CN107115274A - A kind of levo-oxiracetam of injection and preparation method thereof - Google Patents
A kind of levo-oxiracetam of injection and preparation method thereof Download PDFInfo
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- CN107115274A CN107115274A CN201610103836.3A CN201610103836A CN107115274A CN 107115274 A CN107115274 A CN 107115274A CN 201610103836 A CN201610103836 A CN 201610103836A CN 107115274 A CN107115274 A CN 107115274A
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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
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
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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
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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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
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
-
- 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
Abstract
A kind of levo-oxiracetam of injection, it is characterised in that it is made by following supplementary material：Levo-oxiracetam 58% ~ 65%, propane diols 15% ~ 22%, lecithin 18% ~ 25%；Above-mentioned supplementary material is added in material-compound tank, the water of 2/3 recipe quantity is added, stirred, dissolving obtains concentrated wiring liquid；Concentrated wiring liquid is taken, sodium phosphate buffer regulation pH to 6.5 is added, 0.2% ~ 0.6% chitosan is added into above-mentioned solution, is stirred, mixing is stood, filtration, 0.1% ~ 0.3% activated carbon, adsorption bleaching, filtration is added, you can.It is substantially unchanged according to injection levo-oxiracetam sterilization process pH value of solution produced by the present invention, finished product has clarity good, less than No. 0.5 standard turbidity solution of clarity, stability is good, and crystallization will not be produced during storage, the term of validity is long, it can reach more than 18 months, product impurity is few in the term of validity, its total impurities is less than 0.32%, preparation technology simple possible, is worthy to be popularized.
Description
Technical field
The invention mainly relates to pharmaceutical technology field, and in particular to a kind of levo-oxiracetam of injection and its preparation side
Method.
Background technology
It is a kind of promotion study that cereboactive drug, which is also known as cereboactive drug, strengthens the new medicine for central nervous system of memory.
Nootropics requires selection index system in cerebral cortex, with selection activation, protection and promotion damaged nerve cell functional rehabilitation
Feature.Different from other neurologic agents be a little their above-mentioned effect not by network or olfactory bulb, but directly
Act on cortex.Behavior is neither influenceed, also without calm excitation, therefore such medicine has caused the extensive concern of people and emerging
Interest, the demand to such medicine is also growing day by day.
Oxiracetam (oxiracetam, CAS No.：62613-82-5) chemical entitled 4- hydroxyls -2- OXo-1-pyrrolidines
Acetamide, is that (compound is disclosed in the anti anoxia class cereboactive drug that was synthesized first in 1974 of Italian ISFS.P.A companies
US4118396), it is ring GABOB derivatives, Phosphorylcholine and phosphatidyl ethanolamine can be promoted to synthesize, promotes brain metabolism, through blood brain
Barrier, has stimulation to specific nervous centralis road, can improve intelligence and memory, to cerebrovascular disease, brain trauma, brain
Knurl, intracranial infection, brain degenerative disease etc. also have preferable curative effect, and the drug toxicity is extremely low, no mutagenesis and carcinogenic work
With and genotoxicity.Giorgio et al. discloses the chemical constitution and preparation method of Oxiracetam in US4118396,
Chiodini et al. is disclosed in WO9306826A, and clinical effectiveness proves that the drug effect of the Oxiracetam of S configurations (left-handed) is better than R structures
Type (dextrorotation), Oxiracetam and levo-oxiracetam structure are as follows.
The levo-oxiracetam of existing injection its be primarily present pH value of solution in product sterilization process change greatly, finished product it is clear
Easily crystallization is spent during poor, storage clearly, the problems such as impurity is more.
The content of the invention
It is an object of the invention to provide the injection levo-oxiracetam that a kind of clarity is good, stability is good.
Another object of the present invention is to provide the preparation method of above-mentioned injection levo-oxiracetam.
The purpose of the present invention is realized by following technical measures：
A kind of levo-oxiracetam of injection, it is characterised in that it is made by the supplementary material of following weight percents：
Levo-oxiracetam 55%~75%, additives 20%~40%, wherein the additives be glucose, sodium chloride, mannitol,
Glycerine, Serine, sodium glutamate, alanine, glycine, lecithin, propane diols, phenmethylol, anesin, sulfurous acid
One or more in sodium, sodium hydrogensulfite, sodium pyrosulfite.
Inventor has found the specific additives species of selection and consumption, coordinate match somebody with somebody during liquid specific pH adjusting agent and
Specific pH, then handled by a certain amount of chitosan, may be such that this product, pH value of solution change is smaller in sterilization process and can carry
High finished product clarity, finished product storage process will not also be crystallized, and product impurity is few, and stability is more preferable, left-handed Austria of above-mentioned injection
La Xitan, it is characterised in that it is made by the supplementary material of following weight percents：Levo-oxiracetam 58%~65%, third
Glycol 15%~22%, lecithin 18%~25%；Above-mentioned supplementary material is added in material-compound tank, 2/3 recipe quantity is added immediately
Sterilized water for injection, is stirred, and dissolving obtains concentrated wiring liquid；Concentrated wiring liquid is taken, adding sodium phosphate buffer, (precision weighs phosphoric acid hydrogen two
Sodium 65.697g and sodium dihydrogen phosphate 2.346g are placed in 1000ml volumetric flasks, are added purified water dissolving, dilution and are settled to scale,
Produce) regulation pH to 6.0~7.0, the chitosan of cumulative volume 0.2%~0.6% (g/ml) is added into above-mentioned solution, is stirred,
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), inhale
It is attached to decolourize, filtered with 0.45 μm of filter membrane, collect filtrate, added sterilized water for injection to recipe quantity, test qualified through middle product examine,
；
Most preferably, above-mentioned injection levo-oxiracetam, it is characterised in that it is by the former auxiliary of following significant percentage
Material is made：Levo-oxiracetam 59%~63%, propane diols 17%~20%, lecithin 20%~23%；By above-mentioned supplementary material
Add in material-compound tank, the sterilized water for injection of 2/3 recipe quantity is added immediately, stir, dissolving obtains concentrated wiring liquid；Concentrated wiring liquid is taken, is added
Sodium phosphate buffer (precision weighs disodium hydrogen phosphate 65.697g and sodium dihydrogen phosphate 2.346g is placed in 1000ml volumetric flasks,
Add purified water dissolving, dilution be settled to scale, produce) regulation pH to 6.5, into above-mentioned solution add cumulative volume 0.3%~
0.5% (g/ml) chitosan, is stirred, and is mixed, and stands 35~45min, is filtered with 0.8 μm of filter membrane, adds cumulative volume 0.1%
~0.3% (g/ml) activated carbon, adsorption bleaching is filtered with 0.45 μm of filter membrane, collects filtrate, adds sterilized water for injection extremely
Recipe quantity, tests qualified through middle product examine, you can；
A kind of preparation method of the levo-oxiracetam of injection, it is characterised in that it is obtained as follows：
1. concentrated compounding：Above-mentioned supplementary material is added in material-compound tank, the sterilized water for injection of 2/3 recipe quantity is added immediately, is stirred,
Dissolving, obtains concentrated wiring liquid；
2. dilute match somebody with somebody：Concentrated wiring liquid is taken, adding sodium phosphate buffer, (precision weighs disodium hydrogen phosphate 65.697g and di(2-ethylhexyl)phosphate
Hydrogen sodium 2.346g is placed in 1000ml volumetric flasks, is added purified water dissolving, dilution and is settled to scale, produces) pH is adjusted to 6.5,
The chitosan of cumulative volume 0.3%~0.5% (g/ml) is added into above-mentioned solution, is stirred, is mixed, 35~45min is stood, used
0.8 μm of filter membrane filtration, adds the activated carbon of cumulative volume 0.1%~0.3% (g/ml), adsorption bleaching, with 0.45 μm of filter membrane
Filtration, collects filtrate, adds sterilized water for injection to recipe quantity, tests qualified through middle product examine, you can
3. embedding：Intermediate is filtered with 0.22 μm of filter after the assay was approved, checks visible foreign matters, and bacterial endotoxin is closed
After lattice, upper streamline carries out filling, sealing；
4. sterilizing：Canned peace is cutd open into semi-finished product feeding steam sterilization pan sterilizing, 121 DEG C of sterilizing 15min, sterilizing journey
Sequence：10 DEG C/min, 121 DEG C are risen to, 15min is kept at 121 DEG C；3~5 DEG C/min of compressed air air blast cools, and 8~12min is cold
But to 70~80 DEG C, 2~3 DEG C/min of cooling water coolings, 15~18min is cooled to 30 DEG C, and sterilizing is completed, and is examined by rated condition
Leakage；
5. examine：Sample after sterilizing is checked into visible foreign matters, qualified sample will be examined to carry out outsourcing, full inspection is put in storage, i.e.,
.
The present invention has following beneficial effect：
PH value of solution is substantially unchanged in the levo-oxiracetam sterilization process of injection of the present invention, and finished product has clarity
Good, less than No. 0.5 standard turbidity solution of clarity, stability is good, crystallization will not be produced during storage, the term of validity is long, can reach
More than 18 months, product impurity was few in the term of validity, and its total impurities is less than 0.32%, and preparation technology simple possible, worth market is pushed away
Extensively.
Embodiment
The present invention is specifically described below by embodiment, it is necessary to it is pointed out here that be that following examples are only used
It is further described in the present invention, it is impossible to be interpreted as limiting the scope of the invention, without departing substantially from spirit of the invention
In the case of essence, the modifications or substitutions made to the inventive method, step or condition belong to the scope of the present invention.
Embodiment 1
A kind of levo-oxiracetam of injection, is made according to the following steps：
Preparation process：
1. concentrated compounding：Above-mentioned supplementary material is added in material-compound tank, the sterilized water for injection of 2/3 recipe quantity is added immediately, is stirred,
Dissolving, obtains concentrated wiring liquid；
2. dilute match somebody with somebody：Concentrated wiring liquid is taken, adding sodium phosphate buffer, (precision weighs disodium hydrogen phosphate 65.697g and di(2-ethylhexyl)phosphate
Hydrogen sodium 2.346g is placed in 1000ml volumetric flasks, is added purified water dissolving, dilution and is settled to scale, produces), pH is to 6.5 for regulation,
The chitosan of cumulative volume 0.3%~0.5% (g/ml) is added into above-mentioned solution, is stirred, is mixed, 35~45min is stood, used
0.8 μm of filter membrane filtration, adds the activated carbon of cumulative volume 0.1%~0.3% (g/ml), adsorption bleaching, with 0.45 μm of filter membrane
Filtration, collects filtrate, adds sterilized water for injection to recipe quantity, tests qualified through middle product examine, you can
3. embedding：Intermediate is filtered with 0.22 μm of filter after the assay was approved, checks visible foreign matters, and bacterial endotoxin is closed
After lattice, upper streamline carries out filling, sealing；
4. sterilizing：Canned peace is cutd open into semi-finished product feeding steam sterilization pan sterilizing, 121 DEG C of sterilizing 15min, sterilizing journey
Sequence：10 DEG C/min, 121 DEG C are risen to, 15min is kept at 121 DEG C；3~5 DEG C/min of compressed air air blast cools, and 8~12min is cold
But to 70~80 DEG C, 2~3 DEG C/min of cooling water coolings, 15~18min is cooled to 30 DEG C, and sterilizing is completed, and is examined by rated condition
Leakage；
5. examine：Sample after sterilizing is checked into visible foreign matters, qualified sample will be examined to carry out outsourcing, full inspection is put in storage, i.e.,
.
In order to be better understood from the present invention, having for invention medicine is expanded on further below by way of stability test of the present invention
Beneficial effect, rather than limitation of the present invention.
Experiment one：A kind of levo-oxiracetam stability experiment of injection of the present invention
Experiment material：
The Oxiracetam sample of injection：It is made for embodiment 1.
Acceleration study method：The Oxiracetam of injection made from embodiment 1 is packed by listing, Acceleration study case is put
In, certain time sampling is tested to investigation project.
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 is recorded：
Acceleration study result shows：Acceleration sample in June is suitable with the every Testing index quality of 0 month sample, shows that this product adds
Speed is tested June, and quality keeps stable, and this product stability is preferable.
Long-term experiment method：The levo-oxiracetam of injection made from embodiment 1 is packed by listing, puts and keeps sample for a long time
In case, certain time sampling is tested to investigation project.
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 is recorded：
Long term test shows：18 months characters of this product long term test, visible foreign matters, clarity, pH value, relevant material, contain
Amount and sterility test indices meet every relevant regulations of production quality standard draft without significant changes.This
18 months steady qualities of product long term test, therefore minimum 18 months of this product term of validity, long term test is still during continuing to investigate.
Experiment two：A kind of levo-oxiracetam clarity comparative experimental research of injection of the present invention
1. experiment material：
The levo-oxiracetam sample of injection：It is made for embodiment 1
The levo-oxiracetam control sample of injection：The change pH adjusting agent of single factor test, pH value and non-shell adding are poly- respectively
After the factors such as sugar, injection levo-oxiracetam is used as control sample as made from the preparation method of embodiment 1.
2. experimental method：Tested according to the second annex IXB clarity inspection technique of version Chinese Pharmacopoeia in 2010.
3. experimental result see the table below：
| Sample survey | As a result |
| The sample of embodiment 1 | ≤ 0.5 standard turbidity solution |
| Control sample 1：Using sample obtained by sodium acid carbonate as pH adjusting agent | The standard turbidity solution of 0.5 standard turbidity solution≤clarity≤1.0 |
| Control sample 2：PH is adjusted to 7.5~8.0 | The standard turbidity solution of 0.5 standard turbidity solution≤clarity≤1.0 |
| Control sample 3：PH is adjusted to 5.5~6.0 | The standard turbidity solution of 0.5 standard turbidity solution≤clarity≤1.0 |
| Control sample 4：The sample of non-shell adding glycan processing | ≥1.0 |
4. experiment conclusion：Sample clarity obtained by embodiment 1 is better than each control sample.
Experiment three：The influence of pH value of solution before and after different pH adjusting agents sterilize to product
1. experiment material：
The levo-oxiracetam sample of injection：It is made for embodiment 1
The levo-oxiracetam control sample of injection：PH is used as using sodium acid carbonate, sodium hydroxide, disodium hydrogen phosphate respectively
Conditioning agent, injection levo-oxiracetam is used as control sample as made from the preparation method of embodiment 1.
2. experimental method：Before and after being sterilized according to version Chinese Pharmacopoeia first step annex VIIG pH value determination method in 2010 to product
PH value of solution test, investigate the influence of pH before and after different pH adjusting agents sterilize to product.
3. experimental result see the table below：
4. experiment conclusion：PH value of solution is substantially unchanged before and after sample sterilizing obtained by embodiment 1.
Embodiment 2
A kind of levo-oxiracetam of injection, is made according to the following steps：
Preparation process：Preparation technology according to embodiment 1 is made.
By the test method of embodiment 1, stability test investigation, clarity contrast test and pH adjusting agent are carried out respectively
The influence experiment of pH value of solution before and after being sterilized to product, stability test result shows to accelerate sample quality stabilization in June, long-term 18
Month steady quality, therefore minimum 18 months of this product term of validity；Clarity contrast test result of the test shows the sample that embodiment 2 is produced
Product clarity is less than No. 0.5 standard turbidity solution, and this product clarity is good；The shadow of pH value of solution before and after different pH adjusting agents sterilize to product
Ring experiment and show that the front and rear pH value of solution of sample sterilizing obtained by embodiment 2 is substantially unchanged.
Embodiment 3
A kind of levo-oxiracetam of injection, is made according to the following steps：
Preparation process：Preparation technology according to embodiment 1 is made.
By the test method of embodiment 1, stability test investigation, clarity contrast test and pH adjusting agent are carried out respectively
The influence experiment of pH value of solution before and after being sterilized to product, stability test result shows to accelerate sample quality stabilization in June, long-term 18
Month steady quality, therefore minimum 18 months of this product term of validity；Clarity contrast test result of the test shows the sample that embodiment 3 is produced
Product clarity is less than No. 0.5 standard turbidity solution, and this product clarity is good；The shadow of pH value of solution before and after different pH adjusting agents sterilize to product
Ring experiment and show that the front and rear pH value of solution of sample sterilizing obtained by embodiment 3 is substantially unchanged.
Embodiment 4-6：A kind of levo-oxiracetam of injection, is prepared, preparation side by the supplementary material of following weight
Method be the same as Example 1：
| Embodiment | Levo-oxiracetam | Propane diols | Lecithin | Sterilized water for injection |
| 4 | 100g | 28g | 35g | Add water to 2000ml |
| 5 | 100g | 29g | 36g | Add water to 2000ml |
| 6 | 100g | 31g | 37g | Add water to 2000ml |
Preparation process：Preparation technology according to embodiment 1 is made.
By the test method of embodiment 1, the sample obtained by embodiment 4,5,6 carries out stability test investigation respectively, clear
The influence of pH value of solution is tested before and after clear degree contrast test and pH adjusting agent sterilize to product, the stability test of embodiment 4,5,6
As a result show to accelerate sample quality stabilization in June, long-term 18 months steady qualities, therefore the sample obtained by embodiment 4,5,6 is effective
Minimum 18 months of phase；Clarity contrast test result of the test 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；The influence experiment of pH value of solution shows embodiment before and after different pH adjusting agents sterilize to product
4th, pH value of solution is substantially unchanged before and after the sample sterilizing obtained by 5,6.
Claims (3)
1. a kind of levo-oxiracetam of injection, it is characterised in that it is made by the supplementary material of following weight percents：It is left
Revolve Oxiracetam about 58% ~ 65%, propane diols about 15% ~ 22%, lecithin about 18% ~ 25%；Above-mentioned supplementary material is added in material-compound tank,
The sterilized water for injection of 2/3 recipe quantity is added immediately, is stirred, and dissolving obtains concentrated wiring liquid；Concentrated wiring liquid is taken, sodium ascorbyl phosphate buffering is added
Liquid（Precision weighs disodium hydrogen phosphate 65.697g and sodium dihydrogen phosphate 2.346g is placed in 1000ml volumetric flasks, adds purifying water-soluble
Solution, dilution are settled to scale, produce）, pH to 6.0 ~ 7.0 is adjusted, cumulative volume 0.2% ~ 0.6% is added into above-mentioned solution（g/ml）
Chitosan, stir, mix, stand 30 ~ 50min, filtered with 0.8 μm of filter membrane, add cumulative volume 0.1% ~ 0.3%（g/ml）'s
Activated carbon, adsorption bleaching is filtered with 0.45 μm of filter membrane, collects filtrate, sterilized water for injection is added to recipe quantity, through middle product
It is qualified to examine, you can.
2. injection levo-oxiracetam as claimed in claim 1, it is characterised in that it is by the original of following significant percentage
Auxiliary material is made：Levo-oxiracetam about 59% ~ 63%, propane diols about 17% ~ 20%, lecithin about 20% ~ 23%；Above-mentioned supplementary material is added
Enter in material-compound tank, the sterilized water for injection of 2/3 recipe quantity is added immediately, stir, dissolving obtains concentrated wiring liquid；Concentrated wiring liquid is taken, phosphorus is added
Acid sodium-salt buffer solution（Sodium phosphate buffer：Precision weighs disodium hydrogen phosphate 65.697g and sodium dihydrogen phosphate 2.346g is placed in
In 1000ml volumetric flasks, add purified water dissolving, dilution and be settled to scale, produce）, pH to 6.5 is adjusted, is added into above-mentioned solution
Enter cumulative volume 0.3% ~ 0.5%（g/ml）Chitosan, stir, mix, stand 35 ~ 45min, filtered with 0.8 μm of filter membrane, added
Cumulative volume 0.1% ~ 0.3%（g/ml）Activated carbon, adsorption bleaching filters with 0.45 μm of filter membrane, collects filtrate, add sterilizing note
Penetrate with water to recipe quantity, test qualified through middle product examine, you can.
3. a kind of preparation method of the levo-oxiracetam of injection as claimed in claim 1 or 2, it is characterised in that it is
It is obtained as follows：
A. concentrated compounding：Above-mentioned supplementary material is added in material-compound tank, the sterilized water for injection of 2/3 recipe quantity is added immediately, is stirred, it is molten
Solution, obtains concentrated wiring liquid；
B. it is dilute to match somebody with somebody：Concentrated wiring liquid is taken, sodium phosphate buffer is added（Sodium phosphate buffer：Precision weighs disodium hydrogen phosphate
65.697g and sodium dihydrogen phosphate 2.346g are placed in 1000ml volumetric flasks, are added purified water dissolving, dilution and are settled to scale, i.e.,
）, pH to 6.5 is adjusted, cumulative volume 0.3% ~ 0.5% is added into above-mentioned solution（g/ml）Chitosan, stir, mix, stand
35 ~ 45min, is filtered with 0.8 μm of filter membrane, adds cumulative volume 0.1% ~ 0.3%（g/ml）Activated carbon, adsorption bleaching uses 0.45 μ
M filter membrane filtration, collects filtrate, adds sterilized water for injection to recipe quantity, tests qualified through middle product examine, you can；
C. embedding：Intermediate is filtered with 0.22 μm of filter after the assay was approved, checks visible foreign matters, bacterial endotoxin is qualified
Afterwards, upper streamline carries out filling, sealing；
D. sterilize：Canned peace is cutd open into semi-finished product feeding steam sterilization pan sterilizing, 121 DEG C of sterilizing 15min, sterilizing program：10
DEG C/min, 121 DEG C are risen to, 15min is kept at 121 DEG C；3 ~ 5 DEG C/min of compressed air air blast cools, and 8 ~ 12min is cooled to 70 ~
80 DEG C, 2 ~ 3 DEG C/min of cooling water coolings, 15 ~ 18min is cooled to 30 DEG C, and sterilizing is completed, and is hunted leak by rated condition；
E. examine：Sample checks visible foreign matters after sterilizing, and qualified sample will be examined to carry out outsourcing, and full inspection, storage is produced.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610103836.3A CN107115274A (en) | 2016-02-25 | 2016-02-25 | A kind of levo-oxiracetam of injection and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610103836.3A CN107115274A (en) | 2016-02-25 | 2016-02-25 | A kind of levo-oxiracetam of injection and preparation method thereof |
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| CN107115274A true CN107115274A (en) | 2017-09-01 |
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Citations (3)
| 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 |
| CN102512363A (en) * | 2011-12-23 | 2012-06-27 | 重庆药友制药有限责任公司 | Oxiracetam injection and preparation method thereof |
| CN102670497A (en) * | 2012-05-31 | 2012-09-19 | 北京阜康仁生物制药科技有限公司 | Stable S-oxiracetam preparation for injection and preparation method of same |
-
2016
- 2016-02-25 CN CN201610103836.3A patent/CN107115274A/en not_active Withdrawn
Patent Citations (3)
| 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 |
| CN102512363A (en) * | 2011-12-23 | 2012-06-27 | 重庆药友制药有限责任公司 | Oxiracetam injection and preparation method thereof |
| CN102670497A (en) * | 2012-05-31 | 2012-09-19 | 北京阜康仁生物制药科技有限公司 | Stable S-oxiracetam preparation for injection and preparation method of same |
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Application publication date: 20170901 |