CN106943377A - A kind of levo-oxiracetam particle and preparation method thereof - Google Patents
A kind of levo-oxiracetam particle and preparation method thereof Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
- A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- 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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- 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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Abstract
A kind of levo-oxiracetam particle, it is characterised in that it is made by the supplementary material of following weight proportion：1 part of levo-oxiracetam, 0.7 ~ 1.3 part of L cysteines, 0.8 ~ 1.5 part of mannitol, 0.6 ~ 1.2 part of microcrystalline cellulose, 1.0 ~ 1.5 parts of sodium carboxymethylcellulose, 1.0 ~ 1.5 parts of lactose, 0.07 ~ 0.15 part of talcum powder, 0.8 ~ 1.7 part of Macrogol 4000,0.5 ~ 1.2 part of Hydroxypropyl methylcellulose, 0.3 ~ 0.8 part of honey, volume fraction are 70% ~ 90% 9 ~ 16 parts of ethanol；Levo-oxiracetam particulate production impurity incrementss of the present invention are smaller, its increments is only 0.04%, pelletization will not adhesion screen cloth, be easy to granulation, particle bisque amount is few, uniform particle diameter, good fluidity, not sub- angle is less than 37 °, content uniformity is less than 5%, store process stability good, product is difficult moisture absorption caking, 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 particle and preparation method thereof.
Background technology
Oxiracetam (oxiracetam, CAS No.：62613-82-5) chemical entitled 4- hydroxyls -2- OXo-1-pyrrolidines
Acetamide, is that (compound is disclosed in the anti anoxia class cereboactive drug that was synthesized first in 1974 of Italian ISFS.P.A companies
US4118396), it is ring GABOB derivatives, Phosphorylcholine and phosphatidyl ethanolamine can be promoted to synthesize, promote brain metabolism, through blood brain
Barrier, has stimulation to specific nervous centralis road, can improve intelligence and memory, to cerebrovascular disease, brain trauma, brain
Knurl, intracranial infection, brain degenerative disease etc. also have preferable curative effect, 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 particle, which is primarily present impurity in preparation process, increases larger, the easy adhesion screen cloth of pelletization, system
Grain is difficult, and particle bisque is more, and particle diameter is difficult to control, and storage process stability is poor, and particle hygroscopicity is strong, connecting block easy to stick,
The technical problem such as shelf life is short.
The content of the invention
Easily prepared it is an object of the invention to provide a kind of, size tunable, the levo-oxiracetam particle of good stability.
Another object of the present invention is to provide the preparation method of above-mentioned levo-oxiracetam particle.
The purpose of the present invention is realized by following technical measures：
A kind of levo-oxiracetam particle, it is characterised in that it is, using levo-oxiracetam as raw material, to add a certain amount of
Filler, flavouring, adhesive, lubricant, coating material be made；Wherein described filler is starch, lactose, dextrin, sugar
One kind or many in powder, calcium sulfate, sucrose, mannitol, microcrystalline cellulose, glucose, sodium carboxymethylcellulose, Cys
Kind；The flavouring be sucrose, maltose, ethylmaltol, Sucralose, sweet stevia rebaudianum, sorbierite, mannitol, glucose,
One or more in aspartame；Described adhesive is water, ethanol, sucrose, starch slurry, dextrin, carboxymethyl cellulose, poly- second
One or more in alkene pyrrolidone, honey；The lubricant is talcum powder, magnesium stearate, polyethylene glycol, stearic acid, hard
One or more in resin acid calcium, lauryl sodium sulfate, superfine silica gel powder, magnesia, paraffin；The coating material is poly- second two
Alcohol 4000, Macrogol 6000, hydroxypropyl cellulose, Hydroxypropyl methylcellulose, polyethylene acetaldehyde diethyl ester, hydroxypropyl methyl
One or more in cellulose phthalate.
Inventor has found that specific supplementary material species coordinates specific supplementary material consumption proportion relation in research process,
Coordinate special processing mode again, may be such that above-mentioned levo-oxiracetam particulate production impurity incrementss are smaller, pelletized
Journey is easy to granulation, will not adhesion screen cloth, product is difficult moisture absorption, is difficult that adhesion caking, grain diameter are uniform, and content uniformity is small, production
Product good stability, shelf life is long；Above-mentioned levo-oxiracetam particle, it is characterised in that it is by the former auxiliary of following weight proportion
Material is made：1 part of levo-oxiracetam, 0.7~1.3 part of Cys, 0.8~1.5 part of mannitol, microcrystalline cellulose 0.6~
1.2 parts, 1.0~1.5 parts of sodium carboxymethylcellulose, 1.0~1.5 parts of lactose, 0.07~0.15 part of talcum powder, Macrogol 4000
0.8~1.7 part, 0.5~1.2 part of Hydroxypropyl methylcellulose, 0.3~0.8 part of honey, volume fraction be 70%~90% ethanol 9
~16 parts；The honey of recipe quantity is taken, is placed in iron pan, the purified water of 2 times of parts by weight of honey is added, stirs, be heated to 100
~105 DEG C, 20~25 minutes are incubated, is taken out, is used 80 mesh screens, take filtrate, the ethanol of recipe quantity is added after letting cool, is stirred molten
Solution, it is standby；Take the levo-oxiracetam of recipe quantity, Cys, mannitol, microcrystalline cellulose, sodium carboxymethylcellulose, breast
Sugar is placed in Universalpulverizer, was crushed 100 mesh sieves, and was placed in wet granulator, adds previously processed good honey ethanol molten
Liquid, starts granulator (installing 18 mesh nylon mesh), starts granulation；Wet granular is put into fluid bed, hotbed temperature sets 50 DEG C
~70 DEG C, start drying, drying time is 50~55 minutes；Macrogol 4000, the Hydroxypropyl methylcellulose of recipe quantity are taken, is added water
The coating solution that mass fraction is 8%~10% is made, it is standby；Above-mentioned dry particl is put into fluid bed, hot-air is passed through, is allowed to
Suspension fluidization, bed temperature is 40~50 DEG C；Coating solution is continuously added to fluid bed, setting whitewashing speed by the nozzle atomization of fluid bed
50~60rpm is spent, atomizing pressure is 0.8~1.0bar, continues air intake and dries, and solution continues after heating 10~15 minutes after having sprayed
Stop heating, cooling discharging；Coated granule is placed in crushing and pelletizing machine, with 20 mesh sieve whole grains；By the talcum of recipe quantity
Powder crushed 100 mesh sieves, adds in the particle after whole grain, is produced with three-dimensional motion mixer mixing 10min~20min.
Further, in order to further improve the stability of levo-oxiracetam particle, Shelf-life, a kind of left-handed Austria
La Xitan particles, it is characterised in that it is made by the supplementary material of following weight proportion：1 part of levo-oxiracetam, the Guang ammonia of L- half
Acid 0.9~1.2 part, 1.0~1.3 parts of mannitol, 0.8~1.1 part of microcrystalline cellulose, 1.2~1.4 parts of sodium carboxymethylcellulose,
1.1~1.3 parts of lactose, 0.11~0.14 part of talcum powder, 1.1~1.5 parts of Macrogol 4000, Hydroxypropyl methylcellulose 0.7~
1.0 parts, 0.5~0.7 part of honey, volume fraction be 70%~90% 12~15 parts of ethanol；The honey of recipe quantity is taken, iron is placed in
In pot, the purified water of 2 times of parts by weight of honey is added, is stirred, be heated to 100~105 DEG C, be incubated 20~25 minutes, taken out,
80 mesh screens are used, filtrate is taken, the ethanol of recipe quantity is added after letting cool, stirring and dissolving is standby；Take the left-handed Aura west of recipe quantity
Smooth, Cys, mannitol, microcrystalline cellulose, sodium carboxymethylcellulose, lactose are placed in Universalpulverizer, are crushed
100 mesh sieves, are placed in wet granulator, add previously processed good honey ethanol solution, start granulator and (install 18 mesh nylon
Sieve), start granulation；Wet granular is put into fluid bed, hotbed temperature sets 50 DEG C~70 DEG C, starts drying, and drying time is
50~55 minutes；Macrogol 4000, the Hydroxypropyl methylcellulose of recipe quantity are taken, it is 8%~10% to add water and mass fraction is made
Coating solution, it is standby；Above-mentioned dry particl is put into fluid bed, hot-air is passed through, suspension fluidization is allowed to, bed temperature is 40~50 DEG C；
Coating solution is continuously added to fluid bed by the nozzle atomization of fluid bed, 50~60rpm of spouting velocity is set, atomizing pressure is
0.8~1.0bar, continues air intake and dries, and solution continues to stop heating, cooling discharging after heating 10~15 minutes after having sprayed；Will bag
Clothing particle is placed in crushing and pelletizing machine, with 20 mesh sieve whole grains；The talcum powder of recipe quantity was crushed into 100 mesh sieves, added whole
In particle after grain, produced with three-dimensional motion mixer mixing 10min~20min.
A kind of preparation method of levo-oxiracetam particle, it is characterised in that it is obtained as follows：
1. the preparation of adhesive：The honey of recipe quantity is taken, is placed in iron pan, the purified water of 2 times of parts by weight of honey is added, stirs
Mix uniform, be heated to 100~105 DEG C, be incubated 20~25 minutes, take out, use 80 mesh screens, take filtrate, after letting cool at addition
The ethanol of side's amount, stirring and dissolving is produced；
2. supplementary material pre-treatment：The levo-oxiracetam, filler, flavouring of recipe quantity is taken to be placed in Universalpulverizer,
100 mesh sieves were crushed, it is standby；
3. granulation：Gained mixed-powder after pre-treatment is taken, is placed in wet granulator, adhesive is added, starts granulator
(installing 18 mesh nylon mesh), starts granulation；
4. dry：Wet granular is put into fluid bed, hotbed temperature sets 50 DEG C~70 DEG C, starts drying；Observe at any time
Particle boiling situation, air blast situation, prevent the particle-bonded ceramic the bottom of a pan, cause particle coking or gelatinization, and drying time is 50~55 points
Clock, it is ensured that pellet moisture≤3%；
It 5. is coated：
(1) configuration of coating solution：The coating material of recipe quantity is taken, add water the solution for being made that mass fraction is 8%~10%,
It is standby；
(2) coating process：Above-mentioned dry particl is put into fluid bed, hot-air is passed through, is allowed to suspension fluidization, bed temperature is 40
~50 DEG C；Coating solution is continuously added to fluid bed by the nozzle atomization of fluid bed, 50~60rpm of spouting velocity, atomization is set
Pressure is 0.8~1.0bar, continues air intake and dries, and solution continues to stop heating after heating 10~15 minutes after having sprayed, and cools down out
Material, produces coated granule；
6. whole grain, sub-sieve：Coated granule is placed in crushing and pelletizing machine, with 20 mesh sieve whole grains, environment temperature is controlled
Less than 25 DEG C, relative humidity is below 50%；
7. it is total mixed：Lubricant was crushed into 100 mesh sieves, adds in the particle after whole grain, is mixed with three-dimensional motion mixer
10min~20min；
8. interior wrap：Packed with particles packing machine, set packing specification as 1g/ bags, below 25 DEG C of environment temperature of control,
Below relative humidity 50%, produce.
The present invention has following beneficial effect：
Levo-oxiracetam particulate production impurity incrementss of the present invention are smaller, its increments is only 0.04%, granulation
Process will not adhesion screen cloth, be easy to granulation, particle bisque amount is few, uniform particle diameter, good fluidity, and not sub- angle is less than 37 °, and loading amount is poor
Different to be less than 5%, storage process stability is good, and product is difficult moisture absorption caking, and shelf life is up to 24 months, and preparation technology simply may be used
OK, it 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 be interpreted as limiting the scope of the invention, without departing substantially from spirit of the invention
In the case of essence, the modification or replacement made to the inventive method, step or condition belong to the scope of the present invention.
Embodiment 1
A kind of levo-oxiracetam particle, is made according to the following steps：
Preparation process：
1. the preparation of adhesive：The honey of recipe quantity is taken, is placed in iron pan, the purified water of 2 times of parts by weight of honey is added, stirs
Mix uniform, be heated to 100~105 DEG C, be incubated 20~25 minutes, take out, use 80 mesh screens, take filtrate, after letting cool at addition
The ethanol of side's amount, stirring and dissolving is produced；
2. supplementary material pre-treatment：Take the levo-oxiracetam of recipe quantity, Cys, mannitol, microcrystalline cellulose, carboxylic
Sodium carboxymethylcellulose pyce, lactose are placed in Universalpulverizer, crush 100 mesh sieves, standby；
3. granulation：Gained mixed-powder after pre-treatment is taken, is placed in wet granulator, adhesive is added, starts granulator
(installing 18 mesh nylon mesh), starts granulation；
4. dry：Wet granular is put into fluid bed, hotbed temperature sets 50 DEG C~70 DEG C, starts drying；Observe at any time
Particle boiling situation, air blast situation, prevent the particle-bonded ceramic the bottom of a pan, cause particle coking or gelatinization, and drying time is 50~55 points
Clock, it is ensured that pellet moisture≤3%；
It 5. is coated：
(1) configuration of coating solution：Macrogol 4000, the Hydroxypropyl methylcellulose of recipe quantity are taken, adds water and mass fraction is made
It is standby for 8%~10% solution；
(2) coating process：Above-mentioned dry particl is put into fluid bed, hot-air is passed through, is allowed to suspension fluidization, bed temperature is 40
~50 DEG C；Coating solution is continuously added to fluid bed by the nozzle atomization of fluid bed, 50~60rpm of spouting velocity, atomization is set
Pressure is 0.8~1.0bar, continues air intake and dries, and solution continues to stop heating after heating 10~15 minutes after having sprayed, and cools down out
Material, produces coated granule；
6. whole grain, sub-sieve：Coated granule is placed in crushing and pelletizing machine, with 20 mesh sieve whole grains, environment temperature is controlled
Less than 25 DEG C, relative humidity is below 50%；
7. it is total mixed：Talcum powder was crushed into 100 mesh sieves, adds in the particle after whole grain, is mixed with three-dimensional motion mixer
10min~20min；
8. interior wrap：Packed with particles packing machine, set packing specification as 1g/ bags, below 25 DEG C of environment temperature of control,
Below relative humidity 50%, produce.
In pelletization, observation is understood, the pelletization of embodiment 1 does not find the situation of adhesion screen cloth, and product is easy to system
Grain.
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：Particle is stopped sub- angle and determined
1. test material：Sample after the completion of always being mixed in the preparation process of embodiment 1
2. test method：After the completion of embodiment 1 is always mixed, respectively in the upper, middle and lower of three-dimensional motion mixer, left and right each point
Separately sampled measure angle of repose, judges its mobility；
3. result of the test：
4. conclusion (of pressure testing)：It can be seen that by upper table result of the test, five times measurement angle of repose is respectively less than 37 °, shows particle flow
Property is good.
Experiment two：Content uniformity
1. test material：10 bags of particulate samples made from Example 1, shine《Chinese Pharmacopoeia》Two annex of version in 2010
The lower content uniformity inspection of granula.
2. determination method：Take the weight of 10 bags of test sample, respectively weighed every bag of content, every bag of weight and sign loading amount phase
Compare.
3. result of the test：Content uniformity inspection result see the table below：3
4. conclusion (of pressure testing)：This product content uniformity is respectively less than ± 5% it can be seen from upper table result of the test, it was demonstrated that loading amount is poor
Different stabilization, content uniformity is small.
Experiment three：A kind of levo-oxiracetam particle prescription of the present invention is on the increased influence of preparation process impurity
1. experiment material：
Levo-oxiracetam particulate samples：Prepared by embodiment 1.
Levo-oxiracetam control sample：To lack the sample obtained by Cys on the basis of the prescription of embodiment 1
Product, its preparation technology be the same as Example 1.
2. experimental method：In the preparation process of embodiment 1, levo-oxiracetam bulk drug and levo-oxiracetam are determined respectively
The relevant material of finished granule, observation levo-oxiracetam particle impurity in preparation process increases situation.Meanwhile, take and lack L-
The prescription of the embodiment 1 of cysteine is prepared by the preparation method of embodiment 1, equally determined respectively left-handed as control prescription
The relevant material of Oxiracetam bulk drug and levo-oxiracetam finished granule, observation levo-oxiracetam particle is in preparation process
Middle impurity increases situation.
3. experimental result see the table below：
4. experiment conclusion：The prescription of embodiment 1, coordinates specific preparation method, relevant material increase is only 0.02%, hence it is evident that
Better than control sample.
Experiment four：A kind of levo-oxiracetam granule stability experiment of the present invention
Experiment material：
Levo-oxiracetam particle：It is made for embodiment 1.
Acceleration study method：Levo-oxiracetam particle made from embodiment 1 is packed by listing, Acceleration study case is put
In, certain time sampling is tested to investigation project.
Acceleration study temperature：40±2℃
Acceleration study humidity：RH75% ± 5%
The investigation time：0th, 1,2,3, June
Inspection target：Character, moisture, granularity, melting, relevant material, content, microbial limit
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 particle made from embodiment 1 is packed by listing, the long-term case that keeps sample is put
In, certain time sampling is tested to investigation project.
Long-term experiment temperature：25±2℃
Long-term experiment humidity：RH60% ± 10%
The investigation time：0th, 3,6,9,12,18,24 months
Inspection target：Character, moisture, granularity, melting, relevant material, content, microbial limit
Long term test stability is recorded：
Long term test shows：It is 24 months characters of this product long term test, moisture, granularity, melting, relevant material, content, micro-
Biological limit without significant changes, meets every relevant regulations of production quality standard draft.This product long term test 24
Month steady quality, therefore minimum 24 months of this product term of validity, long term test is still during continuing to investigate.
Embodiment 2
A kind of levo-oxiracetam particle, is made according to the following steps：
Preparation process：Preparation technology according to embodiment 1 is made.Observation product pelletization does not find showing for adhesion screen cloth
As product is easy to granulation.Obtained finished product is tested by the test method of embodiment 1, not sub- angle experiment measurement result table
Bright this product mobility of particle is good, and not sub- angle is less than 35 °, and content uniformity experiment shows that this product content uniformity is less than 4%, this product loading amount
Stable, controllable, product prescription influence result of the test increased on preparation process impurity shows this product preparation process impurity incrementss
Smaller, relevant material only increases by 0.03% in preparation process, and stability test result shows to accelerate sample quality stabilization in June, long
24 months phases steady quality, therefore this product term of validity at least 24 months.
Embodiment 3
A kind of levo-oxiracetam particle, is made according to the following steps：
Preparation process：Preparation technology according to embodiment 1 is made.Observation product pelletization does not find showing for adhesion screen cloth
As product is easy to granulation.Obtained finished product is tested by the test method of embodiment 1, not sub- angle experiment measurement result table
Bright this product mobility of particle is good, and not sub- angle is less than 36 °, and content uniformity experiment shows that this product content uniformity is less than 5%, this product loading amount
Stable, controllable, product prescription influence result of the test increased on preparation process impurity shows this product preparation process impurity incrementss
Smaller, relevant material only increases by 0.04% in preparation process, and stability test result shows to accelerate sample quality stabilization in June, long
24 months phases steady quality, therefore this product term of validity at least 24 months.
Embodiment 4-6：A kind of levo-oxiracetam particle, is prepared, preparation method is same by the supplementary material of following weight
Embodiment 1：
| Embodiment | 4 | 5 | 6 |
| Levo-oxiracetam | 1 part | 1 part | 1 part |
| Cys | 1.0 parts | 1.0 parts | 1.1 parts |
| Mannitol | 1.1 parts | 1.2 parts | 1.1 parts |
| Microcrystalline cellulose | 1.0 parts | 0.9 part | 0.9 part |
| Sodium carboxymethylcellulose | 1.4 parts | 1.3 parts | 1.2 parts |
| Lactose | 1.1 parts | 1.2 parts | 1.3 parts |
| Talcum powder | 0.12 part | 0.13 part | 0.14 part |
| Macrogol 4000 | 1.4 parts | 1.3 parts | 1.2 parts |
| Hydroxypropyl methylcellulose | 0.8 part | 0.9 part | 0.8 part |
| Honey | 0.7 part | 0.6 part | 0.5 part |
| Volume fraction is 80% alcohol | 13 parts | 14 parts | 13 parts |
Preparation process：Preparation technology according to embodiment 1 is made.The product preparation process of embodiment 4,5,6 does not find adhesion
The phenomenon of screen cloth, product is easy to granulation.Sample obtained by embodiment 4,5,6 is tested by the test method of embodiment 1, is stopped
Sub- angle experiment measurement result shows that this product mobility of particle is good, and not sub- angle is respectively lower than 35 °, 33 °, 35 °, content uniformity experiment table
The bright product content uniformity of embodiment 4,5,6 is respectively less than 5%, and this product loading amount is stable, controllable, and the product prescription of embodiment 4,5,6 is to system
The standby increased influence result of the test of Process Impurity shows that this product preparation process impurity incrementss are smaller, embodiment 4 in preparation process,
5th, the relevant material of 6 samples only increases by 0.02%, 0.02%, 0.03% respectively, and the stability test result of embodiment 4,5,6 shows to add
Fast sample quality in June is stablized, and long-term 24 months quality are stablized, therefore this product term of validity at least 24 months.
Claims (3)
1. a kind of levo-oxiracetam particle, it is characterised in that it is the supplementary material and preparation method system by following weight proportion
：About 1 part of levo-oxiracetam, about 0.7 ~ 1.3 part of Cys, about 0.8 ~ 1.5 part of mannitol, microcrystalline cellulose about 0.6 ~
1.2 parts, about 1.0 ~ 1.5 parts of sodium carboxymethylcellulose, about 1.0 ~ 1.5 parts of lactose, about 0.07 ~ 0.15 part of talcum powder, polyethylene glycol
4000 about 0.8 ~ 1.7 parts, about 0.5 ~ 1.2 part of Hydroxypropyl methylcellulose, about 0.3 ~ 0.8 part of honey, volume fraction be 70% ~ 90%
About 9 ~ 16 parts of ethanol；The honey of recipe quantity is taken, is placed in iron pan, the purified water of 2 times of parts by weight of honey is added, stirs, plus
Heat is incubated 20 ~ 25 minutes to 100 ~ 105 DEG C, takes out, uses 80 mesh screens, take filtrate, and the ethanol of recipe quantity is added after letting cool,
Stirring and dissolving, it is standby；Take the levo-oxiracetam of recipe quantity, Cys, mannitol, microcrystalline cellulose, carboxymethyl cellulose
Plain sodium, lactose are placed in Universalpulverizer, are crushed 100 mesh sieves, and are placed in wet granulator, add previously processed good honey
Ethanol solution, starts granulator（18 mesh nylon mesh are installed）, start granulation；Wet granular is put into fluid bed, hotbed temperature is set
It is fixed 50 DEG C ~ 70 DEG C, start drying, drying time is 50 ~ 55 minutes；Macrogol 4000, the Hydroxypropyl methylcellulose of recipe quantity are taken,
Add water the coating solution for being made that mass fraction is 8% ~ 10%, standby；Above-mentioned dry particl is put into fluid bed, hot-air is passed through, makes
Suspension fluidization, bed temperature be 40 ~ 50 DEG C；Coating solution is continuously added to fluid bed, setting whitewashing by the nozzle atomization of fluid bed
50 ~ 60rpm of speed, atomizing pressure is 0.8 ~ 1.0bar, continues air intake and dries, and solution continues after heating 10 ~ 15 minutes after having sprayed
Stop heating, cooling discharging；Coated granule is placed in crushing and pelletizing machine, with 20 mesh sieve whole grains；By the talcum of recipe quantity
Powder crushed 100 mesh sieves, adds in the particle after whole grain, is produced with three-dimensional motion mixer mixing 10min ~ 20min.
2. levo-oxiracetam particle as claimed in claim 1, it is characterised in that it is by the supplementary material of following weight proportion
It is made with preparation method：1 part of levo-oxiracetam, 0.9 ~ 1.2 part of Cys, 1.0 ~ 1.3 parts of mannitol, microcrystalline cellulose
0.8 ~ 1.1 part, 1.2 ~ 1.4 parts of sodium carboxymethylcellulose, 1.1 ~ 1.3 parts of lactose, 0.11 ~ 0.14 part of talcum powder, polyethylene glycol
4000 1.1 ~ 1.5 parts, 0.7 ~ 1.0 part of Hydroxypropyl methylcellulose, 0.5 ~ 0.7 part of honey, volume fraction for 70% ~ 90% ethanol 12 ~
15 parts；The honey of recipe quantity is taken, is placed in iron pan, the purified water of 2 times of parts by weight of honey is added, stirs, it is heated to 100 ~
105 DEG C, 20 ~ 25 minutes are incubated, is taken out, is used 80 mesh screens, take filtrate, the ethanol of addition recipe quantity after letting cool, stirring and dissolving,
It is standby；Take the levo-oxiracetam of recipe quantity, Cys, mannitol, microcrystalline cellulose, sodium carboxymethylcellulose, lactose
It is placed in Universalpulverizer, crushed 100 mesh sieves, and be placed in wet granulator, adds previously processed good honey ethanol solution,
Start granulator（18 mesh nylon mesh are installed）, start granulation；Wet granular is put into fluid bed, hotbed temperature setting 50 DEG C ~ 70
DEG C, start drying, drying time is 50 ~ 55 minutes；Macrogol 4000, the Hydroxypropyl methylcellulose of recipe quantity are taken, adds water and is made
Mass fraction is 8% ~ 10% coating solution, standby；Above-mentioned dry particl is put into fluid bed, hot-air is passed through, is allowed to suspension flow
Change, bed temperature is 40 ~ 50 DEG C；Coating solution is continuously added to fluid bed by the nozzle atomization of fluid bed, setting spouting velocity 50 ~
60rpm, atomizing pressure is 0.8 ~ 1.0bar, continues air intake drying, and solution continues to stop adding after heating 10 ~ 15 minutes after having sprayed
Heat, cooling discharging；Coated granule is placed in crushing and pelletizing machine, with 20 mesh sieve whole grains；The talcum powder of recipe quantity is crushed
100 mesh sieves are crossed, adds in the particle after whole grain, is produced with three-dimensional motion mixer mixing 10min ~ 20min.
3. the preparation method of levo-oxiracetam particle as claimed in claim 1 or 2, it is characterised in that it is by following step
It is rapid obtained：
A. the preparation of adhesive：The honey of recipe quantity is taken, is placed in iron pan, the purified water of 2 times of parts by weight of honey is added, stirring is equal
It is even, 100 ~ 105 DEG C are heated to, 20 ~ 25 minutes are incubated, is taken out, is used 80 mesh screens, take filtrate, recipe quantity is added after letting cool
Ethanol, stirring and dissolving is produced；
B. supplementary material pre-treatment：Take the levo-oxiracetam, filler, flavouring of recipe quantity to be placed in Universalpulverizer, crush
100 mesh sieves are crossed, it is standby；
C. pelletize：Gained mixed-powder after pre-treatment is taken, is placed in wet granulator, adhesive is added, starts granulator（Install
18 mesh nylon mesh）, start granulation；
D. dry：Wet granular is put into fluid bed, hotbed temperature sets 50 DEG C ~ 70 DEG C, starts drying；Observation particle boiling at any time
Situation, air blast situation are risen, the particle-bonded ceramic the bottom of a pan is prevented, particle coking or gelatinization is caused, drying time is 50 ~ 55 minutes, it is ensured that
Pellet moisture≤3%；
E. it is coated：
The configuration of E (1) coating solutions：The coating material of recipe quantity is taken, add water the solution for being made that mass fraction is 8% ~ 10%, standby；
E (2) coating process：Above-mentioned dry particl is put into fluid bed, hot-air is passed through, suspension fluidization is allowed to, bed temperature is 40 ~ 50
℃；Coating solution is continuously added to fluid bed by the nozzle atomization of fluid bed, 50 ~ 60rpm of spouting velocity is set, atomizing pressure is
0.8 ~ 1.0bar, continues air intake and dries, and solution continues to stop heating after heating 10 ~ 15 minutes after having sprayed, and cooling discharging produces bag
Clothing particle；
F. whole grain, sub-sieve:Coated granule is placed in crushing and pelletizing machine, with 20 mesh sieve whole grains, 25 DEG C of environment temperature is controlled
Hereinafter, relative humidity is below 50%；
G. it is total mixed：Lubricant was crushed into 100 mesh sieves, added in the particle after whole grain, with three-dimensional motion mixer mixing 10min
~20min；
H. interior bag：Packed with particles packing machine, set packing specification as 1g/ bags, below 25 DEG C of environment temperature of control, relatively
Below humidity 50%, produce.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0243336A1 (en) * | 1986-04-14 | 1987-10-28 | U C B, S.A. | Pharmaceutical compositions for the treatment of intermittent claudication |
| CN101288648A (en) * | 2008-06-16 | 2008-10-22 | 石药集团欧意药业有限公司 | Easy-to-administrate oxiracetam granular formulation and preparation method |
| 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 |
| CN102579386A (en) * | 2012-03-19 | 2012-07-18 | 北京德众万全药物技术开发有限公司 | Stable oxiracetam preparation |
| CN102846600A (en) * | 2012-09-06 | 2013-01-02 | 石药集团欧意药业有限公司 | Oxiracetam drug activity composition and preparation method thereof |
-
2016
- 2016-06-15 CN CN201610427301.1A patent/CN106943377A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0243336A1 (en) * | 1986-04-14 | 1987-10-28 | U C B, S.A. | Pharmaceutical compositions for the treatment of intermittent claudication |
| CN101288648A (en) * | 2008-06-16 | 2008-10-22 | 石药集团欧意药业有限公司 | Easy-to-administrate oxiracetam granular formulation and preparation method |
| 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 |
| CN102579386A (en) * | 2012-03-19 | 2012-07-18 | 北京德众万全药物技术开发有限公司 | Stable oxiracetam preparation |
| CN102846600A (en) * | 2012-09-06 | 2013-01-02 | 石药集团欧意药业有限公司 | Oxiracetam drug activity composition and preparation method thereof |
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Application publication date: 20170714 |