CN110179745A - A kind of Vinpocetine injection and preparation method thereof - Google Patents
A kind of Vinpocetine injection and preparation method thereof Download PDFInfo
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- CN110179745A CN110179745A CN201810774472.0A CN201810774472A CN110179745A CN 110179745 A CN110179745 A CN 110179745A CN 201810774472 A CN201810774472 A CN 201810774472A CN 110179745 A CN110179745 A CN 110179745A
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- vinpocetine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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Abstract
The present invention relates to a kind of Vinpocetine injections and preparation method thereof.Vinpocetine injection of the invention has ensured the sterile level of drug using aseptic filtration mode, it avoids using benzyl alcohol as preservative, the production method using high-temperature sterilization is avoided simultaneously, slow down antioxidant sodium pyrosulfite and the ascorbic degradation speed of auxiliary antioxidant, to reduce the dosage of antioxidant, it is effectively guaranteed the safety of clinical application.
Description
Technical field
The present invention relates to a kind of Vinpocetine injections and preparation method thereof.
Background technique
Vinpocetine (Vinpocetine) is that the structural modification of the natural drug pervone extracted from periwinkle produces
Object belongs to indoles alkaloid, its chemical name is: (13as, 13bs) -13a- ethyl -2,3,5,6-13a, 13b hexahydro -1H- Yin
Diindyl [3,2,1-de] pyridine [3,2,1-ij] [1,5]-benzodiazine -12- carboxylic acid ethyl, molecular formula are as follows: C22H26N2O2.In clinic
On be used to improve the various symptoms of the inductions such as sequelae for cerebral infraction, cerebral hemorrhage sequelae, cerebral arteriosclerosis.
In production and storage and transport process, main ingredient vinpocetine is easily degraded Vinpocetine injection, is caused to change colour or be generated
Degradation impurity, especially because the dopant species of oxidative degradation generation are various and structure is complicated.Although passing through the deoxygenations means such as nitrogen charging
The remnants of oxygen are excluded as far as possible, but still also need to add antioxidant in prescription to reduce in medical fluid residual oxygen as far as possible to Chang Chunxi
The destruction in spit of fland.But common water soluble antioxidants (mainly have sodium pyrosulfite, sodium hydrogensulfite, sodium sulfite, vitamin C
Deng) decompose at relatively high temperatures and increase the dosage of antioxidant quickly and will lead to the worry of drug safety again.Existing Chang Chunxi
In the injection technical solution of spit of fland, the mode (such as 121 DEG C sterilize 15 minutes) for being all made of high-temperature sterilization carries out aseptic controlling, needs to increase
Add the antioxidant dosage in prescription to guarantee the oxidation resistance of drug.
Although the mode for also using aseptic filtration in published technical solution CN101066244 avoids high-temperature sterilization
Operation, but has used vascular stimulation regulator in its prescription --- and benzyl alcohol (substance while having effects that anti-corrosion, by breast
The original of the big pharmaceutical factory Ya Lijirui (Gedeon Richter) production, which is ground, also addition in product), it " is being injected about benzyl alcohol is reinforced
The notice that liquid pipe is managed " " drug of the ingredient containing benzyl alcohol is forbidden for children's flesh for (medicine prison note (2005) 263 is eaten by state) middle requirement
Meat injection ", significantly limits the scope of application of drug.
Therefore, it is necessary to a kind of simple and easy to control, and it can guarantee the Vinpocetine injection production method of product quality.
Summary of the invention
The object of the present invention is to provide a kind of Vinpocetine injections.
The object of the invention is also to provide a kind of simple production process, and quality controllable Vinpocetine injection
Preparation method.
Vinpocetine injection of the invention includes vinpocetine 5-10g, hydrotropy in every 1000ml Vinpocetine injection
Agent 3-5g, antioxidant 0.1-2g, auxiliary antioxidant 0.1-0.5g, stabilizer 50-70g, appropriate pH adjusting agent and supply surplus
Water for injection.
The Vinpocetine injection, includes vinpocetine 5g, cosolvent 4g in every 1000ml Vinpocetine injection,
Antioxidant 0.5g, auxiliary antioxidant 0.25g, stabilizer 60g, pH adjusting agent is appropriate and supplies the water for injection of surplus.
The Vinpocetine injection, wherein the cosolvent is L-TARTARIC ACID, antioxidant is sodium pyrosulfite, auxiliary
One of aid anti-oxidants are vitamin C, and stabilizer is propylene glycol, sorbierite, the sodium bicarbonate that pH adjusting agent is 5% is molten
One of liquid, 1% sodium hydroxide solution.
The preparation method of Vinpocetine injection of the invention, includes the following steps:
(1) 60% water for injection is added, and is heated to 40-60 DEG C；
(2) cosolvent of recipe quantity, auxiliary antioxidant is first added, vinpocetine makes to be completely dissolved under stirring, it is down to room temperature, then
The stabilizer of recipe quantity is sequentially added, antioxidant, to being completely dissolved, adjusting pH value with pH adjusting agent is 3.0-3.5 for stirring；
(3) it is added active carbon stirring and adsorbing 20 minutes of 0.1%, with 0.45 μm of filter membrane coarse filtration, adds to the full amount of water for injection；
(4) with 0.22 μm of filter membrane secondary filtration degerming, encapsulating, packaging.
Vinpocetine injection of the invention has ensured the sterile level of drug using aseptic filtration mode, avoids using benzene
Methanol avoids the production method using high-temperature sterilization as preservative, slows down antioxidant sodium pyrosulfite and auxiliary is anti-
The ascorbic degradation speed of oxygen agent is effectively guaranteed the safety of clinical application to reduce the dosage of antioxidant.
Specific embodiment:
Embodiment 1
Vinpocetine injection composition:
Vinpocetine 500g
Sodium pyrosulfite 50g
L-TARTARIC ACID 400g
Vitamin C 25g
Propylene glycol 6000ml
0.1mol/L Sodium hydroxide q.s.
Water for injection adds to 100000ml
Preparation process:
60% water for injection is taken, temperature is controlled at 40-60 DEG C, sequentially adds L-TARTARIC ACID 400g, vitamin C 25g, Chang Chunxi
Spit of fland 500g, stirring to vinpocetine are completely dissolved, then addition sodium pyrosulfite 50g, propylene glycol 6000g, after stirring and dissolving, are used
It is 3.0-3.5 that 5% sodium bicarbonate solution, which adjusts pH value, is stirred until homogeneous, 0.1% active carbon stirring and adsorbing is added 20 minutes,
It with 0.45 μm of filter membrane coarse filtration, adds to the full amount of water for injection, then with 0.22 μm of filter membrane secondary filtration degerming, encapsulating, packaging.
Embodiment 2
Vinpocetine injection composition:
Vinpocetine 500g
Sodium pyrosulfite 50g
L-TARTARIC ACID 400g
Vitamin C 25g
Sorbierite 6000ml
0.1mol/L Sodium hydroxide q.s.
Water for injection adds to 100000ml
Preparation process:
60% water for injection is taken, temperature is controlled at 40-60 DEG C, sequentially adds L-TARTARIC ACID 400g, vitamin C 25g, Chang Chunxi
Spit of fland 500g, stirring to vinpocetine are completely dissolved, then addition sodium pyrosulfite 50g, sorbierite 6000g, after stirring and dissolving, are used
It is 3.0-3.5 that 1% sodium hydroxide solution, which adjusts pH value, is stirred until homogeneous, 0.1% active carbon stirring and adsorbing is added 20 minutes,
It with 0.45 μm of filter membrane coarse filtration, adds to the full amount of water for injection, then with 0.22 μm of filter membrane secondary filtration degerming, encapsulating, packaging.
Comparative example 1
Compared with Example 1, distinctive points are in this comparative example that preparation process is different, specifically:
Vinpocetine 500g
Sodium pyrosulfite 50g
L-TARTARIC ACID 400g
Vitamin C 25g
Propylene glycol 6000ml
0.1mol/L Sodium hydroxide q.s.
Water for injection adds to 100000ml
Preparation process:
60% water for injection is taken, temperature is controlled at 40-60 DEG C, sequentially adds L-TARTARIC ACID 400g, vitamin C 25g, Chang Chunxi
Spit of fland 500g, stirring to vinpocetine are completely dissolved, then addition sodium pyrosulfite 50g, propylene glycol 6000g, after stirring and dissolving, are used
It is 3.0-3.5 that 5% sodium bicarbonate solution, which adjusts pH value, is stirred until homogeneous, adds to the full amount of water for injection, then with 0.22 μm of filter membrane
Secondary filtration degerming, encapsulating, with 121 DEG C moist heat sterilization 15 minutes, packaging.
Comparative example 2
Compared with Example 2, distinctive points are in this comparative example that preparation process is different, specifically:
Vinpocetine 500g
Sodium pyrosulfite 50g
L-TARTARIC ACID 400g
Vitamin C 25g
Sorbierite 6000ml
0.1mol/L Sodium hydroxide q.s.
Water for injection adds to 100000ml
Preparation process:
60% water for injection is taken, temperature is controlled at 40-60 DEG C, sequentially adds L-TARTARIC ACID 400g, vitamin C 25g, Chang Chunxi
Spit of fland 500g, stirring to vinpocetine are completely dissolved, then addition sodium pyrosulfite 50g, sorbierite 6000g, after stirring and dissolving, are used
It is 3.0-3.5 that 1% sodium hydroxide solution, which adjusts pH value, is stirred until homogeneous, adds to the full amount of water for injection, then with 0.22 μm of filter membrane
Secondary filtration degerming, encapsulating, with 121 DEG C moist heat sterilization 15 minutes, packaging.
The sample of Vinpocetine injection production of the present invention, can reach following quality requirement:
1, character: it should be colourless clear liquid.
2, related substance: Calan should must not cross 0.5%, and Apovincamine acid should must not cross 0.1%, other unknown lists
One impurity must not cross 0.2%, total impurities and 1.0% must not be crossed.
3,0.1mg/ml must not sodium pyrosulfite: be less than.
4,0.02mg/ml must not vitamin C: be less than.
5, sterile: the regulation of Ying Fuhe " Chinese Pharmacopoeia " four general rules 1101 of version in 2015.
Quality control assays:
The stability of Vinpocetine injection obtained by Vinpocetine injection obtained by the embodiment of the present invention and comparative example
It is as follows to investigate experiment:
The investigation of 1 accelerated test of table
The investigation of 2 long term test of table
As data in Tables 1 and 2 as it can be seen that vinpocetine obtained by Vinpocetine injection obtained by the present invention and comparative example
Injection compares, and is significantly better than that for related levels of substance, sodium pyrosulfite and Vitamin C content using high-temperature sterilization work
The Vinpocetine injection of skill production.So Vinpocetine injection of the invention can be effectively reduced the dosage of antioxidant,
And guarantee the stability of drug.
Claims (4)
1. a kind of Vinpocetine injection composition, it is characterised in that: include Chang Chunxi in every 1000ml Vinpocetine injection
Spit of fland 5-10g, cosolvent 3-5g, antioxidant 2-3g, auxiliary antioxidant 0.1-1g, stabilizer 50-70g, appropriate pH adjusting agent and
Supply the water for injection of surplus.
It include vinpocetine 5g in every 1000ml Vinpocetine injection 2. Vinpocetine injection as described in claim 1,
Cosolvent 4g, antioxidant 2.5g, auxiliary antioxidant 0.5g, stabilizer 60g, pH adjusting agent is appropriate and supplies the injection of surplus
Water.
3. Vinpocetine injection as claimed in claim 2, wherein the cosolvent is L-TARTARIC ACID, antioxidant Jiao Ya
One of sodium sulphate, auxiliary antioxidant are vitamin C, and stabilizer is propylene glycol, sorbierite, the carbon that pH adjusting agent is 5%
One of sour hydrogen sodium solution, 1% sodium hydroxide solution.
4. the Vinpocetine injection as described in claim 1-3, preparation methods steps are as follows:
(1) 60% water for injection is added, and is heated to 40-60 DEG C；
(2) cosolvent of recipe quantity, auxiliary antioxidant is first added, vinpocetine makes to be completely dissolved under stirring, it is down to room temperature, then
The stabilizer of recipe quantity is sequentially added, antioxidant, to being completely dissolved, adjusting pH value with pH adjusting agent is 3.0-3.5 for stirring；
(3) it is added active carbon stirring and adsorbing 20 minutes of 0.1%, with 0.45 μm of filter membrane coarse filtration, adds to the full amount of water for injection；
(4) with 0.22 μm of filter membrane secondary filtration degerming, encapsulating, packaging.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810774472.0A CN110179745B (en) | 2018-07-16 | 2018-07-16 | Vinpocetine injection and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810774472.0A CN110179745B (en) | 2018-07-16 | 2018-07-16 | Vinpocetine injection and preparation method thereof |
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| Publication Number | Publication Date |
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| CN110179745A true CN110179745A (en) | 2019-08-30 |
| CN110179745B CN110179745B (en) | 2021-09-10 |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101066244A (en) * | 2006-09-28 | 2007-11-07 | 郑州羚锐制药有限公司 | Small volume vincamine injection and its prepn process |
| CN102091030A (en) * | 2011-01-20 | 2011-06-15 | 罗军 | Vinpocetine injection and preparation method thereof |
| CN102160853A (en) * | 2011-02-11 | 2011-08-24 | 方宝林 | Vinpocetine injection and preparation method thereof |
| CN101889978B (en) * | 2010-04-29 | 2012-01-04 | 袁璐 | Pharmaceutical composition containing vinpocetine, preparation method and application thereof |
-
2018
- 2018-07-16 CN CN201810774472.0A patent/CN110179745B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101066244A (en) * | 2006-09-28 | 2007-11-07 | 郑州羚锐制药有限公司 | Small volume vincamine injection and its prepn process |
| CN101889978B (en) * | 2010-04-29 | 2012-01-04 | 袁璐 | Pharmaceutical composition containing vinpocetine, preparation method and application thereof |
| CN102091030A (en) * | 2011-01-20 | 2011-06-15 | 罗军 | Vinpocetine injection and preparation method thereof |
| CN102160853A (en) * | 2011-02-11 | 2011-08-24 | 方宝林 | Vinpocetine injection and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 陈雪江等: "长春西汀注射液中的基因毒性杂质研究与含量测定", 《中国药物经济学》 * |
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| CN110179745B (en) | 2021-09-10 |
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Effective date of registration: 20230324 Address after: 430000 Workshop 1, 22nd Floor, Building 2, Industrial Plant (Phase II), No. 136 Xingye Road, Jiang'an District, Wuhan City, Hubei Province (Huangpu Science Park) Patentee after: Wuhan Haizhen Pharmaceutical Technology Co.,Ltd. Address before: 6058 (Park), 6 / F, building 2 (block B), No. 11, Xinghuo Road, Science City, Fengtai District, Beijing 100070 Patentee before: Beijing Haizhen Pharmaceutical Technology Co.,Ltd. |