CN107281124A - It is a kind of（S）Oxo-1-pyrrolidine ethanamide freeze-dried powder of -4- hydroxyls -2 and preparation method thereof - Google Patents
It is a kind of（S）Oxo-1-pyrrolidine ethanamide freeze-dried powder of -4- hydroxyls -2 and preparation method thereof Download PDFInfo
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Abstract
It is a kind of（S）The pyrrolidine acetamide freeze-dried powder of 4 hydroxyl, 2 oxo 1, it is（S）The pyrrolidine acetamide of 4 hydroxyl, 2 oxo 1, L serines, mannitol, sodium glutamate, phenmethylol be supplementary material, by concentrated compounding, it is dilute match somebody with somebody, be freeze-dried, roll lid step be made；Wherein described supplementary material consumption is（S）The pyrrolidine acetamide 36% ~ 43% of 4 hydroxyl, 2 oxo 1, L serines 21% ~ 28%, mannitol 30% ~ 35%, sodium glutamate 4% ~ 10%, phenmethylol 1% ~ 3%；According to produced by the present invention（S）The pyrrolidine acetamide freeze-dried powder of 4 hydroxyl, 2 oxo 1 has solid shape, in lyophilized preparation process without spray bottle phenomenon, product homogeneity is good, levels character is consistent, impurity is few, its total impurities is less than 0.26%, and product stability is good, and shelf life is up to 24 months, patient pain feels lighter, good patient compliance in injection process.
Description
Technical field
The invention mainly relates to pharmaceutical technology field, and in particular to the oxo-1-pyrrolidine ethanamide of one kind (S) -4- hydroxyls -2 is freezed
Powder pin and preparation method thereof.
Background technology
Levo-oxiracetam chemical name is：S- (-) -4- hydroxyl -2- oxo-pyrrolidine-N- acetamides, are white micro-crystals shape powder
End, 135~136 DEG C of fusing point, -36 ° of optical activity (C=1.00in water), the dissolubility of levo-oxiracetam is substantially better than racemization
Body.Chemical structural formula is as follows：
The medicine is in 1987 in Italy's listing, and the formulation of listing is tablet, 800mg；Capsule, 800mg；Parenteral solution, 1g/5ml.
It is domestic at present there was only oxiracetam capsule and parenteral solution listing, and main active used is racemic modification.Ye Lei etc. is in public affairs
The number of opening is obvious to the promoting wakening gone into a coma caused by alcoholism to mention levo-oxiracetam in CN 103735545A patents, and right
Rotation Oxiracetam is not acted on substantially, and the awake effect of above-mentioned rush of levo-oxiracetam is 2 times of racemization Oxiracetam；Left-handed Aura west
The smooth promoting wakening to stupor caused by wound, anesthesia is notable.Peak etc. is opened to drape over one's shoulders in Publication No. CN 103599101A patent
Dew levo-oxiracetam has significantly to traumatic brain injury learning and memory in rats cognition dysfunction caused by hydraulic pressure and freely falling body
Improvement result, its drug effect is far above dextrorotation Oxiracetam.And 200mg/kg levo-oxiracetams and 400mg/kg Oxiracetams
Effect is suitable.Pharmacokinetic study results are shown：Levo-oxiracetam and dextrorotation Oxiracetam are in beasle dog body without obvious hand
Property conversion.Beasle dog single intravenous injection gives after left-handed and 2 multiple doses racemization Oxiracetams levo-oxiracetam in blood plasma
The equal no significant difference of main pharmacokinetic parameters.The result of the tests such as safe pharmacology, anxious malicious, long poison show, under isodose level,
Levo-oxiracetam is with Oxiracetam to animal subject or the toxicity no significant difference of cell.Above-mentioned preclinical result of study shows,
Levo-oxiracetam is the main active that drug effect is played in Oxiracetam body, and this product, which is used alone, can reduce Clinical practice dosage,
Reduce potential toxicity.
The existing oxo-1-pyrrolidine ethanamide freeze-dried powder of (S) -4- hydroxyls -2 its be primarily present no solid shape, be difficult to form bone
Easily there is spray bottle phenomenon in frame, freeze-drying process, product stability is poor, and shelf life is short, and product homogeneity is bad, levels character
It is inconsistent, injection process pain substantially, the problems such as patient's poor compliance.
The content of the invention
There is solid form, the oxygen of (S) -4- hydroxyls -2 that stability is good, product homogeneity is good it is an object of the invention to provide a kind of
Generation -1- pyrrolidine acetamide freeze-dried powders.
Another object of the present invention is to provide the preparation side of the above-mentioned oxo-1-pyrrolidine ethanamide freeze-dried powder of (S) -4- hydroxyls -2
Method.
The purpose of the present invention is realized by following technical measures：
The oxo-1-pyrrolidine ethanamide freeze-dried powder of one kind (S) -4- hydroxyls -2, it is characterised in that it is with (S) -4- hydroxyls -2
Oxo-1-pyrrolidine ethanamide is raw material, adds a certain amount of additives and is made；Wherein described additives be sucrose, trehalose,
Mannitol, lactose, glucose, maltose, glucan, albumin, polyethylene glycol, glycerine, Serine, sodium glutamate,
One or more in alanine, glycine, methyl amimoacetic acid, phosphate, acetate, citrate, phenmethylol.
Inventor has found that specific additives species coordinates specific supplementary material consumption proportion relation, coordinates spy again in research process
Fixed Freeze Drying Technique, may be such that the above-mentioned oxo-1-pyrrolidine ethanamide freeze-dried powder of (S) -4- hydroxyls -2 have solid shape,
Easy formation skeleton, product homogeneity are good, levels character is consistent, are not in spray bottle phenomenon in product freeze-drying process, and can
Making product, patient pain's sense declines in use, good patient compliance；The OXo-1-pyrrolidine second of one kind (S) -4- hydroxyls -2
Acid amides freeze-dried powder, it is characterised in that it be the oxo-1-pyrrolidine ethanamide of (S) -4- hydroxyls -2, Serine, mannitol,
Sodium glutamate, phenmethylol be supplementary material, by concentrated compounding, it is dilute match somebody with somebody, be freeze-dried, roll lid step be made；Wherein described supplementary material
The oxo-1-pyrrolidine ethanamide 36%~43% of (S) -4- hydroxyls -2 that consumption is weight percentage, Serine 21%~28%,
Mannitol 30%~35%, sodium glutamate 4%~10%, phenmethylol 1%~3%；The freeze-drying is to be quick by heat conduction oil temperature
- 40 DEG C are refrigerated to, constant temperature is kept 60 minutes, -10 DEG C are warming up to 5 DEG C/h, constant temperature is kept 80 minutes, quickly cooled down
To -40 DEG C, then cryostat 120 minutes is vacuumized drying, is warming up to 10 DEG C/h, -10 DEG C of constant temperature 150 minutes；With
4 DEG C/h are warming up to 0 DEG C, 0 DEG C of constant temperature 300 minutes；Be warming up to 10 DEG C with 5 DEG C/h, 10 DEG C of constant temperature 240 minutes, with 10 DEG C/
Hour is warming up to 30 DEG C, 30 DEG C of constant temperature 60 minutes, while preceding case vacuum drop reaches 10Pa/10 timesharing, freezes and terminates.
Most preferably, the above-mentioned oxo-1-pyrrolidine ethanamide freeze-dried powder of (S) -4- hydroxyls -2, it is characterised in that it is under
The supplementary material of row percentage by weight is made：(S) oxo-1-pyrrolidine ethanamide 38%~40% of -4- hydroxyls -2, Serine
22%~24%, mannitol 31%~33%, sodium glutamate 5%~7%, phenmethylol 1%~2%；The supplementary material of recipe quantity is placed in appearance
In device, the sterilized water for injection stirring of (S) -4- hydroxyl 5 times of parts by weight of -2 oxo-1-pyrrolidine ethanamide is added, after dissolving,
The needle-use activated carbon of mass fraction 0.5% is added, 30min is stirred, is then filtered with 0.45 micrometer Millipore filter membrane, collect filtrate,
It is standby；Sterilized water for injection is added into filtrate to 1000 times of filtrate volume, pH is adjusted to 7.0 with hydrochloric acid or sodium hydroxide,
Then with 0.22 micron of miillpore filter aseptic filtration, take filtrate it is qualified it is rear it is filling be sub-packed in sterile glass vials, it is standby；Quickly
Heat conduction oil temperature is refrigerated to -40 DEG C, constant temperature is kept 60 minutes, -10 DEG C are warming up to 5 DEG C/h, constant temperature is kept 80 minutes,
It is being quickly cooled to -40 DEG C, cryostat 120 minutes.Then drying is vacuumized, is warming up to 10 DEG C/h, -10 DEG C of constant temperature
150 minutes；0 DEG C is warming up to 4 DEG C/h, 0 DEG C of constant temperature 300 minutes；10 DEG C, 10 DEG C of constant temperature 240 are warming up to 5 DEG C/h
Minute, it is warming up to 30 DEG C with 10 DEG C/h, 30 DEG C of constant temperature 60 minutes, while preceding case vacuum drop reaches 10Pa/10 timesharing, freezes
Dry and hard beam.
In order that the obtained oxo-1-pyrrolidine ethanamide freeze-dried powder homogeneity of (S) -4- hydroxyls -2 is good, product levels character
Unanimously, the preparation method of the oxo-1-pyrrolidine ethanamide freeze-dried powder of one kind (S) -4- hydroxyls -2 is worthy of careful study, it is characterised in that
It is obtained as follows：
1. concentrated compounding：The supplementary material of recipe quantity is placed in container, 5 times of -2 oxo-1-pyrrolidine ethanamide of (S) -4- hydroxyls is added
The sterilized water for injection stirring of parts by weight, after dissolving, adds the needle-use activated carbon of mass fraction 0.5%, stirring
30min, is then filtered with 0.45 micrometer Millipore filter membrane, collects filtrate, standby；
2. dilute match somebody with somebody：Sterilized water for injection is added into filtrate to 1000 times of filtrate volume, pH is adjusted with hydrochloric acid or sodium hydroxide
To 7.0, then with 0.22 micron of miillpore filter aseptic filtration, take filtrate it is qualified it is rear it is filling be sub-packed in it is sterile
It is standby in vial；
3. freeze-drying：It is quick that heat conduction oil temperature is refrigerated to -40 DEG C, keep constant temperature 60 minutes, -10 DEG C are warming up to 5 DEG C/h,
Keep constant temperature 80 minutes, be quickly cooled to -40 DEG C, cryostat 120 minutes.Then vacuumize dry
It is dry, it is warming up to 10 DEG C/h, -10 DEG C of constant temperature 150 minutes；0 DEG C, 0 DEG C is warming up to 4 DEG C/h
Constant temperature 300 minutes；10 DEG C are warming up to 5 DEG C/h, 10 DEG C of constant temperature 240 minutes, with 10 DEG C/h
It is warming up to 30 DEG C, 30 DEG C of constant temperature 60 minutes, while preceding case vacuum drop reaches 10Pa/10 timesharing, is freezed
Terminate；
4. roll lid：Aluminium-plastic combined cover needs once purged sterilizing, drying, then carries out rolling lid, produces.
The present invention has following beneficial effect：
The oxo-1-pyrrolidine ethanamide freeze-dried powder of the present invention (S) -4- hydroxyls -2 has solid shape, in lyophilized preparation process
Without spray bottle phenomenon, product homogeneity is good, and levels character is consistent, and impurity is few, and its total impurities is less than 0.26%, product stability
Good, shelf life is up to 24 months, and patient pain feels lighter, good patient compliance in injection process.
Embodiment
The present invention is specifically described below by embodiment, it is necessary to it is pointed out here that be following examples be served only for this
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 and essence
In the case of, the modifications or substitutions made to the inventive method, step or condition belong to the scope of the present invention.
Embodiment 1
The oxo-1-pyrrolidine ethanamide freeze-dried powder of one kind (S) -4- hydroxyls -2, is made according to the following steps：
Preparation process：
1. concentrated compounding：The supplementary material of recipe quantity is placed in container, 5 times of -2 oxo-1-pyrrolidine ethanamide of (S) -4- hydroxyls is added
The sterilized water for injection stirring of parts by weight, after dissolving, adds the needle-use activated carbon of mass fraction 0.5%, stirring
30min, is then filtered with 0.45 micrometer Millipore filter membrane, collects filtrate, standby；
2. dilute match somebody with somebody：Sterilized water for injection is added into filtrate to 1000 times of filtrate volume, pH is adjusted with hydrochloric acid or sodium hydroxide
To 7.0, then with 0.22 micron of miillpore filter aseptic filtration, take filtrate it is qualified it is rear it is filling be sub-packed in it is sterile
It is standby in vial；
3. freeze-drying：It is quick that heat conduction oil temperature is refrigerated to -40 DEG C, keep constant temperature 60 minutes, -10 DEG C are warming up to 5 DEG C/h,
Keep constant temperature 80 minutes, be quickly cooled to -40 DEG C, then cryostat 120 minutes vacuumizes dry
It is dry, it is warming up to 10 DEG C/h, -10 DEG C of constant temperature 150 minutes is warming up to 0 DEG C, 0 DEG C with 4 DEG C/h
Constant temperature 300 minutes, 10 DEG C are warming up to 5 DEG C/h, 10 DEG C of constant temperature 240 minutes, with 10 DEG C/h
It is warming up to 30 DEG C, 30 DEG C of constant temperature 60 minutes, while preceding case vacuum drop reaches 10Pa/10 timesharing, is freezed
Terminate；
4. roll lid：Aluminium-plastic combined cover needs once purged sterilizing, drying, then carries out rolling lid, produces.
In order to be better understood from the present invention, the beneficial effect of invention medicine is expanded on further below by way of stability test of the present invention,
Rather than limitation of the present invention.
Experiment one：The oxo-1-pyrrolidine ethanamide freeze-dried powder stability experiment of present invention one kind (S) -4- hydroxyls -2
Experiment material：
(S) the oxo-1-pyrrolidine ethanamide freeze-dried powder sample of -4- hydroxyls -2：It is made for embodiment 1
Acceleration study method：By the oxo-1-pyrrolidine ethanamide freeze-dried powder of (S) -4- hydroxyls -2 made from embodiment 1 by listing
Packaging, is put in Acceleration study case, certain time sampling, 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, 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 accelerates real
Test June, quality keeps stable, and this product stability is preferable.
Long-term experiment method：By the oxo-1-pyrrolidine ethanamide freeze-dried powder of (S) -4- hydroxyls -2 made from embodiment 1 by listing
Packaging, is put in the long-term case that keeps sample, and certain time sampling is tested to investigation project.
Acceleration study temperature：25±2℃
Humidity：RH60% ± 10%
The investigation time：0th, 3,6,9,12,18,24 months
Inspection target：Character, visible foreign matters, pH, relevant material, content, sterility test
Long term test stability is recorded：
Long term test shows：This product long term test 24 months characters, visible foreign matters, pH value, relevant material, content and nothings
Bacterium checks that indices, without significant changes, meet every relevant regulations of production quality standard draft.This product long term test
24 months steady qualities, therefore minimum 24 months of this product shelf life, long term test is still during continuing to investigate.
Experiment two：(S) spray bottle phenomenon is counted in the oxo-1-pyrrolidine ethanamide freeze-dried powder freezing dry process of -4- hydroxyls -2
1. test objective：Examine the spray bottle phenomenon for wiping different prescriptions in freezing dry process.
2. test method：With control sample the percentage of spray bottle phenomenon occurs in preparation process for the sample of Statistics Implementation example 1,
Control sample prescription see the table below：
Control sample prescription (percentage by weight meter %)
| (S) oxo-1-pyrrolidine ethanamide of -4- hydroxyls -2 | 38% |
| Serine | 25% |
| Mannitol | 35% |
| Sodium glutamate | — |
| Phenmethylol | 2% |
3. result of the test：
| Numbering | Generation spray bottle bottle number | Total inspection bottle number | Spray bottle percentage % |
| Embodiment 1 | 0 | 100 | 0 |
| Control sample | 28 | 100 | 28 |
4. conclusion：Spray bottle phenomenon does not occur in freezing dry process for the sample of embodiment 1, and control sample generation spray bottle phenomenon is
28%, therefore it is believed that the probability that spray bottle occurs for this product can effectively be reduced by adding sodium glutamate.
Experiment three：Pain experiment in mouse writhing method observation injection process
Test specimen：The oxo-1-pyrrolidine ethanamide freeze-dried powder of the hydroxyls of one kind (S)-4- as made from embodiment 1-2 as test sample,
Not plus phenmethylol the oxo-1-pyrrolidine ethanamide freeze-dried powder of prescription (S) -4- as made from embodiment 1 hydroxyls -2
Pin is used as control sample；
Purpose：Compare the pain degree in two kinds of oxo-1-pyrrolidine ethanamide freeze-dried powder injection process of (S) -4- hydroxyls -2
Method：Experimental white mouse is taken, the oxo-1-pyrrolidine ethanamide freeze-dried powder of (S) -4- hydroxyls -2 is subcutaneously injected, and (physiology salt is water-soluble
Solution is diluted to 10ml), whether observation small white mouse can occur writhing response, occur the probability of writhing response to sentence according to mouse
The power of pain in disconnected injection process, 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 | 1 | 3.3% |
| Control sample | 30 | 26 | 86.7% |
Conclusion：As seen from the above table, ache in the oxo-1-pyrrolidine ethanamide freeze-dried powder injection process of present invention one kind (S) -4- hydroxyls -2
Pain is markedly less than control sample.
Embodiment 2
The oxo-1-pyrrolidine ethanamide freeze-dried powder of one kind (S) -4- hydroxyls -2, is made according to the following steps：
| Composition | Consumption (percentage by weight %) |
| (S) oxo-1-pyrrolidine ethanamide of -4- hydroxyls -2 | 40% |
| Serine | 23% |
| Mannitol | 31% |
| Sodium glutamate | 5% |
| Phenmethylol | 1% |
It is made 1000 bottles
Preparation process：Preparation technology according to embodiment 1 is made.
By the test method of embodiment 1, the sample stability result of the test of embodiment 2 shows to accelerate sample quality stabilization in June, long
24 months phases steady quality, therefore minimum 24 months of this product term of validity.Spray bottle phenomenon statistical result shows reality in freezing dry process
Apply the sample of example 2 and do not occur spray bottle phenomenon in freezing dry process.Pain experiment knot in mouse writhing method observation injection process
Fruit shows that pain is markedly less than control sample during the sample injection of embodiment 2.
Embodiment 3
The oxo-1-pyrrolidine ethanamide freeze-dried powder of one kind (S) -4- hydroxyls -2, is made according to the following steps：
| Composition | Consumption (percentage by weight %) |
| (S) oxo-1-pyrrolidine ethanamide of -4- hydroxyls -2 | 39% |
| Serine | 23% |
| Mannitol | 31% |
| Sodium glutamate | 6% |
| Phenmethylol | 1% |
It is made 1000 bottles
Preparation process：Preparation technology according to embodiment 1 is made.
By the test method of embodiment 1, the sample stability result of the test of embodiment 3 shows to accelerate sample quality stabilization in June, long
24 months phases steady quality, therefore minimum 24 months of this product term of validity.Spray bottle phenomenon statistical result shows reality in freezing dry process
Apply the sample of example 3 and do not occur spray bottle phenomenon in freezing dry process.Pain experiment knot in mouse writhing method observation injection process
Fruit shows that pain is markedly less than control sample during the sample injection of embodiment 3.
Embodiment 4-6：The oxo-1-pyrrolidine ethanamide freeze-dried powder of one kind (S) -4- hydroxyls -2, by the supplementary material system of following weight
It is standby and obtain, preparation method be the same as Example 1：
By the test method of embodiment 1, the sample stability result of the test of embodiment 4,5,6 shows that acceleration sample quality in June is steady
It is fixed, long-term 24 months steady qualities, therefore minimum 24 months of this product term of validity.Spray bottle phenomenon statistical result in freezing dry process
Show that spray bottle phenomenon does not occur in freezing dry process for the sample of embodiment 4,5,6.In mouse writhing method observation injection process
Pain result of the test show that pain is markedly less than control sample during the sample injection of embodiment 4,5,6.
Claims (3)
1. it is a kind of（S）The oxo-1-pyrrolidine ethanamide freeze-dried powder of -4- hydroxyls -2, it is characterised in that it is（S）The oxo-1-pyrrolidine ethanamide of -4- hydroxyls -2, Serine, mannitol, sodium glutamate, phenmethylol be supplementary material, by concentrated compounding, it is dilute match somebody with somebody, be freeze-dried, roll lid step be made；What wherein described supplementary material consumption was weight percentage（S）The oxo-1-pyrrolidine ethanamide 36% ~ 43% of -4- hydroxyls -2, Serine 21% ~ 28%, mannitol 30% ~ 35%, sodium glutamate 4% ~ 10%, phenmethylol 1% ~ 3%；Heat conduction oil temperature is refrigerated to -40 DEG C by the freeze-drying to be quick, keeps constant temperature 60 minutes, and -10 DEG C are warming up to 5 DEG C/h, keep constant temperature 80 minutes, be quickly cooled to -40 DEG C, cryostat 120 minutes, then drying is vacuumized, is warming up to 10 DEG C/h, -10 DEG C of constant temperature 150 minutes；0 DEG C is warming up to 4 DEG C/h, 0 DEG C of constant temperature 300 minutes；10 DEG C are warming up to 5 DEG C/h, 10 DEG C of constant temperature 240 minutes is warming up to 30 DEG C with 10 DEG C/h, 30 DEG C of constant temperature 60 minutes, while preceding case vacuum drop reaches 10Pa/10 timesharing, is freezed and terminated.
2. it is as claimed in claim 1（S）The oxo-1-pyrrolidine ethanamide freeze-dried powder of -4- hydroxyls -2, it is characterised in that it is made by the supplementary material of following weight percents：（S）The oxo-1-pyrrolidine ethanamide 38% ~ 40% of -4- hydroxyls -2, Serine 22% ~ 24%, mannitol 31% ~ 33%, sodium glutamate 5% ~ 7%, phenmethylol 1% ~ 2%；The supplementary material of recipe quantity is placed in container, added（S）The sterilized water for injection stirring of -4- hydroxyls 5 times of parts by weight of -2 oxo-1-pyrrolidine ethanamide, after dissolving, adds the needle-use activated carbon of mass fraction 0.5%, stirs 30min, is then filtered with 0.45 micrometer Millipore filter membrane, collects filtrate, standby；Sterilized water for injection is added into filtrate to 1000 times of filtrate volume, pH to 7.0 is adjusted with hydrochloric acid or sodium hydroxide, then with 0.22 micron of miillpore filter aseptic filtration, take filtrate it is qualified it is rear it is filling be sub-packed in sterile glass vials, it is standby；It is quick that heat conduction oil temperature is refrigerated to -40 DEG C, keep constant temperature 60 minutes, -10 DEG C are warming up to 5 DEG C/h, keep constant temperature 80 minutes, be quickly cooled to -40 DEG C, cryostat 120 minutes;Then drying is vacuumized, is warming up to 10 DEG C/h, -10 DEG C of constant temperature 150 minutes；0 DEG C is warming up to 4 DEG C/h, 0 DEG C of constant temperature 300 minutes；10 DEG C are warming up to 5 DEG C/h, 10 DEG C of constant temperature 240 minutes is warming up to 30 DEG C with 10 DEG C/h, 30 DEG C of constant temperature 60 minutes, while preceding case vacuum drop reaches 10Pa/10 timesharing, is freezed and terminated.
3. it is as claimed in claim 1 or 2（S）The preparation method of the oxo-1-pyrrolidine ethanamide freeze-dried powder of -4- hydroxyls -2, it is characterised in that it is obtained as follows：
A. concentrated compounding：The supplementary material of recipe quantity is placed in container, added（S）The sterilized water for injection stirring of -4- hydroxyls 5 times of parts by weight of -2 oxo-1-pyrrolidine ethanamide, after dissolving, adds the needle-use activated carbon of mass fraction 0.5%, stirs 30min, is then filtered with 0.45 micrometer Millipore filter membrane, collects filtrate, standby；
B. it is dilute to match somebody with somebody：Sterilized water for injection is added into filtrate to 1000 times of filtrate volume, pH to 7.0 is adjusted with hydrochloric acid or sodium hydroxide, then with 0.22 micron of miillpore filter aseptic filtration, take filtrate it is qualified it is rear it is filling be sub-packed in sterile glass vials, it is standby；
C. it is freeze-dried：It is quick that heat conduction oil temperature is refrigerated to -40 DEG C, keep constant temperature 60 minutes, -10 DEG C are warming up to 5 DEG C/h, keep constant temperature 80 minutes, be quickly cooled to -40 DEG C, cryostat 120 minutes;Then drying is vacuumized, is warming up to 10 DEG C/h, -10 DEG C of constant temperature 150 minutes；0 DEG C is warming up to 4 DEG C/h, 0 DEG C of constant temperature 300 minutes；10 DEG C are warming up to 5 DEG C/h, 10 DEG C of constant temperature 240 minutes is warming up to 30 DEG C with 10 DEG C/h, 30 DEG C of constant temperature 60 minutes, while preceding case vacuum drop reaches 10Pa/10 timesharing, is freezed and terminated；
D. lid is rolled：Aluminium-plastic combined cover needs once purged sterilizing, drying, then carries out rolling lid, produces.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610194618.5A CN107281124A (en) | 2016-03-31 | 2016-03-31 | It is a kind of（S）Oxo-1-pyrrolidine ethanamide freeze-dried powder of -4- hydroxyls -2 and preparation method thereof |
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| CN201610194618.5A CN107281124A (en) | 2016-03-31 | 2016-03-31 | It is a kind of（S）Oxo-1-pyrrolidine ethanamide freeze-dried powder of -4- hydroxyls -2 and preparation method thereof |
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Citations (2)
| 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 |
| CN102670527A (en) * | 2012-05-28 | 2012-09-19 | 南京优科生物医药研究有限公司 | Freeze-dried powder injection of L-oxiracetam and process for preparing freeze-dried powder injection |
-
2016
- 2016-03-31 CN CN201610194618.5A patent/CN107281124A/en not_active Withdrawn
Patent Citations (2)
| 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 |
| CN102670527A (en) * | 2012-05-28 | 2012-09-19 | 南京优科生物医药研究有限公司 | Freeze-dried powder injection of L-oxiracetam and process for preparing freeze-dried powder injection |
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