CN103638017A - Composition of ginkgolide A and ginkgolide B and application of composition - Google Patents
Composition of ginkgolide A and ginkgolide B and application of composition Download PDFInfo
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Abstract
The invention relates to a traditional Chinese medicament composition for treating cardiovascular diseases and preparations of the traditional Chinese medicament composition, belonging to the technical field of medicaments. The composition comprises two active ingredients of ginkgolide A and ginkgolide B in the weight ratio of 1:(0.2-2). Meanwhile, a plurality of preparation formulations are designed, the application of the composition in medicament preparations is verified, and corresponding quality control methods are established.
Description
Technical field
The invention belongs to medical technical field, be specifically related to compositions and the application thereof of Ginkgolides a and B.
Background technology
Diseases of cardiovascular and cerebrovascular systems is the most common class diseases of the mankind, has become the first cause of the death of world today's population.Treatment cardiovascular disease still mainly be take chemical drugs at present as main, yet along with increase day by day iatrogenic, drug-induced disease, the toxic and side effects of chemical drugs also more and more comes into one's own, and the extract of Chinese patent medicine or natural product is having development faster aspect treatment cardiovascular.
Semen Ginkgo (Ginkgo biloba L.) is Ginkgoaceae (Ginkgo aceae) Ginkgo deciduous tree.Have that the beneficial heart is astringed the lung, the function of removing dampness antidiarrheal.For diseases such as uncomfortable in chest, severe palpitation, leukorrheal diseases, cough phlegm dyspnea, dysentery.Semen Ginkgo is as medicinal, and the < < day that sees the earliest Yuan Dynasty Wu Rui is with herbal > >.Since the sixties in 20th century, Chinese scholars has been carried out a large amount of research to the chemical constitution of Folium Ginkgo, pharmacological action etc.Semen Ginkgo be widely used as medicine along with the eighties in 20th century since the wind of Foreign Epidemic " back to nature " start.Popular the earliest is in the world to come from the Folium Ginkgo extract that German code name is GBE761 (main effective ingredient is flavonoid glycoside and lactone compound), is widely used in the world the diseases such as treatment brain injury sequela and senile brain, cardiovascular system decline due to its remarkable efficacy and saferry.The platelet activating factor (PAF) of finding for 1972 has been played the part of important role in cerebral infarction, 1984, pharmacological research finds that bilobalide has anti-platelet activating factor (the platelet activating factor of specificity, PAF) activity, natural PAF antagonist, wherein especially the highest with the activity of ginkalide B (GB).And pharmacological research also shows, the compositions antiplatelet aggregation intensity of Ginkgolides a and B is obviously better than single bilobalide composition, has significant synergism, is a kind of desirable drug regimen of cardiovascular and cerebrovascular disease for the treatment of.
Summary of the invention
The object of the present invention is to provide a kind of drug regimen for the treatment of cardiovascular and cerebrovascular disease.
Another object of the present invention is to provide the pharmaceutical preparation of a kind of bilobalide-containing A, B compositions.
The present invention is achieved through the following technical solutions:
A bilobalide compositions, is characterized in that described compositions comprises ginkalide A and two kinds of active components of ginkalide B, and the weight ratio of ginkalide A and ginkalide B is 1:0.2 ~ 2.
In above-mentioned composition, content >=85%(injection of ginkalide A and ginkalide B is preferably more than 95%).
Take containing above-mentioned composition is main effective ingredient, adds that pharmaceutically acceptable adjuvant makes pharmaceutical preparation, and dosage form can be tablet, capsule, granule, injection, pill, powder, compound preparation.
The preferred slow-release tablet agent of described dosage form, take ginkalide A and ginkalide B as main effective ingredient, and selecting hypromellose (HPMC) is framework material, and lactose is filler, and magnesium stearate is lubricant, and micropowder silica gel is fluidizer.
The weight ratio of described slow-release tablet agent bilobalide compositions and adjuvant is 1:10
Component and the percentage by weight thereof of Ginkgolides a and B sustained-release matrix preparation of the present invention are: Ginkgolides a and B compositions 10 ~ 40%, HPMC15 ~ 40%, lactose 40 ~ 70%.
The present invention sets up tablet, granule, injection method of quality control according to following assay and drug release determination condition:
(1) assay
Prepare solid preparation need testing solution: precision is got and is approximately equivalent to bilobalide lactone 30mg sample, adds ethyl acetate 50ml reflux, extract, 2h, filter, and wash filter paper by a small amount of ethyl acetate, washing liquid is incorporated in filtrate.Evaporate to dryness filtrate, residue is with dissolve with methanol and be transferred in 5ml volumetric flask, adds methanol to scale, shakes up, and 0.45 μ m microporous filter membrane filters, and gets subsequent filtrate and get final product.
Prepare injection need testing solution: direct sample product are as test sample.
Preparation reference substance solution: it is appropriate that precision takes Ginkgolides a and B reference substance, is also quantitatively diluted to every 1ml bilobalide-containing A 1mg with dissolve with methanol, and the reference substance solution of ginkalide B 1mg, puts in refrigerator and save backup.
Chromatographic condition Hypersil ODS post (250mm * 4.6mm, 5 μ m); Mobile phase: Methanol-water (30:70); Column temperature: 25 ℃; Flow velocity: 1.0mlmin-1; Evaporative light scattering detector ELSD, detected parameters: drift tube temperature: 104 ℃; Flow rate of carrier gas: 2.9Lmin-1.
Assay method
Accurate reference substance solution 2,5, the 10 μ l that draw, need testing solution 10 μ l are injection liquid chromatography respectively, records chromatogram, and the standard curve by the peak area substitution recording by reference substance content logarithm and peak area logarithm regression gained, obtains.
(2) drug release determination
Adopt two appendix XD first methods of < < Chinese Pharmacopoeia > > version in 2010, using 0.1mol/L hydrochloric acid 100ml as release medium, rotating speed 75r/min, temperature (37 ± 0.5 ℃), in 0.5h, 1h, 2h, 4h, 6h, 8h, 12h, 13h timing sampling 1ml(adds equivalent equality of temperature medium in time), through 0.45 μ m filtering with microporous membrane, get subsequent filtrate injection liquid chromatography, according to chromatographic condition under assay item, measure peak area, substitution standard curve equation, calculate cumulative release degree.
The present invention by pharmacodynamic experiment, determines that in bilobalide compositions, ginkalide A is 1:0.2 ~ 2 with the weight ratio of ginkalide B, and its drug effect can reach optimum.
Specific embodiment of the invention scheme is as follows:
The antiplatelet aggregative activity comparative experiments of the different proportion compatibility bilobalide of the present invention compositions.
1, experiment material:
(1) tested medicine
Crystallization 1 (A:B=1:0)
Crystallization 2 (A:B=5:1)
Crystallization 3 (A:B=1:1)
Crystallization 4 (A:B=1:1.5)
Crystallization 5 (A:B=1:3)
Crystallization 6 (A:B=1:8)
Folium Ginkgo extract (A+B=3.57%)
(2) preparation of PAF solution
Get 1.85 μ l dehydrated alcohol in holding the bottle of PAF, fully blow and beat to medicine dissolution, make the mother solution of 10-3mM, be distributed into a plurality of tubules ,-20 ℃ of preservations, become required concentration with front with normal saline dilution.
(3) preparation of Ginkgolides a and B standard substance
Precision takes ginkalide A standard substance 13.1mg, and DMSO is settled to 5mL, fully dissolves and obtains
liquid, gets
liquid 20 μ l add in 80 μ l DMSO, fully mix
liquid, gets
liquid 20 μ l add in 80 μ lDMSO, fully mix
liquid, obtains successively
liquid,
liquid.Used time gets each concentration liquid of 1 μ l and joins in 300 μ l blood plasma, obtains final concentration and is respectively 20.75 μ M, 4.15 μ M, 0.83 μ M, 0.166 μ M, 0.0332 μ M.
Precision takes ginkalide B standard substance 4.3mg, and DMSO is settled to 5mL, fully dissolves and obtains A liquid, gets A liquid 20 μ l and adds in 80 μ lDMSO, fully mixes to obtain B liquid, gets B liquid 20 μ l and adds in 80 μ lDMSO, fully mix
liquid, obtains D liquid, E liquid successively.Used time gets each concentration liquid of 1 μ l and joins in 300 μ l blood plasma, obtains final concentration and is respectively 6.25 μ M, 1.25 μ M, 0.25 μ M, 0.05 μ M, 0.01 μ M.
(4) preparation of need testing solution
Take respectively each extract in EP pipe, sample weighting amount is as follows:
Table 1
The extract taking is dissolved in 1mLDMSO, fully mixes and make mother solution, get mother solution 50 μ l and join in 450 μ l DMSO and be diluted to working solution, the used time gets 1 μ l working solution and joins in 300 μ l blood plasma.
2, experimental technique and result:
(1) impact of different proportioning bilobalide crystallization on people's extracorporeal platelet aggregation
Normal adults, venous blood sampling, puts and is placed with in advance liquor sodii citratis (anticoagulant, blood and anticoagulant anticoagulant ratio 9:1) silication centrifuge tube in, blood and anticoagulant are mixed gently, centrifugal (800rmp) 10 min, sucking-off upper strata ecru suspension is platelet rich plasma (PRP).Remainder, with 3000rmp centrifugal 10min again, is drawn supernatant, makes platelet poor plasma (PPP).Experiment is divided into blank group, solvent control group, each crystallization group.Aggregation inducing agent is 130nM with PAF(final concentration), in every pipe 300 μ l PRP, add different crystallization solutions 1 μ l, in solvent control group PRP, add 1 μ lDMSO.Incubation 5min, adds derivant 10 μ l, detects platelet aggregation rate.
Measure GA, the impact of GB standard substance on the outer platelet suppression ratio of human body, and result has been analyzed, tried to achieve respectively the IC50 of GA, GB.The results are shown in Table 2 ~ 3.
The impact of table 2 GA standard substance on the outer platelet suppression ratio of human body
| Concentration (μ M) | Suppression ratio (%) |
| 0.166 | 8.01 |
| 0.83 | 53.94 |
| 4.15 | 54.30 |
| 20.75 | 70.94 |
| 103.75 | 98.00 |
The impact of table 3 GB standard substance on the outer platelet suppression ratio of human body
| Concentration (μ M) | Suppression ratio (%) |
| 0.25 | 26.11 |
| 0.625 | 37.83 |
| 1.25 | 53.34 |
| 6.25 | 84.99 |
Statistical analysis, visible ginkalide B is obviously better than ginkalide A to the inhibitory action of people's extracorporeal platelet aggregation.
B, the impact of different proportioning bilobalide crystallization on the outer platelet aggregation rate of human body
Measured the impact of each test sample on the outer platelet suppression ratio of human body.The results are shown in Table 4.
The impact of table 4 test sample on the outer platelet suppression ratio of human body
| 1 | 2 | 3 | 4 | 5 | 6 | GB | GBE | |
| Ａ／Ｂ | 1:0 | 1:0.2 | 1:1 | 1:1.5 | 1:3 | 1:8 | ||
| Suppression ratio (%) | 22.48 | 54.27 | 64.08 | 69.48 | 48.99 | 46.22 | 51.95 | 2.09 |
Inhibitory action and the ginkalide B of people's extracorporeal platelet aggregation of 1 pair of PAF induction of crystallization are suitable as shown in Table 4, and crystallization 2,3,4 is better than ginkalide B, and crystallization 1,5,6 effects are slightly poor.
(2) impact of different proportioning bilobalide crystallization on rabbit extracorporeal platelet aggregation
Rabbit, male and female are regardless of, heart blood sampling, put and be placed with in advance liquor sodii citratis (anticoagulant, blood and anticoagulant anticoagulant ratio 9:1) silication centrifuge tube in, blood and anticoagulant are mixed gently, centrifugal (800rmp) 10 min, sucking-off upper strata ecru suspension is platelet rich plasma (PRP).Remainder, with 3000rmp centrifugal 10min again, is drawn supernatant, makes platelet poor plasma (PPP).Experiment is divided into blank group, solvent control group, each crystallization group.Aggregation inducing agent is 6.5nM with PAF(final concentration), in every pipe 300 μ l PRP, add different crystallization solutions 1 μ l, in solvent control group PRP, add 1 μ lDMSO.Incubation 5min, adds derivant 10 μ l, detects platelet aggregation rate, calculates as stated above suppression ratio.
The mensuration of the IC50 of a, Ginkgolides a and B standard substance
Measure GA, the impact of GB standard substance on the external platelet suppression ratio of rabbit, and result has been analyzed, tried to achieve respectively the IC50 of GA, GB.The results are shown in Table 5 ~ 6.
The impact of table 5 GA standard substance on the external platelet suppression ratio of rabbit
| Concentration (μ M) | Suppression ratio (%) |
| 0.83 | 8.39 |
| 2.075 | 30.05 |
| 4.15 | 73.14 |
| 10.38 | 100.00 |
| 20.75 | 95.36 |
The impact of table 6 GB standard substance on the external platelet suppression ratio of rabbit
Statistical analysis, show that the IC50 that ginkalide A suppresses the external platelet of rabbit is 4.00104 μ M, the IC50 that ginkalide B suppresses the external platelet of rabbit is 1.07591 μ M, ginkalide B is also better than ginkalide A to the inhibitory action of rabbit extracorporeal platelet aggregation as can be seen here, but not as the external platelet inhibitory action of human blood obvious difference.
B, the impact of different proportioning bilobalide crystallization on rabbit extracorporeal platelet aggregation rate
Measured the impact of each test sample on the external platelet suppression ratio of rabbit.The results are shown in Table 7.
The impact of table 7 test sample on the external platelet suppression ratio of rabbit
| 1 | 2 | 3 | 4 | 5 | 6 | GB | GBE | |
| Ａ／Ｂ | 1:0 | 1:0.2 | 1:1 | 1:1.5 | 1:3 | 1:8 | ||
| Suppression ratio (%) | 20.30 | 24.59 | 63.86 | 38.42 | 22.34 | 14.30 | 19.31 | 14.18 |
Ginkgolides a and B crystallization by the known various proportionings of table 2.13 is all better than alone ginkalide B and Folium Ginkgo extract group to the inhibitory action of the rabbit extracorporeal platelet aggregation of PAF induction.Best with GA:GB (1:1) effect.
In conjunction with extractive technique, and the result of human blood and Sanguis Leporis seu oryctolagi In Vitro Anti platelet aggregation experiment, determine that in preparation, selecting Ginkgolides a and B ratio in bilobalide complex is 1:0.2 ~ 2.
The specific embodiments of Ginkgolides a and B composite preparation of the present invention:
One, the preparation of Ginkgolides a and B composition sustained-release matrix tablet:
1, preparation method: Ginkgolides a and B extract and various adjuvant, increase progressively principle by equivalent and fully mix in mortar, direct compression.
2, single factor is investigated the release influence factor of sustained-release matrix tablets
(1) impact of HPMC consumption on Release Performance
By the weight ratio of bilobalide compositions and adjuvant, be that the heavy and principal agent of 1:10 stator, fluidizer, lubricant quantity are constant, add respectively and account for sheet and weigh 10%, 20%, 30% HPMCK4M, by method for preparing tablet thereof, prepare Ginkgolides a and B sustained-release matrix tablets, measure and compare rate of releasing drug, result shows, the rate of release of GA, GB slows down with the increase of HPMC consumption.The results are shown in Figure 1 ~ 2.
(2) impact of HPMC viscosity on Release Performance
By recipe quantity, take the HPMC(HPMCE-50 of different viscositys, HPMCK4M, HPMCK15M, HPMCK100M), other adjuvants and principal agent consumption are all identical.By method for preparing tablet thereof, prepare three batches of Ginkgolides a and B sustained-release matrix tablets, measure and compare rate of releasing drug.Result shows, its tablets in vitro speed no significant difference of the matrix tablet that two kinds of viscositys of HPMCK15M and HPMCK100M are made.The results are shown in Figure 3 ~ 4.
(3) impact of tabletting pressure on Release Performance
The pressure of take is made respectively the matrix tablet of different hardness as 7Kg, 9Kg, 11Kg, measures the release of each time point.Result shows, pressure is between 9～11Kg time, the change of pressure on the release of sustained-release matrix tablets without obvious impact.The results are shown in Figure 5 ~ 6.
(4) release evaluation
According to
calculate 2 values between two curves, further the similarity of more above-mentioned 12 hours release profiles.The results are shown in Table 8 ~ 9.
The assessment result of table 8 GA release profiles and modelling factors
The assessment result of table 9 GB release profiles and modelling factors
3, batch mixing uniform design optimization prescription
(1) experimental program
Scheme one: bilobalide compositions 10%, HPMC30%, lactose 60%, magnesium stearate is appropriate, and micropowder silica gel is appropriate.
Scheme two: bilobalide compositions 15%, HPMC15%, lactose 70%, magnesium stearate is appropriate, and micropowder silica gel is appropriate.
Scheme three: bilobalide compositions 15%, HPMC40%, lactose 45%, magnesium stearate is appropriate, and micropowder silica gel is appropriate.
Scheme four: bilobalide compositions 22.5%, HPMC25%, lactose 52.5%, magnesium stearate is appropriate, and micropowder silica gel is appropriate.
Scheme five: bilobalide compositions 27.5%, HPMC15%, lactose 57.5%, magnesium stearate is appropriate, and micropowder silica gel is appropriate.
Scheme six: bilobalide compositions 30%, HPMC30%, lactose 40%, magnesium stearate is appropriate, and micropowder silica gel is appropriate.
Scheme seven: bilobalide compositions 40%, HPMC15%, lactose 45%, magnesium stearate is appropriate, and micropowder silica gel is appropriate.
(2) cumulative release degree measurement result:
Table 10 GA cumulative release degree measurement result
Table 11 GB cumulative release degree measurement result
7 different prescription sample cumulative release degree are used respectively zero level equation, First-order equation, Higuchi equation, Hixcon-Crowell equation, Weibull equation, Peppas equation model, and result shows to take that the matrix tablet that HPMCK4M is prepared as framework material can substantially reach zero level or approximate zero-order release in the proportion of setting.
(3) optimum prescription checking
According to optimum prescription, form, prepare 3 batches of Ginkgolides a and B sustained-release matrix tablets.The cumulative release degree of measuring each time point, the results are shown in Table 12 ~ 13, Fig. 7 ~ 8.
The checking (n=3) of table 12 GA optimum formula
The checking (n=3) of table 13 GB optimum formula
By Peppas equation model, the fit equation that obtains Ginkgolides a and B is respectively:
Ginkalide A:
Ginkalide B:
NA=0.5793, nB=6255, equal 0.45 < n < 0.89, therefore principal agent spreads (diffusion+corrosion) machine-processed release with non-Fick.
Two, the preparation of Ginkgolides a and B composition grain:
1, preparation method: the amount of per diem taking 15mg Ginkgolides a and B is determined the consumption of Ginkgolides a and B compositions, mixs homogeneously with adjuvant, drips the moistening material of appropriate dehydrated alcohol, with appropriate 95% ethanol soft material processed, cross 20 mesh sieves and granulate, 50 ℃ of oven dry again, the granulate that sieves, is prepared into granule.
2, experimental program:
Scheme one: bilobalide compositions 20%, soluble starch 40%, DEXTRIN %.
Scheme two: bilobalide compositions 20%, dextrin 80%.
Scheme three: bilobalide compositions 20%, lactose 60%, dextrin 20%.
Scheme four: bilobalide compositions 20%, lactose 80%.
3, craft screening:
(1) selection of adjuvant:
The conventional adjuvant of granule is Icing Sugar, lactose, dextrin, soluble starch etc.Wherein Icing Sugar has obvious hygroscopicity, and old people is not suitable for taking in a large amount of sugars; Starch is met acid, alkali, or under humidity and heated condition, all can be hydrolyzed gradually and lose expansion, and its water solublity is poor; Therefore inventor selects dextrin, soluble starch and lactose as filler.
(2) selection of binding agent:
According to recipe quantity, fixedly bilobalide compositions and filler ratio, by investigating the impact of different binding agents on soft material and granular mass, thereby determine best binding agent.The results are shown in Table 14.
The investigation of table 14 binding agent kind
| Binding agent kind | Soft material quality |
| PVP solution | Granule is partially hard |
| PVP alcoholic solution | Uniform particles, hardness is moderate, and melting is good |
| Syrup | Binding agent is difficult for being uniformly dispersed, and granule is too hard |
Result demonstration, the soft material granulation of selecting PVP alcoholic solution to prepare is easier to, uniform particles, hardness is moderate, and melting is good.
4, quality examination result:
Above scheme, checks by < < Chinese Pharmacopoeia > > granule and content assaying method of the present invention, the results are shown in Table 15.
Table 15 sample quality check result
| Sample | Character | Granularity | Moisture (%) | Melting | Content (mg/ bag) |
| Scheme one | Faint yellow granule | Qualified | 3.24 | All dissolve | 5.1 |
| Scheme two | Faint yellow granule | Qualified | 4.01 | All dissolve | 4.9 |
| Scheme three | Faint yellow granule | Qualified | 3.77 | All dissolve | 4.8 |
| Scheme four | Faint yellow granule | Qualified | 3.33 | All dissolve | 4.7 |
Three, the preparation of Ginkgolides a and B composition injection:
1, preparation method:
Take recipe quantity Ginkgolides a and B compositions, be dissolved in ethanol, heated and stirred, to dissolving, adds propylene glycol solution to stir, and makes bilobalide compositions concentrated solution; The sodium chloride solution of another preparation 0.9%; Above-mentioned two kinds of solution are mixed, regulate pH value, fill sterilizing and get final product.
2, prescription:
The preferred 0.1mg/ml of Ginkgolides a and B compositions 0.05 ~ 0.2mg/ml()
Ethanol 0.01 ~ 0.05ml/ml
Propylene glycol 0.1 ~ 0.5ml/ml
Sodium chloride 0.9mg/ml
Water for injection is appropriate
3, craft screening:
(1) selection of solvent: according to the safety regulations of injection, available injection solvent is water for injection, ethanol, propylene glycol, Polyethylene Glycol, because vinegar in Semen Ginkgo is insoluble in water, therefore select mixed solvent.Adopt
water for injection: ethanol (1:0.05),
water for injection: propylene glycol (1:0.5),
water for injection: ethanol: propylene glycol (l:0.05:0.5),
water for injection: ethanol: propylene glycol (1:0.01:0.1),
water for injection: ethanol: five kinds of solvents of propylene glycol (1:0.01:0.5), investigate its clarity under 0 ~ 4 ℃ and room temperature.The results are shown in Table 16:
Table 16 Different solution stability result
From result, adopt above several solvents at room temperature all can guarantee the clarity of cruel injection in Semen Ginkgo, but under 0 ~ 4 ℃ of condition
can keep clear and bright, therefore select water for injection: ethanol: propylene glycol 1:0.01 ~ 0.05:0.1 ~ 0. 5) as solvent.
(2) impact of pH value
Because bilobalide is five-membered ring structure, unstable under alkali condition, so, inventor is by the Ginkgolides Sodium Chloride Injection of 9 parts of different pH value of preparation prescription (Ginkgolides a and B composition levels is 5mg/ml) preparation, with salt acid for adjusting pH, be 3.0,3.5,4.0,4.5,5.0,5.5,6.0,6.5,7.0 respectively, the injection of making is positioned over respectively in 60 ℃ of constant temperature ovens and is placed ten days, and the results are shown in Table 17 in 0,5,10 day sampling and measuring:
Table 17 different pH value stability result
Result demonstration, bilobalide is all more stable at acid condition, considers that the suitable pH value scope of injection is 4 ~ 9, go beyond the scope and may human body be produced and be stimulated, and sample slightly declines with upward stability at pH value 6, therefore pH value is comparatively suitable between selecting 4 ~ 5.5.
4, experimental program:
Scheme one:
Ginkgolides a and B compositions 0.1mg/ml
Ethanol 0.02ml/ml
Propylene glycol 0.1ml/ml
Sodium chloride 0.9mg/ml
Water for injection is appropriate
Scheme two:
Ginkgolides a and B compositions 0.1mg/ml
Ethanol 0.02ml/ml
Propylene glycol 0.2ml/ml
Sodium chloride 0.9mg/ml
Water for injection is appropriate
Scheme three:
Ginkgolides a and B compositions 0.1mg/ml
Ethanol 0.02ml/ml
Propylene glycol 0.3ml/ml
Sodium chloride 0.9mg/ml
Water for injection is appropriate
Scheme three:
Ginkgolides a and B compositions 0.1mg/ml
Ethanol 0.01ml/ml
Propylene glycol 0.3ml/ml
Sodium chloride 0.9mg/ml
Water for injection is appropriate
5, experimental result:
Above scheme, checks by < < Chinese Pharmacopoeia > > injection and content assaying method of the present invention, the results are shown in Table 16.
Table 16 sample quality check result
accompanying drawing explanation
Fig. 1 is the affect figure of HPMC consumption on GA Release Performance
Fig. 2 is the affect figure of HPMC consumption on GB Release Performance
Fig. 3 is the affect figure of HPMC viscosity on GA Release Performance
Fig. 4 is the affect figure of HPMC viscosity on GB Release Performance
Fig. 5 is the affect figure of tabletting pressure on GA Release Performance
Fig. 6 is the affect figure of tabletting pressure on GB Release Performance
Fig. 7 is the cumulative release degree figure of GA
Fig. 8 is the cumulative release degree figure of GB.
Claims (6)
1. a bilobalide compositions of being extracted purification by Folium Ginkgo extract, be used for the treatment of cardiovascular and cerebrovascular disease, it is characterized in that described compositions comprises ginkalide A and two kinds of active components of ginkalide B, the weight ratio of ginkalide A and ginkalide B is 1:0.2 ~ 2.
2. bilobalide compositions according to claim 1, is characterized in that content >=85%(injection of ginkalide A and ginkalide B in compositions is with preferably more than 95%).
3. the bilobalide compositions of take described in claim 1,2 is made pharmaceutical preparation as main effective ingredient and pharmaceutically acceptable adjuvant, and dosage form can be tablet, capsule, granule, injection, pill, powder, compound preparation or solid dispersion.
4. medicine according to claim 3, is characterized in that described dosage form is tablet, granule, injection.
5. medicine according to claim 4, is characterized in that the described preferred slow-release tablet agent of dosage form.
6. medicine according to claim 5, slow-release tablet agent described in it is characterized in that be take bilobalide compositions as main effective ingredient, the hypromellose (HPMC) of take is made as framework material, and the weight ratio of described bilobalide compositions and adjuvant is 1:4 ~ 15.
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| CN111184711A (en) * | 2020-01-09 | 2020-05-22 | 广东省第二人民医院（广东省卫生应急医院） | New application of ginkgolide A |
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Application publication date: 20140319 |