CN101036642A - Ginkgolide B nanometric liposomes medicine and the preparing method thereof - Google Patents
Ginkgolide B nanometric liposomes medicine and the preparing method thereof Download PDFInfo
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- CN101036642A CN101036642A CN 200710098391 CN200710098391A CN101036642A CN 101036642 A CN101036642 A CN 101036642A CN 200710098391 CN200710098391 CN 200710098391 CN 200710098391 A CN200710098391 A CN 200710098391A CN 101036642 A CN101036642 A CN 101036642A
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Abstract
The invention relates to a ginkgolide B nanoliposomes drug and a method for preparing the same. The invention provides the ginkgolide B nanoliposomes drug including the following materials and the following radios: 8-12 mol compositions of cephalin and distearoyl choline with mole ratio of 1:3-6; 6-8 mol compositions of sojasterol and cholesterin with mole ratio of 1:2-4; 4-6 mol compositions of gamma-cyclodextrin/2-hychoxypropyl-beta-cyclodextrin and alpha-cyclodextrin with mole ratio of 3:1; 0.2-0.4 mol methoxy polyethylene glycol 2000-hydrogenated soybean phosphatidylethanolamine; 2 mol ginkgolide B; and 0.1-0.5 mol vitamine E. A method for preparing the ginkgolide B nanoliposomes drug is also provided in the invention to produce the ginkgolide B nanoliposomes for target treating blocking of vessel or endothelial cell thereof, with a better healing effect than ordinary preparations of ginkgolide B.
Description
Technical field
The present invention relates to a kind of ginkgolide B nanometric liposomes medicine and preparation method thereof.
Background technology
Existing ginkalide B medicine has been realized complicated Folium Ginkgo extract to the monomer medicine leap, becomes to have international most advanced level treatment cardiovascular and cerebrovascular diseases medicament.But after becoming monomer medicine, the lactone structure of not considering ginkalide B pH value in vivo is that the lactone structure hydrolysis causes the problem that lost efficacy under 7.4 the blood environment.Secondly, do not solve the little and peroxidating problem in vivo of ginkalide B dissolubility in water yet.
Summary of the invention
Dissolubility is little in order to solve in existing ginkalide B medicine lactone structure hydrolysis in vivo, the water, peroxidating problem in vivo, problem such as targeting focus in vivo, the invention provides a kind of ginkgolide B nanometric liposomes medicine.
Technical scheme of the present invention is as follows:
The invention provides a kind of ginkgolide B nanometric liposomes medicine, comprise following proportion raw material:
The mixture 8-12 mole of cephalin and distearyl choline mole ratio 1: 3-6;
The mixture 6-8 mole of soyasterol and cholesterol mole ratio 1: 2-4;
Gamma-cyclodextrin/2-HP-
With 3: 1 mixture 4-6 of alpha-cyclodextrin mol ratio mole;
Methoxy poly (ethylene glycol) 2000-hydrogenated soya phosphatide acyl ethanolamine 0.2-0.4 mole;
Semen Ginkgo lactone B 1-2 mole;
Vitamin E 0.1-0.5 mole.
The present invention also provides the preparation method of above-mentioned ginkgolide B nanometric liposomes medicine, comprises the steps:
(1) described amount ginkalide B is dissolved in dehydrated alcohol/mixed liquor of 2: 1 of ethyl acetate volume ratio;
(2) with described amount gamma-cyclodextrin/2-HP-and 3: 1 mixtures of alpha-cyclodextrin mol ratio, be dissolved in the phosphate buffer of 0.015M/L, pH value 6.0-7.0, make the solution of gamma-cyclodextrin/2-HP-concentration 60-70%;
(3) solution with step (1) preparation adds in the solution of step (2) preparation, and dissolving fully;
(4) under the inflated with nitrogen condition, with described amount vitamin E, cephalin and distearyl choline mole ratio 1: the mixture of the mixture of 3-6, soyasterol and cholesterol mole ratio 1: 2-4 is dissolved in the ether successively, at room temperature reduction vaporization is made liposome membrane to the ether noresidue;
(5) with liposome membrane aquation in phosphate buffer of step (4) preparation, making the distearyl choline concentration is 15mg/ml-25mg/ml, stirring and evenly mixing under nitrogen protection;
(6) mixed liquor with step (3) preparation is added drop-wise in the mixed liquor of step (5) preparation, adds methoxy poly (ethylene glycol) 2000-hydrogenated soya phosphatide acyl ethanolamine, and the dissolving back adds the 17500g-26400g usual excipients;
(7) with the mixed liquor of step (6) preparation, under the above condition of high voltage of 6MPa, successively by 0.2,0.1,0.08 μ m nucleopore membranes, repeated multiple times adds isotonic agent sterile liquid commonly used, makes nano liposome medicament in homogenizer.
As optimization, above-mentioned nano liposome medicament can be made into high-capacity injection, injection with small volume, lyophilized injection, oral formulations or the spray that can receive on the pharmaceutics.
Excipient in the above-mentioned steps (6) is selected from vitamin C, xylitol, mannitol or dextran-40.
The technique effect that the present invention realized is as follows:
The present invention comprises three the lactonic ring structures of ginkalide B and the tert-butyl alcohol side chain of ginkalide B respectively with cyclodextrin, increases ginkalide B dissolubility in water, and keeps the not open loop in human body of lactonic ring structure, keeps physiologically active constant.
The present invention comprises ginkalide B with cyclodextrin and makes liposome " solid core ", makes this " solid core " enter the liposome center, has liposomal encapsulatedly again, makes ginkalide B obtain cyclodextrin and phospholipid multiple protective, keeps its physiologically active highly stable.
The present invention makes ginkgolide B nanometric liposomes, and targeting is in artery-clogging and endotheliocyte thereof, and curative effect is higher than the ginkalide B ordinary preparation.
The untoward reaction that medicine of the present invention has vitamin E antioxidant can avoid oxidation in vitro and in vivo of phospholipid and ginkalide B and peroxidating to cause.
This reaction adopts the modern high technology art to produce advanced modernized Chinese medicine preparation.Effective ingredient is definite, avoids the finger printing trouble, the drug quality stable and controllable, and determined curative effect, safe in utilization.
The present invention adopts high-purity Semen Ginkgo lactone B to make crude drug, and ginkalide B is the strongest effective monomer of activity in bilobalide bunch, because of being to treat the cardiovascular and cerebrovascular disease ideal medicament at present from medicine of the present invention.
The specific embodiment
Embodiment 1:
Present embodiment adopts the ginkgolide B nanometric liposomes medicine prescription, comprises following proportion raw material:
8 moles in cephalin and 1: 3 mixture of distearyl choline mole ratio;
8 moles in soyasterol and 1: 4 mixture of cholesterol mole ratio;
4 moles of 3: 1 mixtures of gamma-cyclodextrin and alpha-cyclodextrin mol ratio;
0.4 mole of methoxy poly (ethylene glycol) 2000-hydrogenated soya phosphatide acyl ethanolamine;
1 mole of Semen Ginkgo lactone B;
0.5 mole of vitamin E.
The preparation method of above-mentioned ginkgolide B nanometric liposomes medicine comprises the steps:
(1) described amount ginkalide B is dissolved in dehydrated alcohol/mixed liquor of 2: 1 of ethyl acetate volume ratio;
(2) with described amount gamma-cyclodextrin and 3: 1 mixtures of alpha-cyclodextrin mol ratio, be dissolved in the phosphate buffer of 0.015M/L, pH value 6.0-7.0, make gamma-cyclodextrin/2-hydroxy propyl-Beta-ring
The solution of dextrin concentration 60-70%;
(3) solution with step (1) preparation adds in the solution of step (2) preparation, and dissolving fully;
(4) under the inflated with nitrogen condition, be dissolved in described amount vitamin E, cephalin and 1: 3 mixture of distearyl choline mole ratio, soyasterol and 1: 2 mixture of cholesterol mole ratio in the ether successively, at room temperature reduction vaporization is made liposome membrane to the ether noresidue;
(5) with liposome membrane aquation in phosphate buffer of step (4) preparation, making the distearyl choline concentration is 15mg/ml-25mg/ml, stirring and evenly mixing under nitrogen protection;
(6) mixed liquor with step (3) preparation is added drop-wise in the mixed liquor of step (5) preparation, adds methoxy poly (ethylene glycol) 2000-hydrogenated soya phosphatide acyl ethanolamine, and the dissolving back adds the 17500g-26400g usual excipients;
(7) mixed liquor with step (6) preparation passes through 0.2,0.1,0.08 μ m nucleopore membranes successively, repeated multiple times, add isotonic agent sterile liquid commonly used, make nano liposome medicament, further make high-capacity injection, injection with small volume, lyophilized injection, oral formulations or the spray that can receive on the pharmaceutics.
Excipient in the above-mentioned steps (6) is selected from vitamin C, xylitol, mannitol or dextran-40.
The pharmacodynamics demonstration test:
1, blood pressure lowering drug effect demonstration test
(1) model and method: select spontaneous hypertensive rat, apoplexy susceptible type hypertensive rat model for use.Elder generation surveys the blood pressure of control period more than one week, administration behind blood pressure stabilization, and the administration phase was 3 weeks, 10 of every treated animal rats.Be effective more than the blood pressure drops 20mmHg after the administration.Intravenous administration.
(2) medicine and dosage:
1 group of medicine ginkgolide B nanometric liposomes medicine 5mg/kg of the present invention is organized in treatment;
2 groups of medicine ginkgolide B nanometric liposomes medicine 2.5mg/kg of the present invention are organized in treatment;
1 group of bilobalide B injection 5mg/kg of matched group;
2 groups of ginkalide B injection of matched group 2.5mg/kg;
3 groups of ginkalide B injection of matched group 10mg/kg.
(3) result of the test:
Blood pressure lowering effective percentage % anaphylaxis rate %
Treatment is organized 1 group 96% 0%
Treatment is organized 2 groups 90% 0%
Matched group 1 group 72% 10%
Matched group 2 groups 65% 7%
Matched group 3 groups 86% 15%
As seen drug dose of the present invention is that four of control drug maximum dose level/for the moment, the both has good curative effect, but the control drug curative effect is still obviously on the low side than the present invention medicine; When both dosage were identical, it is many that curative effect of medication of the present invention just exceeds control drug.Anaphylaxis medicine of the present invention has absolute advantages.Rat is erected hair, shakes behind the liquid medicine injection, is considered as anaphylaxis.
Embodiment 2
Present embodiment adopts the ginkgolide B nanometric liposomes medicine prescription, comprises following proportion raw material:
12 moles in cephalin and 1: 6 mixture of distearyl choline mole ratio;
6 moles in soyasterol and 1: 4 mixture of cholesterol mole ratio;
6 moles of 3: 1 mixtures of 2-HP-and alpha-cyclodextrin mol ratio;
0.2 mole of methoxy poly (ethylene glycol) 2000-hydrogenated soya phosphatide acyl ethanolamine;
2 moles of Semen Ginkgo lactone B;
0.1 mole of vitamin E.
The preparation method of above-mentioned ginkgolide B nanometric liposomes medicine comprises the steps:
(1) described amount ginkalide B is dissolved in dehydrated alcohol/mixed liquor of 2: 1 of ethyl acetate volume ratio;
(2) with described amount 2-HP-and 3: 1 mixtures of alpha-cyclodextrin mol ratio, be dissolved in the phosphate buffer of 0.015M/L, pH value 6.0-7.0, make the solution of gamma-cyclodextrin/2-HP-concentration 60-70%;
(3) solution with step (1) preparation adds in the solution of step (2) preparation, and dissolving fully;
(4) under the inflated with nitrogen condition, be dissolved in described amount vitamin E, cephalin and 1: 6 mixture of distearyl choline mole ratio, soyasterol and 1: 4 mixture of cholesterol mole ratio in the ether successively, at room temperature reduction vaporization is made liposome membrane to the ether noresidue;
(5) with liposome membrane aquation in phosphate buffer of step (4) preparation, making the distearyl choline concentration is 15mg/ml-25mg/ml, stirring and evenly mixing under nitrogen protection;
(6) mixed liquor with step (3) preparation is added drop-wise in the mixed liquor of step (5) preparation, adds methoxy poly (ethylene glycol) 2000-hydrogenated soya phosphatide acyl ethanolamine, and the dissolving back adds the 17500g-26400g usual excipients;
(7) mixed liquor with step (6) preparation passes through 0.2,0.1,0.08 μ m nucleopore membranes successively, repeated multiple times, add isotonic agent sterile liquid commonly used, make nano liposome medicament, further make high-capacity injection, injection with small volume, lyophilized injection, oral formulations or the spray that can receive on the pharmaceutics.
Excipient in the above-mentioned steps (6) is selected from vitamin C, xylitol, mannitol or dextran-40.
The pharmacodynamics demonstration test:
1, blood pressure lowering drug effect demonstration test
(1) model and method: with embodiment 1
(2) medicine and dosage:
1 group of medicine ginkgolide B nanometric liposomes medicine 6mg/kg of the present invention is organized in treatment;
2 groups of medicine ginkgolide B nanometric liposomes medicine 3mg/kg of the present invention are organized in treatment;
1 group of bilobalide B injection 6mg/kg of matched group;
2 groups of bilobalide B injection 3mg/kg of matched group;
3 groups of bilobalide B injection 10mg/kg of matched group.
(3) result of the test is as follows:
Blood pressure lowering effective percentage % anaphylaxis rate %
Treatment group (1) group 96% 0%
Treatment group (2) group 92% 0%
Matched group (1) group 73% 10%
Matched group (2) group 66% 7%
Matched group (3) group 88% 13%
As seen drug dose of the present invention is that four of control drug maximum dose level/for the moment, the both has good curative effect, but the control drug curative effect is still obviously on the low side than the present invention medicine; When both dosage were identical, it is many that curative effect of medication of the present invention just exceeds control drug.Anaphylaxis medicine of the present invention has absolute advantages.Rat is erected hair, shakes behind the liquid medicine injection, is considered as anaphylaxis.
Embodiment 3
Present embodiment adopts the ginkgolide B nanometric liposomes medicine prescription, comprises following proportion raw material:
8 moles in cephalin and 1: 4 mixture of distearyl choline mole ratio;
6 moles in soyasterol and 1: 3 mixture of cholesterol mole ratio;
4 moles of 3: 1 mixtures of gamma-cyclodextrin and alpha-cyclodextrin mol ratio;
0.2 mole of methoxy poly (ethylene glycol) 2000-hydrogenated soya phosphatide acyl ethanolamine;
1 mole of Semen Ginkgo lactone B;
0.1 mole of vitamin E.
The preparation method of above-mentioned ginkgolide B nanometric liposomes medicine comprises the steps:
(1) described amount ginkalide B is dissolved in dehydrated alcohol/mixed liquor of 2: 1 of ethyl acetate volume ratio;
(2) with described amount gamma-cyclodextrin and 3: 1 mixtures of alpha-cyclodextrin mol ratio, be dissolved in the phosphate buffer of 0.015M/L, pH value 6.0-7.0, make the solution of gamma-cyclodextrin concentration 60-70%;
(3) solution with step (1) preparation adds in the solution of step (2) preparation, and dissolving fully;
(4) under the inflated with nitrogen condition, be dissolved in described amount vitamin E, cephalin and 1: 4 mixture of distearyl choline mole ratio, soyasterol and 1: 3 mixture of cholesterol mole ratio in the ether successively, at room temperature reduction vaporization is made liposome membrane to the ether noresidue;
(5) with liposome membrane aquation in phosphate buffer of step (4) preparation, making the distearyl choline concentration is 15mg/ml-25mg/ml, stirring and evenly mixing under nitrogen protection;
(6) mixed liquor with step (3) preparation is added drop-wise in the mixed liquor of step (5) preparation, adds methoxy poly (ethylene glycol) 2000-hydrogenated soya phosphatide acyl ethanolamine, and the dissolving back adds the 17500g-26400g usual excipients;
(7) mixed liquor with step (6) preparation passes through 0.2,0.1,0.08 μ m nucleopore membranes successively, repeated multiple times, add isotonic agent sterile liquid commonly used, make nano liposome medicament, further make high-capacity injection, injection with small volume, lyophilized injection, oral formulations or the spray that can receive on the pharmaceutics.
Excipient in the above-mentioned steps (6) is selected from vitamin C, xylitol, mannitol or dextran-40.
The pharmacodynamics demonstration test:
Blood pressure lowering drug effect demonstration test:
(1) model and method: with embodiment 1
(2) medicine and dosage:
Treatment group (1) group medicine ginkgolide B nanometric liposomes 7mg/kg of the present invention;
Treatment group (2) group medicine ginkgolide B nanometric liposomes 3.5mg/kg of the present invention;
Matched group (1) group ginkalide B injection 7mg/kg;
Matched group (2) group ginkalide B injection 3.5mg/kg;
Matched group (3) group ginkalide B injection 10mg/kg.
(3) result of the test is as follows:
Blood pressure lowering effective percentage % anaphylaxis rate %
Treatment group (1) group 96% 0%
Treatment group (2) group 93% 0%
Matched group (1) group 79% 10%
Matched group (2) group 65% 7%
Matched group (3) group 91% 17%
As seen drug dose of the present invention is that three of control drug maximum dose level/for the moment, the both has good curative effect, but the control drug curative effect is still obviously on the low side than the present invention medicine; When both dosage were identical, it is many that curative effect of medication of the present invention just exceeds control drug.Anaphylaxis medicine of the present invention has absolute advantages.Rat is erected hair, shakes behind the liquid medicine injection, is considered as anaphylaxis.
Embodiment 4
Present embodiment adopts the ginkgolide B nanometric liposomes medicine prescription, comprises following proportion raw material:
12 moles in cephalin and 1: 6 mixture of distearyl choline mole ratio;
8 moles in soyasterol and 1: 2 mixture of cholesterol mole ratio;
6 moles of 3: 1 mixtures of 2-HP-and alpha-cyclodextrin mol ratio;
0.4 mole of methoxy poly (ethylene glycol) 2000-hydrogenated soya phosphatide acyl ethanolamine;
2 moles of Semen Ginkgo lactone B;
0.5 mole of vitamin E.
The preparation method of above-mentioned ginkgolide B nanometric liposomes medicine comprises the steps:
(1) described amount ginkalide B is dissolved in dehydrated alcohol/mixed liquor of 2: 1 of ethyl acetate volume ratio;
(2) with described amount 2-HP-and 3: 1 mixtures of alpha-cyclodextrin mol ratio, be dissolved in the phosphate buffer of 0.015M/L, pH value 6.0-7.0, make the solution of 2-HP-concentration 60-70%;
(3) solution with step (1) preparation adds in the solution of step (2) preparation, and dissolving fully;
(4) under the inflated with nitrogen condition, be dissolved in described amount vitamin E, cephalin and 1: 6 mixture of distearyl choline mole ratio, soyasterol and 1: 2 mixture of cholesterol mole ratio in the ether successively, at room temperature reduction vaporization is made liposome membrane to the ether noresidue;
(5) with liposome membrane aquation in phosphate buffer of step (4) preparation, making the distearyl choline concentration is 15mg/ml-25mg/ml, stirring and evenly mixing under nitrogen protection;
(6) mixed liquor with step (3) preparation is added drop-wise in the mixed liquor of step (5) preparation, adds methoxy poly (ethylene glycol) 2000-hydrogenated soya phosphatide acyl ethanolamine, and the dissolving back adds the 17500g-26400g usual excipients;
(7) mixed liquor with step (6) preparation passes through 0.2,0.1,0.08 μ m nucleopore membranes successively, repeated multiple times, add isotonic agent sterile liquid commonly used, make nano liposome medicament, further make high-capacity injection, injection with small volume, lyophilized injection, oral formulations or the spray that can receive on the pharmaceutics.
Excipient in the above-mentioned steps (6) is selected from vitamin C, xylitol, mannitol or dextran-40.
The pharmacodynamics demonstration test:
1, blood pressure lowering drug effect demonstration test:
(1) the same embodiment of model and method (1)
(2) medicine and dosage:
Treatment group (1) group medicine ginkgolide B nanometric liposomes 4mg/kg of the present invention;
Treatment group (2) group medicine ginkgolide B nanometric liposomes 2mg/kg of the present invention;
Matched group (1) group ginkalide B injection 4mg/kg;
Matched group (2) group ginkalide B injection 2mg/kg;
Matched group (3) group ginkalide B injection 10mg/kg.
(3) result of the test is as follows:
Blood pressure lowering effective percentage % anaphylaxis rate %
Treatment group (1) group 95% 0%
Treatment group (2) group 92% 0%
Matched group (1) group 68% 10%
Matched group (2) group 57% 7%
Matched group (3) group 90% 17%
As seen drug dose of the present invention is that five of control drug maximum dose level/for the moment, the both has good curative effect, but the control drug curative effect is still obviously on the low side than the present invention medicine; When both dosage were identical, it is many that curative effect of medication of the present invention just exceeds control drug.Anaphylaxis medicine of the present invention has absolute advantages.Rat is erected hair, shakes behind the liquid medicine injection, is considered as anaphylaxis.
Embodiment 5
Present embodiment adopts the ginkgolide B nanometric liposomes medicine prescription, comprises following proportion raw material:
8 moles in cephalin and 1: 5 mixture of distearyl choline mole ratio;
6 moles in soyasterol and 1: 4 mixture of cholesterol mole ratio;
4 moles of 3: 1 mixtures of gamma-cyclodextrin and alpha-cyclodextrin mol ratio;
0.4 mole of methoxy poly (ethylene glycol) 2000-hydrogenated soya phosphatide acyl ethanolamine;
2 moles of Semen Ginkgo lactone B;
0.5 mole of vitamin E.
The preparation method of above-mentioned ginkgolide B nanometric liposomes medicine comprises the steps:
(1) described amount ginkalide B is dissolved in dehydrated alcohol/mixed liquor of 2: 1 of ethyl acetate volume ratio;
(2) with described amount gamma-cyclodextrin and 3: 1 mixtures of alpha-cyclodextrin mol ratio, be dissolved in the phosphate buffer of 0.015M/L, pH value 6.0-7.0, make the solution of gamma-cyclodextrin concentration 60-70%;
(3) solution with step (1) preparation adds in the solution of step (2) preparation, and dissolving fully;
(4) under the inflated with nitrogen condition, be dissolved in described amount vitamin E, cephalin and 1: 5 mixture of distearyl choline mole ratio, soyasterol and 1: 4 mixture of cholesterol mole ratio in the ether successively, at room temperature reduction vaporization is made liposome membrane to the ether noresidue;
(5) with liposome membrane aquation in phosphate buffer of step (4) preparation, making the distearyl choline concentration is 15mg/ml-25mg/ml, stirring and evenly mixing under nitrogen protection;
(6) mixed liquor with step (3) preparation is added drop-wise in the mixed liquor of step (5) preparation, adds methoxy poly (ethylene glycol) 2000-hydrogenated soya phosphatide acyl ethanolamine, and the dissolving back adds the 17500g-26400g usual excipients;
(7) step (6) preparation mixed liquor is passed through 0.2,0.1,0.08 μ m nucleopore membranes successively, repeated multiple times, add isotonic agent sterile liquid commonly used, make nano liposome medicament, further make high-capacity injection, injection with small volume, lyophilized injection, oral formulations or the spray that can receive on the pharmaceutics.Excipient in the above-mentioned steps (6) is selected from vitamin C, xylitol, mannitol or dextran-40.
The pharmacodynamics demonstration test
1, blood pressure lowering drug effect test
(1) model and method: same embodiment (1)
(2) medicine and dosage
Treatment group (1) group medicine ginkgolide B nanometric liposomes 6mg/kg of the present invention;
Treatment group (2) group medicine ginkgolide B nanometric liposomes 3mg/kg of the present invention;
Matched group (1) group ginkalide B injection 6mg/kg;
Matched group (2) group ginkalide B injection 3mg/kg;
Matched group (3) group ginkalide B injection 10mg/kg.
(3) result of the test is as follows
Blood pressure lowering effective percentage % anaphylaxis rate %
Treatment group (1) group 96% 0%
Treatment group (2) group 92% 0%
Matched group (1) group 72% 10%
Matched group (2) group 66% 7%
Matched group (3) group 90% 17%
As seen drug dose of the present invention is that three of control drug maximum dose level/for the moment, the both has good curative effect, but the control drug curative effect is still obviously on the low side than the present invention medicine; When both dosage were identical, it is many that curative effect of medication of the present invention just exceeds control drug.Anaphylaxis medicine of the present invention has absolute advantages.Rat is erected hair, shakes behind the liquid medicine injection, is considered as anaphylaxis.
Claims (4)
1. ginkgolide B nanometric liposomes medicine comprises following proportion raw material:
The mixture 8-12 mole of cephalin and distearyl choline mole ratio 1: 3-6;
The mixture 6-8 mole of soyasterol and cholesterol mole ratio 1: 2-4;
Gamma-cyclodextrin/2-HP-
With 3: 1 mixture 4-6 of alpha-cyclodextrin mol ratio mole;
Methoxy poly (ethylene glycol) 2000-hydrogenated soya phosphatide acyl ethanolamine 0.2-0.4 mole;
Semen Ginkgo lactone B 1-2 mole;
Vitamin E 0.1-0.5 mole.
2. prepare the method for the described ginkgolide B nanometric liposomes medicine of claim 1, comprise the steps:
(1) described amount ginkalide B is dissolved in the mixed liquor of dehydrated alcohol/ethyl acetate;
(2) with described amount gamma-cyclodextrin/2-HP-and 3: 1 mixtures of alpha-cyclodextrin mol ratio, be dissolved in the phosphate buffer of 0.015M/L, pH value 6.0-7.0, make the solution of gamma-cyclodextrin/2-HP-concentration 60-70%;
(3) solution with step (1) preparation adds in the solution of step (2) preparation, and dissolving fully;
(4) under the inflated with nitrogen condition, with described amount vitamin E, cephalin and distearyl choline mole ratio 1: the mixture of the mixture of 3-6, soyasterol and cholesterol mole ratio 1: 2-4 is dissolved in the ether successively, at room temperature reduction vaporization is made liposome membrane to the ether noresidue;
(5) with liposome membrane aquation in phosphate buffer of step (4) preparation, making the distearyl choline concentration is 15mg/ml-25mg/ml, stirring and evenly mixing under nitrogen protection;
(6) mixed liquor with step (3) preparation is added drop-wise in the mixed liquor of step (5) preparation, adds methoxy poly (ethylene glycol) 2000-hydrogenated soya phosphatide acyl ethanolamine, and the dissolving back adds the 17500g-26400g usual excipients;
(7) with the mixed liquor of step (6) preparation, successively by 0.2,0.1,0.08 μ m nucleopore membranes, repeated multiple times adds isotonic agent sterile liquid commonly used, makes nano liposome medicament.
3. method according to claim 2 is characterized in that, described nano liposome medicament can be made into high-capacity injection, injection with small volume, lyophilized injection, oral formulations or the spray that can receive on the pharmaceutics.
4. method according to claim 2 is characterized in that, the excipient in the described step (6) is selected from vitamin C, xylitol, mannitol or dextran-40.
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| CN101912364A (en) * | 2010-08-09 | 2010-12-15 | 刘会梅 | Ginkgolide B liposome medicinal composition |
| CN102416026A (en) * | 2011-12-05 | 2012-04-18 | 张皓然 | Nano ginkgo leaf extract external preparation and preparation method thereof |
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| CN101612124B (en) * | 2009-07-15 | 2012-06-20 | 吉林大学 | Lipoid plasmid and preparation method of formulation thereof |
| CN102579342A (en) * | 2012-02-16 | 2012-07-18 | 中国药科大学 | Targeting ginkgolide B solid lipid nanoparticle and preparation method thereof |
| CN105287614A (en) * | 2015-11-19 | 2016-02-03 | 昆药集团股份有限公司 | Dengyin naotong pharmaceutical composition and preparation method thereof, preparation and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1215841C (en) * | 2003-06-20 | 2005-08-24 | 梅世昌 | Prepn. method for injection of ginkgolide |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101612124B (en) * | 2009-07-15 | 2012-06-20 | 吉林大学 | Lipoid plasmid and preparation method of formulation thereof |
| CN101912364A (en) * | 2010-08-09 | 2010-12-15 | 刘会梅 | Ginkgolide B liposome medicinal composition |
| CN101912364B (en) * | 2010-08-09 | 2015-07-15 | 刘会梅 | Ginkgolide B liposome medicinal composition |
| CN102416026A (en) * | 2011-12-05 | 2012-04-18 | 张皓然 | Nano ginkgo leaf extract external preparation and preparation method thereof |
| CN102429934A (en) * | 2011-12-05 | 2012-05-02 | 张皓然 | Nanometer ginkgo leaf extract external preparation and application thereof |
| CN102416026B (en) * | 2011-12-05 | 2013-12-11 | 张皓然 | Preparation method of nano ginkgo leaf extract external preparation |
| CN102579342A (en) * | 2012-02-16 | 2012-07-18 | 中国药科大学 | Targeting ginkgolide B solid lipid nanoparticle and preparation method thereof |
| CN105287614A (en) * | 2015-11-19 | 2016-02-03 | 昆药集团股份有限公司 | Dengyin naotong pharmaceutical composition and preparation method thereof, preparation and application thereof |
| CN105287614B (en) * | 2015-11-19 | 2018-04-13 | 昆药集团股份有限公司 | A kind of Dengyin naotong pharmaceutical composition and preparation method thereof, preparation and application |
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| CN101036642B (en) | 2010-07-14 |
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