CN100569234C - Ginkgo total lactone composition with neuroprotective - Google Patents
Ginkgo total lactone composition with neuroprotective Download PDFInfo
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- CN100569234C CN100569234C CNB2005100461418A CN200510046141A CN100569234C CN 100569234 C CN100569234 C CN 100569234C CN B2005100461418 A CNB2005100461418 A CN B2005100461418A CN 200510046141 A CN200510046141 A CN 200510046141A CN 100569234 C CN100569234 C CN 100569234C
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Abstract
The present invention relates to the ginkgo total lactone composition that contains reactive compound ginkalide A, ginkalide B, ginkalide C and bilobalide that extraction separation obtains from Folium Ginkgo.The content sum of ginkalide A, B, C and bilobalide is greater than 80% in this compositions.Said composition is applicable to makes various folk prescription pharmaceutical preparatioies, can be made into slow release or controlled-release pharmaceutical formulation; Can be made into coelenteron administration, spray delivery, Transdermal absorption or oral pharmaceutical preparation; Can be made into ejection preparation or infusion preparation; Also can form compound medicinal formulation with other medicines (containing Chinese medicine extract or effective ingredient).Above pharmaceutical preparation has clear and definite neuroprotective, can be used for making the pharmaceutical preparation of various nerve degenerations of treatment or injury disease, for example is used for the treatment of apoplexy brain injury, senile dementia and multiple sclerosis etc.
Description
Technical field:
The present invention relates to medical technical field, exactly it is a kind of ginkgo total lactone composition with neuroprotective.
Background technology:
Semen Ginkgo is a Ginkgoaceae Ginkgo plant.The Ginkgo plant comes across the jurassic age before 100,017,000 years, and Semen Ginkgo is the seeds of present unique survival in the Ginkgo plant family, have the title of " living fossil ".Semen Ginkgo has history in 5000 as medicinal at least in China, and it is recorded in " legendary god of farming's BAICAO warp " the earliest.In Compendium of Material Medica, put down in writing Semen Ginkgo " its nature and flavor sweetness and bitterness and puckery; go into lung, kidney two warps; have that relieving asthma and cough, leukorrhagia stopping are turbid, the effect of urine reducing ", record Folium Ginkgo in " Bencao Pinhui Jingyao " " sweet-bitter flavor, puckery, property flat; return lung meridian; can astringe the lung relieving asthma, beneficial heart pain relieving, removing dampness stopping leak " (" China Dispensary " 1997,8 (2): 85-86).
Folium Ginkgo extract is the medical material of including under [item of Pharmacopoeia of the People's Republic of China version in 2000.Its active ingredient mainly contains flavonoid glycoside and Folium Ginkgo terpene lactones two classes.The Folium Ginkgo flavone glycoside mainly contains quercetin glycoside, kaempferol glycoside and bis-flavonoid.Ginkalide A, B, C and bilobalide be from Folium Ginkgo extract, carry altogether 4 main terpenoids.Gingko episperm also contains compositions (" Chinese wild plant resource " 1995 (1): 25 Sheng Soviet Unions such as ginkgoic acid, the inferior ginkgolic acid of hydrogenation, bilobol, Ginnol, asparagine, tannin, flavonoid, saccharide in addition, the chemical constituent of gingko episperm and with [J] " Chinese herbal medicine " 1995,26 (6): 29 Wang Jie, the separation of gingko episperm chemical constituent and evaluation [J]).
Along with deepening continuously of studying, modern study proves that the active component Ginkgo total lactones of Folium Ginkgo is different with the pharmacological action of this two compounds of ginkgetin glycoside in recent years:
Flavone compound is a ubiquitous class natural product in plant, and ginkgetin can obviously be regulated antiotasis, and expansion artery blood vessel, reduction blood vessel wall permeability increase the coronary blood liquid measure; Reduce myocardial oxygen consumption, strengthen the toleration of myocardial cell to hypoxic-ischemic, microcirculation improvement.Ginkgetin is a kind of free radical scavenger simultaneously, so defying age, antitumaous effect (" Chinese pharmacology communication " 2003,20 (2): 68) are arranged.
Ginkgo total lactone composition mainly comprises: ginkalide A, ginkalide B, ginkalide C and bilobalide, this is a class only exists, has special construction and remarkable pharmacologically active in Semen Ginkgo a unique natural product, so far do not find to be present in (" World Science technology-Chinese medicine modernization " 2003,5 (1): the research overview of 33-38 bilobalide) in other plant as yet.The more important thing is that they have unique pharmacological action and therapeutic value.The pharmacological action of Ginkgo total lactones is very extensive, and relevant report is existing a lot.When a large amount of Semen Ginkgo extrac (24% total flavonoid glycoside, 6% total lactone) preparations demonstrate clinically cardiovascular and cerebrovascular disease had excellent curative nervous system is also had certain curative effect, point out Ginkgo total lactones probably neuroprotective to be played main contribution with unique texture.Given this, be object of study with high-purity Semen Ginkgo total lactone composition (ginkalide A, B, C and content of bilobalide are 90%), from integral body to the molecular level, studied its neuroprotective.Experimental result proves; ginkgo total lactone composition can protect rat cortex neurocyte to avoid the infringement of glutamic acid excitatory toxicity; the neuroprotective cell is avoided the oxidative stress infringement of hydrogen peroxide-induced; pair cell lacks sugared anoxia infringement and has protective effect equally; ginkgo total lactone composition also can strengthen the expression of bcl-2 in rat fetus cortex neurocyte that has been weakened by oxygen-derived free radicals in addition, weakens the bax and the P that have been increased by oxygen-derived free radicals
53Expression, thereby bring into play the inductive apoptosis effect of its resistant activity oxygen-derived free radicals.
Summary of the invention:
The purpose of this invention is to provide a kind of ginkgo total lactone composition with neuroprotective.The indication ginkgo total lactone composition mainly contains ginkalide A, ginkalide B, ginkalide C and bilobalide.The content sum of ginkalide A, B, C and bilobalide is greater than 80%, less than 99% in the compositions.The bilobalide proportion is 20%-80% in the described compositions.Described compositions can be used for preparing the pharmaceutical preparation of various nerve degenerations of treatment or injury disease.Described composite preparation comprises special injection or infusion preparation, comprises slow release or controlled-release pharmaceutical formulation, comprises the coelenteron administration, spray delivery, Transdermal absorption or oral pharmaceutical preparation, comprise various folk prescriptions and compound medicinal formulation.
The preparation method of ginkgo total lactone composition of the present invention, its concrete characterization step is as follows:
(1) green drying Folium Ginkgo coarse powder gets extracting solution after the aqueous alcohol reflux, extract.
(2) concentrate or reclaim solvent and filtration, filtrate is removed water-solubility impurity through organic solvent extraction.
(3) extract is dissolved in the aqueous alcohol organic solvent extraction weeding of grease solubility impurity after concentrating.
(4) by polyamide column chromatography, water alcohol eluting concentrates the final vacuum drying.
(5) aqueous alcohol dissolving is filtered, and filtrate decompression concentrates, spraying or vacuum drying, pulverize above-mentioned ginkgo total lactone composition.
Advantage of the present invention is: the result proves by experiment; ginkgo total lactone composition can protect rat cortex neurocyte to avoid the infringement of glutamic acid excitatory toxicity; the neuroprotective cell is avoided the oxidative stress infringement of hydrogen peroxide-induced; pair cell lacks sugared anoxia infringement and has protective effect equally; ginkgo total lactone composition also can strengthen the expression of bcl-2 in rat fetus cortex neurocyte that has been weakened by oxygen-derived free radicals in addition, weakens the bax and the P that have been increased by oxygen-derived free radicals
53Expression, thereby bring into play the inductive apoptosis effect of its resistant activity oxygen-derived free radicals.Said composition is applicable to makes various folk prescription pharmaceutical preparatioies, can be made into slow release or controlled-release pharmaceutical formulation; Can be made into coelenteron administration, spray delivery, Transdermal absorption or oral pharmaceutical preparation; Can be made into ejection preparation or infusion preparation; Also can form compound medicinal formulation with other medicines (containing Chinese medicine extract or effective ingredient).Above pharmaceutical preparation has clear and definite neuroprotective, can be used for making the pharmaceutical preparation of various nerve degenerations of treatment or injury disease, for example is used for the treatment of apoplexy brain injury, senile dementia and multiple sclerosis etc.
Description of drawings:
Fig. 1 passes through HPLC testing result figure for compositions.
Fig. 2 is the RT-PCR testing result figure of ginkgo total lactone composition to the bcl-2 expression of cortex neurocyte.
Fig. 3 is the testing result figure of ginkgo total lactone composition to the RT-PCR of cortex neurocyte bax mRNA expression.
Fig. 4 is the testing result figure of ginkgo total lactone composition to the RT-PCR of cortex neurocyte p53mRNA expression.
1. (8.058min) bilobalide among Fig. 1,2. (9.308min) bilobalide, 3. (17.692min) ginkalide A, 4. (20.092min) ginkalide B.
1 matched group that does not add any medicine among Fig. 2; 2. through H
2O
20.05mM and 0.1mM FeSO
43. of matched groups after the damaging processing add ginkgo total lactone composition 10
-2GL
-1Matched group 4 through 8 hours H
2O
20.05mM and 0.1mM FeSO
4Cell after the damaging processing adds ginkgo total lactone composition 10
-3 GL
-15 through 8 hours H
2O
20.05mM and 0.1mM FeSO
4Cell after the damaging processing adds ginkgo total lactone composition 10
-2GL
-1.6. through 8 hours H
2O
20.05mM and 0.1mM FeSO
4Cell after the damaging processing adds Folium Ginkgo extract EGb76110
-2GL
-1
1. matched groups that do not add any medicine among Fig. 3; 2. through H
2O
20.05mM and 0.1mM FeSO
4Matched group after the damaging processing; 3.. only add ginkgo total lactone composition 10
-2GL
-1Matched group 4. through 8 hours H
2O
20.05mM and 0.1mM FeSO
4Cell after the damaging processing adds ginkgo total lactone composition 10
-3 GL
-15 through 8 hours H
2O
20.05mM and 0.1mM FeSO
4Cell after the damaging processing adds ginkgo total lactone composition 10
-2GL
-1.6. through 8 hours H
2O
20.05mM and 0.1mM FeSO
4Cell after the damaging processing adds Folium Ginkgo extract EGb76110
-2GL
-16. through 8 hours H
2O
20.05mM and 0.1mM FeSO
4Cell after the damaging processing adds Folium Ginkgo extract EGb76110
-2GL
-
1 through 8 hours H among Fig. 4
2O
20.05mM and 0.1mM FeSO
4Cell after the damaging processing adds Folium Ginkgo extract EGb76110
-2GL
-1.2.. through 8 hours H
2O
20.05mM and 0.1mM FeSO
4Cell after the damaging processing adds ginkgo total lactone composition 10
-2 GL
-13. through 8 hours H
2O
20.05mM and 0.1mM FeSO
4Cell after the damaging processing adds ginkgo total lactone composition 10
-3GL
-14Only add ginkgo total lactone composition 10
-2GL
-1Matched group 5. through 8 hours H
2O
20.05mM and 0.1mM FeSO
4Matched group 6. after the damaging processing does not add the matched group of any medicine.
The specific embodiment:
The quantitative analysis of 1 compositions
1.1 described compositions detects (post: ODS by HPLC; Differential refraction detector; Mobile phase: methanol: water (35: 65) provides four peaks (seeing accompanying drawing 1), peak 1 (8.058min) is bilobalide (bilobalide), peak 2 (9.308min) is ginkalide C (ginkgolide C), (17.692min) draws liquid phase working standard curve (with concentration is abscissa, is vertical coordinate with the peak area) (seeing Table 1) for ginkalide A (ginkgolide A) peak 4 (20.092min) respectively for ginkalide B (ginkgolide B) 1.2 reference substances at peak 3
Table 1 ginkgo total lactone composition standard curve
Bilobalide and ginkgolectone AB C are the main terpenoid effective ingredient in the Folium Ginkgo extract, can be by specific technical process, and markization only contains the compositions of bilobalide and ginkgolectone AB C, and Ginkgo total lactones content is not less than 80% in the said composition.
The structure of 2 composition components is identified
Bilobalide
Sample: bilobalide
English name: Bilobalide
Molecular weight: 326
Molecular formula: C
15H
18O
8
Structural confirmation:
IR：3467.3，2962.6，1790.7，1364.3，865.4，792.0
MS：325.3(M-1)
1H-NMR：7.25(1H，d)，6.26(1H，s)，5.40(1H，s)，5.14(1H，d)，4.90(1H，t)，2.89(1H，d)，2.74(1H，d)，2.54(1H，m)，2.06(1H，m)，1.02(9H，s)
13C-NMR：176.9，173.2，172.7，98.9，85.2，82.4，67.8，64.9，57.3，41.1，36.7，35.3，26.1
Ginkalide A
Sample: Semen Ginkgo ester A
English name: Ginkgolide A
Molecular weight: 408
Molecular formula: C
20H
24O
9
Structural confirmation:
IR：3251.9，2962.6，1758.9，1137.9，963.0，798.2
MS：408(M)
1H-NMR: see Table 2
Table 2. bilobalide hydrogen spectrum data
13C-NMR: see Table 3
Table 3. bilobalide carbon spectrum data
Ginkalide B
Sample: ginkalide B
English name: Ginkgolide B
Molecular weight: 424
Molecular formula: C
20H
24O
10
Structural confirmation:
IR：3451.9，2970.3，1780.4，1622.1，946.1，884.1
MS：424(M)
1H-NMR: see Table 2
13C-NMR: see Table 3
Ginkalide C
Sample: ginkalide C
English name: Ginkgolide C
Molecular weight: 440
Molecular formula: C
20H
24O
11
Structural confirmation:
IR：3430.3，2989.3，1785.4，1635.3，935.8，890.9
MS：440(M)
1H-NMR: see Table 2
13C-NMR: see Table 3
Conclusion: based on above analysis, and contrast document, with the literature value basically identical, can judge that four kinds of main components in this compositions are respectively bilobalide (Bilobalide), ginkalide A (Ginkgolie A), ginkalide B (Ginkgolide B), ginkalide C (Ginkgolide C).
3. the neuroprotective of this compositions
3.1 ginkgo total lactone composition is to the influence of the different damage models of rat cortex neurocyte of In vitro culture
3.2 ginkgo total lactone composition is to the influence of the rat cortex neurocyte of cultivation
(1) animal model: the rat cortex neurocyte of In vitro culture
(2) detect index: A
570, the active mensuration of lactic acid dehydrogenase (LDH).
(3) test section the results are shown in Table 4, shown in the table 5:
Table 4 in the normal cortex neurocyte of rat ginkgo total lactone composition to A
570Influence
. annotate: X ± s, n=6, (6h) compares with matched group
△P＜0.05; With matched group (24h). compare * p＜0.05or**p＜0.01
Table 5 ginkgo total lactone composition is to because the protective effect of the injured nerve cell that low serum causes
. annotate: X ± s, n=6, (6h) compares with matched group
△ △P＜0.01; With matched group (12h). compare
★P＜0.05, * * p＜0.01; With matched group (24h). compare
★ ★P＜0.01.
When cell changes low serum culture fluid into, A
570Prolongation in time and descending to some extent gradually, show that viable count reduces to some extent, because have only the Intramitochondrial succinate dehydrogenase of living cells just can make xanchromatic MTT reduce empurpled Jia Keli, but after adding ginkgo total lactone composition, the decline of this cell viability obviously makes moderate progress, when 24h, the increase effect of ginkgo total lactone composition pair cell vigor, within the specific limits, with the increase effect reinforcement of its concentration, ginkgo total lactone composition 10
-1With 10
-2GL
-1The improvement effect particularly evident, this result is consistent with the measurement result of MTT, the results are shown in Table 4.
By table 5 as seen, cell is along with the prolongation with low serum culture fluid incubation time, the LDH that is released in the culture fluid increases, 12h and 24h matched group and 6h matched group relatively, the LDH activity has significant increase trend, at one time in, along with the increase that adds ginkgo total lactone composition concentration, can reduce the release of LDH significantly, the damage of expression ginkgo total lactone composition pair cell has dosage to rely on ground improvement effect, especially with ginkgo total lactone composition 10
-1With 10
-2GL
-1Effect more obvious.
4.1 ginkgo total lactone composition is to the protective effect of cortex neural cell injury due to the glutamic acid
(1) animal model: the rat cortex neurocyte with the glutamic acid processing of In vitro culture.
(2) detect index: cell viability, the active mensuration of lactic acid dehydrogenase (LDH).
(4) test section the results are shown in Table shown in 6:
Table 6 ginkgo total lactone composition is to the protective effect of cortex neural cell injury due to the glutamic acid
To annotate: X ± s (n=6). two groups of handling of matched group ##p＜0.01* glutamic acid are respectively p＜0.05, and * * p＜0.01 shows between matched group and the glutamic acid group and there are differences
By table 6 as seen, cell is handled 12h with 1mM glutamic acid, uses ginkgo total lactone composition simultaneously and can obviously improve this infringement due to the glutamic acid.In addition, before handling cell with glutamic acid, use ginkgo total lactone composition and cell incubation 12h in advance, also visible medicine has significant protective effect, and is the concentration dependence.
4.2 ginkgo total lactone composition is to the protective effect of cortex neural cell injury due to the hydrogen peroxide
(1) animal model: the rat cortex neurocyte of the usefulness hydrogen peroxide treatment of In vitro culture.
(2) detect index: cell viability, the active mensuration of lactic acid dehydrogenase (LDH).
(3) test section the results are shown in Table shown in 7:
Table 7 ginkgo total lactone composition is to the protective effect of cortex neural cell injury due to the hydrogen peroxide
Annotate X ± s (n=6) matched group #p＜0.05##p＜0.01*H
2O
2Two groups that handle are respectively p＜0.05, * * p＜0.01
By table 7 as seen, the hydrogen peroxide of 0.2mM can obviously reduce cell viability, and can increase the release of the LDH in the culture medium, shows the obvious damaging action of pair cell.With ginkgo total lactone composition in advance with cell incubation 12h, medicine can obviously improve the damaging action of hydrogen peroxide pair cell, its valid density is 10
-1With 10
-2GL
-1, and, then do not see obvious influence with ginkgo total lactone composition and hydrogen peroxide while and cell incubation, the pre-clothes of prompting ginkgo total lactone composition can be protected the oxidative stress damage of hydrogen peroxide to neurocyte effectively.
4.3 the ginkgo total lactone composition pair cell lacks the protective effect of sugared anoxia infringement
(1) animal model: the rat cortex neurocyte of the scarce sugar of In vitro culture and anoxic treatment.
(2) detect index: cell viability, the active mensuration of lactic acid dehydrogenase (LDH).
(3) test section the results are shown in Table shown in 8:
Table 8 ginkgo total lactone composition pair cell lacks the protective effect of sugared anoxia infringement
. annotate: X ± s (n=6) matched group #p＜0.05, ##p＜0.011 shows matched group and H
2O
2There are differences between the group
When lacking necessary nutrient substance in the culture fluid of neurocyte,, can think a kind of external model that is similar to the cell " ischemia " of integral experiment as lacking sugar and anoxia.This experimental result shows that behind cell " ischemia " 4h, cell viability significantly reduces, and can be reduced to 79.5 ± 0.6 by 100.0 ± 0.5 of matched group.When before " ischemia " handled, anticipating cell 12h, find that the pair cell vigor does not have obvious influence with ginkgo total lactone composition.The measurement result of LDH shows that also when " ischemia ", the LDH in the cell culture fluid leaks to wherein through cell membrane and raises, but the LDH in the pretreated cell culture fluid of ginkgo total lactone composition does not have obvious minimizing, the results are shown in Table 8.
In a word; experimental result proves; ginkgo total lactone composition can protect rat cortex neurocyte to avoid the infringement of glutamic acid excitatory toxicity, and the neuroprotective cell is avoided the oxidative stress infringement of hydrogen peroxide-induced, and pair cell lacks sugared anoxia infringement and has protective effect equally.
5. ginkgo total lactone composition is to cultivating rat cortex cell bcl-2, the influence that bax and p53mRNA express
5.1 the influence that ginkgo total lactone composition is expressed rat cortex cell bcl-2mRNA
(1) animal model: In vitro culture through H
2O
2And FeSO
4The rat cortex cell of damaging processing.
(2) detect index: (the mensuration of the gray level ratio of band of β-actin) of gene band to be checked and internal standard gene on the 1% gelose gel electrophoresis.
(3) test section the results are shown in shown in the accompanying drawing 2:
PCR result shows that matched group bcl-2mRNA content is higher, and the cell of model group is through H
2O
20.05mM and 0.1mM FeSO
4After the damaging processing, the apparent in view minimizing of the expression of its bcl-2mRNA and matched group, and the ginkgo total lactone composition of visible variable concentrations all can increase the expression of this gene in cortex cell after ginkgo total lactone composition is handled, and be dose-dependence (seeing accompanying drawing 2), EGb761 also has similar effect.In addition, be also shown in ginkgo total lactone composition itself Normocellular bcl-2 is expressed basically not influence.
5.2 the influence that the ginkgo total lactone composition of variable concentrations is expressed bax mRNA in the cortex cell
(1) animal model: In vitro culture through H
2O
2And FeSO
4The rat cortex cell of damaging processing.
(2) detect index: (the mensuration of the gray level ratio of band of β-actin) of gene band to be checked and internal standard gene on the 1% gelose gel electrophoresis.
(3) test section the results are shown in shown in the accompanying drawing 3
The PCR experimental result shows that the model group cell is through H
2O
20.05mM and 0.1mM FeSO
4After the damaging processing, the expression of its bax mRNA is apparently higher than matched group, and at H
2O
20.05mM and 0.1mM FeSO
4In the cell that ginkgo total lactone composition is handled, this expression of gene no longer shows this unusual rising before the damaging processing, the increase of dosage and weaken (seeing accompanying drawing 3) gradually.The bax band that heavy dose of ginkgo total lactone composition is handled cell very a little less than, only slightly as seen.The effect that the bax that EGb761 also has reduction to be caused by oxygen-derived free radicals raises.Ginkgo total lactone composition itself is not expressed Normocellular bax and is changed.
5.3 the influence that p53mRNA expresses in the ginkgo total lactone composition pair cell of variable concentrations
(1) animal model: In vitro culture through H
2O
2And FeSO
4The rat cortex cell of damaging processing.
(2) detect index: (the mensuration of the gray level ratio of band of β-actin) of gene band to be checked and internal standard gene on the 1% gelose gel electrophoresis.
(3) test section the results are shown in shown in the accompanying drawing 4
The PCR experimental result shows that the model group cell is through H
2O
20.05mM and 0.1mM FeSO
4After damage was handled, the expression of its p53mRNA was apparently higher than matched group, and at H
2O
20.05mM and 0.1mM FeSO
4In the cell that ginkgo total lactone composition is handled, this expression of gene no longer shows this unusual rising before the damaging processing, recovers (seeing accompanying drawing 4) gradually with the increase of dosage, and heavy dose of ginkgo total lactone composition is to H
2O
20.05mM and 0.1mM FeSO
4The p53 of damaging processing cell expresses obviously and reduces, and compare P＜0.05 with the model group cell, and EGb761 does not show significantly this effect.Ginkgo total lactone composition is expressed Normocellular P53 and is not made significant difference.
In a word, bcl-2, bax and P
53All participate in the apoptosis regulation process of cell.The result shows, ginkgo total lactone composition can strengthen the expression of bcl-2 in rat fetus cortex neurocyte that has been weakened by oxygen-derived free radicals, weakens the bax and the P that have been increased by oxygen-derived free radicals
53Expression, thereby bring into play the inductive apoptosis effect of its resistant activity oxygen-derived free radicals.
Embodiment:
1. green drying Folium Ginkgo coarse powder 10Kg gets extracting solution after the aqueous alcohol reflux, extract.Concentrate or reclaim solvent and filtration, filtrate is removed water-solubility impurity through organic solvent extraction.Extract is dissolved in the aqueous alcohol organic solvent extraction weeding of grease solubility impurity after concentrating.Discard organic layer, pure water layer is concentrated vacuum drying.Aqueous alcohol dissolving is filtered, and filtrate decompression concentrates, spraying or vacuum drying, pulverize the described ginkgo total lactone composition 50g of claim 1.
2. get Ginkgo total lactones raw material 11g, add 50% propylene glycol solution 500ml and 45g sodium chloride, after-teeming is penetrated water to 5000ml, by the general operation process of injection.Every 5ml contains this compositions 10mg.In conjunction with symptom, prop up every day 1 time or follow the doctor's advice with 2-4 at every turn.
3. this compositions 2g ploughs pure 20g with dextran-40 or mountain and phosphoric acid buffer mixes in right amount, is used for the water for injection dissolving, by the general operation process of injection, and fill, lyophilizing is made every of freeze dried injection and is contained this compositions 0.02g.In conjunction with symptom, prop up with 1-3 at every turn, mix use, every day 1 time with transfusions such as injecting sodium chloride.
4. compositions 10g mixes with microcrystalline Cellulose 45g and magnesium stearate 5g, and mixture is used for beating sheet, every heavy 0.2g, and every contains this compositions 0.02g.In conjunction with symptom, obey the 1-2 sheet, every day 2-3 time at every turn.
5. this compositions 10g with corn starch 50g, adds water and makes soft material, crosses 12 mesh sieve pelletizes, and drying makes granule, incapsulates, and the heavy 0.2g of every capsules content contains this compositions 0.02g.In conjunction with symptom, obey the 1-2 sheet, every day 2-3 time or follow the doctor's advice at every turn.
Claims (4)
1, the ginkgo total lactone composition that has neuroprotective, it is characterized in that: the indication ginkgo total lactone composition mainly contains ginkalide A, ginkalide B, ginkalide C and bilobalide, the content sum of ginkalide A, B, C and bilobalide is greater than 80%, less than 99% in the compositions; The bilobalide proportion is 20%-80%.。
2. as claim 1 or 2 or 3 described ginkgo total lactone compositions with neuroprotective, it is characterized in that: described compositions can be used for preparing the pharmaceutical preparation of various nerve degenerations of treatment or injury disease.
3, the ginkgo total lactone composition with neuroprotective according to claim 4 is characterized in that: described composite preparation comprises special injection or infusion preparation, comprises slow release or controlled-release pharmaceutical formulation, comprises the coelenteron administration, spray delivery, Transdermal absorption or oral pharmaceutical preparation, comprise various folk prescriptions and compound medicinal formulation.
4, a kind of preparation method that has the ginkgo total lactone composition of neuroprotective according to claim 1 is characterized in that:
(1) green drying Folium Ginkgo coarse powder gets extracting solution after the aqueous alcohol reflux, extract;
(2) concentrate or reclaim solvent and filtration, filtrate is removed water-solubility impurity through organic solvent extraction;
(3) extract is dissolved in the aqueous alcohol organic solvent extraction weeding of grease solubility impurity after concentrating;
(4) by polyamide column chromatography, water alcohol eluting concentrates the final vacuum drying;
(5) aqueous alcohol dissolving is filtered, and filtrate decompression concentrates, spraying or vacuum drying, pulverize ginkgo total lactone composition.
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| CN103142532B (en) * | 2011-12-06 | 2015-03-04 | 复旦大学 | Ginkgolide osmotic pump tablet and preparation method thereof |
| CN102659808B (en) * | 2012-04-23 | 2014-10-29 | 成都百裕科技制药有限公司 | Extraction separation method of ginkgolides |
| CN104042607B (en) * | 2014-05-27 | 2016-06-29 | 黑龙江珍宝岛药业股份有限公司 | For pharmaceutical composition treating dementia and preparation method thereof |
| CN107929283B (en) | 2017-12-29 | 2019-05-07 | 江苏康缘药业股份有限公司 | Ginkgo diterpenoid-lactone composition |
| CN111803487B (en) * | 2019-04-10 | 2022-12-02 | 成都百裕制药股份有限公司 | Application of ginkgolide in preparation of medicine for preventing and/or treating Guillain-Barre syndrome |
| US20220193030A1 (en) * | 2019-04-10 | 2022-06-23 | Chengdu Baiyu Pharmaceutical Co., Ltd. | Use of ginkgo terpene lactone in preparing drug for preventing and/or treating guillain-barre-strohl syndrome |
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2005
- 2005-03-30 CN CNB2005100461418A patent/CN100569234C/en not_active Expired - Fee Related
Non-Patent Citations (4)
| Title |
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| 第一军医大学学报. 邓虹珠，易延逵.银杏内酯的研究进展，第21卷第12期，增刊期. 2004 |
| 第一军医大学学报. 邓虹珠，易延逵.银杏内酯的研究进展，第21卷第12期，增刊期. 2004 * |
| 银杏总内酯提取物制备工艺的研究. 仝燕，马振山，李先端等.中国实验方剂学杂志，第10卷第6期. 2004 |
| 银杏总内酯提取物制备工艺的研究. 仝燕，马振山，李先端等.中国实验方剂学杂志，第10卷第6期. 2004 * |
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