CN103121998A - Vinpocetine compound and drug composition thereof - Google Patents
Vinpocetine compound and drug composition thereof Download PDFInfo
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- CN103121998A CN103121998A CN2013100487094A CN201310048709A CN103121998A CN 103121998 A CN103121998 A CN 103121998A CN 2013100487094 A CN2013100487094 A CN 2013100487094A CN 201310048709 A CN201310048709 A CN 201310048709A CN 103121998 A CN103121998 A CN 103121998A
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Abstract
The invention belongs to the technical field of medicine, and particularly relates to vinpocetine compound. The vinpocetine compound is shown in an X-ray powder diffraction spectra I measured by a Cu-K alpha ray. A preparation method of the vinpocetine compound, and a drug composition containing the vinpocetine compound are also provided by the invention. The vinpocetine compound disclosed by the invention is long in storage time, less in impurity content, and good in storage stability; and the drug composition containing the vinpocetine compound is good in storage stability and high in safety performance.
Description
Technical field
The invention belongs to medical technical field, be specifically related to preparation method and the pharmaceutical composition thereof of a kind of vinpocetin compound, this vinpocetin compound.
Background technology
Vinpocetine: English name Vinpocetinum; Molecular formula C22H26N2O2; Molecular weight 350.45; A kind of alkaloid for extracting from bamboo peach section plant is the derivative of vincamine (vlncamlne).Vinpocetin can suppress phosphodiesterase activity, increase the effect of the courier c-GMP of vascular smooth muscle relaxation, optionally increase cerebral blood flow (CBF), can also suppress platelet aggregation in addition, reduce human blood viscosity, strengthen erythrocyte deformabiliy, improve blood fluidity and microcirculation, promote the cerebral tissue ingestion of glucose, increase the brain oxygen-consumption, improve the brain metabolism, but little on cardiovascular and blood pressure impact; Better tolerance, untoward reaction is little; Also can be used for giddy, headache, dysmnesia, action obstacle, aphasia, hypertensive encephalopathy etc., the spirituality or the nervosa symptom that also cause for cerebrum blood cycle penalty.
CN201110028452.7 discloses a kind of semisynthesis that can guarantee to realize under product purity and productive rate prerequisite the suitability for industrialized production vinpocetin, this invention adopts African growing plants Ma Lingguo to extract synthetic desired raw material tabersonine (tobersonina), through four synthetic vinpocetins of step.It is specifically 1 years old) preparation Changchun is climing not bright; 2) preparation vincamine; 3) preparation Changchun amino acid; 4) synthetic vinpocetin gets content and is 99% vinpocetin.This invention has created a complete process from the tabersonine to the vinpocetin, and technique is simple, and yield is high, and cost is lower; Can guarantee to realize the suitability for industrialized production vinpocetin under product purity and productive rate prerequisite.
CN201210151559.5 discloses the synthetic method of vinpocetin, and the raw material vincamine is added in there-necked flask, adds subsequently toluene, and agitation and dropping triethylamine and Methanesulfonyl chloride in ice-water bath stir and slowly be warming up to room temperature after 2 hours, then continues to stir 5 hours; Termination reaction, solvent evaporated adds the second alcohol and water, regulates PH=12 with the unsaturated carbonate potassium solution, and solid is separated out, and filters, and vacuum-drying gets the vinpocetin intermediate; Dehydrated alcohol is added in there-necked flask, stirring slowly added sodium ethylate after 1 hour in ice-water bath, stirred to add the vinpocetin intermediate after 0.5 hour, subsequently reaction flask was positioned in oil bath, set temperature is 80 ℃, react and steam most of solvent after 12 hours, then solution is poured in hydrochloric acid, use ethyl acetate extraction, water is regulated pH value=12, solid is separated out, and filtration drying obtains vinpocetin.The reactions steps of this invention synthetic method is short, and product purity and yield are high, and energy consumption is low, and environmental pollution is little.
The stability in storage of vinpocetin of the prior art is relatively poor, and its related substance can significantly increase in the environment of illumination and humidity, in order to obtain a kind of vinpocetin compound of more excellent performance, special proposition the present invention.
Summary of the invention
The present invention's the first purpose is to provide a kind of vinpocetin compound, and the vinpocetin compound that provides has better stability in storage.
The present invention's the second purpose is to provide a kind of preparation method of above-mentioned vinpocetin.
The 3rd purpose of the present invention is to provide a kind of pharmaceutical composition that contains above-mentioned vinpocetin compound.
In order to realize the foregoing invention purpose, the present invention takes following technical scheme:
A kind of vinpocetin compound, the structural formula of described vinpocetin compound is:
The X-ray powder diffraction spectrogram that described vinpocetin compound use Cu-K alpha-ray measures as shown in Figure 1.
Vinpocetin compound provided by the invention is crystal, the change of its internal crystal structure has caused its physicals that variation has also correspondingly occured, the contriver finds that by stability experiment the special crystallized form of vinpocetin compound provided by the present invention compares with the solid form of the vinpocetin of prior art, has stronger stability in storage.
a kind of preparation method of foregoing vinpocetin compound, described preparation method comprises: with N, N-METHYLFORMAMIDE and ethanol are mixed with mixed solvent with the volume ratio of 2 ~ 4:1, get Vinpocetione crude drug, add N, the mixed solvent of dinethylformamide and ethanol, the volume of described mixed solvent is 4 ~ 6ml:1g with the ratio of the quality of vinpocetin, be warming up to 60 ~ 70 ℃, be stirred to whole dissolvings, insulation, the pH of solution is transferred to 5.5 ~ 6.0, add decolorizing with activated carbon, filter, obtain settled solution, settled solution is moved in reactor, place 12 ~ 48h in 100 ~ 120 ℃ of baking ovens, naturally standing cooling, when temperature is down to below 70 ℃, drive still, add frozen water in settled solution, filter, obtain filter cake, washing leaching cake, drying under reduced pressure 2 ~ 4h again, namely get the white micro-crystals powder.
In the present invention, the contriver passes through experiment repeatedly, constantly change crystallization method and crystallization condition, finally prepare a kind of vinpocetin compound crystal with brand-new crystal formation, this vinpocetin compound crystal has very high lattice energy, the vinpocetin molecule is subjected to the lattice constraint larger, has good preservation stability.
The volume of described frozen water and the volume ratio of mixed solvent are 5-15:1.
It is described that to add the activated carbon degerming be this area common technology means, can process referring to any decolouring, those skilled in the art need not to pay any creative work, can carry out appropriate selection according to the prior art of himself grasping, and realize the object of the invention.
In order further to improve the formulation products quality, the present invention also can be preferably be filtered into the use ultrafiltration membrance filter after decolouring.
The present invention also provides a kind of pharmaceutical composition that contains foregoing vinpocetin compound.
The present invention is by changing the solid structure of vinpocetin compound, the vinpocetin that obtains has higher stability in storage, and then improved the stability in storage of the pharmaceutical composition that contains vinpocetin, compare with the Vinpocetine medicine composition of prior art, the pharmaceutical composition that contains vinpocetin provided by the invention has better stability in storage, has greatly improved patient's drug safety.
Described pharmaceutical composition is solid preparation or liquid preparation.
Preferably, described liquid preparation is aqueous injection; Described solid preparation is sterile powder injection, lyophilized injectable powder or tablet.
By weight, described sterile powder injection comprises 10 parts of vinpocetins, solubility promoter 5-15 part.
Preferably, the solubility promoter in described sterile powder injection comprises one or more in xitix, tartrate and citric acid.
By weight, described Vinpocetine freeze-dried powder for injection comprises the vinpocetin of 10 parts, the frozen-dried supporting agent of 30-70 part, the solubility promoter of 5-15 part.
Preferably, described frozen-dried supporting agent is selected from one or more in N.F,USP MANNITOL, glucose, sorbyl alcohol, sucrose, lactose.
Preferably, the solubility promoter in described frozen-dried supporting agent comprises one or more in xitix, tartrate and citric acid.
By weight, described tablet is Vinpocetine dispersible tablet, and described Vinpocetine dispersible tablet comprises: 10 parts of vinpocetins, weighting agent 20-38 part, disintegrating agent 20-48 part, tackiness agent 1.5-4.5 part, lubricant 0.5-2 part.
Preferably, described weighting agent comprises one or more in lactose, pregelatinized Starch, dextrin, Microcrystalline Cellulose, medical cane sugar, medicinal fructose, described disintegrating agent comprises one or more in cross-linked polyvinylpyrrolidone, croscarmellose sodium, hydroxypropylcellulose, described tackiness agent is selected from one or more in polyvinylpyrrolidone, Vltra tears, Xylo-Mucine, methylcellulose gum, starch slurry, and described lubricant is selected from one or more in Magnesium Stearate, talcum powder, micropowder silica gel, polyoxyethylene glycol.
By weight, described aqueous injection comprises 10 parts of vinpocetins, solubility promoter 15-25 part, antioxidant 0.5-2 part, physically stable agent 20-100 part, vascular stimulation conditioning agent 10-25 part.
Preferably, in described aqueous injection, described antioxidant comprises Sodium Pyrosulfite, and described solubility promoter solubility promoter comprises one or more in xitix, tartrate and citric acid, described physically stable agent comprises sorbyl alcohol, and described vascular stimulation conditioning agent comprises phenylcarbinol.
In the present invention, described sterile powder injection, lyophilized injectable powder, aqueous injection, dispersible tablet all can adopt the preparation method of prior art, those skilled in the art need not to pay any creative work, can carry out appropriate selection according to the prior art of himself grasping, and realize the object of the invention.
Compared with prior art, vinpocetin compound provided by the invention and pharmaceutical composition thereof have following advantage:
(1) to store for a long time foreign matter content few for vinpocetin compound of the present invention, and stability in storage is good;
(2) the pharmaceutical composition stability in storage that contains vinpocetin of the present invention is good, and safety performance is higher.
Description of drawings
The X-ray powder diffraction pattern of the vinpocetin compound that Fig. 1 provides for the embodiment of the present invention 1.
Embodiment
Below by specific embodiment, summary of the invention of the present invention is described further, but does not therefore limit content of the present invention.
Embodiment 1
The preparation of vinpocetin compound
with N, dinethylformamide and ethanol are mixed with mixed solvent with the volume ratio of 2:1, get Vinpocetione crude drug, add N, the mixed solvent of N-METHYLFORMAMIDE and ethanol, the volume of described mixed solvent is 4ml:1g with the ratio of the quality of vinpocetin, be warming up to 60 ℃, be stirred to whole dissolvings, insulation, the pH of solution is transferred to 5.5, add decolorizing with activated carbon, the consumption of gac is the 0.3%(g/ml of the solvent mixture volume), stir 30min, filter, obtain settled solution, settled solution is moved in reactor, place 48h in 100 ℃ of baking ovens, naturally standing cooling, when temperature is down to below 70 ℃, drive still, add frozen water in settled solution, the volume of described frozen water and the volume ratio of mixed solvent are 15:1, filter, obtain filter cake, with the washing with alcohol filter cake of 0 ℃ 3 times, drying under reduced pressure 4h again, namely get the white micro-crystals powder.Yield 74.4%, HPLC content 99.78%.
The X-ray powder diffraction spectrogram that uses the Cu-K alpha-ray to measure is shown as Fig. 1.
Embodiment 2
The preparation of vinpocetin compound
with N, dinethylformamide and ethanol are mixed with mixed solvent with the volume ratio of 4:1, get Vinpocetione crude drug, add N, the mixed solvent of N-METHYLFORMAMIDE and ethanol, the volume of described mixed solvent is 6ml:1g with the ratio of the quality of vinpocetin, be warming up to 70 ℃, be stirred to whole dissolvings, insulation, the pH of solution is transferred to 6.0, add decolorizing with activated carbon, the consumption of gac is the 0.3%(g/ml of the solvent mixture volume), stir 30min, filter, obtain settled solution, settled solution is moved in reactor, place 12h in 120 ℃ of baking ovens, naturally standing cooling, when temperature is down to below 70 ℃, drive still, add frozen water in settled solution, the volume of described frozen water and the volume ratio of mixed solvent are 5:1, filter, obtain filter cake, with the washing with alcohol filter cakes of 5 ℃ 3 times, drying under reduced pressure 2h again, namely get the white micro-crystals powder.Yield 72.5%, HPLC content 99.83%.
The X-ray powder diffraction figure that uses the Cu-K alpha-ray to measure is consistent with the result of embodiment 1.
Embodiment 3
The preparation of vinpocetin sterile powder injection
Take 10 parts of vinpocetins, 5 parts, the xitix of embodiment 1 preparation under aseptic condition, be placed in solid powder mixer and evenly mix, the gained raw material changes the sterile preparation workshop over to, the delicate metering packing, every bottle contains vinpocetin 0.5g, jumps a queue, rolls lid, finished product packing warehouse-in and censorship.
Embodiment 4
The preparation of vinpocetin sterile powder injection
Take 10 parts of vinpocetins, 15 parts, the tartrate of embodiment 1 preparation under aseptic condition, be placed in solid powder mixer and evenly mix, the gained raw material changes the sterile preparation workshop over to, the delicate metering packing, every bottle contains vinpocetin 1.0g, jumps a queue, rolls lid, finished product packing warehouse-in and censorship.
Embodiment 5
Vinpocetine freeze-dried powder for injection
Take vinpocetin 10g, the N.F,USP MANNITOL 30g of embodiment 2 preparation and xitix 5g in liquid-compounding cup, add water for injection 2000ml, then with 1mol/L hydrochloric acid soln adjusting pH to 3.5, vinpocetin is dissolved fully.Add 0.3% (g/ml) gac that accounts for the liquid total amount, under room temperature, whip attachment is 30 minutes, and filtering decarbonization, subsequent filtrate after filtering with microporous membrane, supply can standby again.
With the subsequent filtrate can in injection bottle made, carry out freeze-drying by following freeze-dry process: with 1.5 hours, shelf temperature is down to-45 ℃ of left and right, after products temperature reaches-35 ℃, beginning timing insulation approximately 4 hours, after being incubated, condenser temperature is down to fast below-50 ℃, opens case trap valve, be evacuated to the 10pa left and right, shelf temperature be set be-3 ℃.Shelf temperature is slowly risen to-3 ℃ with being no less than 2 hours, be incubated to the ice crystal disappearance, then continue insulation 4 hours.With 40 minutes, shelf temperature was risen to 18 ℃ of maintenances after 1 hour, shelf continues to be warming up to 40 ℃, and when products temperature reached 35 ℃, beginning timing insulation approximately 3 hours checked the vacuum tightness changing conditions, finishes whole freeze-drying process, total head plug, outlet.Every bottle contains vinpocetin 1.0g.
Embodiment 6
Vinpocetine freeze-dried powder for injection
Take vinpocetin 10g, the sorbyl alcohol 70g of embodiment 2 preparation and tartrate 15g in liquid-compounding cup, add water for injection 2000ml, then with 1mol/L hydrochloric acid soln adjusting pH to 3.5, vinpocetin is dissolved fully.Add 0.3% (g/ml) gac that accounts for the liquid total amount, under room temperature, whip attachment is 30 minutes, and filtering decarbonization, subsequent filtrate after filtering with microporous membrane, supply can standby again.
With the subsequent filtrate can in injection bottle made, carry out freeze-drying by following freeze-dry process: with 1.5 hours, shelf temperature is down to-45 ℃ of left and right, after products temperature reaches-35 ℃, beginning timing insulation approximately 4 hours, after being incubated, condenser temperature is down to fast below-50 ℃, opens case trap valve, be evacuated to the 10pa left and right, shelf temperature be set be-3 ℃.Shelf temperature is slowly risen to-3 ℃ with being no less than 2 hours, be incubated to the ice crystal disappearance, then continue insulation 4 hours.With 40 minutes, shelf temperature was risen to 18 ℃ of maintenances after 1 hour, shelf continues to be warming up to 40 ℃, and when products temperature reached 35 ℃, beginning timing insulation approximately 3 hours checked the vacuum tightness changing conditions, finishes whole freeze-drying process, total head plug, outlet.Every bottle contains vinpocetin 1.0g.
Embodiment 7
Vinpocetine dispersible tablet
Get vinpocetin 10g, Microcrystalline Cellulose 20g, hydroxypropylcellulose 48g, the Xylo-Mucine 1.5g of embodiment 2 preparations, silicon-dioxide 2g, mixing is that wetting agent is granulated with 95% ethanol, 60 ℃ of dryings, whole grain; After passed examination, be pressed into 1000, packing.
Embodiment 8
Vinpocetine dispersible tablet
Get vinpocetin 10g, Microcrystalline Cellulose 38g, hydroxypropylcellulose 20g, silicon-dioxide 0.2g, the Xylo-Mucine 4.5g of embodiment 2 preparations, mixing is that wetting agent is granulated with 95% ethanol, 60 ℃ of dryings, whole grain; After passed examination, be pressed into 1000, packing.
Embodiment 9
The vinpocetin aqueous injection
Get 100 parts of vinpocetins, 150 parts of Trisodium Citrates, 5 parts of Sodium Pyrosulfites, 200 parts of sorbyl alcohols, 100 parts of phenylcarbinols, it is 1000 times of vinpocetin weight that water for injection adds to liquor capacity, the salt acid for adjusting pH value to 3.5 that adds 1mol/L, carry out packing according to specification 0.1g/ bottle or 0.2g/ bottle, the preparation aqueous injection.
The vinpocetin aqueous injection
Get 100 parts of vinpocetins, 250 parts of Trisodium Citrates, 20 parts of Sodium Pyrosulfites, 1000 parts of sorbyl alcohols, 250 parts of phenylcarbinols, it is 1000 times of vinpocetin weight that water for injection adds to liquor capacity, the salt acid for adjusting pH value to 3.5 that adds 1mol/L, carry out packing according to specification 0.1g/ bottle or 0.2g/ bottle, the preparation aqueous injection.
Experimental example 1
This test example detects related substance in the prepared vinpocetin of embodiment 1 ~ 2, and this test is carried out according to 2010 editions second appendix VIII P residual solvent assay method of Chinese Pharmacopoeia, appendix XIX F medicine impurity analysis governing principle, and it the results are shown in Table 1:
The assay of table 1 related substance
| Preparation | DMF | Ethanol | Other related substance |
| Embodiment 1 product | Up to specification | Up to specification | Up to specification |
| Embodiment 2 products | Up to specification | Up to specification | Up to specification |
Experimental example 2
This experimental example has been investigated the stability of vinpocetin provided by the invention
This test is carried out according to 2005 editions second appendix XIX C medicine stability test governing principle of Chinese Pharmacopoeia, and result is as follows:
Table 2, accelerated test assay result
| ? | 0 month | 1 month | 3 months | 6 months | 9 months |
| 1 | 99.98% | 99.97% | 99.95% | 99.90% | 99.70% |
| 2 | 99.75% | 99.74% | 99.71% | 99.67% | 99.49% |
| 3 | 99.79% | 99.77% | 99.60% | 99.02% | 98.30% |
| 4 | 99.85% | 99.79% | 99.44% | 99.15% | 98.50% |
Table 3, test of long duration assay result
| ? | 0 month | 3 months | 6 months | 9 months | 15 months | 24 months |
| 1 | 99.98% | 99.93% | 99.90% | 99.85% | 99.70% | 99.58% |
| 2 | 99.75% | 99.69% | 99.65% | 99.60% | 99.41% | 99.21% |
| 3 | 99.79% | 99.72% | 99.67% | 99.32% | 98.65% | 97.81% |
| 4 | 99.85% | 99.78% | 99.44% | 99.15% | 98.53% | 97.75% |
Sample 1 is the product of the embodiment of the present invention 1;
Sample 2 is the product of the embodiment of the present invention 2;
Sample 3 is that HPLC is 99.874% with reference to the vinpocetin of CN201110028452.7 embodiment 1 preparation;
Sample 4 is that HPLC is 99.86% with reference to the vinpocetin of CN201210151559.5 embodiment 1 preparation;
Accelerated test by this experimental example and test of long duration as can be known, compared with prior art, the stability of vinpocetin provided by the invention is better.
Claims (10)
1. a vinpocetin compound, is characterized in that, the structural formula of described vinpocetin compound is:
The X-ray powder diffraction spectrogram that described vinpocetin compound use Cu-K alpha-ray measures as shown in Figure 1.
2. the preparation method of a vinpocetin compound claimed in claim 1, it is characterized in that, described preparation method comprises: with N, N-METHYLFORMAMIDE and ethanol are mixed with mixed solvent with the volume ratio of 2 ~ 4:1, get Vinpocetione crude drug, add N, the mixed solvent of N-METHYLFORMAMIDE and ethanol, the volume of described mixed solvent is 4 ~ 6ml:1g with the ratio of the quality of vinpocetin, be warming up to 60 ~ 70 ℃, be stirred to whole dissolvings, insulation, the pH of solution is transferred to 5.5 ~ 6.0, add decolorizing with activated carbon, filter, obtain settled solution, settled solution is moved in reactor, place 12 ~ 48h in 100 ~ 120 ℃ of baking ovens, naturally standing cooling, when temperature is down to below 70 ℃, drive still, add frozen water in settled solution, filter, obtain filter cake, washing leaching cake, drying under reduced pressure 2 ~ 4h again, namely get the white micro-crystals powder.
3. preparation method according to claim 2, is characterized in that, the volume of described frozen water and the volume ratio of mixed solvent are 5-15:1.
4. pharmaceutical composition that contains vinpocetin compound claimed in claim 1.
5. pharmaceutical composition according to claim 4, is characterized in that, described pharmaceutical composition is solid preparation or liquid preparation.
6. pharmaceutical composition according to claim 5, is characterized in that, described liquid preparation is aqueous injection; Described solid preparation is sterile powder injection, lyophilized injectable powder or tablet.
7. pharmaceutical composition according to claim 6, is characterized in that, by weight, described sterile powder injection comprises 10 parts of vinpocetins, solubility promoter 5-15 part.
8. pharmaceutical composition according to claim 6, is characterized in that, by weight, described lyophilized injectable powder comprises the vinpocetin of 10 parts, the frozen-dried supporting agent of 30-70 part, the solubility promoter of 5-15 part.
9. pharmaceutical composition according to claim 6, it is characterized in that, by weight, described tablet is Vinpocetine dispersible tablet, described Vinpocetine dispersible tablet comprises: described Vinpocetine dispersible tablet comprises: 10 parts of vinpocetins, weighting agent 20-38 part, disintegrating agent 20-48 part, tackiness agent 1.5-4.5 part, lubricant 0.5-2 part.
10. pharmaceutical composition according to claim 6, is characterized in that, by weight, described aqueous injection comprises 10 parts of vinpocetins, solubility promoter 15-25 part, antioxidant 0.5-2 part, physically stable agent 20-100 part, vascular stimulation conditioning agent 10-25 part.
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| CN201310048709.4A CN103121998B (en) | 2013-02-06 | 2013-02-06 | Vinpocetine compound and drug composition thereof |
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| CN201310048709.4A CN103121998B (en) | 2013-02-06 | 2013-02-06 | Vinpocetine compound and drug composition thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104083329A (en) * | 2014-02-21 | 2014-10-08 | 杭州长典医药科技有限公司 | Vinpocetine special ultrafine powder lyophilized preparation and preparation method thereof |
| CN105837567A (en) * | 2015-01-13 | 2016-08-10 | 匈牙利吉瑞大药厂 | Method for preparing vinpocetine through new technology and application of vinpocetine to prepare pharmaceutical composition |
| CN111171016A (en) * | 2020-01-07 | 2020-05-19 | 北京大学 | Pharmaceutical use of indole alkaloids and derivatives thereof |
| CN112326843A (en) * | 2020-11-27 | 2021-02-05 | 北京康立生医药技术开发有限公司 | Quantitative method of related substances of vinpocetine |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1058966A (en) * | 1991-08-30 | 1992-02-26 | 东北制药总厂 | The novel method of vincamine amino acid ester preparation |
| CN102311432A (en) * | 2011-08-26 | 2012-01-11 | 贺金凤 | Stable vinpocetine compound and pharmaceutical composition thereof |
-
2013
- 2013-02-06 CN CN201310048709.4A patent/CN103121998B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1058966A (en) * | 1991-08-30 | 1992-02-26 | 东北制药总厂 | The novel method of vincamine amino acid ester preparation |
| CN102311432A (en) * | 2011-08-26 | 2012-01-11 | 贺金凤 | Stable vinpocetine compound and pharmaceutical composition thereof |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104083329A (en) * | 2014-02-21 | 2014-10-08 | 杭州长典医药科技有限公司 | Vinpocetine special ultrafine powder lyophilized preparation and preparation method thereof |
| CN105837567A (en) * | 2015-01-13 | 2016-08-10 | 匈牙利吉瑞大药厂 | Method for preparing vinpocetine through new technology and application of vinpocetine to prepare pharmaceutical composition |
| CN111171016A (en) * | 2020-01-07 | 2020-05-19 | 北京大学 | Pharmaceutical use of indole alkaloids and derivatives thereof |
| CN112326843A (en) * | 2020-11-27 | 2021-02-05 | 北京康立生医药技术开发有限公司 | Quantitative method of related substances of vinpocetine |
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| CN103121998B (en) | 2015-03-04 |
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