CN100408033C - Fat emulsion of biobalide B and preparation method - Google Patents
Fat emulsion of biobalide B and preparation method Download PDFInfo
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- CN100408033C CN100408033C CNB2005101056664A CN200510105666A CN100408033C CN 100408033 C CN100408033 C CN 100408033C CN B2005101056664 A CNB2005101056664 A CN B2005101056664A CN 200510105666 A CN200510105666 A CN 200510105666A CN 100408033 C CN100408033 C CN 100408033C
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Abstract
The present invention relates to a fat emulsion of ginkolide B and a preparation method thereof, which is a medicine preparation with the effect of strongly antagonizing platelet activating factors, more specifically a fat emulsion with ginkolide B extracted from ginkgo leaves of ginkgoaceae plants as active ingredients.
Description
Technical field
The present invention relates to a kind of very strong antagonism platelet activating factor (obvious anti-platelet aggregation that has, anti-senile dementia etc.) Zuo Yong pharmaceutical preparation, specifically be a kind of be the lipomul of active component with the ginkalide B that from Ginkgoaceae plant Ginkgo biloba leaf, extracts.
Background technology
Semen Ginkgo (Ginkgo Biloba L.) is a Ginkgoaceae, and the Ginkgo plant has another name called Semen Ginkgo, Gong Sunshu, and China is distributed more widely.The history that its seed was used as medicine existing more than 600 year as " Semen Ginkgo " has found that to the seventies in 20th century Folium Ginkgo extract has good curative effect to cardiovascular and cerebrovascular disease, and the medical value of Semen Ginkgo just has been subjected to paying close attention to widely.
Bilobalide (ginkgolide) is one of main active of Folium Ginkgo.Furukawa in 1932 separates from Folium Ginkgo first and obtains the terpene lactones chemical compound.Maruyama in 1967 etc. separate the chemical constitution that has obtained ginkalide A, B, C and M and determined them from the root bark of Semen Ginkgo.Weinges isolated bilobalide J from Folium Ginkgo in 1987.The bilobalide molecule has 12 unique carbon skeleton structures, is embedded with a tert-butyl group and six five-membered rings, comprises a spiral shell [4,4] nonane, an oxolane ring and three lactonic rings.Ginkalide A, B, C, M and J represent with code name BN52020, BN52021, BN52022, BN52023 and BN52024 that respectively wherein the content of BN52021 in Semen Ginkgo is 0.2%, and structural formula is:
From the eighties in 20th century, discover that bilobalide is the strong antagonist of platelet activating factor (PAB), have significant curative effect for cardiovascular and cerebrovascular disease, cause the climax of Semen Ginkgo research in the world, major part research is wherein carried out at bilobalide.Proof such as Braquet in 1984 bilobalide is to platelet activating factor (platelet activating factor, PAF) receptor has powerful specificity to suppress active, cardiovascular and cerebrovascular vessel had unique pharmacological action, be considered to have most the natural paf receptor antagonists of potential applicability in clinical practice at present, wherein the activity with ginkalide B (BN52021) is the strongest.
Ginkalide B is a kind of strong platelet activating factor (PAF) antagonist.Platelet activating factor is the biological active substances of a kind of mammal endogenous, main morbidity with the allosome repulsion of allergy, ulcer, asthma, thrombosis, some inflammation, organ transplantation, the myocardial damage that the coronary disease patient causes owing to anoxia etc. is closely related, so platelet activating factor antagonist can be used for the control of above-mentioned disease.
Ginkalide B is water insoluble, absorption difference in the body, owing to cost an arm and a leg, bioavailability is not high to have caused great waste, and the technology of existing preparation does not have to solve the problem of absorption difference, the present invention proposes to solve the effective scheme that improves bioavailability.
Summary of the invention
The invention discloses with ginkalide B as Liposyn (also claiming Emulsion) of active constituents of medicine and preparation method thereof.The injectable dosage forms that the purpose of this invention is to provide a kind of ginkalide B can be used for the artery and vein injection.Lipomul of the present invention can be used for diseases of cardiovascular and cerebrovascular systems such as coronary heart disease, angina pectoris, cerebral arteries hard, and the dizziness that causes of cerebral blood supply insufficiency, headache, dizzy, anxiety, tinnitus, hypomnesis, and the treatment that is used for alzheimer disease.The present invention finds unexpectedly, and the ginkalide B of indissoluble is prepared into lipomul, can improve the action activity of this class medicine; The present invention finds, adds ginkalide B in the infatmul agent, can obviously increase the concentration of medicine at positions such as internal organs and lymphs after the injection body is interior, thereby can improve curative effect.
Lipomul of the present invention is a kind of drug particles transmission system, this system has lymphsystem and mononuclear phagocyte system targeting as pharmaceutical carrier, and the emulsion droplet in the Emulsion can be transported to lymphsystem or be engulfed by reticuloendothelial cell and concentrate at lymph fluid and the organs and tissues that is rich in mononuclear phagocyte system.
Lipomul of the present invention contains following composition, and their percentage by weight is:
Ginkalide B 0.001-0.25%, fatty oil 1.0-45%, surfactant 1.0-40%, isotonic agent 0.5-35%, solubilizing agent 0.5-35%, antioxidant 0.001-0.2%, water for injection 10-90%.
The said fatty oil of the present invention is as the oil ﹠ fat of origin of heat (energy source) in any high alimentation of being everlasting etc., comprising: various plants oil, as soybean oil, Oleum sesami, olive oil, Semen Maydis oil, perilla oil, Storax oil, Semen Lini oil, Oleum Cocois, Oleum Camelliae, Oleum Sesami, safflower oil, the cotton seed wet goods; Fish oil, as pilchard oil, cod-liver oil etc.; Chain fatty acid triglycerides (LCT) as necessary fatty acid source; And carbon number is generally one or two or more kinds the mixture in the MCT Oil (MCT) of 8-10.In addition, described fat also comprises the triglyceride of chemistry definition, 2-Caulis et Folium Lini acyl group-1 for example, 3-two caprylyl glycerol, 2-Caulis et Folium Lini acyl group 1,3-didecyl acylglycerol etc.These materials can use separately, also can use with.
The said surfactant of the present invention is for adopting any conventional emulsifying agent that uses, for example, phospholipid, as Ovum Gallus domesticus Flavus lecithin, hydrogenated yolk lecithin, soybean lecithin, hydrogenated soy phosphatidyl choline etc., highly purified phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE, serinephosphatide, the phosphatidyl glycerol, phosphatidic acid, LYSOLECITHIN SUNLECITHIN A, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene fatty acid ester, polyoxyethylene castor oil, the polyoxyethylene hydrogenated castor oil derivant, the polyoxyethylene higher alcohol, polyoxyethylene polyoxypropylene alkyl ether etc., general sieve stream Buddhist nun, pluronic F-68, polyoxyethylene sorbitan monoleate, the mixture of one or two or more kinds in the deoxidation choline sodium.
The said isotonic agent of the present invention is selected from: the mixture of glycerol for injection, glucose, xylitol, maltose, mannitol and these regulators.
The said solubilizing agent of the present invention is selected from: hydroxypropyl beta cyclodextrin, Polyethylene Glycol, polyvidone, sodium lactate, dextran, starch derivatives, gelatin.
Except that mentioned component, in case of necessity, also can add emulsifying adjuvant, stabilizing agent etc. in the lipomul of the present invention, also comprise antioxidant.
Described emulsifying adjuvant preferably has 6～22 carbon atoms, even more preferably has saturated or unsaturated fatty acid or its officinal salt of 12-20 carbon atom.Its example comprises lauric acid, myristic acid, Palmic acid, stearic acid, oleic acid etc.The use amount of emulsifying adjuvant be based on the lipomul total amount be 3% (w/v) or below, preferably 1% (w/v) and following amount thereof.
The preferred cholesterol class of described stabilizing agent or phosphatidic acid etc.Its consumption is preferably below 5% (w/v).
Described antioxidant is selected from ascorbic acid, alpha-tocopherol etc., preferably alpha-tocopherol.Consumption is 0.001-0.2%, preferably below 0.1% (w/v).
The present invention preferably fills a prescription as follows:
Ginkalide B 0.001-0.20%, soybean oil 5-40%, phosphatidase 11 .0-15%, polyoxyethylene sorbitan monoleate 1.0-10, glycerol 1-12%, alpha-tocopherol 0.01-0.1%, solubilizing agent is selected from dextran and/or hydroxypropyl beta cyclodextrin 1-15%, and isotonic agent is selected from glucose or xylitol 0.5-10%.
Phospholipid in the aforementioned lipomul is Ovum Gallus domesticus Flavus lecithin, soybean lecithin or synthetic phospholipids such as phosphatidylcholine, serinephosphatide.Also comprise water for injection 10-90% in the composition, as be added into 100ml.
The present invention more preferably fills a prescription composed as follows:
Ginkalide B 0.01-0.180%, soybean oil 10-25%, soybean lecithin 1.5-5%, polyoxyethylene sorbitan monoleate 0.5-2%, dextran 1.0-8.0%, glucose 2.0-10%.
Water for injection was 10-90% during aforementioned lipomul was formed, as added to 100ml.
Lipomul of the present invention can specifically can adopt following method according to the routine techniques preparation of galenic pharmacy,
Method one:
Get fatty oil, ginkalide B in 50-200 ℃ of mixing, temperature adds surfactant during to 50-95 ℃, can add or not add antioxidant, mixes forming mixed liquor (1); Water for injection, surfactant, isoosmotic adjusting agent mix with solubilizing agent, form water (2); Water (2) is mixed with mixed liquor (1), after high speed dispersion under the 50-95 ℃ of condition, made colostrum in mechanical agitation 2-3 hour, behind PH regulator adjusting PH to 3-8, carry out homogenize again; Make bilobalide-containing B and get lipomul.
Method two:
Get fatty oil, ginkalide B after 50-180 ℃ of mixing, be cooled to 50-95 ℃, add phospholipid, can add or not add antioxidant, mix, form mixed liquor (1); Surfactant is mixed with 50-95 ℃ of water for injection, mix with the water liquid that contains isotonic agent and solubilizing agent again, form water (2); Water (2) is poured in the mixed liquor (1), after high speed dispersion under the 50-95 ℃ of condition, made colostrum in mechanical agitation 2-3 hour, regulate PH to 5-7.5 with the PH regulator; Carry out homogenize again, make the lipomul of bilobalide-containing B.
Lipomul of the present invention can be made cryodesiccated preparation through freezing dry process.At this moment can further add excipient in the preparation.Spendable excipient has mannitol, lactose, maltose, sucrose, inositol etc.During use, get final product with the solvent for injection dissolving.
Prescription of the present invention is formed and preparation method, and particularly preferred composition and method obtain through screening, have very good galenic pharmacy characteristics.As good stability, the bioavailability height, side effect is little, and nonirritant is painless, and curative effect is good.
Following data declaration beneficial effect of the present invention by experiment:
Pharmacodynamic experiment
One, the influence of ginkalide B Liposyn rat cerebral infarction scope.
[medicine and reagent]: be subjected to reagent ginkalide B lipomul (according to the method preparation of the embodiment of the invention 1, every bottle of 100ml, per 100 milliliters of bilobalide-containing B 50mg), rat consumption 8,4,2mg/kg/ day.(every milliliter contains flavonoid glycoside 0.84mg, lot number to the positive controls Ginaton injection for Dr Willmar Schwabe, every 5ml: 2071003) rat consumption 3.5ml/kg/ day.
[animal]: the SD rat, the male and female dual-purpose, body weight 200-240g is provided by China Medicine University's Experimental Animal Center.The quality certification number: 05004.
[method and result]:
One, the ginkalide B lipomul is to middle cerebral artery thrombus model (Middle Cerebral ArteryThrombosis, MCAT) influence of rat nervous symptoms.
(1), grouping and administration: laboratory animal is divided into six groups at random, and promptly MCAT model group, ginkalide B lipomul 8,4,2mg/kg group, Ginaton injection 3.5ml/kg organize sham operated rats.Modeling is tested a few days ago, and abdominal cavity every day (ip) drug administration by injection once; After the modeling at once abdominal cavity (ip) be administered once, the 4th administration (ip) drawn materials in back one hour.The administration group gives corresponding medicine; MCAT model group and sham operated rats are all given equivalent normal saline 20ml/kg body weight.
(2), implement the modeling operation: press the method for Tamura etc., improvement a little.Rats by intraperitoneal injection 12% chloral hydrate solution (300mg/kg) intraperitoneal injection of anesthesia.The rat right arm reclining is fixed, make a curved incision at left eye outer canthus and left external auditory canal line mid point, be about 1.5cm, the pinch off temporalis also cuts, expose temporal bone, under stero microscope, make a diameter 2.5mm bone window at cheekbone and temporo squamosum joint to oral-lateral 1mm place with dental burr, the cleaning residue exposes middle cerebral artery (between tractus olfactorius and inferior cerebral vein).There is the small pieces quantitative filter paper of 50% ferric chloride solution (1mol/L hydrochloric acid), 10 μ l to apply on this section middle cerebral artery suction, about 30min treats to take off filter paper after the blackening of blood vessel color, use the normal saline flushing local organization, layer-by-layer suture steams again and raises (room temperature is controlled at 25 ℃).Sham operated rats is except that not dripping the ferric chloride solution the same model group of all the other operating procedures.
(3) neurobehavioral detection method: (6h 24h), is improved by the method for Bederson etc. different time, and animal is carried out behavior scoring after surgery.1. carry Mus tail built on stilts, observe forelimb flexing situation.Stretch to ground as two forelimb symmetries, be designated as 0 fen; As the flexing that shoulder flexing, elbow flexing, shoulder inward turning or existing wrist elbow appear in the offside forelimb of performing the operation has inward turning person again, is designated as 1 fen.2. animal is placed on the level and smooth ground, push away both shoulders respectively, check resistance to side shifting.As bilateral resistance equity and be designated as 0 fen effectively; As resistance descender when the operation offside promotes, be designated as 1 fen.3. animal two forelimbs are put on the wire netting, observed muscular tension.Bilateral muscular tension equity and strong person are 0 minute; Operation offside muscle of anterior limb tension force descends and is designated as 1 fen.4. it is liftoff to carry the Mus tail, and animal has ceaselessly to operation offside revolver, is designated as 1 fen.According to above standard scoring, full marks are 4 minutes, and mark is high more, and the behavior disorder of animal is serious more.
(4), interpretation of result: to behavior detect the marking value organize between relatively, the t check.
The result shows that dystropy changes between the sham operated rats end, and the MCAT model group is 6h after surgery, and hemiplegia sample symptom appears in 24h, mainly show as in the operation offside forelimb to receive, and the shoulder inward turning, muscle of anterior limb tension force reduces, and the shoulder drag descends.The rat of each dosage group of ginkalide B Liposyn is 24h after surgery, and its nervous symptoms all has improvement in various degree, statistical procedures, significant difference (P＜0.05).
Two, the ginkalide B lipomul is to the influence of MCAT rat cerebral infarction scope
The assay method of cerebral infarction scope: behind the animal via behavior scoring, promptly broken end is got brain, and brain is put 10min in the ice-cold normal saline, removes olfactory bulb, cerebellum and low brain stem, crownly is cut into 5.Rapidly the brain sheet is placed triphenyltetrazolium chloride (TTC) dye liquor (the 5ml dye liquor to be contained 4%TTC 1.5ml, 1mol/L K
2HPO
40.1ml), 37 ℃ of lucifuge temperature were incubated 30 minutes, took out again, placed 10% formalin to keep in Dark Place.The non-ischemic region in dyed back is a rose, and infarct is a white.White organized carefully to dig down weigh, the percentage ratio that accounts for brain weight with blocking tissue's weight is as the cerebral infarction scope.Relatively, t checks the result between organizing.The results are shown in Table 1.
Table 1 ginkalide B lipomul is to the influence of MCAT rat cerebral tissue infarction size
Annotate: compare * * P＜0.01 with the MCAT model group
The result shows, postoperative 24h, and except that the sham operated rats no abnormality seen changed, the rat of MCAT model group, each administration group had all in various degree that focus of infarct, ginkalide B lipomul can obviously reduce the infraction degree.
The present invention shows that the ginkalide B lipomul can significantly reduce the infarction size of focal cerebral ischemia in rats.
Characteristics of the present invention are that preparation method is simple, and not high and do not have specific (special) requirements to the equipment requirements used in the preparation process, the time is short, and cost is low, is beneficial to production in enormous quantities.
The specific embodiment
Further specify the present invention by the following examples, but not as limitation of the present invention.
Embodiment 1:
Soybean oil 20g is filtered the back with film filter drop into container, ginkalide B 175mg puts in the container, after high temperature (200 ℃) mechanical agitation treats that medicine disperses, be cooled to 95 ℃, input soybean lecithin 2g,, continue mechanical agitation and treat the phospholipid dissolving, mix homogeneously forms mixed liquor; Water for injection 80ml is placed another container, be heated to 95 ℃, add surfactant, soybean lecithin 4.0g, polyoxyethylene sorbitan monoleate 3.5g dispersed with stirring, with isoosmotic adjusting agent glucose 2.5g, solubilizing agent dextran 4g, use water dissolution, filter the back with film filter and add wherein.
Will pour under the water restir mix in the oil phase, again under 95 ℃ of conditions after the high speed dispersion mechanical agitation made colostrum in 3 hours, regulate PH to 7.5 with the 0.1M sodium hydroxide solution, the colostrum that makes is moved into high pressure homogenization machine, secondary homogenize;
Through filtering with microporous membrane, nitrogen is filled in fill, gland.
Fill is good that fat milk places the rotation high-pressure sterilizing pot to sterilize.
Embodiment 2:
(1) injection soybean oil 10g filters the back through the mocromembrane filter and drops into container, and ginkalide B 150mg also puts in the container, is heated to 50 ℃ and stir, and adds soybean lecithin 2.0g, continues mechanical agitation and make mix homogeneously, the formation mixed liquor.(2) in another preparation container, add 90ml water, be heated to 50 ℃, add surfactant soybean phospholipid 3.0g, polyoxyethylene sorbitan monoleate 3.5g dispersed with stirring.Glucose 2.5g, dextran 4.5g water dissolution are with also adding in the container after the filtration of mocromembrane filter.(3) water that step (2) is obtained is under agitation poured in the mixed phase that step (1) obtains, and mechanical agitation was made colostrum in 2 hours after high speed dispersion under 50 ℃ of conditions, regulates PH to 7.4 with the 0.1M sodium hydroxide solution.Finely dispersed emulsion is carried out twice emulsifying through the high pressure dispersing emulsification machine then with the mocromembrane filtration.Under agitation add water to capacity, transfer PH to check semi-finished product, through mocromembrane filtration, fill.Fill nitrogen, add plug and jewelling lid.At 121 ℃ of 15min that sterilize down.After sterilization finishes, cooling gradually.
Embodiment 3:
(1) injection soybean oil 25g filters the back through the mocromembrane filter and drops into container, and ginkalide B 100mg also puts in the container, is heated to 50 ℃ and stir, and adds alpha-tocopherol 50mg, continues mechanical agitation and makes mix homogeneously, the formation mixed liquor.(2) in another preparation container, add suitable quantity of water, be heated to 50 ℃, add soybean phospholipid 2.0g, pluronic F-68 3.0g dispersed with stirring.Glycerol 3.0g water dissolution is with also adding in the container after the filtration of mocromembrane filter.(3) water that step (2) is obtained is under agitation poured in the mixed phase that step (1) obtains, and mechanical agitation was made colostrum in 2 hours after high speed dispersion under 50 ℃ of conditions.Finely dispersed emulsion is carried out twice emulsifying through the high pressure dispersing emulsification machine then with the mocromembrane filtration.Under agitation add water to 100ml, transfer PH to check semi-finished product, through mocromembrane filtration, fill.Fill nitrogen, add plug and jewelling lid.At 121 ℃ of 15min that sterilize down.After sterilization finishes, cooling gradually.
Embodiment 4:
Injection soybean oil 20g, MCT Oil 20g are filtered the back with film filter drop into container, ginkalide B 50mg puts in the container, after high temperature (200 ℃) mechanical agitation treats that medicine disperses, be cooled to 95 ℃, have high input fabaceous lecithin 1.0g,, continue mechanical agitation and treat the phospholipid dissolving, mix homogeneously forms mixed liquor; 100ml water for injection is placed another container, be heated to 95 ℃, add soybean phospholipid 2.0g dispersed with stirring, with glucose 3.0g, solubilizer polyethylene glycol 4.0g, dextran 5g water dissolution filter the back with film filter and add wherein.
Will pour under the water restir mix in the oil phase, again under 95 ℃ of conditions after the high speed dispersion mechanical agitation made colostrum in 3 hours, regulate PH to 7.4 with the 0.1M sodium hydroxide solution, then the colostrum that makes is moved into high pressure homogenization machine, secondary homogenize;
Through filtering with microporous membrane, nitrogen is filled in fill, gland.
Fill is good that fat milk places the rotation high-pressure sterilizing pot to sterilize.
Embodiment 5:
Injection soybean oil 15g, MCT Oil 15g are filtered the back with film filter drop into container, ginkalide B 20mg, alpha-tocopherol 100mg put in the container, after high temperature (200 ℃) mechanical agitation treats that medicine disperses, be cooled to 95 ℃, have high input fabaceous lecithin 2.5g,, continue mechanical agitation and treat the phospholipid dissolving, mix homogeneously forms mixed liquor;
100ml water for injection is placed another container, be heated to 95 ℃, add soybean phospholipid 3.5g dispersed with stirring, with glucose 2.0g, solubilizing agent starch derivatives 3.5g, dextran 3.5g water dissolution filter the back with film filter and add wherein.
Will pour under the water restir mix in the oil phase, again under 95 ℃ of conditions after the high speed dispersion mechanical agitation made colostrum in 3 hours, then the colostrum that makes is moved into high pressure homogenization machine, secondary homogenize;
Through filtering with microporous membrane, nitrogen is filled in fill, gland.
Fill is good that fat milk places the rotation high-pressure sterilizing pot to sterilize.
Claims (2)
1. the lipomul of a ginkalide B is characterized in that, contains the following component of percentage by weight:
Ginkalide B 0.001-0.20%, soybean oil 5-40%, phosphatidase 11 .0-15%, polyoxyethylene sorbitan monoleate 1.0-10%, glycerol 1-12%, alpha-tocopherol 0.01-0.1%, dextran 1-15%, glucose 0.5-10%, all the other are water for injection.
2. according to the lipomul of claim 1, it is characterized in that phospholipid wherein is selected from Ovum Gallus domesticus Flavus lecithin, soybean lecithin, phosphatidylcholine, serinephosphatide.
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2005101056664A CN100408033C (en) | 2005-09-29 | 2005-09-29 | Fat emulsion of biobalide B and preparation method |
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| CN100408033C true CN100408033C (en) | 2008-08-06 |
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Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103040742B (en) * | 2012-12-20 | 2014-04-16 | 海南百思特医药科技有限公司 | Ginkgolide B lipid microsphere injection |
| EP3213749B1 (en) * | 2014-10-30 | 2020-08-12 | Chengdu Baiyu Pharmaceutical Co., Ltd. | Pharmaceutical composition containing ginkgolide b and xa factor inhibitor, preparation method thereof and use thereof |
| CN105832667B (en) * | 2016-04-29 | 2018-11-30 | 济南康和医药科技有限公司 | A kind of long chain fat emulsion injection and preparation method thereof containing olive oil |
| CN110433157B (en) * | 2018-05-02 | 2022-10-18 | 成都百裕制药股份有限公司 | Application of ginkgolide in preparation of medicine for preventing and/or treating vertigo |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1315175A (en) * | 2000-03-24 | 2001-10-03 | 中国科学院上海药物研究所 | Process for preparing ginkgolide injection |
| CN1335157A (en) * | 2001-06-29 | 2002-02-13 | 成都新世纪科技有限责任公司 | Systemic separation process and prepn of ginkgetin, ginkgolide and bilobalide |
| CN1457776A (en) * | 2003-06-02 | 2003-11-26 | 沈阳药科大学 | Self emulsified soft capsule of ginkgo leaf extract and its preparing method |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1315175A (en) * | 2000-03-24 | 2001-10-03 | 中国科学院上海药物研究所 | Process for preparing ginkgolide injection |
| CN1335157A (en) * | 2001-06-29 | 2002-02-13 | 成都新世纪科技有限责任公司 | Systemic separation process and prepn of ginkgetin, ginkgolide and bilobalide |
| CN1457776A (en) * | 2003-06-02 | 2003-11-26 | 沈阳药科大学 | Self emulsified soft capsule of ginkgo leaf extract and its preparing method |
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