CN106466294A - Few (S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection of a kind of impurity and preparation method thereof - Google Patents
Few (S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection of a kind of impurity and preparation method thereof Download PDFInfo
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Abstract
A kind of impurity is few（S）- 4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection it is characterised in that：It is with（S）- 4- hydroxyl -2 oxo-1-pyrrolidine ethanamide, propylene glycol, lecithin, vitamin C, ethylenediaminetetraacetic acid be supplementary material, by dense join, dilute join, embedding, sterilizing, test package step be obtained；It is obtained according to the present invention（S）- 4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection has product during storage and will not crystallize, be difficult impurity incrementss in oxidized, sterilization process and be only 0.02%, good stability, it is valid up to more than 18 months, in effect duration, product impurity is few, its total impurities is less than 0.26%, and product clarity is good, and clarity is less than No. 0.5 standard turbidity solution, preparation process is simple is feasible, worth marketing.
Description
Technical field
The invention mainly relates to pharmaceutical technology field is and in particular to a kind of few (S) -4- hydroxyl of impurity -2 oxo -1- pyrroles
Alkyl acetamide injection and preparation method thereof.
Background technology
Nootropics are a kind of promotion study also known as cereboactive drug, the new medicine for central nervous system of memory reinforcing.Promote
Intelligence medicine requires selection in cerebral cortex, has and selects activation, protection and promote damaged nerve cell functional rehabilitation
Feature.Different from other neurologic agents be a little their above-mentioned effect not by reticular system or olfactory bulb, but directly
Connect and act on cortex.Neither affect behavior, also no calm excitation, therefore such medicine has caused the extensive pass of people
Note and interest, also grow with each passing day to the demand of such medicine.
Oxiracetam (oxiracetam, CAS No.：62613-82-5) chemical entitled 4- hydroxyl -2- OXo-1-pyrrolidine second
Amide, (compound is disclosed in the anti-hypoxia class nootropics synthesizing first in 1974 for Italian ISFS.P.A company
US4118396), it is ring GABOB derivant, Phosphorylcholine and phosphatidyl ethanolamine synthesis can be promoted, promote brain metabolism,
Through blood brain barrier, have stimulation to specificity nervus centraliss road, intelligence and memory can be improved, to cerebrovascular,
Cerebral trauma, cerebroma, intracranial infection, brain degenerative disease etc. also have preferable curative effect, and this drug toxicity is extremely low, no
Mutagenesis and carcinogenesis and genotoxicity.Giorgio et al. discloses the chemistry knot of oxiracetam in US4118396
Structure and preparation method, Chiodini et al. discloses in WO9306826A, and clinical effectiveness proves S configuration (left-handed)
The drug effect of oxiracetam is better than R configuration (dextrorotation), and oxiracetam and levo-oxiracetam structure are as follows.
Existing (S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection its to be primarily present stability bad, store process
In easily crystallize, sterilization process is oxidizable so that product impurity increases, the problems such as clarity is bad.
Content of the invention
It is an object of the invention to provide few (S) -4- hydroxyl -2 OXo-1-pyrrolidine acetyl of a kind of good stability, impurity
Amine injection.
Another object of the present invention is to providing the preparation of above-mentioned (S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection
Method.
The purpose of the present invention is realized by following technical measures：
A kind of few (S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection of impurity is it is characterised in that it is with (S)
- 4- hydroxyl -2 oxo-1-pyrrolidine ethanamide is raw material, adds a certain amount of additives and is obtained；Wherein said additives
For glucose, sodium chloride, Mannitol, glycerol, L-Serine, sodium glutamate, alanine, glycine, lecithin,
In propylene glycol, benzyl alcohol, chlorobutanol, sodium sulfite, sodium sulfite, sodium pyrosulfite, vitamin C, second
One or more of ethylenediamine tetraacetic acid (EDTA).
Inventor finds in research process, selects a certain proportion of propylene glycol, lecithin, vitamin C and ethylenediamine tetraacetic
The compound additives of acetic acid composition, then coordinate specific preparation technology, product total impurities in sterilization process can be made to increase
Less, product stability is good, will not crystallize during storage, and product clarity significantly improves；Above-mentioned (S) -4- hydroxyl
- 2 oxo-1-pyrrolidine ethanamide injections it is characterised in that：It is with (S) -4- hydroxyl -2 OXo-1-pyrrolidine acetyl
Amine, propylene glycol, lecithin, vitamin C, ethylenediaminetetraacetic acid are supplementary material, are joined, dilute joined, embedding, go out by dense
Bacterium, test package step is obtained；(S) -4- hydroxyl -2 oxo -1- that the consumption of wherein said supplementary material is weight percentage
Pyrrolidine acetamide 50%～70%, propylene glycol 15%～30%, lecithin 10%～18%, vitamin C 3%～8%, second
Ethylenediamine tetraacetic acid (EDTA) 2%～5%；Described dense step of joining is to add supplementary material in material-compound tank, adds sterilized water for injection immediately,
Stirring, dissolving, obtain concentrated wiring liquid；Described dilute step of joining is to take concentrated wiring liquid, adds 0.1mol/L～0.5mol/L sodium hydroxide
Solution, adjusts pH to 6.5～7.0, adds the shitosan of cumulative volume 0.2%～0.6% (g/ml), stir in above-mentioned solution
Mix, mix, stand 30～50min, with 0.8 μm of filter membrane filtration, add cumulative volume 0.1%～0.3% (g/ml)
Activated carbon, adsorption bleaching, with 0.45 μm of filter membrane filtration, collect filtrate, add sterilized water for injection to recipe quantity,
It is qualified to test through middle product examine, you can；Described sterilization steps are canned peace to be cutd open semi-finished product send into steam sterilization pan sterilizing,
121 DEG C of sterilizing 15min, sterilizing program：10 DEG C/min, rise to 121 DEG C, keep 15min at 121 DEG C；Compressed air
3～5 DEG C/min of air blast lowers the temperature, and 8～12min is cooled to 70～80 DEG C, and 2～3 DEG C/min of cooling water lowers the temperature, and 15～18min is cold
But to 30 DEG C, sterilizing completes.
Most preferably, above-mentioned (S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection it is characterised in that it be by
The supplementary material of following significant percentage is obtained：(S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide 55%～65%, propylene glycol
18%～25%, lecithin 12%～16%, vitamin C 3%～5%, ethylenediaminetetraacetic acid 2%～4%, will be above-mentioned former auxiliary
Material adds in material-compound tank, adds the sterilized water for injection of 1/3 recipe quantity immediately, stirring, and dissolving obtains concentrated wiring liquid；Take dense
Join liquid, add 0.1mol/L sodium hydroxide solution, adjust pH to 6.5～7.0, add cumulative volume in above-mentioned solution
The shitosan of 0.2%～0.6% (g/ml), stirring, mix, stand 30～50min, filtered with 0.8 μm of filter membrane,
Add the activated carbon of cumulative volume 0.1%～0.3% (g/ml), adsorption bleaching, with 0.45 μm of filter membrane filtration, collect filter
Liquid, adds sterilized water for injection to recipe quantity, it is qualified to test through middle product examine, you can；Canned peace is cutd open semi-finished product send
Enter steam sterilization pan sterilizing, 121 DEG C of sterilizing 15min, sterilizing program：10 DEG C/min, rise to 121 DEG C, protect at 121 DEG C
Hold 15min；3～5 DEG C/min of compressed air air blast lowers the temperature, and 8～12min is cooled to 70～80 DEG C, 2～3 DEG C/min of cooling water
Cooling, 15～18min is cooled to 30 DEG C, and sterilizing completes.
A kind of preparation method of few (S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection of impurity it is characterised in that
It is obtained as follows：
1. dense join：Supplementary material is added in material-compound tank, adds the sterilized water for injection of 1/3 recipe quantity immediately, stirring,
Dissolving, obtains concentrated wiring liquid；
2. dilute join：Take concentrated wiring liquid, add 0.1mol/L sodium hydroxide solution, adjust pH to 6.5～7.0, to above-mentioned
Add the shitosan of cumulative volume 0.2%～0.6% mass volume ratio, stirring in solution, mix, stand 30～50min,
With 0.8 μm of filter membrane filtration, add the activated carbon of cumulative volume 0.1%～0.3% mass volume ratio, adsorption bleaching, use
0.45 μm of filter membrane filtration, collects filtrate, adds sterilized water for injection to recipe quantity, it is qualified to test through middle product examine,
?；
3. embedding：Intermediate is filtered with 0.22 μm of filter after the assay was approved, checks visible foreign matters, antibacterial endogenous toxin
After element is qualified, upper streamline carries out fill, and the nitrogen that pouring process need to be filled with purity 99.99% makes injection in tank
Oxygen content in water is less than 0.01%, seals after inflated with nitrogen；
4. sterilize：Canned peace is cutd open semi-finished product and sends into steam sterilization pan sterilizing, 121 DEG C of sterilizing 15min, sterilizing
Program：10 DEG C/min, rise to 121 DEG C, keep 15min at 121 DEG C；3～5 DEG C/min of compressed air air blast lowers the temperature,
8～12min is cooled to 70～80 DEG C, and 2～3 DEG C/min of cooling water lowers the temperature, and 15～18min is cooled to 30 DEG C, has sterilized
Become, by rated condition leak detection.
5. check：After sterilizing, sample checks visible foreign matters, the sample checking qualified is packed, full inspection, warehouse-in.
The present invention has following beneficial effect：
The present invention (S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection have product during storage will not crystallize,
It is difficult impurity incrementss in oxidized, sterilization process and be only 0.02%, good stability, it is valid up to more than 18 months,
In effect duration, product impurity is few, and its total impurities is less than 0.26%, and product clarity is good, and it is turbid that clarity is less than No. 0.5 standard
Degree liquid, preparation process is simple is feasible, worth marketing.
Specific embodiment
Below by embodiment, the present invention is specifically described it is necessary to it is pointed out here that be that following examples are served only for
The present invention is further described it is impossible to be interpreted as limiting the scope of the invention, without departing substantially from present invention spirit
In the case of essence, the modification that the inventive method, step or condition are made or replacement, belong to the scope of the present invention.
Embodiment 1
A kind of few (S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection of impurity, is obtained according to the following steps：
Preparation process：
1. dense join：Supplementary material is added in material-compound tank, adds the sterilized water for injection of 1/3 recipe quantity immediately, stirring,
Dissolving, obtains concentrated wiring liquid；
2. dilute join：Take concentrated wiring liquid, add 0.1mol/L sodium hydroxide solution, adjust pH to 6.5～7.0, to above-mentioned
Add the shitosan of cumulative volume 0.2%～0.6% mass volume ratio, stirring in solution, mix, stand 30～50min,
With 0.8 μm of filter membrane filtration, add the activated carbon of cumulative volume 0.1%～0.3% mass volume ratio, adsorption bleaching, use
0.45 μm of filter membrane filtration, collects filtrate, adds sterilized water for injection to recipe quantity, it is qualified to test through middle product examine,
?；
3. embedding：Intermediate is filtered with 0.22 μm of filter after the assay was approved, checks visible foreign matters, antibacterial endogenous toxin
After element is qualified, upper streamline carries out fill, and the nitrogen that pouring process need to be filled with purity 99.99% makes injection in tank
Oxygen content in water is less than 0.01%, seals after inflated with nitrogen；
4. sterilize：Canned peace is cutd open semi-finished product and sends into steam sterilization pan sterilizing, 121 DEG C of sterilizing 15min, sterilizing
Program：10 DEG C/min, rise to 121 DEG C, keep 15min at 121 DEG C；3～5 DEG C/min of compressed air air blast lowers the temperature,
8～12min is cooled to 70～80 DEG C, and 2～3 DEG C/min of cooling water lowers the temperature, and 15～18min is cooled to 30 DEG C, has sterilized
Become, by rated condition leak detection.
5. check：After sterilizing, sample checks visible foreign matters, the sample checking qualified is packed, full inspection, warehouse-in.
In order to be better understood from the present invention, test the beneficial effect of invention medicine is expanded on further below by way of the present invention,
Rather than limitation of the present invention.
Experiment one：A kind of few (S) -4- hydroxyl of impurity of the present invention -2 oxo-1-pyrrolidine ethanamide injection stability experiment
Experiment material：
(S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection sample：It is obtained for embodiment 1
Acceleration study method：(S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection that embodiment 1 is obtained is pressed upper
City packs, and puts in Acceleration study case, and certain time samples, and investigation project is tested.
Acceleration study temperature：40±2℃
Humidity：RH75% ± 5%
The investigation time：0th, 1,2,3, June
Inspection target：Character, visible foreign matters, clarity, pH, relevant material, content, sterility test
Accelerated test stability record：
Acceleration study result shows：Accelerate June sample suitable with 0 month sample items Testing index quality, show that this product adds
In speed experiment June, quality keeps stable, and this product stability is preferable.
Long-term experiment method：(S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection that embodiment 1 is obtained is pressed upper
City packs, and puts and keeps sample in case for a long time, and certain time samples, and investigation project is tested.
Acceleration study temperature：25±2℃
Humidity：RH60% ± 10%
The investigation time：0th, 3,6,9,12,18 months
Inspection target：Character, visible foreign matters, clarity, pH, relevant material, content, sterility test
Long term test stability record：
Long term test shows：18 months character of this product long term test, visible foreign matters, clarity, pH value, relevant material,
Content and sterility test indices all no significant changes, all meet the every related rule of production quality standard draft
Fixed.18 months steady qualities of this product long term test, therefore minimum 18 months of this product effect duration, long term test still is continuing to examine
During examining.
Experiment two：A kind of few (S) -4- hydroxyl of impurity of the present invention -2 oxo-1-pyrrolidine ethanamide injection sterilization process is to miscellaneous
The impact that matter increases
1. experiment material：
(S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection sample：Prepare by embodiment 1.
(S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection control sample 1：For lacking vitamin C and ethylenediamine
The sample of tetraacethyl, its preparation technology is with embodiment 1.
(S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection control sample 2：For the prescription of embodiment 1, sterilize
Temperature is 115 DEG C, and sterilization time is 32 minutes, obtained product.
2. experimental technique：In embodiment 1 preparation process, sample afterwards before sterilization respectively, detect that it, about material, is investigated
To the impact about material before and after sterilizing.Meanwhile, take the prescription lacking vitamin C and ethylenediaminetetraacetic acid as comparison at
Side, by the preparation method preparation of embodiment 1, equally sampling detects that it, about material, investigates sterilization process afterwards before sterilization
To the impact about material.Meanwhile, the prescription of Example 1, is changed to 115 DEG C according to sterilising temp, and sterilization time is
Prepare within 32 minutes sample, sampling detects relevant material afterwards before sterilization respectively, investigate sterilization process to the impact about material.
3. experimental result see table：
4. experiment conclusion：The prescription of embodiment 1, the specific sterilization process of cooperation, relevant material increase only 0.02%, bright
Show better than other two control samples.
Experiment three：A kind of few (S) -4- hydroxyl of impurity of the present invention -2 oxo-1-pyrrolidine ethanamide injection clarity is to having a competition
Test research
1. experiment material：
(S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection sample：It is obtained for embodiment 1
(S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection control sample：Monofactorial change pH regulator respectively
Agent, pH value and after being not added with the factors such as shitosan, (S) -4- hydroxyl -2 oxo -1- of the injection being obtained by embodiment 1
Pyrrolidine acetamide sample is as control sample.
2. experimental technique：Test according to version pharmacopeia annex IXB clarity inspection technique in 2010.
3. experimental result see table：
| Sample survey | Result |
| Embodiment 1 sample | ≤ 0.5 standard turbidity solution |
| Control sample 1：Using sodium bicarbonate as sample obtained by pH adjusting agent | 0.5 standard turbidity solution≤clarity≤1.0 standard turbidity solution |
| Control sample 2：PH regulator is to 7.5～8.0 | 0.5 standard turbidity solution≤clarity≤1.0 standard turbidity solution |
| Control sample 3：PH regulator is to 6.0～6.5 | 0.5 standard turbidity solution≤clarity≤1.0 standard turbidity solution |
| Control sample 4：Not plus treatment with chitosan sample | ≥1.0 |
4. experiment conclusion：Sample clarity obtained by embodiment 1 is better than each control sample.
Embodiment 2
A kind of few (S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection of impurity, is obtained according to the following steps：
Preparation process：Preparation technology according to embodiment 1 is obtained.
By the test method of embodiment 1, carry out stability test investigation respectively, impact that sterilization process increases examination to impurity
Test and clarity contrast test, stability test result shows to accelerate June sample quality stable, long-term 18 months quality
Stable, therefore minimum 18 months of this product effect duration.Sterilization process shows embodiment 2 to the impact result of the test that impurity increases
Prescription, coordinate specific sterilization process, relevant material increase is substantially better than its control sample.Clarity contrast test is tied
Fruit shows that the sample clarity that embodiment 2 is produced is less than No. 0.5 standard turbidity solution, and this product clarity is good.
Embodiment 3
A kind of few (S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection of impurity, is obtained according to the following steps：
Preparation process：Preparation technology according to embodiment 1 is obtained.
By the test method of embodiment 1, carry out stability test investigation respectively, impact that sterilization process increases examination to impurity
Test and clarity contrast test, stability test result shows to accelerate June sample quality stable, long-term 18 months quality
Stable, therefore minimum 18 months of this product effect duration.Sterilization process shows embodiment 3 to the impact result of the test that impurity increases
Prescription, coordinate specific sterilization process, relevant material increase is substantially better than its control sample.Clarity contrast test is tied
Fruit shows that the sample clarity that embodiment 3 is produced is less than No. 0.5 standard turbidity solution, and this product clarity is good.
Embodiment 4-6：A kind of (S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection, former auxiliary by following weight
Material is prepared, and preparation method is with embodiment 1：
By the test method of embodiment 1, carry out stability test investigation respectively, impact that sterilization process increases examination to impurity
Test and clarity contrast test, embodiment 4,5,6 stability test result shows to accelerate June sample quality stable, long
18 months phases steady quality, therefore minimum 18 months of this product effect duration.The impact result of the test that sterilization process increases to impurity
Show the prescription of embodiment 4,5,6, coordinate specific sterilization process, relevant material increase is substantially better than its control sample.
Clarity comparative test result shows that the sample clarity that embodiment 4,5,6 is produced is less than No. 0.5 standard turbidity solution,
This product clarity is good.
Claims (3)
1. a kind of impurity is few（S）- 4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection it is characterised in that：It is with（S）- 4- hydroxyl -2 oxo-1-pyrrolidine ethanamide, propylene glycol, lecithin, vitamin C, ethylenediaminetetraacetic acid be supplementary material, by dense join, dilute join, embedding, sterilizing, test package step be obtained；The consumption of wherein said supplementary material is weight percentage（S）- 4- hydroxyl -2 oxo-1-pyrrolidine ethanamide 50% ~ 70%, propylene glycol 15% ~ 30%, lecithin 10% ~ 18%, vitamin C 3% ~ 8%, ethylenediaminetetraacetic acid 2% ~ 5%；Described dense step of joining is to add in material-compound tank by supplementary material, adds sterilized water for injection, stirring, dissolving immediately, obtains concentrated wiring liquid；Described dilute step of joining is to take concentrated wiring liquid, adds 0.1mol/L ~ 0.5mol/L sodium hydroxide solution, adjusts pH to 6.5 ~ 7.0, adds cumulative volume 0.2% ~ 0.6% in above-mentioned solution（g/ml）Shitosan, stirring, mix, stand 30 ~ 50min, with the filtration of 0.8 μm of filter membrane, add cumulative volume 0.1% ~ 0.3%（g/ml）Activated carbon, adsorption bleaching, with the filtration of 0.45 μm of filter membrane, collect filtrate, add sterilized water for injection to recipe quantity, it is qualified to test through middle product examine, you can；Described sterilization steps are canned peace to be cutd open semi-finished product send into steam sterilization pan sterilizing, 121 DEG C of sterilizing 15min, sterilizing program：10 DEG C/min, rise to 121 DEG C, keep 15min at 121 DEG C；3 ~ 5 DEG C/min of compressed air air blast lowers the temperature, and 8 ~ 12min is cooled to 70 ~ 80 DEG C, and 2 ~ 3 DEG C/min of cooling water lowers the temperature, and 15 ~ 18min is cooled to 30 DEG C, and sterilizing completes.
2. as claimed in claim 1（S）- 4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection is it is characterised in that it is to be obtained by the supplementary material of following significant percentage：（S）- 4- hydroxyl -2 oxo-1-pyrrolidine ethanamide 55% ~ 65%, propylene glycol 18% ~ 25%, lecithin 12% ~ 16%, vitamin C 3% ~ 5%, ethylenediaminetetraacetic acid 2% ~ 4%, above-mentioned supplementary material is added in material-compound tank, adds the sterilized water for injection of 1/3 recipe quantity immediately, stirring, dissolving, obtain concentrated wiring liquid；Take concentrated wiring liquid, add 0.1mol/L sodium hydroxide solution, adjust pH to 6.5 ~ 7.0, add cumulative volume 0.2% ~ 0.6% in above-mentioned solution（g/ml）Shitosan, stirring, mix, stand 30 ~ 50min, with the filtration of 0.8 μm of filter membrane, add cumulative volume 0.1% ~ 0.3%（g/ml）Activated carbon, adsorption bleaching, with the filtration of 0.45 μm of filter membrane, collect filtrate, add sterilized water for injection to recipe quantity, it is qualified to test through middle product examine, you can；Canned peace is cutd open semi-finished product and sends into steam sterilization pan sterilizing, 121 DEG C of sterilizing 15min, sterilizing program：10 DEG C/min, rise to 121 DEG C, keep 15min at 121 DEG C；3 ~ 5 DEG C/min of compressed air air blast lowers the temperature, and 8 ~ 12min is cooled to 70 ~ 80 DEG C, and 2 ~ 3 DEG C/min of cooling water lowers the temperature, and 15 ~ 18min is cooled to 30 DEG C, and sterilizing completes.
3. a kind of impurity is few as claimed in claim 1 or 2（S）The preparation method of -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection is it is characterised in that it is obtained as follows：
A. dense join：Supplementary material is added in material-compound tank, adds the sterilized water for injection of 1/3 recipe quantity immediately, stirring, dissolving, obtain concentrated wiring liquid；
B. dilute join：Take concentrated wiring liquid, add 0.1mol/L sodium hydroxide solution, adjust pH to 6.5 ~ 7.0, add the shitosan of cumulative volume 0.2% ~ 0.6% mass volume ratio, stirring in above-mentioned solution, mix, standing 30 ~ 50min, with 0.8 μm of filter membrane filtration, adds the activated carbon of cumulative volume 0.1% ~ 0.3% mass volume ratio, adsorption bleaching, with 0.45 μm of filter membrane filtration, collect filtrate, add sterilized water for injection to recipe quantity, it is qualified to test through middle product examine, you can；
C. embedding：Intermediate is filtered with 0.22 μm of filter after the assay was approved, check visible foreign matters, after bacterial endotoxin is qualified, upper streamline carries out fill, the nitrogen that pouring process need to be filled with purity 99.99% makes the oxygen content in water for injection in tank be less than 0.01%, seals after inflated with nitrogen；
D. sterilize：Canned peace is cutd open semi-finished product and sends into steam sterilization pan sterilizing, 121 DEG C of sterilizing 15min, sterilizing program：10 DEG C/min, rise to 121 DEG C, keep 15min at 121 DEG C；3 ~ 5 DEG C/min of compressed air air blast lowers the temperature, and 8 ~ 12min is cooled to 70 ~ 80 DEG C, and 2 ~ 3 DEG C/min of cooling water lowers the temperature, and 15 ~ 18min is cooled to 30 DEG C, and sterilizing completes, by rated condition leak detection；
E. check：After sterilizing, sample checks visible foreign matters, the sample checking qualified is packed, full inspection, warehouse-in.
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| CN201510511546.8A CN106466294A (en) | 2015-08-19 | 2015-08-19 | Few (S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection of a kind of impurity and preparation method thereof |
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| CN201510511546.8A CN106466294A (en) | 2015-08-19 | 2015-08-19 | Few (S) -4- hydroxyl -2 oxo-1-pyrrolidine ethanamide injection of a kind of impurity and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
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- 2015-08-19 CN CN201510511546.8A patent/CN106466294A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
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