CN105267160A - Vinpocetine freeze-drying preparation composition for injection and preparing method thereof - Google Patents
Vinpocetine freeze-drying preparation composition for injection and preparing method thereof Download PDFInfo
- Publication number
- CN105267160A CN105267160A CN201510820610.0A CN201510820610A CN105267160A CN 105267160 A CN105267160 A CN 105267160A CN 201510820610 A CN201510820610 A CN 201510820610A CN 105267160 A CN105267160 A CN 105267160A
- Authority
- CN
- China
- Prior art keywords
- injection
- vinpocetine
- lyophilized formulations
- water
- mannitol
- 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.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention provides a vinpocetine freeze-drying preparation composition for injection and a preparing method thereof. The vinpocetine freeze-drying preparation composition for injection is prepared from vinpocetine, citric acid, mannitol, isobutanol, acetamide and the like. The vinpocetine freeze-drying preparation composition for injection has the advantages of being high in stability, low in related substance content, suitable for industrial production and the like.
Description
Technical field
The present invention relates to technical field of medicine, be specifically related to a kind of novel injection vinpocetine lyophilized formulations composition and method of making the same.
Background technology
Vinpocetine (Vinpocetine) is cerebral vasodilator, phosphodiesterase activity can be suppressed, increase the effect of the courier c-GMP of vascular smooth muscle relaxation, optionally increase cerebral blood flow, can also platelet aggregation be suppressed in addition, reduce human blood viscosity, strengthen erythrocyte deformabiliy, improve blood fluidity and microcirculation, promote cerebral tissue ingestion of glucose, increase brain oxygen consumption, improve brain metabolism.Vinpocetine is applicable to improve the various symptoms that cerebral infarction sequela, apoplexy sequela, cerebral arteriosclerosis etc. are brought out.The chemistry of vinpocetine " ethyl (13as, 13bs)-13a-ethyl-2,3,5,6-13a, 13b-six hydrogen-1H-indole [3,2,1--de] pyridine [3,2,1--ij] [1,5]-benzodiazine-12-carboxylic acid " by name, structural formula is as follows:
Vinpocetine is easily oxidized, and in injection, normal interpolation sodium pyrosulfite etc. exist the adjuvant of potential hazard.In prior art, CN200410045419.7, CN200810089085.X, CN201210042786.4 etc. have all carried out certain research to vinpocetine lyophilized formulations, but still there is the higher or problem such as rate of increase is larger in storage process of its related substances, do not provide effective solution to problems such as the stability of vinpocetine lyophilized formulations always.
Therefore, develop that a kind of stability is high, its related substances is low, be applicable to the urgent needs that the injection vinpocetine lyophilized formulations composition and method of making the same of suitability for industrialized production becomes those skilled in the art.
Summary of the invention
The object of the invention is just to be to provide that a kind of stability is high, its related substances is low, be applicable to the injection vinpocetine lyophilized formulations compositions of suitability for industrialized production.
In order to solve the problems of the technologies described above, the technical solution used in the present invention is as follows:
The invention provides a kind of injection vinpocetine lyophilized formulations compositions, after it is dissolved in water for injection by following component, lyophilizing forms:
Vinpocetine 500 weight portion,
Citric acid 550 weight portion,
Mannitol 3000 weight portion,
Isobutanol 0.1-0.2 weight portion,
Acetamide 10-30 weight portion.
Wherein, the pH value of described injection vinpocetine lyophilized formulations compositions is 3.0-4.5.
Especially, the invention provides following three kinds of injection vinpocetine lyophilized formulations compositionss:
（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 preparation method of described injection vinpocetine lyophilized formulations compositions is as follows:
1) vinpocetine of recipe quantity, mannitol are added appropriate water for injection, stir;
2) after citric acid adds the dissolving of appropriate water for injection, add in step 1) solution, continue the isobutanol, the acetamide that add recipe quantity, be stirred to medicinal liquid clarification;
3) adjust ph 3.0-4.5;
4) water for injection standardize solution, adds active carbon, stirs, and filters;
5) aseptic filtration, divide and be filled in cillin bottle, lyophilizing, rolls lid, packaging.
Wherein said step of freeze drying is preferably as follows:
1) pre-freeze: sample enters freeze drying box, cools the temperature to less than-40 DEG C, insulation 1-2 hour;
2) distil: freeze drying box is evacuated to 10-15Pa, is slowly warming up to 15 DEG C, sublimation drying 2-3 hour;
3) dry: temperature to be risen to 35 DEG C ~ 40 DEG C, be incubated 2 ~ 4 hours, parsing-desiccation, tamponade outlet.
On the other hand, the invention still further relates to the preparation method of described injection vinpocetine lyophilized formulations compositions, comprising:
1) vinpocetine of recipe quantity, mannitol are added appropriate water for injection, stir;
2) after citric acid adds the dissolving of appropriate water for injection, add in step 1) solution, continue the isobutanol, the acetamide that add recipe quantity, be stirred to medicinal liquid clarification;
3) adjust ph 3.0-4.5;
4) water for injection standardize solution, adds active carbon, stirs, and filters;
5) aseptic filtration, divide and be filled in cillin bottle, lyophilizing, rolls lid, packaging.
Based on technique scheme, the present invention achieves following beneficial effect and technological progress:
Injection vinpocetine lyophilized formulations compositions of the present invention has that stability is high, its related substances is low, is applicable to suitability for industrialized production, adjuvant safety and the feature such as consumption is few.
Detailed description of the invention
Detailed description of the invention is only and further explains and describes the present invention, should not be interpreted as any limitation of the invention.
In embodiment, supplementary material used is commercial.
embodiment 1 injection vinpocetine of the present invention lyophilized formulations compositions
Prescription:
Vinpocetine 5g,
Citric acid 5.5g,
Mannitol 30g,
Isobutanol 1mg,
Acetamide 100mg,
Water for injection adds to 1000ml.
Preparation method:
1) vinpocetine of recipe quantity, mannitol are added appropriate water for injection, stir;
2) after citric acid adds the dissolving of appropriate water for injection, add in step 1) solution, continue the isobutanol, the acetamide that add recipe quantity, be stirred to medicinal liquid clarification;
3) adjust ph 3.0-4.5;
4) water for injection is settled to 1000ml, adds active carbon, stirs, and filters;
5) use 0.22 μm of filter membrane aseptic filtration, divide and be filled in 1000 cillin bottles, lyophilizing, rolls lid, packaging.
Wherein step of freeze drying is as follows:
1) pre-freeze: sample enters freeze drying box, cools the temperature to less than-40 DEG C, insulation 1-2 hour;
2) distil: freeze drying box is evacuated to 10-15Pa, is slowly warming up to 15 DEG C, sublimation drying 2-3 hour;
3) dry: temperature to be risen to 35 DEG C ~ 40 DEG C, be incubated 2 ~ 4 hours, parsing-desiccation, tamponade outlet.
embodiment 2 injection vinpocetine of the present invention lyophilized formulations compositions
Prescription:
Vinpocetine 5g,
Citric acid 5.5g,
Mannitol 30g,
Isobutanol 2mg,
Acetamide 300mg,
Water for injection adds to 1000ml.
Preparation method:
With embodiment 1.
embodiment 3 injection vinpocetine of the present invention lyophilized formulations compositions
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.
reference examples 1 injection vinpocetine lyophilized formulations compositions
Prescription:
Vinpocetine 5g,
Citric acid 5.5g,
Mannitol 30g,
Water for injection adds to 1000ml.
Preparation method:
With embodiment 1.
reference examples 2 injection vinpocetine lyophilized formulations compositions
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 formulations compositions
The vinpocetine lyophilized formulations compositions that Example 1-3 and reference examples 1-2 is obtained, commercially available back, place 6 months in the constant incubator under temperature 40 DEG C ± 2 DEG C, relative humidity 75% ± 5% condition same with commercialized product, respectively at 1,2,3,6 samplings at the end of month, investigate the situation of change of character, visible foreign matters, related substance etc.Wherein, the detection method of related substance is as follows:
Chromatographic condition and system suitability octadecylsilane chemically bonded silica are filler, with 0.2mol/L ammonium acetate-acetonitrile (30:70) for mobile phase, determined wavelength is 280nm, adjustment proportion of mobile phase makes the retention time at vinpocetine peak be about 13 minutes, and number of theoretical plate calculates should be not less than 3000 by vinpocetine.
Algoscopy gets this product appropriate (being about equivalent to vinpocetine 50mg), puts in 100ml measuring bottle, adds mobile phase and dissolve and be diluted to scale, shake up, as need testing solution; Precision measures need testing solution 1ml, puts in 100ml measuring bottle, is diluted to scale with mobile phase, in contrast solution.According to high performance liquid chromatography (Chinese Pharmacopoeia version in 2010 two annex VD), precision gets contrast solution 20 μ l injection liquid chromatography, regulates detection sensitivity, makes main constituent chromatograph peak height be about the 10-25% of full scale; Get contrast solution and each 20 μ l injection liquid chromatographies of need testing solution again, record chromatogram is to 2 times of main peak retention time.As display impurity peaks in the chromatogram of need testing solution, outside deduction adjuvant peak, single impurity peaks peak area must not be greater than the 1/2(0.5% of contrast solution main peak area), each impurity peaks second, your sum, must not be greater than contrast solution main peak area (1.0%).
Testing result:
Visible, the stability of injection vinpocetine lyophilized formulations compositions (embodiment 1-3) of the present invention is obviously better than reference examples and commercialized product.
Claims (8)
1. an injection vinpocetine lyophilized formulations compositions, after it is dissolved in water for injection by following component, lyophilizing forms:
Vinpocetine 500 weight portion,
Citric acid 550 weight portion,
Mannitol 3000 weight portion,
Isobutanol 0.1-0.2 weight portion,
Acetamide 10-30 weight portion.
2. injection vinpocetine lyophilized formulations compositions according to claim 1, its pH value is 3.0-4.5.
3. injection vinpocetine lyophilized formulations compositions according to claim 1, its preparation method is as follows:
1) vinpocetine of recipe quantity, mannitol are added appropriate water for injection, stir;
2) after citric acid adds the dissolving of appropriate water for injection, add in step 1) solution, continue the isobutanol, the acetamide that add recipe quantity, be stirred to medicinal liquid clarification;
3) adjust ph 3.0-4.5;
4) water for injection standardize solution, adds active carbon, stirs, and filters;
5) aseptic filtration, divide and be filled in cillin bottle, lyophilizing, rolls lid, packaging.
4. injection vinpocetine lyophilized formulations compositions according to claim 2, wherein said step of freeze drying is as follows:
1) pre-freeze: sample enters freeze drying box, cools the temperature to less than-40 DEG C, insulation 1-2 hour;
2) distil: freeze drying box is evacuated to 10-15Pa, is slowly warming up to 15 DEG C, sublimation drying 1-2 hour;
3) dry: temperature to be risen to 35 DEG C ~ 40 DEG C, be incubated 2 ~ 4 hours, parsing-desiccation, tamponade outlet.
5. injection vinpocetine lyophilized formulations compositions according to claim 1, it is composed as follows:
Citric acid 5.5g,
Mannitol 30g,
Isobutanol 1.5mg,
Acetamide 200mg,
Water for injection adds to 1000ml.
6. injection vinpocetine lyophilized formulations compositions according to claim 1, it is composed as follows:
Vinpocetine 5g,
Citric acid 5.5g,
Mannitol 30g,
Isobutanol 2mg,
Acetamide 300mg,
Water for injection adds to 1000ml.
7. injection vinpocetine lyophilized formulations compositions according to claim 1, it is composed as follows:
Vinpocetine 5g,
Citric acid 5.5g,
Mannitol 30g,
Isobutanol 1.5mg,
Acetamide 200mg,
Water for injection adds to 1000ml.
8. the preparation method of the arbitrary described injection vinpocetine lyophilized formulations compositions of claim 1-7, comprising:
1) vinpocetine of recipe quantity, mannitol are added appropriate water for injection, stir;
2) after citric acid adds the dissolving of appropriate water for injection, add in step 1) solution, continue the isobutanol, the acetamide that add recipe quantity, be stirred to medicinal liquid clarification;
3) adjust ph 3.0-4.5;
4) water for injection standardize solution, adds active carbon, stirs, and filters;
5) aseptic filtration, divide and be filled in cillin bottle, lyophilizing, rolls lid, packaging.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510820610.0A CN105267160B (en) | 2015-11-24 | 2015-11-24 | A kind of injection vinpocetine lyophilized preparation composition and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510820610.0A CN105267160B (en) | 2015-11-24 | 2015-11-24 | A kind of injection vinpocetine lyophilized preparation composition and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105267160A true CN105267160A (en) | 2016-01-27 |
| CN105267160B CN105267160B (en) | 2019-05-14 |
Family
ID=55137568
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510820610.0A Active CN105267160B (en) | 2015-11-24 | 2015-11-24 | A kind of injection vinpocetine lyophilized preparation composition and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105267160B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
-
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 |
Non-Patent Citations (2)
| Title |
|---|
| 贾益群等: "《食品添加剂和药剂辅料质谱与红外光谱鉴定》", 31 August 2007, 吉林大学出版社 * |
| 赵鹤皋等: "《冷冻干燥技术与设备》", 30 June 2005, 华中科技大学出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109364021A (en) * | 2018-10-26 | 2019-02-22 | 山西普德药业有限公司 | A kind of injection vinpocetine |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105267160B (en) | 2019-05-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2842957B1 (en) | Method for extracting and separating ginkgolides | |
| CN101869551B (en) | Temozolomide freeze-dried preparation | |
| CN108659104B (en) | Preparation method of terlipressin and pharmaceutical composition thereof | |
| CN102525963B (en) | Netilmicin sulfate lyophiled powder injection and preparation method thereof | |
| CN101899074B (en) | Preparation method for monosialotetrahexosyl ganglioside and monosialotetrahexosyl ganglioside sodium injection or freeze-dried powder injection | |
| JP3714951B2 (en) | IL-6-containing pharmaceutical composition | |
| CN105267160A (en) | Vinpocetine freeze-drying preparation composition for injection and preparing method thereof | |
| AU2013377601B2 (en) | Stable nocathiacin lyophilized powder injection agent | |
| CN102895200B (en) | Mecobalamine freeze-drying composition and preparation method thereof | |
| CN102274233B (en) | Medicinal composition of cefoperazone sodium and tazobactam sodium | |
| CN113769081A (en) | Stable high-concentration anti-human IL-5 monoclonal antibody liquid preparation | |
| CN102743342B (en) | Sodium fusidate lyophilized composition for injection | |
| CN106389359B (en) | His pharmaceutical composition of the Baily department of injection and preparation method thereof | |
| CN105287371A (en) | Pazufloxacin mesilate injection composition and preparation method thereof | |
| CN104771369A (en) | Fludarabine phosphate freeze-dried powder injection | |
| CN104856964B (en) | Alanyl glutamine lyophilized formulations and preparation method thereof | |
| CN108676085B (en) | A kind of preparation method and its pharmaceutical composition of thymalfasin | |
| CN103271880A (en) | Cefodizime sodium injection and preparation method thereof | |
| CN105287600A (en) | Gram-negative bacterium-resistant cefoxitin sodium freeze-dried powder for injection | |
| CN104173280A (en) | Ornithine aspartate injection composition | |
| CN103877579B (en) | A kind of pharmaceutical composition and preparation thereof containing famotidine | |
| CN108774285B (en) | Preparation method of somatostatin and pharmaceutical composition thereof | |
| CN105267161B (en) | A kind of cobamamide lyophilized preparation for injection composition and preparation method thereof | |
| CN104262436A (en) | Amorphous calcium bucladesine sterile powder | |
| CN110101670A (en) | A kind of aztreonam ejection preparation and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| CB02 | Change of applicant information |
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 |
|
| COR | Change of bibliographic data | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |