CN107281130A - A kind of levo-oxiracetam aseptic powdery injection and preparation method thereof - Google Patents
A kind of levo-oxiracetam aseptic powdery injection and preparation method thereof Download PDFInfo
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
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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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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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
Abstract
A kind of levo-oxiracetam aseptic powdery injection, it be using levo-oxiracetam, L serines, mannitol, polyethylene glycol and phenmethylol as supplementary material, by concentrated compounding, it is dilute match somebody with somebody, be freeze-dried and roll lid step be made；The levo-oxiracetam 55% ~ 62% that wherein described supplementary material consumption is weight percentage, L serines 18% ~ 23%, mannitol 12% ~ 19%, polyethylene glycol 2000 3% ~ 8%, phenmethylol 1% ~ 3%；There is solid shape, the phenomenon without drying shrinkage and bubbling in lyophilized preparation process according to levo-oxiracetam aseptic powdery injection produced by the present invention, product homogeneity is good, levels character is consistent, impurity is few, its total impurities is less than 0.27%, and product stability is good, and shelf life is up to 24 months, 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 aseptic powdery injection and its preparation side
Method.
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 the A patents of CN 103735545, 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 the A of Publication No. CN 103599101 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.
Existing injection levo-oxiracetam aseptic powdery its be primarily present no solid shape, be difficult to form skeleton, drying shrinkage easily occur
With bubbling phenomenon, substantially, patient's poor compliance, product stability is poor, and shelf life is short, and product is homogeneous for product injection process pain
Bad, the problems such as levels character is inconsistent of property.
The content of the invention
It is an object of the invention to provide a kind of sterile with solid form, stability is good, product homogeneity is good levo-oxiracetam
Injectable powder.
Another object of the present invention is to provide the preparation method of above-mentioned levo-oxiracetam aseptic powdery injection.
The purpose of the present invention is realized by following technical measures：
A kind of levo-oxiracetam aseptic powdery injection, it is characterised in that it is, using levo-oxiracetam as raw material, to add
A certain amount of additives are made；Wherein described additives be sucrose, trehalose, mannitol, lactose, glucose, maltose,
Glucan, albumin, polyethylene glycol, glycerine, Serine, sodium glutamate, alanine, glycine, methyl amimoacetic acid, phosphoric acid
One or more in salt, acetate, citrate, phenmethylol.
Inventor has found that the specific supplementary product kind of selection coordinates specific supplementary material consumption proportion, coordinates special again in research process
Freeze-drying process technology, may be such that above-mentioned levo-oxiracetam aseptic powdery injection have solid shape, easily formed skeleton,
Product homogeneity is good, levels character consistent, and product is less prone to drying shrinkage and bubbling phenomenon, and stability is good, shelf life extension,
And can making product, patient pain's sense declines in use, good patient compliance；Above-mentioned levo-oxiracetam aseptic powdery note
Penetrate agent, it is characterised in that it is auxiliary using levo-oxiracetam, Serine, mannitol, polyethylene glycol and phenmethylol as original
Material, by concentrated compounding, it is dilute match somebody with somebody, be freeze-dried and roll lid step be made；The left side that wherein described supplementary material consumption is weight percentage
Revolve Oxiracetam 55%~62%, Serine 18%~23%, mannitol 12%~19%, polyethylene glycol 2000 3%~8%, benzene
Methanol 1%~3%；Heat conduction oil temperature is refrigerated to -40 DEG C by the freeze-drying step to be quick, keeps constant temperature 60 minutes, with 5 DEG C/
Hour is warming up to -10 DEG C, keeps constant temperature 80 minutes, is being quickly cooled to -40 DEG C, then cryostat 120 minutes vacuumizes
Dry, be 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, and 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,
Case vacuum drop reaches 10Pa/10 timesharing before simultaneously, freezes and terminates.
Further, a kind of levo-oxiracetam aseptic powdery injection, it is characterised in that it is by following weight percents
Supplementary material is made：Levo-oxiracetam 57%~61%, Serine 19%~22%, mannitol 13%~16%, polyethylene glycol 2000
4%~6%, phenmethylol 1%~2%；The supplementary material of recipe quantity is placed in container, 5 times of parts by weight of levo-oxiracetam are added
Sterilized water for injection is stirred, after dissolving, adds the needle-use activated carbon of mass fraction 0.5%, stirs 30min, then micro- with 0.45
Rice miillpore filter filtration, collects filtrate, standby；Sterilized water for injection is added into filtrate to 1000 times of filtrate volume, salt is used
Acid or sodium hydroxide regulation pH to 7.0, then with 0.22 micron of miillpore filter aseptic filtration, take the qualified rear filling packing of filtrate
It is standby 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, then cryostat 120 minutes vacuumizes drying, 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/
Hour is warming up to 10 DEG C, 10 DEG C of constant temperature 240 minutes, and 30 DEG C are warming up to 10 DEG C/h, 30 DEG C of constant temperature 60 minutes, while before
Case vacuum drop reaches 10Pa/10 timesharing, freezes and terminates.
A kind of preparation method of levo-oxiracetam freeze-dried powder, it is characterised in that it is obtained as follows：
1. 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, then micro- with 0.45
Rice miillpore filter filtration, 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 drying,
It 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, 10 DEG C of constant temperature 240 minutes, with 10 DEG C/h of heatings
To 30 DEG C, 30 DEG C of constant temperature 60 minutes, while preceding case vacuum drop reaches 10Pa/10 timesharing, is freezed and terminated；
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 aseptic powdery injection of the present invention has solid shape, in lyophilized preparation process without drying shrinkage and bubbling
Phenomenon, product homogeneity is good, and levels character is consistent, and impurity is few, and its total impurities is less than 0.27%, and product stability is good, goods
The frame phase is up to 24 months, and pain is lighter in patient injection procedure, good patient compliance.
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
A kind of levo-oxiracetam aseptic powdery injection, is made according to the following steps：
Preparation process：
1. 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, then micro- with 0.45
Rice miillpore filter filtration, 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：A kind of levo-oxiracetam aseptic powdery injection stability experiment of the present invention
Experiment material：
Levo-oxiracetam aseptic powdery injection sample：It is made for embodiment 1
Acceleration study method：Levo-oxiracetam aseptic powdery injection made from embodiment 1 is packed by listing, acceleration is put real
In tryoff, 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 accelerates real
Test June, quality keeps stable, and this product stability is preferable.
Long-term experiment method：Levo-oxiracetam aseptic powdery injection made from embodiment 1 is packed by listing, puts and stays for a long time
In sample 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 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：Pain experiment in mouse writhing method observation injection process
Test specimen：A kind of levo-oxiracetam aseptic powdery injection as made from embodiment 1 does not add phenmethylol as test sample
Prescription levo-oxiracetam injection as made from embodiment 1 is used as control sample；
Purpose：Compare the pain degree in two kinds of levo-oxiracetam aseptic powdery injection injection process
Method：Experimental white mouse is taken, levo-oxiracetam aseptic powdery injection (physiological saline solution is diluted to 10ml) is subcutaneously injected,
Whether observation small white mouse can occur writhing response, and the probability of writhing response occurs according to mouse to judge to ache in injection process
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 | 7 | 23.3% |
| Control sample | 30 | 23 | 76.6% |
Conclusion：As seen from the above table, pain is markedly less than pair in a kind of injection levo-oxiracetam aseptic powdery injection process of the invention
Product in the same old way.
Embodiment 2
A kind of levo-oxiracetam aseptic powdery 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, 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.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 2.
Embodiment 3
A kind of levo-oxiracetam aseptic powdery 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, 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.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 3.
Embodiment 4-6：A kind of levo-oxiracetam aseptic powdery injection, 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 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.Pain in mouse writhing method observation injection process
Sense result of the test shows that pain is markedly less than control sample during the sample injection of embodiment 4,5,6.
Claims (3)
1. a kind of levo-oxiracetam aseptic powdery injection, it is characterised in that it is, using levo-oxiracetam, Serine, mannitol, polyethylene glycol and phenmethylol as supplementary material, by concentrated compounding, dilute to match somebody with somebody, be freeze-dried and roll the steps such as lid and be made；The levo-oxiracetam 55% ~ 62% that wherein described supplementary material consumption is weight percentage, Serine 18% ~ 23%, mannitol 12% ~ 19%, polyethylene glycol 2000 3% ~ 8%, phenmethylol 1% ~ 3%；The freeze-drying step is that heat conduction oil temperature quickly is refrigerated into -40 DEG C, keep constant temperature 60 minutes, -10 DEG C or so are warming up to 5 DEG C/h, keep constant temperature 80 minutes or so, it is being quickly cooled to -40 DEG C, cryostat 120 minutes, then vacuumizes drying, and -10 DEG C of constant temperature is warming up to 150 minutes with 10 DEG C/h；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. levo-oxiracetam aseptic powdery injection as claimed in claim 1, it is characterised in that it is made by the supplementary material of following weight percents：Levo-oxiracetam 57% ~ 61%, Serine 19% ~ 22%, mannitol 13% ~ 16%, polyethylene glycol 2000 4% ~ 6%, phenmethylol 1% ~ 2%；The supplementary material of recipe quantity is placed in container, the sterilized water for injection stirring of 5 times of parts by weight of levo-oxiracetam is added, after dissolving, adds the needle-use activated carbon of mass fraction 0.5%, stir 30min, 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 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, -10 DEG C of constant temperature is warming up to 150 minutes with 10 DEG C/h；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. a kind of preparation method of levo-oxiracetam aseptic powdery injection as claimed in claim 1 or 2, it is characterised in that it is obtained as follows：
A. concentrated compounding：The supplementary material of recipe quantity is placed in container, the sterilized water for injection stirring of 5 times of parts by weight of levo-oxiracetam is added, after dissolving, adds the needle-use activated carbon of mass fraction 0.5%, stir 30min, then filtered with 0.45 micrometer Millipore filter membrane, 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 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 |
|---|---|---|---|
| CN201610194970.9A CN107281130A (en) | 2016-03-31 | 2016-03-31 | A kind of levo-oxiracetam aseptic powdery injection and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610194970.9A CN107281130A (en) | 2016-03-31 | 2016-03-31 | A kind of levo-oxiracetam aseptic powdery injection and preparation method thereof |
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| CN107281130A true CN107281130A (en) | 2017-10-24 |
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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 CN201610194970.9A patent/CN107281130A/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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Application publication date: 20171024 |
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