CN107281133A - 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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- CN107281133A CN107281133A CN201610195042.4A CN201610195042A CN107281133A CN 107281133 A CN107281133 A CN 107281133A CN 201610195042 A CN201610195042 A CN 201610195042A CN 107281133 A CN107281133 A CN 107281133A
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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
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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
Abstract
A kind of levo-oxiracetam freeze-dried powder, it be levo-oxiracetam, L serines, mannitol, sodium glutamate, methionine be supplementary material, by concentrated compounding, it is dilute match somebody with somebody, be freeze-dried, roll lid step be made；The levo-oxiracetam 38% ~ 47% that wherein described supplementary material consumption is weight percentage, L serines 20% ~ 28%, mannitol 26% ~ 35%, sodium glutamate 3% ~ 8%, methionine 2% ~ 8%；According to the levo-oxiracetam freeze-dried powder of the invention obtained, less, the impurity incrementss of impurity increase are only 0.02% in preparation process, product has solid shape, in lyophilized preparation process without spray bottle phenomenon, product homogeneity is good, levels character is consistent, impurity is few, impurity is less than 0.28% in the term of validity, and product stability is good, and shelf life is up to 24 months.
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
The problems such as layer character is inconsistent.
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.
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；A kind of left-handed Austria
La Xitan freeze-dried powders, it is characterised in that it is levo-oxiracetam, Serine, mannitol, sodium glutamate, methionine
For supplementary material, by concentrated compounding, dilute match somebody with somebody, be freeze-dried, roll lid step and be made；What wherein described supplementary material consumption was weight percentage
Levo-oxiracetam 38%~47%, Serine 20%~28%, mannitol 26%~35%, sodium glutamate 3%~8%,
Methionine 2%~8%；Heat conduction oil temperature is refrigerated to -40 DEG C by the freeze-drying to be quick, keeps constant temperature 60 minutes, with 5
- 10 DEG C DEG C/h are warming up to, constant temperature is kept 80 minutes, -40 DEG C is being quickly cooled to, is being vacuumized after cryostat combustion in 120 minutes
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；With
5 DEG C/h are 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, simultaneously
Preceding case vacuum drop reaches 10Pa/10 timesharing, freezes and terminates.
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 40%~44%, Serine 21%~23%, mannitol 28%~31%, sodium glutamate
4%~7%, methionine 3%~6%；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%, stirs 30min, then use
0.45 micrometer Millipore filter membrane is filtered, and collects filtrate, standby；Sterilized water for injection is added into filtrate to the 1000 of filtrate volume
Times, pH to 7.0 is adjusted with hydrochloric acid or sodium hydroxide, then with 0.22 micron of miillpore filter aseptic filtration, after taking filtrate qualified
It is filling to 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, 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, 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 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 before
Case vacuum drop reaches 10Pa/10 timesharing, freezes and terminates.
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
0.02%, 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.
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：
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 | 40% |
| Serine | 23% |
| Mannitol | 31% |
| Sodium glutamate | —— |
| Methionine | 6% |
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 | 27 | 100 | 27 |
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 27%, 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 | 0.17% | 0.19% | 0.02% |
| Control sample 1 | 0.18% | 0.31% | 0.13% |
4. experiment conclusion：The prescription of embodiment 1, the relevant material increase of preparation process is only 0.02%, hence it is evident that better than control
Sample.
Embodiment 2
A kind of levo-oxiracetam freeze-dried powder, is made according to the following steps：
Preparation process：Preparation technology according to embodiment 1 is made.
By the test method of embodiment 1, spray bottle phenomenon statistical experiment in stability test, freezing dry process is carried out respectively
And preparation process influence increased on impurity is tested, the sample stability result of the test of embodiment 2 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 2 in freezing dry process not
Generation spray bottle phenomenon.The influence increased on impurity of the preparation process of embodiment 2 is test result indicates that this product product in preparation process
Impurity incrementss are smaller, meet product requirement.
Embodiment 3
A kind of levo-oxiracetam freeze-dried powder, is made according to the following steps：
Preparation process：Preparation technology according to embodiment 1 is made.
By the test method of embodiment 1, spray bottle phenomenon statistical experiment in stability test, freezing dry process is carried out respectively
And preparation process influence increased on impurity is tested, the sample stability result of the test of embodiment 3 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 3 in freezing dry process not
Generation spray bottle phenomenon.The influence increased on impurity of the preparation process of embodiment 3 is test result indicates that this product product in preparation process
Impurity incrementss are smaller, meet product requirement.
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 obtained by embodiment 4,5,6 carries out stability test, freezing and done respectively
Spray bottle phenomenon statistical experiment and preparation process influence experiment increased on impurity during dry, the sample of embodiment 4,5,6 are stable
Property result of the test show to accelerate June sample quality stable, long-term 24 months steady qualities, therefore minimum 24 months of this product term of validity；
Spray bottle phenomenon does not occur in freezing dry process for the sample of embodiment 4,5,6.The preparation process of embodiment 4,5,6 is to impurity increase
Influence test result indicates that this product product impurity incrementss in preparation process are smaller, meet product requirement.
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 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 is used
Measure the levo-oxiracetam about 38% ~ 47% being weight percentage, Serine about 20% ~ 28%, mannitol about 26% ~ 35%, paddy ammonia
Sour sodium about 3% ~ 8%, methionine about 2% ~ 8%；Heat conduction oil temperature is refrigerated to -40 DEG C by the freeze-drying to be quick, keeps permanent
Temperature 60 minutes, -10 DEG C are warming up to 5 DEG C/h, keep constant temperature 80 minutes, are being quickly cooled to -40 DEG C, 120 points of cryostat
Clock, then vacuumizes drying, 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, and 10 DEG C of constant temperature 240 minutes is warming up to 30 DEG C, 30 DEG C of perseverances with 10 DEG C/h
Temperature 60 minutes, while preceding case vacuum drop reaches 10Pa/10 timesharing, freezes and terminates.
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 40% ~ 44%, Serine 21% ~ 23%, mannitol 28% ~ 31%, sodium glutamate 4% ~ 7%,
Methionine 3% ~ 6%；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%, 30min is stirred, then with 0.45 micrometer Millipore filter membrane
Filtration, collects filtrate, standby；Sterilized water for injection is added into filtrate to 1000 times of filtrate volume, with hydrochloric acid or hydroxide
Sodium adjusts pH to 7.0, then with 0.22 micron of miillpore filter aseptic filtration, takes filtrate is qualified rear filling to be sub-packed in sterile glass
It is standby in bottle；It is quick that heat conduction oil temperature is refrigerated to -40 DEG C, keep constant temperature 60 minutes, -10 DEG C, guarantor are warming up to 5 DEG C/h
Hold constant temperature 80 minutes, be quickly cooled to -40 DEG C, cryostat 120 minutes；Then drying is vacuumized, 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.
3. the preparation method of levo-oxiracetam freeze-dried powder as claimed in claim 1 or 2, it is characterised in that it is by such as
Made from lower step：
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, then cryostat 120 minutes vacuumizes 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.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610195042.4A CN107281133A (en) | 2016-03-31 | 2016-03-31 | A kind of levo-oxiracetam freeze-dried powder and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610195042.4A CN107281133A (en) | 2016-03-31 | 2016-03-31 | A kind of levo-oxiracetam freeze-dried powder and preparation method thereof |
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| Publication Number | Publication Date |
|---|---|
| CN107281133A true CN107281133A (en) | 2017-10-24 |
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ID=60087665
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610195042.4A Withdrawn CN107281133A (en) | 2016-03-31 | 2016-03-31 | A kind of levo-oxiracetam freeze-dried powder and preparation method thereof |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101766595A (en) * | 2008-12-31 | 2010-07-07 | 北京利乐生制药科技有限公司 | Solid 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 CN201610195042.4A patent/CN107281133A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101766595A (en) * | 2008-12-31 | 2010-07-07 | 北京利乐生制药科技有限公司 | Solid 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 |