CN107536814A - Injection levo-oxiracetam freeze-dried powder - Google Patents
Injection levo-oxiracetam freeze-dried powder Download PDFInfo
- Publication number
- CN107536814A CN107536814A CN201610495339.2A CN201610495339A CN107536814A CN 107536814 A CN107536814 A CN 107536814A CN 201610495339 A CN201610495339 A CN 201610495339A CN 107536814 A CN107536814 A CN 107536814A
- Authority
- CN
- China
- Prior art keywords
- freeze
- oxiracetam
- dried powder
- levo
- temperature
- 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.)
- Withdrawn
Links
Abstract
The invention discloses a kind of injection levo-oxiracetam freeze-dried powder；Contain the supplementary material of following mass fraction in the freeze-dried powder：1 part of levo-oxiracetam, 0.4~0.6 part of methionine, 0.5~0.9 part of lactose, 0.2~0.4 part of triethanolamine, 0.01~0.02 part of Tween 80,0.01~0.03 part of phenol；The present invention utilizes specific excipient composition and freeze-drying curve, the sublimation temperature in redrying stage can be improved, shorten the preparation production cycle, powder dispersion phenomenon will not occur again, the indices such as its content meet regulation, and product clarity is good, less than No. 0.5 standard turbidity solution, and antibiotic property is strong, steriling test is qualified.
Description
Technical field
The invention belongs to pharmaceutical field, and in particular to a kind of injection levo-oxiracetam freeze-dried powder.
Background technology
Cereboactive drug is also known as cereboactive drug, is a kind of new medicine for central nervous system for promoting study, strengthening memory.Promote intelligence
Medicine requires that selection index system in cerebral cortex, has selection activation, protection and the feature for promoting damaged nerve cell functional rehabilitation.
Different from other neurologic agents be a little their above-mentioned effect not by network or olfactory bulb, but directly act on skin
Layer.Behavior is neither influenceed, also without calm excitation, therefore such medicine has caused the extensive concern and interest of people, to this
The demand of class medicine is also growing day by day.
Oxiracetam (oxiracetam, CAS No.：62613-82-5) the entitled Esomeprazole of chemistry,
The anti anoxia class cereboactive drug (compound is disclosed in US4118396) synthesized first in 1974 for Italian ISFS.P.A companies,
It is ring GABOB derivatives, Phosphorylcholine and phosphatidyl ethanolamine can be promoted to synthesize, promotes brain metabolism, it is right through blood-brain barrier
Specific nervous centralis road has stimulation, can improve intelligence and memory, to cerebrovascular disease, brain trauma, brain tumor, encephalic
Infection, brain degenerative disease etc. also have the effect of preferable, and the drug toxicity is extremely low, no mutagenesis and carcinogenesis and reproduction
Toxicity.Giorgio et al. discloses the chemical constitution and preparation method, Chiodini et al. of Oxiracetam in US4118396
Disclosed in WO9306826A, it is (right that clinical effectiveness proves that the drug effect of the Oxiracetam of S configurations (left-handed) is better than R configurations
Rotation), Oxiracetam and levo-oxiracetam structure are as follows.
But inventor has found in existing injection levo-oxiracetam freeze-dried powder preparation process, in the redrying stage, it rises
Magnificent temperature is relatively low, and its temperature so greatly extends the production cycle of preparation not above 20 DEG C, if improving redrying
The phenomenon of powder dispersion will occur for the temperature in stage, preparation, and its content is remarkably decreased, and product clarity is unqualified.Separately
Outside, existing injection levo-oxiracetam freeze-dried powder antibiotic property is also poor, easily causes steriling test unqualified.
The content of the invention
In view of this, it is an object of the invention to provide a kind of injection levo-oxiracetam freeze-dried powder, redrying can be improved
The sublimation temperature in stage, shortening the preparation production cycle, powder dispersion phenomenon will not occur again, its content, product clarity are qualified,
And antibiotic property is strong, steriling test is qualified.
To reach above-mentioned purpose, the present invention provides following technical scheme：
A kind of injection levo-oxiracetam freeze-dried powder, the supplementary material of following mass fraction is contained in the freeze-dried powder：Left-handed Aura
Western smooth 1 part, 0.4~0.6 part of methionine, 0.5~0.9 part of lactose, 0.2~0.4 part of triethanolamine, Tween 80 0.01~0.02
Part, 0.01~0.03 part of phenol；The preparation method of the freeze-dried powder is：By levo-oxiracetam, methionine, lactose, three
Monoethanolamine, Tween 80 and phenol are dissolved in water for injection, pH value are adjusted to 5.5 with hydrochloric acid solution, then according to following step
Rapid freeze-drying：
(1) the pre-freeze stage：Temperature is refrigerated to -14~-18 DEG C in 5~15min；- 10~-8 DEG C are then heated to, heating
Time is 30~60min；Temperature is refrigerated to -32~-36 DEG C in 5~15min again；- 20~-26 DEG C are then heated to,
Heating-up time is 90~120min；Temperature is finally refrigerated to -42~-46 DEG C in 5~15min again, temperature keeps 120~
180min；
(2) the lyophilization stage：When vacuum in drying box reaches 800mTorr~600mTorr, drying temperature is risen to
- 12~-10 DEG C, 60~90min of used time, 360~480min of soaking time；
(3) the re-dry stage：Re-dry temperature is increased to 35~45 DEG C, 90~150min of used time；Will be true in drying box
Reciprocal of duty cycle is evacuated to 5mTorr~0mTorr, 240~300min of soaking time, obtains freeze-dried powder.
Further, the supplementary material of following mass fraction is contained in the freeze-dried powder：1 part of levo-oxiracetam, methionine 0.5
Part, 0.7 part of lactose, 0.3 part of triethanolamine, 0.01 part of Tween 80,0.02 part of phenol.
The beneficial effects of the present invention are：
The present invention utilizes specific excipient composition and freeze-drying curve, can improve the sublimation temperature in redrying stage, shortens system
The agent production cycle, powder dispersion phenomenon will not occur again, the indices such as its content meet regulation, and product clarity is good, low
In No. 0.5 standard turbidity solution, and antibiotic property is strong, and steriling test is qualified.
Embodiment
In order that the purpose of the present invention, technical scheme and beneficial effect are clearer, the preferred embodiments of the present invention will be entered below
The detailed description of row.
Embodiment 1
The prescription of the injection levo-oxiracetam freeze-dried powder of embodiment 1 is as shown in the table：
| Prescription | Percentage by weight |
| Levo-oxiracetam | 200g |
| Methionine | 100g |
| Lactose | 140g |
| Triethanolamine | 60g |
| Tween 80 | 2g |
| Phenol | 4g |
| Water for injection | Add to 1000mL |
The preparation method of the injection levo-oxiracetam freeze-dried powder of embodiment 1, comprises the following steps：
The levo-oxiracetam of recipe quantity, methionine, lactose, triethanolamine, Tween 80 and phenol are dissolved in water for injection
In, pH value is adjusted to 5.5 with 0.1mol/L hydrochloric acid solutions, is then freeze-dried according to following steps：
(1) the pre-freeze stage：Temperature is refrigerated to -15 DEG C in 10min；- 10 DEG C are then heated to, heating-up time 40min；
Temperature is refrigerated to -35 DEG C in 10min again；- 25 DEG C are then heated to, heating-up time 100min；Finally again in 10min
Interior that temperature is refrigerated into -45 DEG C, temperature keeps 150min；
(2) the lyophilization stage：When vacuum in drying box reaches 700mTorr, drying temperature is risen to -11 DEG C, the used time
80min, soaking time 400min；
(3) the re-dry stage：Re-dry temperature is increased to 40 DEG C, used time 120min；Vacuum in drying box is evacuated to
3mTorr, soaking time 280min, obtains freeze-dried powder.
Embodiment 2
The prescription of the injection levo-oxiracetam freeze-dried powder of embodiment 2 is as shown in the table：
| Prescription | Percentage by weight |
| Levo-oxiracetam | 200g |
| Methionine | 80g |
| Lactose | 100g |
| Triethanolamine | 40g |
| Tween 80 | 3g |
| Phenol | 2g |
| Water for injection | Add to 1000mL |
The preparation method of the injection levo-oxiracetam freeze-dried powder of embodiment 2, comprises the following steps：
The levo-oxiracetam of recipe quantity, methionine, lactose, triethanolamine, Tween 80 and phenol are dissolved in water for injection
In, pH value is adjusted to 5.5 with 0.1mol/L hydrochloric acid solutions, is then freeze-dried according to following steps：
(1) the pre-freeze stage：Temperature is refrigerated to -15 DEG C in 5min；- 9 DEG C are then heated to, heating-up time 30min；
Temperature is refrigerated to -32 DEG C in 5min again；- 20 DEG C are then heated to, heating-up time 90min；Finally again in 5min
Interior that temperature is refrigerated into -42 DEG C, temperature keeps 120min；
(2) the lyophilization stage：When vacuum in drying box reaches 800mTorr, drying temperature is risen to -12 DEG C, the used time
60min, soaking time 360min；
(3) the re-dry stage：Re-dry temperature is increased to 35 DEG C, used time 90min；Vacuum in drying box is evacuated to
5mTorr, soaking time 240min, obtains freeze-dried powder.
Embodiment 3
The prescription of the injection levo-oxiracetam freeze-dried powder of embodiment 3 is as shown in the table：
| Prescription | Percentage by weight |
| Levo-oxiracetam | 200g |
| Methionine | 120g |
| Lactose | 180g |
| Triethanolamine | 80g |
| Tween 80 | 4g |
| Phenol | 6g |
| Water for injection | Add to 1000mL |
The preparation method of the injection levo-oxiracetam freeze-dried powder of embodiment 3, comprises the following steps：
The levo-oxiracetam of recipe quantity, methionine, lactose, triethanolamine, Tween 80 and phenol are dissolved in water for injection
In, pH value is adjusted to 5.5 with 0.1mol/L hydrochloric acid solutions, is then freeze-dried according to following steps：
(1) the pre-freeze stage：Temperature is refrigerated to -18 DEG C in 15min；- 8 DEG C are then heated to, heating-up time 60min；
Temperature is refrigerated to -36 DEG C in 15min again；- 26 DEG C are then heated to, heating-up time 120min；Finally again in 15min
Interior that temperature is refrigerated into -46 DEG C, temperature keeps 180min；
(2) the lyophilization stage：When vacuum in drying box reaches 600mTorr, drying temperature is risen to -10 DEG C, the used time
90min, soaking time 480min；
(3) the re-dry stage：Re-dry temperature is increased to 45 DEG C, used time 150min；Vacuum in drying box is evacuated to
0mTorr, soaking time 300min, obtains freeze-dried powder.
Comparative example 1
The injection levo-oxiracetam freeze-dried powder of comparative example 1 does not add phenol, remaining component and preparation method and embodiment 1
It is identical.
Embodiment 1-3 finished product preparation is placed in 25 DEG C of climatic chambers, investigated respectively at sampling in the 0th, 12,24 month outer
See character, moisture, redissolve time, the change about material and content, result of the test is shown in Table 1.
The embodiment 1-3 of table 1 finished product preparation long term test investigates result
Investigate result more than, the appearance character of embodiment 1-3 finished product preparation, moisture, the redissolution time, clarity,
Meet regulation about the indices such as material and content, it was demonstrated that the present invention can improve the redrying stage sublimation temperature (35~
45 DEG C), shorten the preparation production cycle, powder dispersion phenomenon will not occur again, the indices such as its content meet regulation, and
And product clarity is good, less than No. 0.5 standard turbidity solution.
Each 20 bottles of injection levo-oxiracetam freeze-dried powder, are placed in nature made from Example 1 and comparative example 1 after open bottle cover
Under the conditions of (25 DEG C ± 5 DEG C of temperature, relative humidity 70% ± 10%) place 15 days, respectively at 0 day, 5 days, 10 days, 15
Its sampling, each time point take 5 bottles, carry out Sterility testing according to version Chinese Pharmacopoeia in 2010, result of the test is shown in Table 2.
The finished product preparation antibacterial ability of the embodiment 1 of table 2 and comparative example 1 is tested
From Sterility testing result, the finished product preparation antibacterial ability of embodiment 1 is substantially better than the finished product preparation of comparative example 1.
Finally illustrate, preferred embodiment above is merely illustrative of the technical solution of the present invention and unrestricted, although by above-mentioned
The present invention is described in detail for preferred embodiment, it is to be understood by those skilled in the art that can in form and
Various changes are made in details to it, without departing from claims of the present invention limited range.
Claims (2)
- A kind of 1. injection levo-oxiracetam freeze-dried powder, it is characterised in that：Contain the supplementary material of following mass fraction in the freeze-dried powder：1 part of levo-oxiracetam, 0.4~0.6 part of methionine, 0.5~0.9 part of lactose, 0.2~0.4 part of triethanolamine, 0.01~0.02 part of Tween 80,0.01~0.03 part of phenol；The preparation method of the freeze-dried powder is：Levo-oxiracetam, methionine, lactose, triethanolamine, Tween 80 and phenol are dissolved in water for injection, pH value is adjusted to 5.5 with hydrochloric acid solution, is then freeze-dried according to following steps：（1）The pre-freeze stage：Temperature is refrigerated to -14~-18 DEG C in 5~15min；- 10~-8 DEG C are then heated to, the heating-up time is 30~60min；Temperature is refrigerated to -32~-36 DEG C in 5~15min again；- 20~-26 DEG C are then heated to, the heating-up time is 90~120min；Temperature is finally refrigerated to -42~-46 DEG C in 5~15min again, temperature keeps 120~180 min；（2）The lyophilization stage：When vacuum in drying box reaches 800mTorr~600mTorr, drying temperature is risen to -12~-10 DEG C, 60~90min of used time, 360~480min of soaking time；（3）The re-dry stage：Re-dry temperature is increased to 35~45 DEG C, 90~150min of used time；Vacuum in drying box is evacuated to 5mTorr~0mTorr, 240~300min of soaking time, obtains freeze-dried powder.
- 2. injection levo-oxiracetam freeze-dried powder according to claim 1, it is characterised in that：Contain the supplementary material of following mass fraction in the freeze-dried powder：1 part of levo-oxiracetam, 0.5 part of methionine, 0.7 part of lactose, 0.3 part of triethanolamine, 0.01 part of Tween 80,0.02 part of phenol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610495339.2A CN107536814A (en) | 2016-06-29 | 2016-06-29 | Injection levo-oxiracetam freeze-dried powder |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610495339.2A CN107536814A (en) | 2016-06-29 | 2016-06-29 | Injection levo-oxiracetam freeze-dried powder |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107536814A true CN107536814A (en) | 2018-01-05 |
Family
ID=60965503
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610495339.2A Withdrawn CN107536814A (en) | 2016-06-29 | 2016-06-29 | Injection levo-oxiracetam freeze-dried powder |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107536814A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008150080A1 (en) * | 2007-06-04 | 2008-12-11 | Dong-A Pharm. Co., Ltd. | Injectable ready to use solutions comprising human chorionic gonadotropin |
| CN101766597A (en) * | 2008-12-31 | 2010-07-07 | 北京利乐生制药科技有限公司 | Injection preparation with levo-oxiracetam as active component |
| CN103446067A (en) * | 2013-09-16 | 2013-12-18 | 石药集团欧意药业有限公司 | Oxiracetam freeze-drying preparation for injection and preparation method thereof |
-
2016
- 2016-06-29 CN CN201610495339.2A patent/CN107536814A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008150080A1 (en) * | 2007-06-04 | 2008-12-11 | Dong-A Pharm. Co., Ltd. | Injectable ready to use solutions comprising human chorionic gonadotropin |
| CN101766597A (en) * | 2008-12-31 | 2010-07-07 | 北京利乐生制药科技有限公司 | Injection preparation with levo-oxiracetam as active component |
| CN103446067A (en) * | 2013-09-16 | 2013-12-18 | 石药集团欧意药业有限公司 | Oxiracetam freeze-drying preparation for injection and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 颜素华 等: "奥拉西坦注射液的研制", 《中国现代医学杂志》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103446067B (en) | Oxiracetam freeze-drying preparation for injection and preparation method thereof | |
| CN105434373B (en) | A kind of injection Oxiracetam lyophilized preparation and preparation method thereof | |
| CN102512378B (en) | Stable and safe oxiracetam pharmaceutical composition for injection | |
| CN102302461A (en) | Dantrolene sodium freeze-dried powder injection for injection and preparation method thereof | |
| CN107536814A (en) | Injection levo-oxiracetam freeze-dried powder | |
| CN101444492B (en) | Lomefloxacin hydrochloride lyophilized powder for injection and preparation method therefor | |
| CN107536812A (en) | Injection levo-oxiracetam freeze-dried powder | |
| CN107536811A (en) | Levo-oxiracetam aseptic powdery | |
| CN107550869A (en) | Levo-oxiracetam aseptic powdery | |
| CN107550868A (en) | (S) preparation method of-Esomeprazole freeze-dried powder | |
| CN107536809A (en) | (S) preparation method of the pyrrolidine acetamide freeze-dried powder of 4 hydroxyl, 2 oxo 1 | |
| CN102614201B (en) | Combretastain diphosphate tetrasodium composition for injection and preparation method thereof | |
| CN107536815A (en) | The preparation method of injection levo-oxiracetam freeze drying powder injection | |
| CN107536813A (en) | The preparation method of injection levo-oxiracetam freeze drying powder injection | |
| CN100394929C (en) | Ginseng stem leaves general saponin freeze-drying powder injection and its preparation method | |
| CN108272755B (en) | A kind of hydrochloride for injection mycophenolate mofetil lyophilized preparation and preparation method thereof | |
| CN107432865A (en) | Levo-oxiracetam aseptic powdery and preparation method thereof | |
| CN107397725A (en) | Injection levo-oxiracetam freeze-dried composition and preparation method thereof | |
| CN104721183B (en) | A kind of drug combination preparation containing Piracetam and preparation method thereof | |
| CN105078907B (en) | The freeze-drying method of hydrochloride for injection ligustrazine lyophilized preparation | |
| CN107397723A (en) | Levo-oxiracetam aseptic powdery and preparation method thereof | |
| CN106692072A (en) | L-oxiracetam sterile powder with good stability and preparation method thereof | |
| CN107536810A (en) | The pyrrolidine acetamide aseptic powdery of 2 oxo of injection (S) 4 hydroxyl 1 | |
| CN107281134A (en) | Good levo-oxiracetam aseptic powdery of a kind of stability and preparation method thereof | |
| CN107281119A (en) | Few levo-oxiracetam aseptic powdery of a kind of impurity and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20180105 |