CN105267160B - A kind of injection vinpocetine lyophilized preparation composition and preparation method thereof - Google Patents
A kind of injection vinpocetine lyophilized preparation composition and preparation method thereof Download PDFInfo
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- CN105267160B CN105267160B CN201510820610.0A CN201510820610A CN105267160B CN 105267160 B CN105267160 B CN 105267160B CN 201510820610 A CN201510820610 A CN 201510820610A CN 105267160 B CN105267160 B CN 105267160B
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Abstract
The present invention provides a kind of injection vinpocetine lyophilized preparation compositions and preparation method thereof.Injection vinpocetine lyophilized preparation composition of the invention is made of vinpocetine, citric acid, mannitol, isobutanol, acetamide etc..Injection vinpocetine lyophilized preparation composition of the invention has the characteristics that high, the related content of material of stability is low, is suitble to industrialized production.
Description
Technical field
The present invention relates to technical field of medicine, and in particular to a kind of novel injection vinpocetine lyophilized preparation group
Close object and preparation method thereof.
Background technique
Vinpocetine (Vinpocetine) is cerebral vasodilator, can inhibit phosphodiesterase activity, increases vascular smooth
The effect of the courier c-GMP of muscular relaxation, selectively increases cerebral blood flow (CBF), furthermore can also inhibit platelet aggregation, reduces human body
Blood viscosity enhances erythrocyte deformabiliy, improves blood fluidity and microcirculation, and brain tissue is promoted to absorb glucose, increases brain
Oxygen demand improves brain metabolism.Vinpocetine is suitable for improving sequelae for cerebral infraction, cerebral hemorrhage sequelae, cerebral arteriosclerosis etc.
The various symptoms of induction.Chemistry entitled " ethyl (13as, 13bs) -13a- ethyl -2,3,5,6-13a, the 13b- six of vinpocetine
Hydrogen -1H- indoles [3,2,1--de] pyridine [3,2,1--ij] [1,5]-benzodiazine -12- carboxylic acid ", structural formula is as follows:
Vinpocetine is easily oxidized, and sodium pyrosulfite etc. is often added in injection, and there are the auxiliary materials of potential hazard.Existing skill
In art, CN200410045419.7, CN200810089085.X, CN201210042786.4 etc. are to vinpocetine lyophilized preparation
Certain research is carried out, but still higher there are related content of material or the problems such as growth rate is larger during storage, always
Effective solution is not provided to the problems such as stability of vinpocetine lyophilized preparation.
Therefore, a kind of stability injection vinpocetine that is high, low in relation to content of material, being suitble to industrialized production is developed to freeze
Dry preparation composition and preparation method thereof becomes the urgent need of those skilled in the art.
Summary of the invention
The purpose of the present invention is be just to provide a kind of stability note that is high, low in relation to content of material, being suitble to industrialized production
It penetrates with vinpocetine lyophilized preparation composition.
In order to solve the above-mentioned technical problem, The technical solution adopted by the invention is as follows:
The present invention provides a kind of injection vinpocetine lyophilized preparation compositions, are dissolved in water for injection by following components
After be lyophilized:
500 parts by weight of vinpocetine,
550 parts by weight of citric acid,
3000 parts by weight of mannitol,
Isobutanol 0.1-0.2 parts by weight,
Acetamide 10-30 parts by weight.
Wherein, the pH value of the injection vinpocetine lyophilized preparation composition is 3.0-4.5.
Particularly, the present invention provides following three kinds of injections vinpocetine lyophilized preparation composition:
(1)
Vinpocetine 5g,
Citric acid 5.5g,
Mannitol 30g,
Isobutanol 1mg,
Acetamide 100mg,
Water for injection adds to 1000ml.
(2)
Vinpocetine 5g,
Citric acid 5.5g,
Mannitol 30g,
Isobutanol 2mg,
Acetamide 300mg,
Water for injection adds to 1000ml.
(3)
Vinpocetine 5g,
Citric acid 5.5g,
Mannitol 30g,
Isobutanol 1.5mg,
Acetamide 200mg,
Water for injection adds to 1000ml.
Wherein, the injection vinpocetine lyophilized preparation composition the preparation method is as follows:
1) appropriate water for injection is added in the vinpocetine of recipe quantity, mannitol, stirred evenly；
2) it after appropriate water for injection dissolution is added in citric acid, is added in step 1) solution, continuously adds the isobutyl of recipe quantity
Alcohol, acetamide, stirring to medical fluid are clarified；
3) pH value 3.0-4.5 is adjusted；
4) active carbon is added in water for injection constant volume, stirs, filtering；
5) it is sterile filtered, dispenses into cillin bottle, lid is rolled in freeze-drying, packs.
Wherein the step of freeze drying is preferably as follows:
1) pre-freeze: sample enters freeze drying box, cools the temperature to -40 DEG C hereinafter, heat preservation 1-2 hours；
2) it distils: freeze drying box being evacuated to 10-15Pa, is to slowly warm up to 15 DEG C, lyophilization 2-3 hours；
3) dry: temperature is risen to 35 DEG C~40 DEG C, keeps the temperature 2~4 hours, parsing-desiccation, tamponade outlet.
On the other hand, the invention further relates to the preparation methods of the injection vinpocetine lyophilized preparation composition, comprising:
1) appropriate water for injection is added in the vinpocetine of recipe quantity, mannitol, stirred evenly；
2) it after appropriate water for injection dissolution is added in citric acid, is added in step 1) solution, continuously adds the isobutyl of recipe quantity
Alcohol, acetamide, stirring to medical fluid are clarified；
3) pH value 3.0-4.5 is adjusted；
4) active carbon is added in water for injection constant volume, stirs, filtering；
5) it is sterile filtered, dispenses into cillin bottle, lid is rolled in freeze-drying, packs.
Based on the above-mentioned technical proposal, the present invention achieves following beneficial effect and technological progress:
Injection vinpocetine lyophilized preparation composition of the invention has high, the related content of material of stability low, suitable
The features such as industrialized production, auxiliary material safety and dosage are few.
Specific embodiment
Specific embodiment is only that the present invention is further explained and described, and is not necessarily to be construed as to any limit of the invention
System.
Supplementary material used is commercially available in embodiment.
The injection vinpocetine lyophilized preparation composition of the invention of embodiment 1
Prescription:
Vinpocetine 5g,
Citric acid 5.5g,
Mannitol 30g,
Isobutanol 1mg,
Acetamide 100mg,
Water for injection adds to 1000ml.
Preparation method:
1) appropriate water for injection is added in the vinpocetine of recipe quantity, mannitol, stirred evenly；
2) it after appropriate water for injection dissolution is added in citric acid, is added in step 1) solution, continuously adds the isobutyl of recipe quantity
Alcohol, acetamide, stirring to medical fluid are clarified；
3) pH value 3.0-4.5 is adjusted；
4) water for injection is settled to 1000ml, and active carbon is added, and stirs, filtering；
5) it is sterile filtered, is dispensed into 1000 cillin bottles using 0.22 μm of filter membrane, lid is rolled in freeze-drying, packs.
Wherein step of freeze drying is as follows:
1) pre-freeze: sample enters freeze drying box, cools the temperature to -40 DEG C hereinafter, heat preservation 1-2 hours；
2) it distils: freeze drying box being evacuated to 10-15Pa, is to slowly warm up to 15 DEG C, lyophilization 2-3 hours；
3) dry: temperature is risen to 35 DEG C~40 DEG C, keeps the temperature 2~4 hours, parsing-desiccation, tamponade outlet.
The injection vinpocetine lyophilized preparation composition of the invention of embodiment 2
Prescription:
Vinpocetine 5g,
Citric acid 5.5g,
Mannitol 30g,
Isobutanol 2mg,
Acetamide 300mg,
Water for injection adds to 1000ml.
Preparation method:
With embodiment 1.
The injection vinpocetine lyophilized preparation composition of the invention of embodiment 3
Prescription:
Vinpocetine 5g,
Citric acid 5.5g,
Mannitol 30g,
Isobutanol 1.5mg,
Acetamide 200mg,
Water for injection adds to 1000ml.
Preparation method:
With embodiment 1.
1 injection vinpocetine lyophilized preparation composition of reference examples
Prescription:
Vinpocetine 5g,
Citric acid 5.5g,
Mannitol 30g,
Water for injection adds to 1000ml.
Preparation method:
With embodiment 1.
2 injection vinpocetine lyophilized preparation composition of reference examples
Prescription:
Vinpocetine 5g,
Citric acid 5.5g,
Mannitol 30g,
Acetamide 400mg,
Water for injection adds to 1000ml.
Preparation method:
With embodiment 1.
Test example: the stability study of injection vinpocetine lyophilized preparation composition
Vinpocetine lyophilized preparation composition made from Example 1-3 and reference examples 1-2, commercially available back are produced with listing
It places 6 months in constant incubator of the product equally under the conditions of 40 DEG C ± 2 DEG C of temperature, relative humidity 75% ± 5%, respectively at 1,
2,3,6 the end of month samplings, investigate character, visible foreign matters, the situation of change in relation to substance etc..Wherein, the detection side in relation to substance
Method is as follows:
Chromatographic condition and system suitability are filler with octadecylsilane chemically bonded silica, with 0.2mol/L vinegar
Sour ammonium-acetonitrile (30:70) is mobile phase, and Detection wavelength 280nm, adjusting proportion of mobile phase makes the retention time at vinpocetine peak
About 13 minutes, number of theoretical plate is calculated by vinpocetine should be not less than 3000.
Measuring method takes this product appropriate (being approximately equivalent to vinpocetine 50mg), sets in 100ml measuring bottle, adds flowing phased soln simultaneously
It is diluted to scale, is shaken up, as test solution；Precision measures test solution 1ml, sets in 100ml measuring bottle, dilute with mobile phase
It releases to scale, as contrast solution.According to high performance liquid chromatography (two annex VD of Chinese Pharmacopoeia version in 2010), precision is got pair
Liquid chromatograph is injected according to 20 μ l of solution, adjusts detection sensitivity, making principal component chromatography peak height is about the 10-25% of full scale；Again
Take contrast solution and test solution each 20 μ l injection liquid chromatograph, 2 times of record chromatogram to main peak retention time.For examination
Such as display impurity peaks in the chromatogram of product solution, deduct outside auxiliary material peak, single impurity peaks peak area is not greater than contrast solution master
The 1/2(0.5% of peak area), each impurity peaks second you the sum of, be not greater than contrast solution main peak area (1.0%).
Testing result:
As it can be seen that the stability of injection vinpocetine lyophilized preparation composition (embodiment 1-3) of the invention is substantially better than
Reference examples and commercialized product.
Claims (8)
1. a kind of injection vinpocetine lyophilized preparation composition, is lyophilized after being dissolved in water for injection by following components:
2. injection vinpocetine lyophilized preparation composition according to claim 1, pH value 3.0-4.5.
3. injection vinpocetine lyophilized preparation composition according to claim 1, preparation method are as follows:
1) appropriate water for injection is added in the vinpocetine of recipe quantity, mannitol, stirred evenly；
2) it after appropriate water for injection dissolution is added in citric acid, is added in step 1) solution, continuously adds isobutanol, the second of recipe quantity
Amide, stirring to medical fluid are clarified；
3) pH value 3.0-4.5 is adjusted；
4) active carbon is added in water for injection constant volume, stirs, filtering；
5) it is sterile filtered, dispenses into cillin bottle, lid is rolled in freeze-drying, packs.
4. injection vinpocetine lyophilized preparation composition according to claim 2, wherein the step of freeze drying is as follows:
1) pre-freeze: sample enters freeze drying box, cools the temperature to -40 DEG C hereinafter, heat preservation 1-2 hours；
2) it distils: freeze drying box being evacuated to 10-15Pa, is to slowly warm up to 15 DEG C, lyophilization 1-2 hours；
3) dry: temperature is risen to 35 DEG C~40 DEG C, keeps the temperature 2~4 hours, parsing-desiccation, tamponade outlet.
5. injection vinpocetine lyophilized preparation composition according to claim 1 forms as follows:
6. injection vinpocetine lyophilized preparation composition according to claim 1 forms as follows:
7. injection vinpocetine lyophilized preparation composition according to claim 1 forms as follows:
8. the preparation method of any injection vinpocetine lyophilized preparation composition of claim 1-7, comprising:
1) appropriate water for injection is added in the vinpocetine of recipe quantity, mannitol, stirred evenly；
2) it after appropriate water for injection dissolution is added in citric acid, is added in step 1) solution, continuously adds isobutanol, the second of recipe quantity
Amide, stirring to medical fluid are clarified；
3) pH value 3.0-4.5 is adjusted；
4) active carbon is added in water for injection constant volume, stirs, filtering；
5) it is sterile filtered, dispenses into cillin bottle, lid is rolled in freeze-drying, packs.
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| CN201510820610.0A CN105267160B (en) | 2015-11-24 | 2015-11-24 | A kind of injection vinpocetine lyophilized preparation composition and preparation method thereof |
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| CN105267160B true CN105267160B (en) | 2019-05-14 |
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| CN109364021A (en) * | 2018-10-26 | 2019-02-22 | 山西普德药业有限公司 | A kind of injection vinpocetine |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1572296A (en) * | 2003-06-11 | 2005-02-02 | 山东绿叶制药股份有限公司 | Freeze dried vinpocetine powder injection and its preparation process |
| CN101264064A (en) * | 2008-04-17 | 2008-09-17 | 孙向阳 | Vinpocetine freeze-dried powder for injection and preparation thereof |
| WO2008151415A1 (en) * | 2007-06-11 | 2008-12-18 | Nathan Bryson | Combination for treatment of diabetes mellitus |
| CN101721361A (en) * | 2009-12-08 | 2010-06-09 | 李荣立 | Pervone vincamine injection and preparation process thereof |
| CN101791310A (en) * | 2010-02-24 | 2010-08-04 | 王保明 | Vinpocetine medicine composition and preparation method thereof |
| CN102091030A (en) * | 2011-01-20 | 2011-06-15 | 罗军 | Vinpocetine injection and preparation method thereof |
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2015
- 2015-11-24 CN CN201510820610.0A patent/CN105267160B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1572296A (en) * | 2003-06-11 | 2005-02-02 | 山东绿叶制药股份有限公司 | Freeze dried vinpocetine powder injection and its preparation process |
| WO2008151415A1 (en) * | 2007-06-11 | 2008-12-18 | Nathan Bryson | Combination for treatment of diabetes mellitus |
| CN101264064A (en) * | 2008-04-17 | 2008-09-17 | 孙向阳 | Vinpocetine freeze-dried powder for injection and preparation thereof |
| CN101721361A (en) * | 2009-12-08 | 2010-06-09 | 李荣立 | Pervone vincamine injection and preparation process thereof |
| CN101791310A (en) * | 2010-02-24 | 2010-08-04 | 王保明 | Vinpocetine medicine composition and preparation method thereof |
| CN102091030A (en) * | 2011-01-20 | 2011-06-15 | 罗军 | Vinpocetine injection and preparation method thereof |
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Address after: Gucheng Dingxing County in Hebei province Baoding City No. 072650 Applicant after: Hebei wisdom biopharmaceutical Limited by Share Ltd Address before: Gucheng Dingxing County in Hebei province Baoding City No. 072650 Applicant before: Hebei Zhi Tong Biology Pharmacy Co., Ltd |
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