CN102688186A - Medicine composition containing vinpocetine raw material - Google Patents
Medicine composition containing vinpocetine raw material Download PDFInfo
- Publication number
- CN102688186A CN102688186A CN2012101872018A CN201210187201A CN102688186A CN 102688186 A CN102688186 A CN 102688186A CN 2012101872018 A CN2012101872018 A CN 2012101872018A CN 201210187201 A CN201210187201 A CN 201210187201A CN 102688186 A CN102688186 A CN 102688186A
- Authority
- CN
- China
- Prior art keywords
- vinpocetine
- raw material
- impurity
- weight percentage
- cosolvent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of medicines, and provides a medicine composition containing vinpocetine raw material. The medicine composition comprises vinpocetine raw material, sodium chloride and cosolvent, and is prepared into aqueous solution. Research indicates that: the vinpocetine raw material and cosolvent have higher stability at a certain weight proportion; and further research shows that: the quality of the vinpocetine raw material has certain impact on the stability. The stability test shows that: the preparation prepared from the composition provided by the invention has higher stability.
Description
Technical field
The invention belongs to medical technical field, be specifically related to contain the pharmaceutical composition and the preparation thereof of vinpocetine.
Background technology
Vinpocetine has another name called apovincaminic acid ethyl ester see vinpocetine, white or off-white color crystalline powder, and chemical name is: (3 α, 4 α)-eburnamenine-14-carboxylic acid, ethyl ester, molecular formula is C
22H
26N
2O
2, molecular weight 350.64.Vinpocetine belongs to indoles alkaloid, is used to improve the various symptoms that cerebral infarction sequela, apoplexy sequela, cerebral arteriosclerosis etc. are brought out.Vinpocetine can suppress phosphodiesterase activity, increases the effect of the courier c-GMP of vascular smooth muscle relaxation, optionally the cerebral blood flow increasing amount; Can also suppress platelet aggregation in addition, reduce human blood viscosity, strengthen RBC deformation power; Improve blood fluidity and microcirculation; Promote the cerebral tissue ingestion of glucose, increase the brain oxygen consumption, improve the brain metabolism.
The preparation that contains vinpocetine that uses clinically is mainly ejection preparation, comprises infusion solution and lyophilized injectable powder.Vinpocetine can not intravenous injection or intramuscular injection, has shortcomings such as pain, injection site redness during intravenous drip, and patient's compliance is poor.Vinpocetine freeze-dried powder solubility is bad simultaneously, and aqueous solution content descends fast, and pH value reduces, and clarity is put shortcomings such as defective for a long time.Therefore, in clinical use, infusion preparation is clinician's a first-selected preparation always.One Chinese patent application numbers 200910013530.9 discloses a kind of infusion preparation that contains the vinpocetine raw material; This patent discloses the technology that adjuvants such as using the cosolvent citric acid prepares the infusion preparation of vinpocetine; But should technology just go research, not carry out deep research to the quality of the pharmaceutical preparations from vinpocetine dissolubility angle, and as infusion preparation; Improve its product quality, strengthen security of products and be even more important.
Summary of the invention
For these reasons; The applicant is in the process of research cosolvent dissolving vinpocetine; It is unexpected that cosolvent weight and the preparation stability found have confidential relation; Research shows, the weight ratio 1 of vinpocetine raw material and cosolvent: the preparation of the preparation of pharmaceutical compositions of the scope of 05-0.7 has good stability.
The applicant is in research process; Find to add cosolvent on the necessary satisfactory basis of quality of vinpocetine raw material, the vinpocetine infusion solution that can make meets quality standard in stability test; Be the content that the vinpocetine raw material must be controlled impurity; Through the content of control impurity, with cosolvent and osmotic pressure regulator combination, just can be prepared into the outstanding infusion preparation of quality again.Wherein the vinpocetine raw material must meet following requirement: in the raw material vinpocetine in the vinpocetine raw material impurity Calan weight percentage smaller or equal to 0.40%; Wherein in the vinpocetine raw material impurity dihydro vinpocetine weight percentage smaller or equal to 0.10%; Wherein in the vinpocetine raw material impurity apo-vincamine weight percentage smaller or equal to 0.30%, wherein in the vinpocetine raw material impurity methoxyl group vinpocetine weight percentage smaller or equal to 0.30%.
The present invention realizes through following technical proposals.
A kind of pharmaceutical composition that contains the vinpocetine raw material comprises vinpocetine raw material, sodium chloride and cosolvent in the pharmaceutical composition, preparation of pharmaceutical compositions becomes aqueous solution, and wherein the weight ratio of vinpocetine raw material and cosolvent is 1: 0.5-0.7.
Impurity Calan weight percentage is smaller or equal to 0.40% in the above-mentioned vinpocetine raw material,
Impurity dihydro vinpocetine weight percentage is smaller or equal to 0.10% in the above-mentioned vinpocetine raw material.
Impurity apo-vincamine weight percentage is smaller or equal to 0.30% in the above-mentioned vinpocetine raw material.
Impurity methoxyl group vinpocetine weight percentage is smaller or equal to 0.30% in the above-mentioned vinpocetine raw material.
A kind of pharmaceutical composition that contains the vinpocetine raw material comprises vinpocetine raw material, sodium chloride and cosolvent in the pharmaceutical composition, preparation of pharmaceutical compositions becomes aqueous solution, and the weight ratio of vinpocetine and cosolvent is 1: 0.5-1.10.
Wherein in the vinpocetine raw material impurity Calan weight percentage smaller or equal to 0.40%; Impurity dihydro vinpocetine weight percentage is smaller or equal to 0.10%; Impurity apo-vincamine weight percentage is smaller or equal to 0.30%, and impurity methoxyl group vinpocetine weight percentage is smaller or equal to 0.30% in the vinpocetine raw material.
Wherein in the vinpocetine raw material vinpocetine content more than or equal to 98.5%.
Above-mentioned cosolvent comprises one or more in citric acid, tartaric acid, glutamic acid, lactic acid, sorbic acid, the L-threonine.
The weight ratio of preferred vinpocetine raw material and cosolvent is 1: 0.6 in the aforementioned pharmaceutical compositions.
Preferred co-solvents is a citric acid in the aforementioned pharmaceutical compositions.
Cosolvent is citric acid and L-threonine in the aforementioned pharmaceutical compositions;
Wherein the weight ratio of pharmaceutical composition preferred co-solvents citric acid and L-threonine is 1: 0.1-0.5.
The above-mentioned said a kind of application of pharmaceutical composition in preparation treatment cerebral infarction sequela, apoplexy sequela, cerebral arteriosclerosis disease drug that contains vinpocetine.
Contain vinpocetine more than or equal to 98.5% in the vinpocetine raw material of the present invention.
The present invention has following beneficial technical effects:
1, the present invention further improves stability of formulation through the weight ratio of control vinpocetine raw material and cosolvent.
2, infusion preparation is more special ejection preparation, because contain a large amount of water and sodium chloride, therefore; Need to combine the test of preparation, carry out deep research, promptly meeting on the basis of European Pharmacopoeia for the quality of raw material; Further control (the vinpocetine raw material that meets what quality just can be prepared into better preparation of stability, and this needs performing creative labour) for the vinpocetine raw materials quality; The present invention is through research; The limit of four kinds of impurity in the control vinpocetine raw material, thus transfusion become with different cosolvent combined preparation, and this transfusion has better stability.
3, the present invention further studies and shows that the compositions of citric acid and L-threonine has better stability as the transfusion that cosolvent is prepared into.
One, check and analysis method
(1) impurity check and analysis method
1, chromatographic condition:
Use octadecylsilane chemically bonded silica to be filler; With 0.2mol/L Spirit of Mindererus .-acetonitrile (40: 60) is mobile phase, and the detection wavelength is 280nm, and it is an amount of to take by weighing Calan, apo-vincamine and vinpocetine reference substance respectively; Put in the same measuring bottle; Add mobile phase dissolving and dilution and process the solution that all contains 0.02mg among every 1ml,, get 10 μ l and inject chromatograph of liquid as system suitability testing liquid; The record chromatogram, the separating degree between impurity Calan, impurity apo-vincamine and the vinpocetine all should meet the requirements.Theoretical cam curve is calculated by the vinpocetine peak and is not less than 3000.
2, detection method: measure according to HPLC (two appendix V of Chinese Pharmacopoeia version in 2010 D).
These article of getting an amount of (being equivalent to vinpocetine raw material 50mg approximately) are put in the 50ml measuring bottle, are diluted to scale with mobile phase, shake up, as need testing solution; Precision is measured in right amount, quantitatively dilutes with mobile phase and processes the solution that contains 5 μ g among every 1ml, as contrast solution.Precision is measured contrast solution and each 10 μ l of need testing solution, injects chromatograph of liquid respectively, the record chromatogram.In the chromatogram of need testing solution as show impurity peaks; The impurity Calan is 0.40 to the RRT of vinpocetine; Impurity dihydro vinpocetine is 0.66 to the RRT of vinpocetine; Impurity apo-vincamine is 0.78 to the RRT of vinpocetine, and impurity methoxyl group vinpocetine is 0.87 to the RRT of vinpocetine.Calculate the content of each impurity according to area normalization method.
(2) content detection analytical method
1, chromatographic condition: use octadecylsilane chemically bonded silica to be filler; With 0.2mol/L Spirit of Mindererus .-acetonitrile (40: 60) is mobile phase, and the detection wavelength is 280nm, and it is an amount of to take by weighing Calan, apo-vincamine and vinpocetine reference substance respectively; Put in the same measuring bottle; Add mobile phase dissolving and dilution and process the solution that all contains 0.02mg among every 1ml,, get 10 μ l and inject chromatograph of liquid as system suitability testing liquid; The record chromatogram, the separating degree between impurity Calan, impurity apo-vincamine and the vinpocetine all should meet the requirements.Theoretical cam curve is calculated by the vinpocetine peak and is not less than 3000.
2, detection method: measure according to HPLC (two appendix V of Chinese Pharmacopoeia version in 2010 D).
Algoscopy: get these article, precision is measured or is taken by weighing in right amount and (is equivalent to vinpocetine 10mg approximately), puts in the 50ml measuring bottle; Be diluted to scale with methanol, shake up, precision is measured 5ml; Put in the 50ml measuring bottle, be diluted to scale, shake up with mobile phase; Precision is measured 10 μ l and is injected chromatograph of liquid, the record chromatogram; Other gets the vinpocetine reference substance, measures with method,, promptly gets with calculated by peak area by external standard method.
Above-mentioned said reference substance is all available from National Institute for Food and Drugs Control.
Vinpocetine raw material of the present invention meets and contains vinpocetine more than or equal to 98.5% standard.
Described following test is on the basis of test of many times, the concluding test that claimed technical scheme is carried out according to the present invention.
Two, cosolvent is for the I that influences of preparation stability
1, test raw material
Vinpocetine raw material (Northeast Pharmaceutical Group Co., Ltd.); According to above-mentioned check and analysis method; Vinpocetine content is 98.82% in the vinpocetine raw material, impurity Calan weight percentage 0.42% in the raw material vinpocetine, impurity dihydro vinpocetine weight percentage 0.12%; Impurity apo-vincamine weight percentage 0.32%, impurity methoxyl group vinpocetine weight percentage 0.31%.
2, test preparation
1 group in preparation: vinpocetine raw material 1g, citric acid 0.4g, sodium chloride 90g, water for injection 10L.
2 groups in preparation: vinpocetine raw material 1g, citric acid 0.5g, sodium chloride 90g, water for injection 10L.
3 groups in preparation: vinpocetine raw material 1g, citric acid 0.6g, sodium chloride 90g, water for injection 10L.
4 groups in preparation: vinpocetine raw material 1g, citric acid 0.7g, sodium chloride 90g, water for injection 10L.
1 group in preparation: vinpocetine raw material 1g, citric acid 0.8g, sodium chloride 90g, water for injection 10L.
3, method for preparing: get cosolvent and add injection water, be prepared into 0.4% solution, add the vinpocetine raw material; Add sodium chloride, add into recipe quantity water for injection, dissolving fully; With 0.45 μ m filtering with microporous membrane, fill charges into carbon dioxide in infusion bottle; The sealing of jumping a queue, sterilization obtains each 100 bottles in sample.
4, test method:
Get above-mentioned different preparation, under temperature (40 ± 2) ℃, relative humidity 75% ± 5% condition, deposit,, measure the content of preparation impurity respectively at 1,2,3 sampling at the end of month.
5, result of the test is seen table 1, table 2, table 3:
The impurity of 1 month different preparation of table 1 relatively
The impurity of 2 months different preparations of table 2 relatively
The impurity of 3 months different preparations of table 3 relatively
Annotate: the impurity summation conforms to quality requirements less than 1.50%.
Three, cosolvent is for the II that influences of preparation stability
1, test raw material
Vinpocetine raw material (Northeast Pharmaceutical Group Co., Ltd.); According to above-mentioned check and analysis method; Vinpocetine content is 99.01% in the vinpocetine raw material, impurity Calan weight percentage 0.40% in the raw material vinpocetine, impurity dihydro vinpocetine weight percentage 0.08%; Impurity apo-vincamine weight percentage 0.20%, impurity methoxyl group vinpocetine weight percentage 0.28%.
Preparation prescription, method for preparing, test method are with the influence I of cosolvent for preparation stability.
Result of the test: see table 4-table 6.
The impurity of 1 month different preparation of table 4 relatively
The impurity of 2 months different preparations of table 5 relatively
The impurity of 3 months different preparations of table 3 relatively
Annotate: impurity content meets the requirements less than 1.50%.
Conclusion (of pressure testing): above-mentioned cosolvent shows that for the result that influences of preparation stability the weight ratio of vinpocetine raw material and cosolvent has very big influence for stability of formulation, no matter the vinpocetine raw material of what quality; As long as the two weight ratio be 1: 0.4 with weight ratio be 1: 0.8 o'clock the preparation long sodium chloride infusion preparation, through 3 months investigation, its impurity altered a great deal; Can cause preparation security to reduce, and the two weight ratio is 1: in the time of in the 05-0.7 scope, the impurity rate of change is very little; Particularly the two weight ratio is 1: 0.6 o'clock; The impurity rate of increase is littler, proves absolutely, when the transfusion of preparation vinpocetine sodium chloride; The weight of cosolvent plays crucial effects for product stability; This effect possibly be since vinpocetine raw material, sodium chloride, cosolvent citric acid in aqueous solution, through behind the high temperature, interacting each other causes.Therefore, in order to guarantee the quality of product, through above-mentioned optimization test, the weight ratio of in the transfusion of preparation vinpocetine sodium chloride, should keep writing out a prescription vinpocetine raw material and citric acid is 1: in the scope of 0.5-0.7.
Three, the vinpocetine raw material is for the influence of stability
1, test raw material:
1 group of raw material: vinpocetine raw material (Northeast Pharmaceutical Group Co., Ltd.); According to above-mentioned check and analysis method; Vinpocetine content is 98.77% in the vinpocetine raw material, impurity Calan weight percentage 0.46% in the raw material vinpocetine, impurity dihydro vinpocetine weight percentage 0.12%; Impurity apo-vincamine weight percentage 0.32%, impurity methoxyl group vinpocetine weight percentage 0.31%.
2 groups of raw materials: vinpocetine raw material (Northeast Pharmaceutical Group Co., Ltd.); According to above-mentioned check and analysis method; Vinpocetine content is 99.01% in the vinpocetine raw material, impurity Calan weight percentage 0.40% in the raw material vinpocetine, impurity dihydro vinpocetine weight percentage 0.08%; Impurity apo-vincamine weight percentage 0.20%, impurity methoxyl group vinpocetine weight percentage 0.28%.
2, test preparation
1 group in preparation: the vinpocetine raw material 2g that raw material is 1 group, sodium chloride 180g, tartaric acid 2.1g, water for injection 20L.
2 groups in preparation: the vinpocetine raw material 2g that raw material is 1 group, sodium chloride 180g, citric acid and L-threonine 1.1g (citric acid 0.9g, L-threonine 0.2g), water for injection 20L.
3 groups in preparation: the vinpocetine raw material 2g that raw material is 1 group, sodium chloride 180g, citric acid and L-threonine 1.4g (citric acid 1g, L-threonine 0.4g), water for injection 20L.
4 groups in preparation: the vinpocetine raw material 2g that raw material is 1 group, sodium chloride 180g, glutamic acid 2.2g, water for injection 20L.
5 groups in preparation: the vinpocetine raw material 2g that raw material is 2 groups, sodium chloride 180g, tartaric acid 2.1g, water for injection 20L.
6 groups in preparation: the vinpocetine raw material 2g that raw material is 2 groups, sodium chloride 180g, citric acid and L-threonine 1.1g (citric acid 0.9g, L-threonine 0.2g), water for injection 20L.
7 groups in preparation: the vinpocetine raw material 2g that raw material is 2 groups, sodium chloride 180g, citric acid and L-threonine 1.4g (citric acid 1g, L-threonine 0.4g), water for injection 20L.
8 groups in preparation: the vinpocetine raw material 2g that raw material is 2 groups, sodium chloride 180g, glutamic acid 2.2g, water for injection 20L.
3, method for preparing: get cosolvent and add injection water and be prepared into 0.4% solution, add the vinpocetine raw material, add sodium chloride; Add into recipe quantity water for injection, dissolving is complete, with 0.45 μ m filtering with microporous membrane; Fill charges into carbon dioxide in infusion bottle, the sealing of jumping a queue; Sterilization obtains each 200 bottles in sample.
4, test method:
Get above-mentioned different preparation, under temperature (60 ± 2) ℃, relative humidity 75% ± 5% condition, deposit,, measure the content of preparation impurity respectively at 1,2,3 sampling at the end of month.
5, result of the test is seen table 7, table 8, table 9:
The impurity of 1 month different preparation of table 7 relatively
The impurity of 2 months different preparations of table 8 relatively
The impurity of 3 months different preparations of table 9 relatively
Annotate: the impurity summation conforms to quality requirements less than 2.00%.
What adopt in the above-mentioned test is that the bigger sample of impurity content makes an experiment, and (vinpocetine content is 99.87% to the better vinpocetine raw material of applicant's service property (quality) in research process in the vinpocetine raw material, impurity Calan weight percentage 0.09% in the raw material vinpocetine; Impurity dihydro vinpocetine does not detect; Impurity apo-vincamine weight percentage 0.02%, impurity methoxyl group vinpocetine does not detect), carry out above-mentioned test; Investigation through 3 months above-mentioned conditions; Impurity Calan content 0.12% in the preparation, impurity dihydro vinpocetine does not detect, impurity apo-vincamine content 0.04%; Impurity methoxyl group vinpocetine 0.03% proves absolutely that the quality of vinpocetine raw material is significant for stability of formulation.
Conclusion (of pressure testing): from above-mentioned test; We can analyze, and the size of impurity and stability of formulation have confidential relation in the vinpocetine raw material, under the situation that adds same cosolvent; It is better that impurity meets the preparation stability of certain standard; Make an experiment according to the method described above, the vinpocetine raw material must meet following mark standard: impurity Calan weight percentage is smaller or equal to 0.40% in the vinpocetine raw material, and impurity dihydro vinpocetine weight percentage is smaller or equal to 0.10%; Impurity apo-vincamine weight percentage is smaller or equal to 0.30%, and impurity methoxyl group vinpocetine weight percentage is smaller or equal to 0.30%.
Above-mentioned test shows that further the compositions of using citric acid and L-threonine is as cosolvent, and the stability of product is higher.
Three, pharmacological test example
Influence to tentative transient cerebral ischemia appearance outbreak phospholipid level
Experimental animal: kunming mice, male and female are not limit, and body weight is 30-35g, available from Department Of Medicine, Peking University's Experimental Animal Center.
Trial drug: tert-butyl peroxide, available from Beijing chemical reagent work; Lysophosphatide acidity test cover reagent is available from Beijing Tai Fushi scientific and technological development company.
1 group of trial drug: vinpocetine raw material (Northeast Pharmaceutical Group Co., Ltd.); According to above-mentioned check and analysis method; Vinpocetine content is 98.92% in the vinpocetine raw material, impurity Calan weight percentage 0.41% in the raw material vinpocetine, impurity dihydro vinpocetine weight percentage 0.13%; Impurity apo-vincamine weight percentage 0.15%, impurity methoxyl group vinpocetine weight percentage 0.37%.
Preparation prescription: above-mentioned vinpocetine raw material 2g, citric acid 2g, sodium chloride 180g, water for injection 20L.
2 groups of trial drugs: vinpocetine raw material (Northeast Pharmaceutical Group Co., Ltd.); According to above-mentioned check and analysis method; Vinpocetine content is 99.24% in the vinpocetine raw material, impurity Calan weight percentage 0.35% in the raw material vinpocetine, impurity dihydro vinpocetine weight percentage 0.05%; Impurity apo-vincamine weight percentage 0.11%, impurity methoxyl group vinpocetine weight percentage 0.21%.
Preparation prescription: above-mentioned vinpocetine raw material raw material 2g, citric acid 1.2g, sodium chloride 180g, water for injection 20L.
3 groups of trial drugs: vinpocetine raw material (Northeast Pharmaceutical Group Co., Ltd.); According to above-mentioned check and analysis method; Vinpocetine content is 99.24% in the vinpocetine raw material, impurity Calan weight percentage 0.35% in the raw material vinpocetine, impurity dihydro vinpocetine weight percentage 0.05%; Impurity apo-vincamine weight percentage 0.11%, impurity methoxyl group vinpocetine weight percentage 0.21%.
Preparation prescription: above-mentioned vinpocetine raw material 2g, citric acid 1.0g, L-threonine 0.2g, sodium chloride 180g, water for injection 20L.
Method for preparing: get cosolvent and add injection water and be prepared into 0.4% solution, add the vinpocetine raw material, add sodium chloride; Add into recipe quantity water for injection, dissolving is complete, with 0.45 μ m filtering with microporous membrane; Fill charges into carbon dioxide in infusion bottle, the sealing of jumping a queue; Sterilization obtains each 200 bottles in sample.
Test method: get above-mentioned different preparation, after depositing 3 months under temperature (60 ± 2) ℃, relative humidity 75% ± 5% condition, get preparation and carry out following pharmacological evaluation.
Get the mice random packet: normal control group, test control group, experimental animal group, carry out the TIA animal model and make: the model [Wu Qizhuan, Wang Runying, Bao Heqiu, the Chen Qingtang that set up the outbreak of mice TIA appearance with reference to the Wu Shi method.The experimental model [J] of mice transience incomplete brain blood supply appearance outbreak.Preclinical medicine and clinical, 1995; 15:222].0.11molL
-1Tertbutanol peroxide, tail vein injection (0.1mlkg
-1Body weight) behind the 20min, brings out and finish.The normal control group, directly broken end is got hematometry LPA and PA.After the 1st TIA of mice brought out, trial drug group abdominal cavity gave 1.5mgkg
-1D
-1The different tests preparation, test control group gives normal saline, waits the appearance inequality, 1 week of successive administration, bring out TIA once more, bring out the TIA broken end in the 2nd time and get hematometry LPA and PA.Phospholipid determination: get whole blood, place to add the test tube that special anticoagulant is arranged, with 3500rmin
-1Centrifugal 10-15min sucts clearly, extracting LPA and PA composition, concentrates, separates, filters, colour developing at last.Place 5min in 90 ℃ of water-baths, take out in room temperature and place 35min, utilize 754 spectrophotometers to carry out spectrodensitometry, calculate the two content, result of calculation.
Result of the test: see table 4.
Different preparations are to the influence (
n=20) of plasma lysophosphatidic acid (LPA) and acidic phospholipid (PA) level behind table 4 stability test
Annotate: compare * * P＜0.01 with test control group; Compare #P＜0.05 for 1 group with trial drug.
Conclusion (of pressure testing): above-mentioned test shows; Test 1 group preparation, after depositing 3 months under temperature (60 ± 2) ℃, relative humidity 75% ± 5% condition, relatively do not have significant difference with test control group; And test 2 groups with the test 3 groups; Relatively have utmost point significant difference (P＜0.01) with test control group, and test 2 groups with 1 group of 3 groups of tests and test relatively, have significant difference (P＜0.05); This pharmacological testing further specifies, and raw materials quality must meet certain standard, just has good stability after making up with cosolvent; Simultaneously, meet at raw material on the basis of certain standard, select for use " citric acid " or " compositions of L-threonine and citric acid " as cosolvent; The preparation that is prepared into has better stability, and on the basis that guarantees stability, the active component in the preparation does not change; Impurity does not increase, thereby causes having great pharmacological effects.
Preparation embodiment
Embodiment 1
Vinpocetine raw material (Northeast Pharmaceutical Group Co., Ltd.); According to above-mentioned check and analysis method; Vinpocetine content is 99.24% in the vinpocetine raw material, impurity Calan weight percentage 0.35% in the raw material vinpocetine, impurity dihydro vinpocetine weight percentage 0.05%; Impurity apo-vincamine weight percentage 0.11%, impurity methoxyl group vinpocetine weight percentage 0.21%.
Preparation prescription: above-mentioned vinpocetine raw material 2.0g, glutamic acid 2.1g, sodium chloride 180g, water for injection 20L.
Method for preparing: get cosolvent and add injection water and be prepared into 0.4% solution, add the vinpocetine raw material, add sodium chloride; Add into recipe quantity water for injection, dissolving is complete, with 0.45 μ m filtering with microporous membrane; Fill charges into carbon dioxide in infusion bottle, the sealing of jumping a queue; Sterilization obtains each 200 bottles in sample.
Embodiment 2
Vinpocetine raw material (Northeast Pharmaceutical Group Co., Ltd.); According to above-mentioned check and analysis method; Vinpocetine content is 99.24% in the vinpocetine raw material, impurity Calan weight percentage 0.35% in the raw material vinpocetine, impurity dihydro vinpocetine weight percentage 0.05%; Impurity apo-vincamine weight percentage 0.11%, impurity methoxyl group vinpocetine weight percentage 0.21%.
Preparation prescription: above-mentioned vinpocetine raw material 2.0g, citric acid 1.3g, L-threonine 0.2g, sodium chloride 180g, water for injection 20L.
Method for preparing: get cosolvent and add injection water and be prepared into 0.4% solution, add the vinpocetine raw material, add sodium chloride; Add into recipe quantity water for injection, dissolving is complete, with 0.45 μ m filtering with microporous membrane; Fill charges into carbon dioxide in infusion bottle, the sealing of jumping a queue; Sterilization obtains each 200 bottles in sample.
Embodiment 3
Vinpocetine raw material (Northeast Pharmaceutical Group Co., Ltd.); According to above-mentioned check and analysis method; Vinpocetine content is 99.24% in the vinpocetine raw material, impurity Calan weight percentage 0.35% in the raw material vinpocetine, impurity dihydro vinpocetine weight percentage 0.05%; Impurity apo-vincamine weight percentage 0.11%, impurity methoxyl group vinpocetine weight percentage 0.21%.
Preparation prescription: above-mentioned vinpocetine raw material 2.0g, L-threonine 1.2g, sodium chloride 180g, water for injection 20L.
Method for preparing: get cosolvent and add injection water and be prepared into 0.4% solution, add the vinpocetine raw material, add sodium chloride; Add into recipe quantity water for injection, dissolving is complete, with 0.45 μ m filtering with microporous membrane; Fill charges into carbon dioxide in infusion bottle, the sealing of jumping a queue; Sterilization obtains each 200 bottles in sample.
Embodiment 4
Vinpocetine raw material (Northeast Pharmaceutical Group Co., Ltd.); According to above-mentioned check and analysis method; Vinpocetine content is 99.19% in the vinpocetine raw material, impurity Calan weight percentage 0.35% in the raw material vinpocetine, impurity dihydro vinpocetine weight percentage 0.05%; Impurity apo-vincamine weight percentage 0.11%, impurity methoxyl group vinpocetine weight percentage 0.21%.
Preparation prescription: above-mentioned vinpocetine raw material 20g, citric acid 12.5g, L-threonine 2.5g, sodium chloride 1800g, water for injection 200L.
Method for preparing: get cosolvent and add injection water and be prepared into 0.4% solution, add the vinpocetine raw material, add sodium chloride; Add into recipe quantity water for injection, dissolving is complete, with 0.45 μ m filtering with microporous membrane; Fill charges into carbon dioxide in infusion bottle, the sealing of jumping a queue; Sterilization obtains each 2000 bottles in sample.
Embodiment 5
Vinpocetine raw material (Northeast Pharmaceutical Group Co., Ltd.); According to above-mentioned check and analysis method; Vinpocetine content is 99.68% in the vinpocetine raw material, and the impurity Calan does not detect in the raw material vinpocetine, impurity dihydro vinpocetine weight percentage 0.04%; Impurity apo-vincamine weight percentage 0.09%, impurity methoxyl group vinpocetine weight percentage 0.17%.
Preparation prescription: above-mentioned vinpocetine raw material 2g, citric acid 1g, L-threonine 0.5g, sodium chloride 180g, water for injection 20L.
Method for preparing: get cosolvent and add injection water and be prepared into 0.4% solution, add the vinpocetine raw material, add sodium chloride; Add into recipe quantity water for injection, dissolving is complete, with 0.45 μ m filtering with microporous membrane; Fill charges into carbon dioxide in infusion bottle, the sealing of jumping a queue; Sterilization obtains each 200 bottles in sample.
Embodiment 6
Vinpocetine raw material (Northeast Pharmaceutical Group Co., Ltd.); According to above-mentioned check and analysis method; Vinpocetine content is 99.55% in the vinpocetine raw material, impurity Calan weight percentage 0.30% in the raw material vinpocetine, and impurity dihydro vinpocetine does not detect; Impurity apo-vincamine does not detect, impurity methoxyl group vinpocetine weight percentage 0.12%.
Preparation prescription: above-mentioned vinpocetine raw material 2.0g, citric acid 1.2g, L-threonine 0.3g, sodium chloride 180g, water for injection 20L.
Method for preparing: get cosolvent and add injection water and be prepared into 0.4% solution, add the vinpocetine raw material, add sodium chloride; Add into recipe quantity water for injection, dissolving is complete, with 0.45 μ m filtering with microporous membrane; Fill charges into carbon dioxide in infusion bottle, the sealing of jumping a queue; Sterilization obtains each 200 bottles in sample.
Embodiment 7
Vinpocetine raw material (Northeast Pharmaceutical Group Co., Ltd.); According to above-mentioned check and analysis method; Vinpocetine content is 99.82% in the vinpocetine raw material, impurity Calan weight percentage 0.12% in the raw material vinpocetine, impurity dihydro vinpocetine weight percentage 0.03%; Impurity apo-vincamine does not detect, and impurity methoxyl group vinpocetine does not detect.
Preparation prescription: above-mentioned vinpocetine raw material 2.0g, citric acid 12g, sodium chloride 180g, water for injection 20L.
Method for preparing: get cosolvent and add injection water and be prepared into 0.4% solution, add the vinpocetine raw material, add sodium chloride; Add into recipe quantity water for injection, dissolving is complete, with 0.45 μ m filtering with microporous membrane; Fill charges into carbon dioxide in infusion bottle, the sealing of jumping a queue; Sterilization obtains each 200 bottles in sample.
Embodiment 8
Vinpocetine raw material (Northeast Pharmaceutical Group Co., Ltd.); According to above-mentioned check and analysis method; Vinpocetine content is 99.75% in the vinpocetine raw material, impurity Calan weight percentage 0.08% in the raw material vinpocetine, and impurity dihydro vinpocetine does not detect; Impurity apo-vincamine weight percentage 0.03%, impurity methoxyl group vinpocetine weight percentage 0.10%.
Preparation prescription: above-mentioned vinpocetine raw material 2.0g, citric acid 1.1g, sodium chloride 180g, water for injection 20L.
Method for preparing: get cosolvent and add injection water and be prepared into 0.4% solution, add the vinpocetine raw material, add sodium chloride; Add into recipe quantity water for injection, dissolving is complete, with 0.45 μ m filtering with microporous membrane; Fill charges into carbon dioxide in infusion bottle, the sealing of jumping a queue; Sterilization obtains each 200 bottles in sample.
Embodiment 9
Vinpocetine raw material (Northeast Pharmaceutical Group Co., Ltd.); According to above-mentioned check and analysis method; Vinpocetine content is 99.67% in the vinpocetine raw material, and the impurity Calan does not detect in the raw material vinpocetine, impurity dihydro vinpocetine weight percentage 0.06%; Impurity apo-vincamine weight percentage 0.24%, impurity methoxyl group vinpocetine does not detect.
Preparation prescription: above-mentioned vinpocetine raw material 2.0g, citric acid 1.4g, sodium chloride 180g, water for injection 20L.
Method for preparing: get cosolvent and add injection water and be prepared into 0.4% solution, add the vinpocetine raw material, add sodium chloride; Add into recipe quantity water for injection, dissolving is complete, with 0.45 μ m filtering with microporous membrane; Fill charges into carbon dioxide in infusion bottle, the sealing of jumping a queue; Sterilization obtains each 200 bottles in sample.
More than description through the specific embodiment the present invention is described further; But this is not to be limitation of the present invention; Those skilled in the art are according to basic thought of the present invention; Can make various modifications or improvement, but only otherwise break away from basic thought of the present invention, all within scope of the present invention.
Claims (11)
1. a pharmaceutical composition that contains the vinpocetine raw material comprises vinpocetine raw material, sodium chloride and cosolvent in the pharmaceutical composition, and preparation of pharmaceutical compositions becomes aqueous solution, and the weight ratio that it is characterized in that vinpocetine and cosolvent is 1: 0.5-0.7.
2. a kind of pharmaceutical composition that contains vinpocetine according to claim 1, wherein in the vinpocetine raw material impurity Calan weight percentage smaller or equal to 0.40%.
3. a kind of pharmaceutical composition that contains vinpocetine according to claim 1, wherein in the vinpocetine raw material impurity dihydro vinpocetine weight percentage smaller or equal to 0.10%.
4. a kind of pharmaceutical composition that contains vinpocetine according to claim 1, wherein in the vinpocetine raw material impurity apo-vincamine weight percentage smaller or equal to 0.30%.
5. a kind of pharmaceutical composition that contains vinpocetine according to claim 1, wherein in the vinpocetine raw material impurity methoxyl group vinpocetine weight percentage smaller or equal to 0.30%.
6. pharmaceutical composition that contains the vinpocetine raw material; Comprise vinpocetine raw material, sodium chloride and cosolvent in the pharmaceutical composition; Preparation of pharmaceutical compositions becomes aqueous solution; The weight ratio that it is characterized in that vinpocetine and cosolvent is 1: 0.5-1.10, and wherein impurity Calan weight percentage is smaller or equal to 0.40% in the vinpocetine raw material, and impurity dihydro vinpocetine weight percentage is smaller or equal to 0.10%; Impurity apo-vincamine weight percentage is smaller or equal to 0.30%, and impurity methoxyl group vinpocetine weight percentage is smaller or equal to 0.30% in the vinpocetine raw material.
7. according to claim 1 or 6 described a kind of pharmaceutical compositions that contain vinpocetine, wherein cosolvent comprises one or more in citric acid, tartaric acid, glutamic acid, lactic acid, sorbic acid, the L-threonine.
8. according to claim 1 or 6 described a kind of pharmaceutical compositions that contain vinpocetine, wherein the weight ratio of vinpocetine raw material and cosolvent is 1: 0.6 in the pharmaceutical composition.
9. according to claim 1 or 6 described a kind of pharmaceutical compositions that contain vinpocetine, wherein cosolvent is a citric acid in the pharmaceutical composition.
10. according to claim 1 or 6 described a kind of pharmaceutical compositions that contain vinpocetine, wherein cosolvent is citric acid and L-threonine in the pharmaceutical composition; Wherein the weight ratio of cosolvent citric acid and L-threonine is 1 in the pharmaceutical composition: 0.1-0.5.
11. according to claim 1 or 6 each said a kind of pharmaceutical composition application in preparation treatment cerebral infarction sequela, apoplexy sequela, cerebral arteriosclerosis disease drug that contain vinpocetine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101872018A CN102688186A (en) | 2012-06-08 | 2012-06-08 | Medicine composition containing vinpocetine raw material |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101872018A CN102688186A (en) | 2012-06-08 | 2012-06-08 | Medicine composition containing vinpocetine raw material |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102688186A true CN102688186A (en) | 2012-09-26 |
Family
ID=46854035
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012101872018A Pending CN102688186A (en) | 2012-06-08 | 2012-06-08 | Medicine composition containing vinpocetine raw material |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102688186A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106117198A (en) * | 2016-07-01 | 2016-11-16 | 江苏正大清江制药有限公司 | The crystal formation of the salt that a kind of vinpocetine is formed with D tartaric acid and preparation method |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101991530A (en) * | 2009-08-28 | 2011-03-30 | 沈阳志鹰制药厂 | Vinpocetine containing high-capacity sodium chloride injection and preparation method thereof |
| CN102038680A (en) * | 2010-11-24 | 2011-05-04 | 常建晖 | Medical composition |
| CN102091030A (en) * | 2011-01-20 | 2011-06-15 | 罗军 | Vinpocetine injection and preparation method thereof |
| CN102228428A (en) * | 2011-06-30 | 2011-11-02 | 武汉同源药业有限公司 | Large volume injection composition containing vinpocetine and preparation method thereof |
-
2012
- 2012-06-08 CN CN2012101872018A patent/CN102688186A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101991530A (en) * | 2009-08-28 | 2011-03-30 | 沈阳志鹰制药厂 | Vinpocetine containing high-capacity sodium chloride injection and preparation method thereof |
| CN102038680A (en) * | 2010-11-24 | 2011-05-04 | 常建晖 | Medical composition |
| CN102091030A (en) * | 2011-01-20 | 2011-06-15 | 罗军 | Vinpocetine injection and preparation method thereof |
| CN102228428A (en) * | 2011-06-30 | 2011-11-02 | 武汉同源药业有限公司 | Large volume injection composition containing vinpocetine and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 张秀杰: "注射用长春西汀稳定性考察", 《中国医药导报》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106117198A (en) * | 2016-07-01 | 2016-11-16 | 江苏正大清江制药有限公司 | The crystal formation of the salt that a kind of vinpocetine is formed with D tartaric acid and preparation method |
| CN106117198B (en) * | 2016-07-01 | 2017-10-17 | 江苏正大清江制药有限公司 | The crystal formation and preparation method of a kind of vinpocetine and the salt of D tartaric acid formation |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zeng et al. | Pharmacokinetics and safety of ginsenoside Rd following a single or multiple intravenous dose in healthy Chinese volunteers | |
| CN102091030A (en) | Vinpocetine injection and preparation method thereof | |
| CN102552294A (en) | Compound vitamin (3) freeze-dried powder injection for injection and preparation method and analysis method thereof | |
| CN103989677A (en) | Use of demethyleneberberine in preparation of blood sugar-reduction drug | |
| CN103919775A (en) | Application of 9-demethylberberine in preparation of hpyerglycemic drug | |
| CN102743401B (en) | Application of panaxadiol saponins fraction in preparing medicine for preventing epilepsia | |
| CN102499923A (en) | Drug combination, as well as preparation method and application of same | |
| CN105078909A (en) | Cisatracurium besilate freeze dried composition for injection and preparation method thereof | |
| CN102038680B (en) | Medical composition | |
| CN102688186A (en) | Medicine composition containing vinpocetine raw material | |
| CN102351722B (en) | L-carnitine compound and composite thereof | |
| CN102440998A (en) | Compound doxycycline hyclate suspension injection and preparation method thereof | |
| CN101485632B (en) | Nimodipine lipid microsphere injection and preparation method thereof | |
| CN100396289C (en) | Scutellarin injection preparation and its preparing method | |
| CN104490902B (en) | A kind of composite vitamin for injection freeze drying powder injection composition and preparation method thereof | |
| CN103520186B (en) | Pharmaceutical composition of a kind of fat-soluble vitamin for injection and preparation method thereof | |
| CN102552210B (en) | Entecavir capsule and preparation method thereof | |
| CN105560607A (en) | Preparation method and application of preparation having antithrombotic and anti-myocardial ischemic effects | |
| CN102247372B (en) | Methionine-containing medicinal composition and preparation method thereof | |
| CN100457101C (en) | Propylgallate injection with favorable solubility and its preparation process | |
| CN105147664B (en) | Puerarin injection and preparation method | |
| CN103393595A (en) | Pharmaceutical composition of edaravone | |
| CN103638017A (en) | Composition of ginkgolide A and ginkgolide B and application of composition | |
| CN112426429B (en) | Carbohydrate composition for nourishing yin and supplementing blood for yin and blood deficiency syndrome | |
| CN107184548A (en) | A kind of safe L-ornidazole injection liquid and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| ASS | Succession or assignment of patent right |
Owner name: BEIJING YMKY PHARMACEUTICAL TECHNOLOGY CO. LTD. Free format text: FORMER OWNER: TIBET YIMING XIYA BIOMEDICAL TECHNOLOGY CO., LTD. Effective date: 20120823 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20120823 Address after: 100098 Beijing city Haidian District No. 48 Zhichun Road Yingdu building B block 22 layer Applicant after: Beijing Yiming Kangyuan Pharmaceutical Technology Co., Ltd. Address before: 100098 Beijing city Haidian District No. 48 Zhichun Road Yingdu building B block 22 layer Applicant before: Tibet Yiming Xiya Biological Medical Technology Co., Ltd. |
|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C53 | Correction of patent of invention or patent application | ||
| CB02 | Change of applicant information |
Address after: 100098 Beijing city Haidian District No. 48 Zhichun Road Yingdu building C-4-15A Applicant after: Beijing Yiming Kangyuan Pharmaceutical Technology Co., Ltd. Address before: 100098 Beijing city Haidian District No. 48 Zhichun Road Yingdu building B block 22 layer Applicant before: Beijing Yiming Kangyuan Pharmaceutical Technology Co., Ltd. |
|
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20120926 |