CN107661315A - A kind of levo-oxiracetam capsule for being sustained release and preparation method thereof - Google Patents
A kind of levo-oxiracetam capsule for being sustained release and preparation method thereof Download PDFInfo
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- CN107661315A CN107661315A CN201610614013.7A CN201610614013A CN107661315A CN 107661315 A CN107661315 A CN 107661315A CN 201610614013 A CN201610614013 A CN 201610614013A CN 107661315 A CN107661315 A CN 107661315A
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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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
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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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1611—Inorganic compounds
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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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
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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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
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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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1664—Compounds of unknown constitution, e.g. material from plants or animals
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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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
Abstract
A kind of levo-oxiracetam capsule slowly discharged is made by following supplementary material：1 part of levo-oxiracetam, 1.1 parts ~ 1.9 parts of lactose, 1.5 parts ~ 2.2 parts of HPMC K4M, 0.9 part ~ 1.5 parts of HPMC K15M, 0.5 part ~ 1.1 parts of Brazil wax, 0.18 part ~ 0.31 part of octadecanol, 0.2 ~ 0.9 part of calcium monohydrogen phosphate, 0.3 ~ 1.0 part of superfine silica gel powder, 0.21 ~ 0.28 part of sodium thiosulfate, 3.1 parts ~ 3.8 parts of 5% ~ 10% PVP K30 ethanol solution；Bisque is few after the present invention has particle whole grain, and product yield is up to 91.6%, and release uniformity is good, and each time point release RSD is respectively less than 6% between different samples, and rate of release is slow, and deenergized period is up to 12 hours；Meanwhile this product stability is good, capsule adhesion phenomenon will not occur for storage process, and impurity increment is only 0.05%, 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 capsule slowly discharged and its
Preparation method.
Background technology
Oxiracetam listed in 1987 in Italy, and the formulation of listing is tablet, 800mg；Capsule, 800mg；Injection
Liquid, 1g/5ml.It is domestic at present there was only oxiracetam capsule and parenteral solution listing, and main active used is racemic
Body.Ye Lei etc. mentions levo-oxiracetam to the rush gone into a coma caused by alcoholism in the A patents of Publication No. CN 103735545
Effect of waking up is obvious, and dextrorotation Oxiracetam does not act on substantially, and the above-mentioned rush of levo-oxiracetam wakes up effect for racemization Aura west
Smooth 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 the study note 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.
Oxiracetam (oxiracetam, CAS No.：62613-82-5) the entitled 4- hydroxyls -2- OXo-1-pyrrolidines of chemistry
Acetamide, (compound is disclosed in the anti anoxia class cereboactive drug synthesized first in 1974 for Italian ISFS.P.A companies
US4118396), it is ring GABOB derivatives, Phosphorylcholine and phosphatidyl ethanolamine can be promoted to synthesize, promotes brain metabolism, through blood brain
Barrier, there is stimulation to specific nervous centralis road, intelligence and memory can be improved, to cerebrovascular disease, brain trauma, brain
Knurl, intracranial infection, brain degenerative disease etc. also have the effect of preferable, and the drug toxicity is extremely low, no mutagenesis and carcinogenic work
With and genotoxicity.Giorgio et al. discloses the chemical constitution and preparation method of Oxiracetam in US4118396,
Chiodini et al. is disclosed in WO9306826A, and clinical effectiveness proves that the drug effect of the Oxiracetam of S configurations (left-handed) is better than R structures
Type (dextrorotation), Oxiracetam and levo-oxiracetam structure are as follows.
Existing oxiracetam capsule is primarily present release and can not preferably controlled, it is impossible to reaches the requirement of sustained release preparation, together
The release for criticizing different samples in product differs greatly, and causes product quality variance larger, and particle bisque is more after whole grain, into
Product yield is low, and adhesion caking easily occurs in storage process capsule, the technical problems such as relevant material increment is larger.
The content of the invention
It is an object of the invention to provide a kind of levo-oxiracetam capsule slowly discharged.
Another object of the present invention is to provide the preparation method of the above-mentioned levo-oxiracetam capsule slowly discharged.
The purpose of the present invention is realized by following technical measures：
A kind of levo-oxiracetam capsule slowly discharged, it is characterised in that it be using levo-oxiracetam as raw material, then
A certain amount of sustained-release matrix material, retarding agent, lubricant, adhesive and stabilizer is added to be made；Wherein described sustained-release matrix material
Expect for HPMC, ethyl cellulose, polyethylene, polypropylene, polysiloxanes, polyoxyethylene, lactose, fructose, sucrose,
One or more in mannitol, sodium alginate, agar, chitin, galactolipin；The retarding agent is fat, beeswax, Brazil
One kind in palm wax, hydrogenated vegetable oil, stearyl alcohol, glycerin monostearate, superfine silica gel powder, calcium monohydrogen phosphate, microcrystalline cellulose
It is or several；The lubricant is the one or more in magnesium stearate, talcum powder, silica, octadecanol；Adhesive therefor
For any of ethanol solution, starch slurry, sucrose solution, water, PVP ethanol solution；The stabilizer is vitamin C, first
Methyllanthionine, the one or more in sodium thiosulfate, citric acid, tartaric acid, cysteine, glutathione.
Inventor has found in research process, specific supplementary material species and supplementary material consumption proportion relation, coordinates special
Fixed supplementary material pre-treating method, particle bisque is few after may be such that above-mentioned levo-oxiracetam capsule whole grain, and product yield is high, releases
Time length is put, and it is good with the release uniformity between batch product difference sample, and storage process is not in capsule adhesion caking
Phenomenon, relevant material increment is smaller, the above-mentioned levo-oxiracetam capsule slowly discharged, it is characterised in that it is by following
The supplementary material of weight proportion is made：1 part of levo-oxiracetam, 1.1 parts~1.9 parts of lactose, 1.5 parts of HPMC K4M
~2.2 parts, 0.9 part~1.5 parts of HPMC K15M, 0.5 part~1.1 parts of Brazil wax, 0.18 part of octadecanol
~0.31 part, 0.2~0.9 part of calcium monohydrogen phosphate, 0.3~1.0 part of superfine silica gel powder, 0.21~0.28 part of sodium thiosulfate, quality point
Number is 5%~10% 3.1 parts~3.8 parts of PVP K30 ethanol solution；Take the levo-oxiracetam, lactose, hydroxypropyl of recipe quantity
Methylcellulose K4M, HPMC K15M, Brazil wax, calcium monohydrogen phosphate, superfine silica gel powder, sodium thiosulfate are put mixed
Close co-grinding in pulverizer (all to sieve by No. 5 into fine powder and can must not be less than the 95% of total amount by the amounts of No. 6 sieves), mistake
Sieve；PVP K30 ethanol solution is added, with 18 mesh sieve mixing granulations, manufactured wet granular is placed in hot-air oven, is set
40~60 DEG C of temperature, dry to pellet moisture≤3%, whole grain (crosses 24 mesh sieves), standby；Octadecanol be crushed into 100 mesh sieves,
Add in the particle after whole grain, with three-dimensional motion mixer mixing 10min~20min.
Further, in order that the levo-oxiracetam capsule difference sample room release uniformity that must slowly discharge is more preferable,
Bisque is less after Product organization, and yield is higher, the above-mentioned levo-oxiracetam capsule slowly discharged, it is characterised in that it be by
The supplementary material of following weight proportion is made：1 part of levo-oxiracetam, 1.3 parts~1.6 parts of lactose, HPMC K4M
1.8 parts~2.0 parts, 1.2 parts~1.4 parts of HPMC K15M, 0.7 part~1.0 parts of Brazil wax, octadecanol
0.22 part~0.26 part, 0.5~0.7 part of calcium monohydrogen phosphate, 0.6~0.9 part of superfine silica gel powder, 0.23~0.26 part of sodium thiosulfate,
Mass fraction is 6%~8% 3.2 parts~3.5 parts of PVP K30 ethanol solution；Take levo-oxiracetam, the breast of recipe quantity
Sugar, HPMC K4M, HPMC K15M, Brazil wax, calcium monohydrogen phosphate, superfine silica gel powder, thiosulfuric acid
Sodium puts co-grinding in mixing mill and (is all sieved by No. 5 into fine powder and can must not be less than total amount by the amounts of No. 6 sieves
95%), sieve；PVP K30 ethanol solution is added, with 18 mesh sieve mixing granulations, by manufactured wet granular, is placed in hot-air oven
In, 40~60 DEG C of temperature is set, dried to pellet moisture≤3%, whole grain (crosses 24 mesh sieves), standby；Octadecanol crushed
100 mesh sieves, add in the particle after whole grain, with three-dimensional motion mixer mixing 10min~20min.
A kind of preparation method of the levo-oxiracetam capsule slowly discharged, it is characterised in that it is to make as follows
：
1. supplementary material pre-treatment：Main ingredient, sustained-release matrix material, retarding agent and the stabilizer of recipe quantity is taken to put co-grinding
Co-grinding (is all sieved by No. 5 into fine powder and can must not be less than the 95% of total amount by the amounts of No. 6 sieves) in machine, sieving；
2. granulation：Adhesive is added, with 18 mesh sieve mixing granulations, manufactured wet granular is placed in hot-air oven, is set
40~60 DEG C of temperature, dry to pellet moisture≤3%, whole grain (crosses 24 mesh sieves), standby；
It is 3. total mixed：Lubricant be crushed into 100 mesh sieves, add in the particle after whole grain, mixed with three-dimensional motion mixer
10min~20min；
4. filling：Filled with fully-automatic capsule filler, adjust loading amount 0.5g/ grains, whole filling process need to control relatively
Humidity is below 50%；
It is 5. aluminum-plastic packaged：Dispensed with aluminium-plastic bubble plate packing machine, per plate 10, operation room relative humidity have to be lower than 50%；
6. outsourcing produces.
The present invention has following beneficial effect：
Bisque is few after a kind of levo-oxiracetam capsule slowly discharged of the present invention has particle whole grain, and product yield is up to
91.6%, release uniformity is good, and each time point release RSD is respectively less than 6% between different samples, and rate of release is slow, release week
Phase is up to 12 hours；Meanwhile this product stability is good, capsule adhesion phenomenon will not occur for storage process, and impurity increment is only
0.05%, shelf life is up to 24 months, preparation technology simple possible, is worth marketing.
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 limiting the scope of the invention is interpreted as, 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 capsule slowly discharged, is made according to the following steps：
Preparation process：
1. supplementary material pre-treatment：Take levo-oxiracetam, lactose, HPMC K4M, the hydroxypropyl of recipe quantity
Cellulose K15M, Brazil wax, calcium monohydrogen phosphate, superfine silica gel powder, sodium thiosulfate put in mixing mill co-grinding into thin
Powder (is all sieved by No. 5 and can must not be less than the 95% of total amount by the amounts of No. 6 sieves), sieving；
2. adding PVP K30 ethanol solution, with 18 mesh sieve mixing granulations, by manufactured wet granular, hot-air oven is placed in
In, 40~60 DEG C of temperature is set, dried to pellet moisture≤3%, whole grain (crosses 24 mesh sieves), standby；
It is 3. total mixed：Octadecanol be crushed into 100 mesh sieves, add in the particle after whole grain, mixed with three-dimensional motion mixer
Close 10min~20min.
4. filling：Filled with fully-automatic capsule filler, adjust loading amount 0.5g/ grains, whole filling process need to control relatively
Humidity is below 50%；
It is 5. aluminum-plastic packaged：Dispensed with aluminium-plastic bubble plate packing machine, per plate 10, operation room relative humidity have to be lower than 50%；
6. outsourcing 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：Yield calculates
1. test material：Gained finished product in the preparation process of embodiment 1
2. test method：With quality obtained by the quality of inventory and finished product, product yield is calculated；
3. result of the test：It see the table below
| Name of product | Inventory | Packaging material weight | Finished weight | Yield |
| Embodiment 1 | 512.6g | 36.8g | 503.2g | 91.6% |
4. conclusion (of pressure testing)：It can be seen that product yield is up to 91.6% by upper table result of the test.
Experiment two：Drug release determination
1. test material：The test specimen of Example 1
2. test method：Spansule obtained above is taken as sample, according to release inspection technique (Chinese Pharmacopoeia 2010 editions
Two the second methods of annex X D), using the device of the method for dissolution method second, using water 900ml as dissolution medium, rotating speed is every
100 turns of minute, operate in accordance with the law, through 1,2,4,6,8,12 hour, take release solution 10ml, filtered with 0.45 μm of miillpore filter,
Subsequent filtrate is taken as need testing solution, and supplements dissolution medium 10ml in process container in time.Another precision weighs left-handed Aura
Western smooth reference substance about 10mg is put in 25ml measuring bottles, is dissolved with water and is diluted to scale, shaken up, as reference substance solution.Essence respectively
It is close to measure above-mentioned reference substance solution and each 20 μ l of need testing solution, determined according to the chromatographic condition of assay.Calculate every
Release (refers to Accumulation dissolution).
3. result of the test：The measurement result of the release of spansule sample of the present invention see the table below
4. conclusion (of pressure testing)：The levo-oxiracetam capsule main ingredient levo-oxiracetam slowly discharged discharges into slow release
For up to 12 hours, different sample room release behaviors were suitable, and each time point RSD of release is respectively less than 6%.
Experiment three：A kind of levo-oxiracetam capsule stability experiment slowly discharged of the present invention
Experiment material：
Levo-oxiracetam capsule：It is made for embodiment 1.
Acceleration study method：Levo-oxiracetam spansule made from embodiment 1 is packed by listing, puts Acceleration study
In case, certain time sampling, investigation project is tested.
Acceleration study temperature：40±2℃
Humidity：RH75% ± 5%
Investigate the time：0th, 1,2,3, June
Inspection target：
Character, moisture, relevant material, release, content, microbial limit
Accelerated test stability records：
Acceleration study result shows：Acceleration sample in June is suitable with 0 month sample items Testing index quality, 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 capsule made from embodiment 1 is packed by listing, puts the long-term case that keeps sample
In, certain time sampling, investigation project is tested.
Acceleration study temperature：25±2℃
Humidity：RH60% ± 10%
Investigate the time：0th, 3,6,9,12,18,24 months
Character, moisture, relevant material, release, content, microbial limit
Long term test stability records：
Long term test shows：24 months characters of this product long term test, moisture, relevant material, release, content, microorganism
Limit meets every relevant regulations of production quality standard draft without significant changes.24 lunar geology of this product long term test
Amount is stable, and impurity increment is only 0.05%, therefore minimum 24 months of this product term of validity, and long term test is still during investigation is continued.
Embodiment 2
A kind of levo-oxiracetam capsule slowly discharged, is made according to the following steps：
Preparation process：It is made according to the preparation technology of embodiment 1.Tested by the test method of embodiment 1, release is surveyed
Determine result of the test and show that levo-oxiracetam is up to 12 hours in slowly release, release time, different time points each sample is released
Degree of putting RSD is respectively less than 5%, and yield measurement result shows this product high income up to more than 93.8%, and this product yield is good, stability test
As a result show to accelerate sample quality stabilization in June, impurity increment is only 0.06%, and long-term 24 months steady qualities, impurity increment is only
For 0.05%, storage process has no that capsule adhesion is lumpd, therefore this product term of validity at least 24 months.
Embodiment 3
A kind of levo-oxiracetam capsule slowly discharged, is made according to the following steps：
Preparation process：It is made according to the preparation technology of embodiment 1.Tested by the test method of embodiment 1, release is surveyed
Determine result of the test and show that levo-oxiracetam is up to 12 hours in slowly release, release time, different time points each sample is released
Degree of putting RSD is respectively less than 6%, and yield measurement result shows this product high income up to more than 94.5%, and this product yield is good, stability test
As a result show to accelerate sample quality stabilization in June, impurity increment is only 0.05%, and long-term 24 months steady qualities, impurity increment is only
For 0.05%, storage process has no that capsule adhesion is lumpd, therefore this product term of validity at least 24 months.
Embodiment 4-6：A kind of levo-oxiracetam capsule slowly discharged, is prepared by the supplementary material of following weight,
Preparation method is the same as embodiment 1：
Preparation process：It is made according to the preparation technology of embodiment 1.Tested by the test method of embodiment 1, embodiment 4,
5th, 6 drug release determination result of the tests show that levo-oxiracetam is up to 12 hours in slowly release, release time, different time points
The release RSD of each sample is respectively smaller than 6%, 5%, 5%, and the yield measurement result of embodiment 4,5,6 shows this product high income, its
Yield is respectively 93.2%, 94.1%, 93.8%, and the stability test result of embodiment 4,5,6 shows that acceleration sample quality in June is steady
It is fixed, capsule adhesion phenomenon is had no, impurity increment is only 0.05%, 0.06%, 0.04% respectively, long-term 24 months steady qualities,
Have no capsule adhesion phenomenon, impurity increment is only 0.05%, 0.06%, 0.05% respectively, therefore this product term of validity at least 24 months.
Claims (3)
1. a kind of levo-oxiracetam capsule slowly discharged, it is characterised in that it is by the supplementary material system of following weight proportion
：1 part of levo-oxiracetam, 1.1 parts ~ 1.9 parts of lactose, 1.5 parts ~ 2.2 parts of HPMC K4M, hydroxypropyl methylcellulose
Plain 0.9 part ~ 1.5 parts of K15M, 0.5 part ~ 1.1 parts of Brazil wax, 0.18 part ~ 0.31 part of octadecanol, calcium monohydrogen phosphate 0.2 ~
0.9 part, 0.3 ~ 1.0 part of superfine silica gel powder, 0.21 ~ 0.28 part of sodium thiosulfate, mass fraction is 5% ~ 10% PVP K30 ethanol
3.1 parts ~ 3.8 parts of solution；Take levo-oxiracetam, lactose, HPMC K4M, the HPMC of recipe quantity
K15M, Brazil wax, calcium monohydrogen phosphate, superfine silica gel powder, sodium thiosulfate put in mixing mill co-grinding into fine powder（Entirely
Portion is by No. 5 sieves and can must not be less than the 95% of total amount by the amount of No. 6 sieves）, sieving；PVP K30 ethanol solution is added, is used
18 mesh sieve mixing granulations, manufactured wet granular is placed in hot-air oven, sets about 40 ~ 60 DEG C of temperature, is dried to pellet moisture
≤ 3%, whole grain（Cross 24 mesh sieves）, it is standby；Octadecanol be crushed into about 100 mesh sieves, added in the particle after whole grain, with three-dimensional
Movement mixer mixes 10min ~ 20min.
2. levo-oxiracetam capsule as claimed in claim 1, it is characterised in that it is by the supplementary material of following weight proportion
It is made：1 part of levo-oxiracetam, 1.3 parts ~ 1.6 parts of lactose, 1.8 parts ~ 2.0 parts of HPMC K4M, hydroxypropyl are fine
Tie up plain 1.2 parts ~ 1.4 parts of K15M, 0.7 part ~ 1.0 parts of Brazil wax, 0.22 part ~ 0.26 part of octadecanol, calcium monohydrogen phosphate 0.5 ~
0.7 part, 0.6 ~ 0.9 part of superfine silica gel powder, 0.23 ~ 0.26 part of sodium thiosulfate, mass fraction is 6% ~ 8% PVP K30 ethanol
3.2 parts ~ 3.5 parts of solution；Take levo-oxiracetam, lactose, HPMC K4M, the HPMC of recipe quantity
K15M, Brazil wax, calcium monohydrogen phosphate, superfine silica gel powder, sodium thiosulfate put in mixing mill co-grinding into fine powder（Entirely
Portion is by No. 5 sieves and can must not be less than the 95% of total amount by the amount of No. 6 sieves）, sieving；PVP K30 ethanol solution is added, is used
18 mesh sieve mixing granulations, manufactured wet granular is placed in hot-air oven, 40 ~ 60 DEG C of temperature of setting, and drying to pellet moisture≤
3%, whole grain（Cross 24 mesh sieves）, it is standby；Octadecanol be crushed into 100 mesh sieves, add in the particle after whole grain, use three-dimensional motion
Mixer mixing 10min ~ 20min.
3. the preparation method of levo-oxiracetam capsule as claimed in claim 1 or 2, it is characterised in that it is by following step
It is rapid obtained：
A. supplementary material pre-treatment：Main ingredient, sustained-release matrix material, retarding agent and the stabilizer of recipe quantity is taken to put in mixing mill
Co-grinding is into fine powder（All sieved by No. 5 and can must not be less than the 95% of total amount by the amounts of No. 6 sieves）, sieving；
B. pelletize：Adhesive is added, with 18 mesh sieve mixing granulations, manufactured wet granular is placed in hot-air oven, temperature is set
40 ~ 60 DEG C, dry to pellet moisture≤3%, whole grain（Cross 24 mesh sieves）, it is standby；
C. it is total mixed：Lubricant be crushed into 100 mesh sieves, added in the particle after whole grain, with three-dimensional motion mixer mixing 10min
~20min；
D. fill：Filled with fully-automatic capsule filler, adjust loading amount 0.5g/ grains, whole filling process need to control relative humidity
Below 50%；
E. it is aluminum-plastic packaged：Dispensed with aluminium-plastic bubble plate packing machine, per plate 10, operation room relative humidity have to be lower than 50%；
F. outsourcing produces.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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Citations (3)
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| WO1993006826A1 (en) * | 1991-10-08 | 1993-04-15 | Smithkline Beecham Farmaceutici S.P.A. | Composition comprising s-oxiracetame for use as nootropic |
| CN102249975A (en) * | 2010-05-21 | 2011-11-23 | 重庆润泽医疗器械有限公司 | (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide crystal form I and preparation method and application thereof |
| CN103599083A (en) * | 2013-12-06 | 2014-02-26 | 重庆东泽医药科技发展有限公司 | Levo-oxiracetam slow-release tablet and preparation method thereof |
-
2016
- 2016-07-28 CN CN201610614013.7A patent/CN107661315A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993006826A1 (en) * | 1991-10-08 | 1993-04-15 | Smithkline Beecham Farmaceutici S.P.A. | Composition comprising s-oxiracetame for use as nootropic |
| CN102249975A (en) * | 2010-05-21 | 2011-11-23 | 重庆润泽医疗器械有限公司 | (S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide crystal form I and preparation method and application thereof |
| CN103599083A (en) * | 2013-12-06 | 2014-02-26 | 重庆东泽医药科技发展有限公司 | Levo-oxiracetam slow-release tablet and preparation method thereof |
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