CN107281122A - A kind of levo-oxiracetam freeze-dried powder and preparation method thereof - Google Patents
A kind of levo-oxiracetam freeze-dried powder and preparation method thereof Download PDFInfo
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Abstract
A kind of levo-oxiracetam freeze-dried powder, it be levo-oxiracetam, L serines, mannitol, sodium glutamate, methionine, phenmethylol be supplementary material, by concentrated compounding, it is dilute match somebody with somebody, be freeze-dried, roll lid step be made；The levo-oxiracetam 35% ~ 41% that wherein described supplementary material consumption is weight percentage, L serines 23% ~ 30%, mannitol 18% ~ 28%, sodium glutamate 5% ~ 12%, methionine 3% ~ 10%, phenmethylol 1% ~ 3%；According to levo-oxiracetam freeze-dried powder produced by the present invention, the less, incrementss of impurity increase are only 0.03% in preparation process, product has solid shape, in lyophilized preparation process without spray bottle phenomenon, product homogeneity is good, levels character is consistent, and impurity is few, and impurity is less than 0.28% in the term of validity, product stability is good, shelf life is up to 24 months, and pain is lighter in patient injection procedure, good patient compliance.
Description
Technical field
The invention mainly relates to pharmaceutical technology field, and in particular to a kind of levo-oxiracetam freeze-dried powder and its preparation side
Method.
Background technology
Levo-oxiracetam chemical name is：S- (-) -4- hydroxyl -2- oxo-pyrrolidine-N- acetamides, are white micro-crystals
Sprills, 135~136 DEG C of fusing point, -36 ° of optical activity (C=1.00in water), the dissolubility of levo-oxiracetam is substantially excellent
In raceme.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
Deng mentioning levo-oxiracetam in the A patents of Publication No. CN 103735545 to the promoting wakening gone into a coma caused by alcoholism
Substantially, and dextrorotation Oxiracetam is not acted on substantially, the above-mentioned rush of levo-oxiracetam wake up that effect is racemization Oxiracetam 2
Times；Levo-oxiracetam is notable to the promoting wakening of stupor caused by wound, anesthesia.Peak etc. is opened in Publication No. CN
Levo-oxiracetam is disclosed in 103599101 A patent to remember the study of traumatic brain injury rat caused by hydraulic pressure and freely falling body
Recall cognition dysfunction to improve significantly, its drug effect is far above dextrorotation Oxiracetam.And the left-handed Auras of 200mg/kg
It is western smooth suitable with the effect of 400mg/kg Oxiracetams.Pharmacokinetic study results are shown：Levo-oxiracetam and dextrorotation are difficult to understand
La Xitan is in beasle dog body without obvious chiral inversion.It is difficult to understand that beasle dog single intravenous injection gives left-handed and 2 multiple doses racemizations
The equal no significant difference of the main pharmacokinetic parameters of levo-oxiracetam in blood plasma after La Xitan.The examinations such as safe pharmacology, anxious malicious, long poison
Test result to show, under isodose level, levo-oxiracetam is with Oxiracetam to the toxicity of animal subject or cell without bright
Significant difference is different.Above-mentioned preclinical result of study shows that levo-oxiracetam is the chief active that drug effect is played in Oxiracetam body
Composition, this product, which is used alone, can reduce Clinical practice dosage, reduce potential toxicity.
Existing levo-oxiracetam freeze-dried powder its be primarily present preparation process impurity increase substantially, without solid shape, no
Easily formed in skeleton, freeze-drying process and easily spray bottle phenomenon occur, product stability is poor, and shelf life is short, and product homogeneity is bad, up and down
Layer character is inconsistent, and product injection process pain is substantially, the problems such as patient's poor compliance.
The content of the invention
There is solid form, the left-handed Aura that stability is good, product homogeneity is good it is an object of the invention to provide a kind of
Western smooth freeze-dried powder.
Another object of the present invention is to provide the preparation method of above-mentioned levo-oxiracetam freeze-dried powder.
The purpose of the present invention is realized by following technical measures：
A kind of levo-oxiracetam freeze-dried powder, it is characterised in that it is, using levo-oxiracetam as raw material, to add one
Quantitative additives are made；Wherein described additives be sucrose, trehalose, mannitol, lactose, glucose, maltose, Portugal gather
Sugar, albumin, polyethylene glycol, glycerine, Serine, vitamin C, sodium thiosulfate, methionine, sodium glutamate, alanine,
One or more in glycine, methyl amimoacetic acid, phosphate, acetate, citrate, phenmethylol.
Specific additives species and consumption are found in inventor's research process, coordinates specific Freeze Drying Technique,
It may be such that above-mentioned levo-oxiracetam freeze-dried powder is smaller in preparation process impurity level increase, product has solid shape, easy shape
Into skeleton, homogeneity be good, levels character is consistent, and be not in spray bottle phenomenon in product freeze-drying process, and product is noted
The process pain of penetrating has mitigated；A kind of levo-oxiracetam freeze-dried powder, it is characterised in that it is levo-oxiracetam, L-
Serine, mannitol, sodium glutamate, methionine, phenmethylol be supplementary material, by concentrated compounding, it is dilute match somebody with somebody, be freeze-dried, roll lid step
It is rapid to be made；The levo-oxiracetam 35%~41% that wherein described supplementary material consumption is weight percentage, Serine 23%~
30%, mannitol 18%~28%, sodium glutamate 5%~12%, methionine 3%~10%, phenmethylol 1%~3%；It is described
It is freeze-dried as heat conduction oil temperature quickly is refrigerated into -40 DEG C, keeps constant temperature 60 minutes, -10 DEG C, guarantor is warming up to 5 DEG C/h
Hold constant temperature 80 minutes, be quickly cooled to -40 DEG C, then cryostat 120 minutes vacuumizes drying, with 10 DEG C/h of heatings
Extremely, -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, 30 DEG C are warming up to 10 DEG C/h, 30 DEG C of constant temperature 60 minutes, while preceding case vacuum drop reaches 10Pa/
10 timesharing, freeze and terminate.
Most preferably, above-mentioned levo-oxiracetam freeze-dried powder, it is characterised in that it is the original by following weight percents
Auxiliary material is made：Levo-oxiracetam 37%~40%, Serine 25%~28%, mannitol 20%~24%, sodium glutamate
7%~10%, methionine 5%~8%, phenmethylol 1%~2%；The supplementary material of recipe quantity is placed in container, added left-handed
The sterilized water for injection stirring of 5 times of parts by weight of Oxiracetam, 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；Sterilized water for injection is added into filtrate to filtrate
1000 times of volume, adjust pH 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；It is quick that heat conduction oil temperature is refrigerated to -40 DEG C, keep constant temperature 60
Minute, -10 DEG C are warming up to 5 DEG C/h, constant temperature is kept 80 minutes, -40 DEG C, cryostat 120 minutes are being quickly cooled to.
Then drying is vacuumized, is warming up to 10 DEG C/h, -10 DEG C of constant temperature 150 minutes；0 DEG C, 0 DEG C of constant temperature are warming up to 4 DEG C/h
300 minutes；10 DEG C are warming up to 5 DEG C/h, and 10 DEG C of constant temperature 240 minutes is warming up to 30 DEG C, 30 DEG C of constant temperature 60 with 10 DEG C/h
Minute, while preceding case vacuum drop reaches 10Pa/10 timesharing, freeze and terminate.
In order that obtained levo-oxiracetam freeze-dried powder homogeneity is good, product levels character is consistent, a kind of left-handed
The preparation method of Oxiracetam freeze-dried powder 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, the sterile injection of 5 times of parts by weight of levo-oxiracetam is added
Blunge, after dissolving, add the needle-use activated carbon of mass fraction 0.5%, stir 30min, then filtered with 0.45 micrometer Millipore
Membrane filtration mistake, collects filtrate, standby；
2. dilute match somebody with somebody：Sterilized water for injection is added into filtrate to 1000 times of filtrate volume, is adjusted with hydrochloric acid or sodium hydroxide
PH to 7.0 is saved, then with 0.22 micron of miillpore filter aseptic filtration, takes filtrate is qualified rear filling to be sub-packed in sterile glass vials
In, it is standby；
3. freeze-drying：It is quick that heat conduction oil temperature is refrigerated to -40 DEG C, constant temperature is kept 60 minutes, with 5 DEG C/h of heatings
To -10 DEG C, constant temperature is kept 80 minutes, be quickly cooled to -40 DEG C, cryostat 120 minutes.Then drying is vacuumized, with 10
DEG C/h it is warming up to, -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；With 5 DEG C/h
It is warming up to 10 DEG C, 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, freezes and terminates.
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：
Levo-oxiracetam freeze-dried powder of the present invention impurity in preparation process increases less, impurity incrementss and is only
0.03%, product has solid shape, in lyophilized preparation process without spray bottle phenomenon, product homogeneity is good, levels character one
Cause, impurity is few, impurity is less than 0.28% in the term of validity, and product stability is good, shelf life is up to 24 months, ache in patient injection procedure
Lighter, the good patient compliance of pain.
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 freeze-dried powder, is made according to the following steps：
| Composition | Consumption (percentage by weight %) |
| Levo-oxiracetam | 37% |
| Serine | 27% |
| Mannitol | 22% |
| Sodium glutamate | 7% |
| Methionine | 6% |
| Phenmethylol | 1% |
It is made 1000 bottles
Preparation process：
1. concentrated compounding：The supplementary material of recipe quantity is placed in container, the sterile injection of 5 times of parts by weight of levo-oxiracetam is added
Blunge, after dissolving, add the needle-use activated carbon of mass fraction 0.5%, stir 30min, then filtered with 0.45 micrometer Millipore
Membrane filtration mistake, collects filtrate, standby；
2. dilute match somebody with somebody：Sterilized water for injection is added into filtrate to 1000 times of filtrate volume, is adjusted with hydrochloric acid or sodium hydroxide
PH to 7.0 is saved, then with 0.22 micron of miillpore filter aseptic filtration, takes filtrate is qualified rear filling to be sub-packed in sterile glass vials
In, it is standby；
3. freeze-drying：It is quick that heat conduction oil temperature is refrigerated to -40 DEG C, constant temperature is kept 60 minutes, with 5 DEG C/h of heatings
To -10 DEG C, constant temperature is kept 80 minutes, be quickly cooled to -40 DEG C, cryostat 120 minutes.Then drying is vacuumized, with 10
DEG C/h it is warming up to, -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；With 5 DEG C/h
It is warming up to 10 DEG C, 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, freezes and terminates.
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, 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 freeze-dried powder stability experiment of the present invention
Experiment material：
Levo-oxiracetam freeze-dried powder sample：It is made for embodiment 1
Acceleration study method：Levo-oxiracetam freeze-dried powder made from embodiment 1 is packed by listing, Acceleration study is put
In case, 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, 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：Levo-oxiracetam freeze-dried powder 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, 3,6,9,12,18,24 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 is tried for a long time
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：Spray bottle phenomenon is counted in levo-oxiracetam freeze-dried powder freezing dry process
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 %)
| Levo-oxiracetam | 37% |
| Serine | 29% |
| Mannitol | 24% |
| Sodium glutamate | —— |
| Methionine | 8% |
| 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 | 36 | 100 | 36 |
4. conclusion：Spray bottle phenomenon does not occur in freezing dry process for the sample of embodiment 1, and control sample occurs spray bottle and showed
As for 36%, therefore it is believed that the probability that spray bottle occurs for this product can effectively be reduced by adding sodium glutamate.
Experiment three：A kind of levo-oxiracetam freeze-dried powder preparation process of the present invention is on the increased influence of impurity
1. experiment material：
Levo-oxiracetam freeze-dried powder sample：Prepared by embodiment 1.
Levo-oxiracetam freeze-dried powder control sample：To lack the sample of methionine, its preparation technology be the same as Example
1。
2. experimental method：In the preparation process of embodiment 1, sampled respectively before and after preparing, detect that it, about material, investigates system
Standby process is to the influence about material.Meanwhile, the prescription for lacking methionine is taken as control prescription, by the preparation of embodiment 1
Prepared by method, sampling detects it about material equally before and after preparing, and investigates preparation process to the influence about material.
3. experimental result see the table below：
| Test sample | Relevant material % before preparing | Relevant material % after preparation | The relevant material incrementss % of preparation process |
| Embodiment 1 | 0.15% | 0.18% | 0.03% |
| Control sample 1 | 0.16% | 0.37% | 0.21% |
4. experiment conclusion：The prescription of embodiment 1, the relevant material increase of preparation process is only 0.03%, hence it is evident that better than control
Sample.
Experiment four：Pain experiment in mouse writhing method observation injection process
Test specimen：A kind of levo-oxiracetam freeze-dried powder as made from embodiment 1 does not add phenmethylol as test sample
Prescription levo-oxiracetam freeze-dried powder as made from embodiment 1 be used as control sample；
Purpose：Compare the pain degree in two kinds of levo-oxiracetam freeze-dried powder injection process
Method：Experimental white mouse is taken, levo-oxiracetam freeze-dried powder is subcutaneously injected, and (physiological saline solution is diluted to
10ml), whether observation small white mouse can occur writhing response, occur the probability of writhing response to judge in injection process according to mouse
The power of pain, 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 | 22 | 73.3% |
Conclusion：As seen from the above table, pain is substantially weak in a kind of levo-oxiracetam freeze-dried powder injection process of the invention
In control sample.
Embodiment 2
A kind of levo-oxiracetam freeze-dried powder, is made according to the following steps：
| Composition | Consumption (percentage by weight %) |
| Levo-oxiracetam | 40% |
| Serine | 25% |
| Mannitol | 20% |
| Sodium glutamate | 8% |
| Methionine | 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 2 shows to accelerate sample quality stabilization in June,
Long-term 24 months steady qualities, therefore minimum 24 months of this product term of validity；The sample of embodiment 2 does not spray in freezing dry process
Bottle phenomenon.The influence increased on impurity of the preparation process of embodiment 2 is test result indicates that this product product impurity in preparation process increases
Dosage is smaller, meets product requirement.Mouse writhing method observation injection process in pain result of the test show, the sample of embodiment 2
Pain is markedly less than control sample in product injection process.
Embodiment 3
A kind of levo-oxiracetam freeze-dried powder, is made according to the following steps：
| Composition | Consumption (percentage by weight %) |
| Levo-oxiracetam | 38% |
| Serine | 26% |
| Mannitol | 22% |
| Sodium glutamate | 8% |
| Methionine | 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 3 shows to accelerate sample quality stabilization in June,
Long-term 24 months steady qualities, therefore minimum 24 months of this product term of validity；The sample of embodiment 3 does not spray in freezing dry process
Bottle phenomenon.The influence increased on impurity of the preparation process of embodiment 3 is test result indicates that this product product impurity in preparation process increases
Dosage is smaller, meets product requirement.Mouse writhing method observation injection process in pain result of the test show, the sample of embodiment 3
Pain is markedly less than control sample in product injection process.
Embodiment 4-6：A kind of levo-oxiracetam freeze-dried powder, is prepared, preparation side by the supplementary material of following weight
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 to accelerate sample quality in June
It is stable, long-term 24 months steady qualities, therefore minimum 24 months of this product term of validity；The sample of embodiment 4,5,6 is in freezing dry process
In do not occur spray bottle phenomenon.The influence increased on impurity of the preparation process of embodiment 4,5,6 is test result indicates that prepared by this product
During product impurity incrementss it is smaller, meet product requirement.Pain experiment in mouse writhing method observation injection process
As a result show, pain is markedly less than control sample during the sample injection of embodiment 4,5,6.
Claims (3)
1. a kind of levo-oxiracetam freeze-dried powder, it is characterised in that it is levo-oxiracetam, Serine, mannitol, paddy
Propylhomoserin sodium, methionine, phenmethylol be supplementary material, by concentrated compounding, it is dilute match somebody with somebody, be freeze-dried, roll lid step be made；Wherein described original
The levo-oxiracetam 35% ~ 41% that supplementary product consumption is weight percentage, Serine 23% ~ 30%, mannitol 18% ~ 28%, paddy ammonia
Sour sodium 5% ~ 12%, methionine 3% ~ 10%, phenmethylol 1% ~ 3%；The freeze-drying for it is quick 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, perseverance
Temperature freezing 120 minutes, is then vacuumized drying, is warming up to 10 DEG C/h, -10 DEG C of constant temperature 150 minutes；Risen with 4 DEG C/h
Temperature is to 0 DEG C, 0 DEG C of constant temperature 300 minutes；10 DEG C are warming up to 5 DEG C/h, and 10 DEG C of constant temperature 240 minutes is warming up to 10 DEG C/h
30 DEG C, 30 DEG C of constant temperature 60 minutes, while preceding case vacuum drop reaches 10Pa/10 timesharing, is freezed and terminated.
2. levo-oxiracetam freeze-dried powder as claimed in claim 1, it is characterised in that it is by following weight percents
Supplementary material is made：Levo-oxiracetam 37% ~ 40%, Serine 25% ~ 28%, mannitol 20% ~ 24%, sodium glutamate 7% ~ 10%,
Methionine 5% ~ 8%, phenmethylol 1% ~ 2%；The supplementary material of recipe quantity is placed in container, 5 times of weight of levo-oxiracetam are added
The sterilized water for injection stirring of part, after dissolving, adds the needle-use activated carbon of mass fraction 0.5%, 30min is stirred, then with 0.45
Micrometer Millipore filter membrane is filtered, and collects filtrate, standby；Sterilized water for injection is added into filtrate to 1000 times of filtrate volume, is used
Hydrochloric acid or sodium hydroxide regulation pH to 7.0, then with 0.22 micron of miillpore filter aseptic filtration, take qualified latter filling point of filtrate
It is standby loaded in sterile glass vials；It is quick that heat conduction oil temperature is refrigerated to -40 DEG C, keep constant temperature 60 minutes, risen with 5 DEG C/h
Temperature keeps constant temperature 80 minutes to -10 DEG C, is being quickly cooled to -40 DEG C, cryostat 120 minutes;Then drying is vacuumized, with
10 DEG C/h are warming up to, -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；With 5 DEG C/it is small
When be warming up to 10 DEG C, 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 is true
It is airborne to reach 10Pa/10 timesharing, freeze and terminate.
3. a kind of preparation method of levo-oxiracetam freeze-dried powder as claimed in claim 1 or 2, it is characterised in that it is
It is obtained as follows：
A. concentrated compounding：The supplementary material of recipe quantity is placed in container, the sterilized water for injection of 5 times of parts by weight of levo-oxiracetam is added
Stirring, 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
Cross, collect filtrate, it is 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 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 sterile glass vials, it is standby
With；
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 are warming up to 5 DEG C/h
DEG C, keep constant temperature 80 minutes, be quickly cooled to -40 DEG C, cryostat 120 minutes；Then vacuumize drying, with 10 DEG C/it is small
When be warming up to, -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；It is warming up to 5 DEG C/h
10 DEG C, 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, freezes and terminates；
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 |
|---|---|---|---|
| CN201610194570.8A CN107281122A (en) | 2016-03-31 | 2016-03-31 | A kind of levo-oxiracetam freeze-dried powder and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610194570.8A CN107281122A (en) | 2016-03-31 | 2016-03-31 | A kind of levo-oxiracetam freeze-dried powder and preparation method thereof |
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| Application Number | Title | Priority Date | Filing Date |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109010795A (en) * | 2018-09-12 | 2018-12-18 | 南京康舟医药科技有限公司 | Terlipressin injection with and preparation method thereof |
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 CN201610194570.8A patent/CN107281122A/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 |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109010795A (en) * | 2018-09-12 | 2018-12-18 | 南京康舟医药科技有限公司 | Terlipressin injection with and preparation method thereof |
| CN109010795B (en) * | 2018-09-12 | 2021-10-22 | 南京康舟医药科技有限公司 | Terlipressin acetate injection and preparation method thereof |
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