves standstill 12 hours.Get the supernatant of medicinal liquid behind the precipitate with ethanol, filter, filtrate recycling ethanol is condensed into extractum.
The preparation of microsphere: with the polylactide-co-glycolide of medicinal substances extract 500mg and 1000mg (lactide: Acetic acid, hydroxy-, bimol. cyclic ester=50: 50) be dissolved in 10ml dichloromethane and be cooled to 15 ℃, include 0.01mol/L with 400ml in addition.The aqueous solution of Tris and 0.01% polyvinyl alcohol (pHt=8.0) is as continuous water, slowly be injected in continuous phase by tubule decentralized photo, at 15 degrees centigrade with emulsator emulsifying 15 minutes, add 1600ml then, 15 ℃ distilled water is used magnetic stirrer 20 minutes, stirs 15 minutes under the evacuation state again, sieve, lyophilized promptly gets 1～10 micron microsphere.
Embodiment 7
Take off and state medical material: Radix Salviae Miltiorrhizae 31.12g Radix Notoginseng 9.21g Borneolum Syntheticum 0.50g
The extraction of Salvia miltiorrhiza and Panax notoginseng medical material: the Radix Salviae Miltiorrhizae of the coarse pulverization of learning from else's experience, pseudo-ginseng add 5 times of water gagings to extraction pot, decoct 2 hours, filter, and filtering residue carries out the second time and extracts, and adds 4 times of water gagings, decocts 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, slowly adds 95% ethanol, makes medicinal liquid contain determining alcohol 69～71%, leaves standstill 12 hours.Get the supernatant of medicinal liquid behind the precipitate with ethanol, filter, filtrate recycling ethanol is condensed into extractum.
The preparation of microsphere: take by weighing medicinal substances extract 100mg, polylactic acid-polyglycolic acid, 4.0g are in small beaker, and 41ml adds methylene chloride, electromagnetic agitation adopts the spray drying method for preparation microsphere to fully dissolving, records particle diameter 1～50 μ m, mean diameter 13.261 μ m, sterilization, packing.
Embodiment 8
Take off and state medical material: Radix Salviae Miltiorrhizae 31.12g Radix Notoginseng 9.21g Borneolum Syntheticum 0.50g
The extraction of Salvia miltiorrhiza and Panax notoginseng medical material: the Radix Salviae Miltiorrhizae of the coarse pulverization of learning from else's experience, pseudo-ginseng add 5 times of water gagings to extraction pot, decoct 2 hours, filter, and filtering residue carries out the second time and extracts, and adds 4 times of water gagings, decocts 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, slowly adds 95% ethanol, makes medicinal liquid contain determining alcohol 69～71%, leaves standstill 12 hours.Get the supernatant of medicinal liquid behind the precipitate with ethanol, filter, filtrate recycling ethanol is condensed into extractum.
The preparation of microsphere: 100mg drug extract, poly butyric ester-hydroxyl valerate 200mg are dissolved in the 3ml dichloromethane, under high degree of agitation, it are included 10% of 3.5Ghlb=14 emulsifying agent to 300ml is housed with syringe.In the three-necked bottle of PVA, after fully emulsified 1 hour, under the pressure of 30 ℃ of 0.03MPa, solvent flashing 1.5 hours, centrifugalize is washed reactant three times with distillation, in 30 ℃ of vacuum drying ovens, dry, 30 ℃ of sterilizations 48 hours, guarantee residual ethylene oxide content below 5ppm, fill with oxirane.
Claims (8)
1. compound red sage root extended release microsphere, by 0.2～50% be that 50～99.8% molecular weight ranges of active component and microsphere weight is 5 by the extract of Radix Salviae Miltiorrhizae, pseudo-ginseng and Borneolum Syntheticum, biodegradable medicinal high polymer adjuvant between 000～1,000,000 dalton is formed; The weight percentage of active component Radix Salviae Miltiorrhizae wherein, Radix Notoginseng and Borneolum Syntheticum crude drug is a Radix Salviae Miltiorrhizae 48%～97%, Radix Notoginseng 2%～50%, Borneolum Syntheticum 0.2%～3%; Wherein medicinal high polymer adjuvant is a polylactide-co-glycolide, and lactide and Acetic acid, hydroxy-, bimol. cyclic ester polymerization ratio are between 40: 60～60: 40 in the polylactide-co-glycolide.
2. the described microsphere of claim 1, its molecular weight of wherein said polylactide-co-glycolide is between 12000～15000 dalton.
3. the described microsphere of claim 1, the weight percentage of active component Radix Salviae Miltiorrhizae wherein, Radix Notoginseng and Borneolum Syntheticum crude drug is a Radix Salviae Miltiorrhizae 63.0%～94%, Radix Notoginseng 4.0%～35.0%, Borneolum Syntheticum 0.5%～2.0%.
4. the described microsphere of claim 1, the weight percentage of active component Radix Salviae Miltiorrhizae wherein, Radix Notoginseng and Borneolum Syntheticum crude drug is a Radix Salviae Miltiorrhizae 75.2%～90%, Radix Notoginseng 9%～23.5%, Borneolum Syntheticum 0.5%～1.3%.
5. the described microsphere of claim 1, the weight percentage of active component Radix Salviae Miltiorrhizae wherein, Radix Notoginseng and Borneolum Syntheticum crude drug is a Radix Salviae Miltiorrhizae 82.87%, Radix Notoginseng 16.21%, Borneolum Syntheticum 0.92%.
6. the preparation method of the described microsphere of claim 1, it is to adopt the emulsifying dispersion method to make, it is characterized in that using dichloromethane, chloroform, ethyl acetate, dioxane, ether, acetone, oxolane, glacial acetic acid and the mixed acid be made up of them are medicinal substances extract and the dissolving of biodegradable pharmaceutic adjuvant, wherein the bulking value percent of pharmaceutic adjuvant in organic solvent is 1～30%, the emulsifying agent that organic facies adopts is the nonionic emulsifier of HLB=4.5～6.0, uses polyvinyl alcohol, polyvinyl pyrrolidone, consumption is 0.01～12% of an organic facies; Sodium polymethacrylate, sodium polyacrylate, sodium carboxymethyl cellulose solution in addition, prepare continuous water, wherein they are 0.01～10.0 in the percetage by weight of aqueous phase, and the emulsifying agent of aqueous phase is the nonionic emulsifier of HLB=14.0～15.5, and consumption is 0.01～12% of a water; Decentralized photo slowly is injected in the continuous phase by tubule, and emulsifying is sieved then, is drying to obtain.
7. the preparation method of the described microsphere of claim 1, it is to adopt solvent evaporation method to make, the mixed acid that it is characterized in that forming with dichloromethane, chloroform, ethyl acetate, dioxane, ether, acetone, oxolane, glacial acetic acid and by them is medicinal substances extract and the dissolving of biodegradable pharmaceutic adjuvant, wherein the bulking value percent of pharmaceutic adjuvant in organic solvent is 1～30%, the emulsifying agent that organic facies adopts is the nonionic emulsifier of HLB=4.5～6.0, and consumption is 0.01～12% of an organic facies; Use polyvinyl alcohol, polyvinyl pyrrolidone, sodium polymethacrylate, sodium polyacrylate, sodium carboxymethyl cellulose solution in addition, prepare continuous water, wherein they are 0.01～10.0 in the percetage by weight of aqueous phase, the emulsifying agent of aqueous phase is the nonionic emulsifier of HLB=14.0～15.5, and consumption is 0.01～12% of a water; Decentralized photo slowly is injected in the continuous phase by tubule, fully emulsified, the solvent flashing that reduces pressure then, centrifugalize is drying to obtain.
8. the preparation method of the described microsphere of claim 1, it is to adopt spray drying method to make, the molecular weight that it is characterized in that mixed-acid dissolution 0.2～50% medicinal substances extract formed with dichloromethane, chloroform, ethyl acetate, dioxane, ether, acetone, oxolane, glacial acetic acid and by them and derivant and 50～99.8% is at 5000～1000000 daltonian biodegradable medical high-molecular additives, after stirring fully dissolving, filter, adopt spray drying method to make microsphere.
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| CN1348815A (en) * | 2001-11-09 | 2002-05-15 | 天津天士力制药股份有限公司 | Medicine for preventing and treating coronary heart disease and angina pectoris and its prepn and other use |
| CN1349818A (en) * | 2001-10-24 | 2002-05-22 | 沈阳药科大学 | Effective part group in red sage mixture and its delayed release prepn. medicinal use and prepn process |
| CN1415294A (en) * | 2002-11-07 | 2003-05-07 | 上海医药工业研究院 | Long acting injection microsphere combination of naltrexone, its preparation method and application |
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| CN1349818A (en) * | 2001-10-24 | 2002-05-22 | 沈阳药科大学 | Effective part group in red sage mixture and its delayed release prepn. medicinal use and prepn process |
| CN1348815A (en) * | 2001-11-09 | 2002-05-15 | 天津天士力制药股份有限公司 | Medicine for preventing and treating coronary heart disease and angina pectoris and its prepn and other use |
| CN1415294A (en) * | 2002-11-07 | 2003-05-07 | 上海医药工业研究院 | Long acting injection microsphere combination of naltrexone, its preparation method and application |
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