CN106692134A - (S)-4- hydroxyl-2 oxo-1-pyrrolidine acetamide aqueous injection used for injection, and preparation method thereof - Google Patents
(S)-4- hydroxyl-2 oxo-1-pyrrolidine acetamide aqueous injection used for injection, and preparation method thereof Download PDFInfo
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- CN106692134A CN106692134A CN201510511681.2A CN201510511681A CN106692134A CN 106692134 A CN106692134 A CN 106692134A CN 201510511681 A CN201510511681 A CN 201510511681A CN 106692134 A CN106692134 A CN 106692134A
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Abstract
The invention discloses a (S)-4- hydroxyl-2- oxo-1-pyrrolidine acetamide aqueous injection used for injection. According to a preparation method, by weight, 65 to 75% of (S)-4- hydroxyl-2 oxo-1-pyrrolidine acetamide, 7 to 15% of propylene glycol, 10 to 20% of lecithin, 3 to 8% of vitamin C, 3 to 5% of ethylene diamine tetraacetic acid, and 1 to 3% of phenylcarbinol are taken as raw and auxiliary materials, and the (S)-4- hydroxyl-2 oxo-1-pyrrolidine acetamide aqueous injection is prepared via steps of concentrated solution preparation, diluted solution preparation, filling, sterilizing, and examining and packaging. In storing process, crystallization and oxidation of the (S)-4- hydroxyl-2- oxo-1-pyrrolidine acetamide aqueous injection are not caused; impurity adding amount in sterilizing process is only 0.04%; stability is high; self life is as long as 18 months or longer; impurity is little in self life; total impurity amount is lower than 0.28%; pain of patients in injection process is relieved obviously; patient compliance is high; and the (S)-4- hydroxyl-2 oxo-1-pyrrolidine acetamide aqueous injection is worthy of market promotion.
Description
Technical field
The invention mainly relates to pharmaceutical technology field, and in particular to a kind of OXo-1-pyrrolidine of injection (S) -4- hydroxyls -2
Acetamide liquid drugs injection and preparation method thereof.
Background technology
Cereboactive drug is a kind of new medicine for central nervous system for promoting study, strengthening memory also known as cereboactive drug.Promote
Intelligence medicine requirement selection index system activates, protects and promotes damaged nerve cell functional rehabilitation in cerebral cortex with selection
Feature.Different from other neurologic agents be a little their above-mentioned effect not by network or olfactory bulb, but directly
Connect and act on cortex.Behavior is neither influenceed, also without calm excitation, therefore such medicine has caused the extensive pass of people
Note and interest, the demand to such medicine are also growing day by day.
Oxiracetam was listed in 1987 in Italy, and the formulation of listing is tablet, 800mg；Capsule, 800mg；Note
Penetrate liquid, 1g/5ml.Domestic at present only have oxiracetam capsule and parenteral solution listing, and main active used be it is outer
Raceme.Caused by Ye Lei etc. mentions levo-oxiracetam to alcoholism in the A patents of Publication No. CN 103735545
The promoting wakening of stupor is obvious, and dextrorotation Oxiracetam is not acted on substantially, and the awake effect of above-mentioned rush of levo-oxiracetam is
2 times of racemization Oxiracetam；Levo-oxiracetam is notable to the promoting wakening of stupor caused by wound, anesthesia.Open peak etc.
It is traumatic caused by levo-oxiracetam is disclosed in the patent of the A of Publication No. CN 103599101 to hydraulic pressure and freely falling body
Brain injury in rats learning and memory cognition dysfunction improves significantly, and its drug effect is far above dextrorotation Oxiracetam.
And 200mg/kg levo-oxiracetams are suitable with the effect of 400mg/kg Oxiracetams.Pharmacokinetic study results show：
Levo-oxiracetam and dextrorotation Oxiracetam are in beasle dog body without obvious chiral inversion.Beasle dog single intravenous injection gives
The main pharmacokinetic parameters of levo-oxiracetam nothing is substantially poor in blood plasma after left-handed and 2 multiple doses racemization Oxiracetam
It is different.The result of the tests such as safe pharmacology, anxious poison malicious, long show, under isodose level, levo-oxiracetam and Aura
It is western smooth to animal subject or the toxicity no significant difference of cell.Above-mentioned preclinical result of study shows, levo-oxiracetam
It is the main active that drug effect is played in Oxiracetam body, this product is used alone can reduce Clinical practice dosage, reduces latent
Toxicity.
The existing oxo-1-pyrrolidine ethanamide liquid drugs injection of injection (S) -4- hydroxyls -2 its be primarily present product stability it is bad easily
Oxidation, storage during easily crystallization, sterilization process easily cause impurity increase, patient injection procedure's pain substantially, comply with
Property difference the problems such as.
The content of the invention
It is an object of the invention to provide a kind of oxo of good stability, product not oxidizable injection (S) -4- hydroxyls -2
- 1- pyrrolidine acetamide liquid drugs injections.
Preparation side another object of the present invention is to provide the above-mentioned oxo-1-pyrrolidine ethanamide liquid drugs injection of (S) -4- hydroxyls -2
Method.
The purpose of the present invention is realized by following technical measures：
The oxo-1-pyrrolidine ethanamide liquid drugs injection of (S) -4- hydroxyls -2 of a kind of injection, it is characterised in that it is with (S)
The oxo-1-pyrrolidine ethanamide of -4- hydroxyls -2 is raw material, adds a certain amount of additives and is obtained；Wherein described additives
For glucose, sodium chloride, mannitol, glycerine, Serine, sodium glutamate, alanine, glycine, lecithin,
In propane diols, phenmethylol, anesin, sodium sulfite, sodium hydrogensulfite, sodium pyrosulfite, vitamin C, second
One or more of ethylenediamine tetraacetic acid (EDTA).
Inventor had found in research process, and a certain proportion of propane diols, lecithin and phenmethylol are selected in composition described above
The compound additives of composition, add a certain amount of vitamin C and ethylenediamine tetra-acetic acid, coordinate specific sterilization process step,
May be such that the above-mentioned oxo-1-pyrrolidine ethanamide injection of (S) -4- hydroxyls -2 has good stability, during storage not
Can crystallize, pain reduction in patient injection procedure, product total impurities increase in sterilization process is smaller, and product was stored
It is difficult to be oxidized in journey, the above-mentioned oxo-1-pyrrolidine ethanamide liquid drugs injection of injection (S) -4- hydroxyls -2, it is characterised in that：
It is with the oxo-1-pyrrolidine ethanamide of (S) -4- hydroxyls -2, propane diols, lecithin, vitamin, ethylenediamine tetra-acetic acid,
Phenmethylol is supplementary material, by concentrated compounding, it is dilute match somebody with somebody, embedding, sterilizing, test package step be obtained；Wherein described supplementary material
The oxo-1-pyrrolidine ethanamide 65%~75% of (S) -4- hydroxyls -2 that is weight percentage of consumption, propane diols 7%~15%,
Lecithin 10%~20%, vitamin C 3%~8%, ethylenediamine tetra-acetic acid 3%~5%, phenmethylol 1%~3%；Wherein institute
It is that canned peace is cutd open into semi-finished product feeding steam sterilization pan sterilizing, 121 DEG C of sterilizing 15min, sterilizing journey to state sterilization steps
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 lowers the temperature, 8~12min
70~80 DEG C are cooled to, 2~3 DEG C/min of cooling water coolings, 15~18min is cooled to 30 DEG C, and sterilizing is completed.
Further, sterilized in order that obtaining the above-mentioned oxo-1-pyrrolidine ethanamide liquid drugs injection of injection (S) -4- hydroxyls -2
Impurity increases and further reduces in journey, and stability is more preferable, a kind of OXo-1-pyrrolidine acetyl of injection (S) -4- hydroxyls -2
Aqueous amine pin, it is characterised in that it is obtained by the supplementary material of following significant percentage：(S) oxo -1- pyrroles of -4- hydroxyls -2
Cough up alkyl acetamide 67%~73%, propane diols 8%~13%, lecithin 11%~17%, vitamin C 3%~7%, ethylenediamine
Tetraacethyl 3%~5%, phenmethylol 1%~3%；Above-mentioned supplementary material is placed in material-compound tank, sterilized water for injection is added, stirred
Dissolving is mixed, concentrated wiring liquid is obtained；Take concentrated wiring liquid, plus sodium acid carbonate or salt acid for adjusting pH are to 6.0~7.0, add the mass fraction to be
0.1%~0.3% activated carbon, adsorption bleaching is filtered with 0.45 μm of filter membrane, collects filtrate, adds sterile injection to use
Water tests qualified to prescription through middle product examine, you can；Intermediate is filtered with 0.22 μm of filter after the assay was approved, inspection
Visible foreign matters are looked into, after bacterial endotoxin is qualified, upper streamline carries out filling, and pouring process need to be filled with purity 99.99%
Nitrogen causes that the oxygen content in tank in water for injection, no more than 0.01%, is sealed after inflated with nitrogen；Canned peace is cutd open half
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, 121
DEG C keep 15min；3~5 DEG C/min of compressed air air blast lowers the temperature, and 8~12min is cooled to 70~80 DEG C, cooling water 2~3
DEG C/min coolings, 15~18min is cooled to 30 DEG C, sterilizes and complete, by rated condition leak detection.
A kind of preparation method of the oxo-1-pyrrolidine ethanamide liquid drugs injection of injection (S) -4- hydroxyls -2, it is characterised in that it
It is obtained as follows：
1. concentrated compounding：To the sterilized water for injection that 1/3 recipe quantity is added in material-compound tank, the supplementary material of recipe quantity is added, stirred
Mix, dissolve, obtain concentrated wiring liquid；
2. it is dilute to match somebody with somebody：Take concentrated wiring liquid, plus sodium acid carbonate or salt acid for adjusting pH are to 6.0~7.0, add the mass fraction to be
0.1%~0.3% activated carbon, adsorption bleaching is filtered with 0.45 μm of filter membrane, collects filtrate, adds sterile injection
With water to prescription, test 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, bacterium endogenous toxic material
After element is qualified, upper streamline carries out filling, and pouring process need to be filled with the nitrogen of purity 99.99% so that injection in tank
Oxygen content in water is no more than 0.01%, is sealed after inflated with nitrogen；
4. 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 lowers the temperature,
8~12min is cooled to 70~80 DEG C, and 2~3 DEG C/min of cooling water coolings, 15~18min is cooled to 30 DEG C, has sterilized
Into by rated condition leak detection.
5. check：Sample checks visible foreign matters after sterilizing, and qualified sample will be checked to be packed, full inspection, storage.
The present invention has following beneficial effect：
The oxo-1-pyrrolidine ethanamide injection of the present invention (S) -4- hydroxyls -2 have storage during product will not crystallize,
It is difficult to be oxidized, impurity incrementss are only 0.04% in sterilization process, good stability is valid up to more than 18 months,
Product impurity is few in the term of validity, and its total impurities is less than 0.28%, and pain is substantially reduced in patient injection procedure, Huan Zheshun
Answering property is good, is worth marketing.
Specific 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 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 spirit of the invention
In the case of essence, the modification or replacement made to the inventive method, step or condition belong to the scope of the present invention.
Embodiment 1
A kind of oxo-1-pyrrolidine ethanamide liquid drugs injection of injection (S) -4- hydroxyls -2, is obtained according to the following steps：
| Composition | Consumption |
| (S) oxo-1-pyrrolidine ethanamide of -4- hydroxyls -2 | 100g |
| Propane diols | 16g |
| Lecithin | 19g |
| Vitamin C | 7g |
| Ethylenediamine tetra-acetic acid | 5g |
| Phenmethylol | 2g |
| Sterilized water for injection | Add to 2000ml |
It is made 1000
Preparation process：
1. concentrated compounding：To the sterilized water for injection that 1/3 recipe quantity is added in material-compound tank, the supplementary material of recipe quantity is added, stirred
Mix, dissolve, obtain concentrated wiring liquid；
2. it is dilute to match somebody with somebody：Take concentrated wiring liquid, plus sodium acid carbonate or salt acid for adjusting pH are to 6.0~7.0, add the mass fraction to be
0.1%~0.3% activated carbon, adsorption bleaching is filtered with 0.45 μm of filter membrane, collects filtrate, adds sterile injection
With water to prescription, test 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, bacterium endogenous toxic material
After element is qualified, upper streamline carries out filling, and pouring process need to be filled with the nitrogen of purity 99.99% so that injection in tank
Oxygen content in water is no more than 0.01%, is sealed after inflated with nitrogen；
4. 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 lowers the temperature,
8~12min is cooled to 70~80 DEG C, and 2~3 DEG C/min of cooling water coolings, 15~18min is cooled to 30 DEG C, has sterilized
Into by rated condition leak detection.
5. check：Sample checks visible foreign matters after sterilizing, and qualified sample will be checked to be packed, full inspection, storage.
In order to be better understood from the present invention, the beneficial of invention medicine is expanded on further below by way of stability test of the present invention
Effect, rather than limitation of the present invention.
Experiment one：A kind of oxo-1-pyrrolidine ethanamide liquid drugs injection stability experiment of injection (S) -4- hydroxyls -2 of the present invention
Experiment material：
(S) the oxo-1-pyrrolidine ethanamide liquid drugs injection sample of -4- hydroxyls -2：For embodiment 1 is obtained
Acceleration study method：By the oxo-1-pyrrolidine ethanamide liquid drugs injection of (S) -4- hydroxyls -2 obtained in embodiment 1 by listing
Packaging, is put in Acceleration study case, and certain hour sampling is tested to investigation project.
Acceleration study temperature：40±2℃
Humidity：RH75% ± 5%
The investigation time：0th, 1,2,3, June
Inspection target：Proterties, visible foreign matters, pH, relevant material, content, sterility test
Accelerated test stability is recorded：
Acceleration study result shows：Accelerate June sample suitable with 0 month sample items Testing index quality, show that this product adds
Speed experiment June, quality keeps stabilization, and this product stability is preferable.
Long-term experiment method：By the oxo-1-pyrrolidine ethanamide liquid drugs injection of injection (S) -4- hydroxyls -2 obtained in embodiment 1
Packed by listing, put in the long-term case that keeps sample, certain hour 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：Proterties, visible foreign matters, pH, relevant material, content, sterility test
Long term test stability is recorded：
Long term test shows：18 months proterties of this product long term test, visible foreign matters, pH value, relevant material, content with
And sterility test indices meet every relevant regulations of production quality standard draft without significant changes.This product
18 months steady qualities of 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 oxo-1-pyrrolidine ethanamide liquid drugs injection sterilization process of injection (S) -4- hydroxyls -2 of the present invention increases to impurity
Plus influence
1. experiment material：
The oxo-1-pyrrolidine ethanamide liquid drugs injection sample of injection (S) -4- hydroxyls -2：Prepared by embodiment 1.
The oxo-1-pyrrolidine ethanamide liquid drugs injection control sample 1 of injection (S) -4- hydroxyls -2：To lack vitamin C and second
The sample of ethylenediamine tetraacetic acid (EDTA), its preparation technology is with embodiment 1.
The oxo-1-pyrrolidine ethanamide liquid drugs injection control sample 2 of injection (S) -4- hydroxyls -2：It is the prescription of embodiment 1,
Sterilising temp is 115 DEG C, and sterilization time is 32 minutes, obtained product.
2. experimental technique：In the preparation process of embodiment 1, sample afterwards before sterilization respectively, detect that it, about material, is investigated
To the influence about material before and after sterilizing.Meanwhile, take the prescription for lacking vitamin C and ethylenediamine tetra-acetic acid as control at
Side, is prepared by the preparation method of embodiment 1, and equally sampling detects that it, about material, investigates sterilization process afterwards before sterilization
To the influence about material.Meanwhile, the prescription of Example 1 is changed to 115 DEG C according to sterilising temp, and sterilization time is
Sample is prepared within 32 minutes, sampling detects relevant material afterwards before sterilization respectively, investigate sterilization process to the influence about material.
3. experimental result see the table below：
4. experiment conclusion：The prescription of embodiment 1, coordinates specific sterilization process, and it is only 0.04% that relevant material increases, bright
It is aobvious to be better than other two control samples.
Experiment three：Pain experiment in mouse writhing method observation injection process
Test specimen：The oxo-1-pyrrolidine ethanamide liquid drugs injection of the hydroxyls of injection (the S)-4- as obtained in embodiment 1-2 is used as trying
Product, the oxo -1- pyrroles of prescription injection (S) -4- as obtained in embodiment 1 hydroxyls -2 of phenmethylol is not added
Alkyl acetamide liquid drugs injection is used as control sample；
Purpose：Compare the pain degree in two kinds of oxo-1-pyrrolidine ethanamide liquid drugs injection injection process of injection (S) -4- hydroxyls -2
Method：Small white mouse is taken, whether the oxo-1-pyrrolidine ethanamide liquid drugs injection of hypodermic injection (S) -4- hydroxyls -2 observes small white mouse
Writhing response can occur, the probability of writhing response occurs according to mouse to judge the strong of pain in injection process
Weak, test sample respectively repeats 30 experiments with control sample；
Result of the test：Result of the test see the table below：
| Name of product | Experiment sample (mouse) | Generation writhing response number of individuals | Writhing response incidence % |
| Test sample | 30 | 5 | 16.7% |
| Control sample | 30 | 23 | 76.7% |
Conclusion：As seen from the above table, ache in the oxo-1-pyrrolidine ethanamide injection injection process of the present invention (S) -4- hydroxyls -2
Pain is markedly less than control sample.
Embodiment 2
A kind of oxo-1-pyrrolidine ethanamide liquid drugs injection of injection (S) -4- hydroxyls -2, is obtained according to the following steps：
| Composition | Consumption |
| (S) oxo-1-pyrrolidine ethanamide of -4- hydroxyls -2 | 100g |
| Propane diols | 11g |
| Lecithin | 16g |
| Vitamin C | 4g |
| Ethylenediamine tetra-acetic acid | 4g |
| Phenmethylol | 2g |
| Sterilized water for injection | Add to 2000ml |
It is made 1000
Preparation process：Preparation technology according to embodiment 1 is obtained.
By the test method of embodiment 1, the sample of embodiment 2 is carried out into stability test investigation, sterilization process to miscellaneous respectively
The increased influence experiment of matter, stability test result shows to accelerate June sample quality stabilization, and long-term 18 months quality are steady
It is fixed, therefore minimum 18 months of this product term of validity.Sterilization process influence result of the test increased on impurity shows embodiment 2
Prescription, coordinates specific sterilization process, and relevant material increase is substantially better than its control sample.Mouse writhing method observation injection
During pain result of the test show that pain is markedly less than control sample in the left injection process of the sample of embodiment 2.
Embodiment 3
A kind of oxo-1-pyrrolidine ethanamide liquid drugs injection of injection (S) -4- hydroxyls -2, is obtained according to the following steps：
| Composition | Consumption |
| (S) oxo-1-pyrrolidine ethanamide of -4- hydroxyls -2 | 100g |
| Propane diols | 13g |
| Lecithin | 16g |
| Vitamin C | 8g |
| Ethylenediamine tetra-acetic acid | 5g |
| Phenmethylol | 3g |
| Sterilized water for injection | Add to 2000ml |
It is made 1000
Preparation process：Preparation technology according to embodiment 1 is obtained.
By the test method of embodiment 1, the sample of embodiment 3 is carried out into stability test investigation, sterilization process to miscellaneous respectively
The increased influence experiment of matter, stability test result shows to accelerate June sample quality stabilization, and long-term 18 months quality are steady
It is fixed, therefore minimum 18 months of this product term of validity.Sterilization process influence result of the test increased on impurity shows embodiment 3
Prescription, coordinates specific sterilization process, and relevant material increase is substantially better than its control sample.Mouse writhing method observation injection
During pain result of the test show that pain is markedly less than control sample in the left injection process of the sample of embodiment 3.
Embodiment 4-6：A kind of oxo-1-pyrrolidine ethanamide liquid drugs injection of injection (S) -4- hydroxyls -2, by following weight
Supplementary material is prepared, and preparation method is with embodiment 1：
By the test method of embodiment 1, the sample of embodiment 4,5,6 is carried out into stability test investigation, sterilizing work respectively
Skill influence experiment increased on impurity, the stability test result of embodiment 4,5,6 shows to accelerate June sample quality stabilization,
Long-term 18 months steady qualities, therefore minimum 18 months of this product term of validity.Sterilization process influence experiment knot increased on impurity
Fruit shows the prescription of embodiment 4,5,6, coordinates specific sterilization process, and relevant material increase is substantially better than its control sample
Product.Pain result of the test in mouse writhing method observation injection process shows that the sample of embodiment 4,5,6 is left to be injected
Pain is markedly less than control sample in journey.
Claims (3)
1. a kind of injection（S）The oxo-1-pyrrolidine ethanamide liquid drugs injection of -4- hydroxyls -2, it is characterised in that：It is with（S）The oxo-1-pyrrolidine ethanamide of -4- hydroxyls -2, propane diols, lecithin, vitamin, ethylenediamine tetra-acetic acid, phenmethylol be supplementary material, by concentrated compounding, it is dilute match somebody with somebody, embedding, sterilizing, test package step be obtained；What the consumption of wherein described supplementary material was weight percentage（S）The oxo-1-pyrrolidine ethanamide 65% ~ 75% of -4- hydroxyls -2, propane diols 7% ~ 15%, lecithin 10% ~ 20%, vitamin C 3% ~ 8%, ethylenediamine tetra-acetic acid 3% ~ 5%, phenmethylol 1% ~ 3%；The sterilization steps are that 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 lowers the temperature, and 8 ~ 12min is cooled to 70 ~ 80 DEG C, and 2 ~ 3 DEG C/min of cooling water coolings, 15 ~ 18min is cooled to 30 DEG C, and sterilizing is completed.
2. injection as claimed in claim 1（S）The oxo-1-pyrrolidine ethanamide liquid drugs injection of -4- hydroxyls -2, it is characterised in that it is obtained by the supplementary material of following significant percentage：（S）The oxo-1-pyrrolidine ethanamide 67% ~ 73% of -4- hydroxyls -2, propane diols 8% ~ 13%, lecithin 11% ~ 17%, vitamin C 3% ~ 7%, ethylenediamine tetra-acetic acid 3% ~ 5%, phenmethylol 1% ~ 3%；Above-mentioned supplementary material is placed in material-compound tank, sterilized water for injection is added, stirring and dissolving obtains concentrated wiring liquid；Concentrated wiring liquid, plus sodium acid carbonate or salt acid for adjusting pH are taken to 6.0 ~ 7.0, add the activated carbon that mass fraction is 0.1% ~ 0.3%, adsorption bleaching to be filtered with 0.45 μm of filter membrane, collect filtrate, add sterilized water for injection to prescription, test qualified through middle product examine, you can；Intermediate is filtered with 0.22 μm of filter after the assay was approved, visible foreign matters are checked, after bacterial endotoxin is qualified, upper streamline carries out filling, pouring process need to be filled with the nitrogen of purity 99.99% so that the oxygen content in tank in water for injection is sealed no more than 0.01% after inflated with nitrogen；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 lowers the temperature, and 8 ~ 12min is cooled to 70 ~ 80 DEG C, and 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.
3. a kind of injection as claimed in claim 1 or 2（S）The preparation method of the oxo-1-pyrrolidine ethanamide liquid drugs injection of -4- hydroxyls -2, it is characterised in that it is obtained as follows：
A. concentrated compounding：To the sterilized water for injection that 1/3 recipe quantity is added in material-compound tank, the supplementary material of recipe quantity is added, stirring, dissolving obtains concentrated wiring liquid；
B. it is dilute to match somebody with somebody：Concentrated wiring liquid, plus sodium acid carbonate or salt acid for adjusting pH are taken to 6.0 ~ 7.0, add the activated carbon that mass fraction is 0.1% ~ 0.3%, adsorption bleaching to be filtered with 0.45 μm of filter membrane, collect filtrate, add sterilized water for injection to prescription, test qualified through middle product examine, you can；
C. embedding：Intermediate is filtered with 0.22 μm of filter after the assay was approved, visible foreign matters are checked, after bacterial endotoxin is qualified, upper streamline carries out filling, pouring process need to be filled with the nitrogen of purity 99.99% so that the oxygen content in tank in water for injection is sealed no more than 0.01% after inflated with nitrogen；
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 lowers the temperature, and 8 ~ 12min is cooled to 70 ~ 80 DEG C, and 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. check：Sample checks visible foreign matters after sterilizing, and qualified sample will be checked to be packed, full inspection, storage.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510511681.2A CN106692134A (en) | 2015-08-19 | 2015-08-19 | (S)-4- hydroxyl-2 oxo-1-pyrrolidine acetamide aqueous injection used for injection, and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510511681.2A CN106692134A (en) | 2015-08-19 | 2015-08-19 | (S)-4- hydroxyl-2 oxo-1-pyrrolidine acetamide aqueous injection used for injection, and preparation method thereof |
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| Publication Number | Publication Date |
|---|---|
| CN106692134A true CN106692134A (en) | 2017-05-24 |
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ID=58924413
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510511681.2A Withdrawn CN106692134A (en) | 2015-08-19 | 2015-08-19 | (S)-4- hydroxyl-2 oxo-1-pyrrolidine acetamide aqueous injection used for injection, and preparation method thereof |
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| Country | Link |
|---|---|
| CN (1) | CN106692134A (en) |
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 |
-
2015
- 2015-08-19 CN CN201510511681.2A patent/CN106692134A/en not_active Withdrawn
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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Effective date of registration: 20170824 Address after: 400042 Chongqing city Yubei District Qinye Road No. 9 Applicant after: Chongqing Runze Pharmaceutical Co., Ltd. Address before: 400030 Chongqing city Shapingba District Yubei Road No. 50 of No. 13-15-6A Applicant before: DONGZE PHARMACEUTICAL SCIENCE AND TECHNOLOGY CO., LTD. |
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Application publication date: 20170524 |