CN109692167A - The pharmaceutical composition and preparation method thereof for treating cognition dysfunction - Google Patents
The pharmaceutical composition and preparation method thereof for treating cognition dysfunction Download PDFInfo
- Publication number
- CN109692167A CN109692167A CN201811188850.3A CN201811188850A CN109692167A CN 109692167 A CN109692167 A CN 109692167A CN 201811188850 A CN201811188850 A CN 201811188850A CN 109692167 A CN109692167 A CN 109692167A
- Authority
- CN
- China
- Prior art keywords
- nuclear layer
- oxiracetam
- auxiliary material
- preparation
- inner nuclear
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- 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
- A61K9/48—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
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Abstract
The present invention provides a kind of pharmaceutical composition for treating cognition dysfunction, the pharmaceutical composition is using oxiracetam intestines as active constituent, the mixture that mass ratio using polyacrylic resin and polyvinyl acetate phthalate is 2~3:1 is mainly disintegrated release as oxiracetam enteric coated particles prepared by coating material in intestinal juice, bioavilability is high, and toxic side effect is low.Content and the release result of 60min change unobvious compared with 0 day after oxiracetam particle of the present invention is placed 24 months under the conditions of 25 DEG C ± 2 DEG C of temperature, relative humidity 60% ± 10%, the release of 60min is greater than 80%, illustrate that oxiracetam particle acid-resistant strength of the present invention is strong, drug release rate has good stability.Oxiracetam particle appearance prepared by the present invention is subsphaeroidal, and good fluidity, particle is more uniform, and uniformity of dosage units is good, is suitble to industrialized production.
Description
Technical field
The present invention relates to a kind of pharmaceutical compositions and preparation method thereof for treating cognition dysfunction.
Background technique
Cognition is that human brain receives external information, by working process, inherent psychological activity is converted into, to obtain knowledge
Or the process of working knowledge.It includes memory, language, visual space, execution, calculating and understands judge etc..Cognitive disorder is
Refer to one or more impaired in above-mentioned several cognitive functions, and influences the daily or social ability of individual.Age is to influence to recognize
The main factor for knowing dysfunction disease incidence, increases with the age, and the disease incidence of cognition dysfunction rises rapidly, cognitive function
Obstacle has become the important diseases for influencing middle-aged and the old's Health and Living quality, and the performance of cognition dysfunction not only includes memory
Obstacle, aphasia, agnosia, appraxia and visual space obstacle etc., can also with anxiety, depression, it is intense, impulsion etc. affective behaviors obstacle,
Just medically it is defined as when patient at least while shows above-mentioned three kinds of symptoms with cognitive disorder disease, these feelings
Sense and behavior disorder the reason of also patient is disabled, heavy burden is brought to society and family.
Currently, the drug for the treatment of cognition dysfunction, clinically proposes a variety of drugs for the hypothesis of different pathogeny
Treatment method, such as huperzine, donepezil, Rivastigmine, galanthamine, Memantine, Nimodipine, ergot bases, A Si
Woods, brufen, statins etc..But these drug some clinically used are because curative effect is bad, some is because its poison is secondary again
It acts on and limits its application, it is therefore necessary to develop the drug of new treatment cognition dysfunction.Studies have shown that pyrroles's gastral cavity
Class drug oxiracetam, No. CAR is 62613-82-5, for preventing or treating memory dysfunction good effect, and safety
It is good, it is the drug of novel therapeutic treatment cognition dysfunction.
About oxiracetam preparation, clinically mainly there are injection, capsule and conventional tablet at present.Injection,
Directly quickly enter human body, the protection of no human body normal physiological barrier, if therefore dosage it is improper or inject too fast or drug quality
There are problems, are possible to bring harm to patient, or even cause the consequence that can not be retrieved；Furthermore injection pain, cannot be by suffering from
Person's self-administer, injection site generate that scleroma and intravenous injection are existing when to cause vascular inflammation all be clinical application important to ask
Topic.Thus, consider in drug safety, preferentially selects oral preparation (such as capsule, tablet).The hydroxyl oxygen of clinical application at present
There are apparent drawbacks for pyrrole vinegar amine oral preparation (capsule or tablet): pharmacodynamics effect is unstable, and a large amount of oxiracetams exist
It is dissolved out in stomach, with the extension of residence time, some drugs are decomposed by gastric acid, it is difficult to effectively be absorbed by enteron aisle, to reduce
The pharmacological activity of oxiracetam enteric coated particles, while also increasing security risks.
Summary of the invention
The first object of the present invention is to provide a kind of pharmaceutical composition for treating cognition dysfunction, the pharmaceutical composition
For the treatment of cognition dysfunction, good effect is highly-safe.Unless otherwise specified, number of the present invention is parts by weight,
The percentage is mass percent.
The present inventor study repeatedly how to reduce oxiracetam decomposition amount under one's belt during, guarantee preparation
On the basis of particle mainly discharges in intestinal juice, by improving the type and proportion of auxiliary material, a kind of hydroxyl oxygen pyrrole vinegar has been prepared
Amine enteric coated particles；And pleasantly surprised discovery, particle also has good mobility while reducing decomposition amount in stomach, and particle is thin
Small uniformly hardness is moderate, is suitble to capsule or powder packing.
To achieve the above object, the technical solution of the present invention is as follows:
The pharmaceutical composition that the present invention treats cognition dysfunction includes oxiracetam enteric coated particles.
Oxiracetam enteric coated particles of the present invention, including inner nuclear layer and outer nuclear layer；The inner nuclear layer includes hydroxyl oxygen pyrrole
Vinegar amine and inner nuclear layer auxiliary material, the outer nuclear layer include outer core layer material and outer nuclear layer auxiliary material, wherein oxiracetam 50-70%,
Inner nuclear layer auxiliary material 15-30%, outer core layer material 8-20%, outer nuclear layer auxiliary material are 0.1-3%, by percentage to the quality.The present invention
The inner nuclear layer auxiliary material of the oxiracetam enteric coated particles by xanthan gum, sodium alginate, methylcellulose, hydroxyethyl cellulose,
Any one or a few composition in chitin, microcrystalline cellulose, povidone or hydroxypropyl methyl cellulose.Hydroxyl of the present invention
The outer core layer material of oxygen pyrrole vinegar amine enteric coated particles is the mixture of polyacrylic resin and polyvinyl acetate phthalate,
The mass ratio of middle polyacrylic resin and polyvinyl acetate phthalate is 2~3:1.Polyacrylic resin of the present invention
It is preferred that Eudragit L or Eudragit S；More preferable Eudragit L30D, Eudragit L100 or Eudragit S100.
Preferably, it includes oxiracetam particle, the hydroxyl oxygen that the present invention, which treats the pharmaceutical composition of cognition dysfunction,
Pyrrole vinegar amine particle includes inner nuclear layer and outer nuclear layer；The inner nuclear layer includes oxiracetam and inner nuclear layer auxiliary material, the outer nuclear layer
Including outer core layer material and outer nuclear layer auxiliary material, wherein oxiracetam 50-70%, inner nuclear layer auxiliary material 15-30%, outer core layer material
8-20%, outer nuclear layer auxiliary material 0.1-3%；The inner nuclear layer auxiliary material is xanthan gum, sodium alginate, methylcellulose, ethoxy fibre
Tie up any one or a few composition in element, chitin, microcrystalline cellulose, povidone or hydroxypropyl methyl cellulose；It is described outer
Core layer material is the mixture of polyacrylic resin and polyvinyl acetate phthalate, wherein polyacrylic resin and poly- second
The mass ratio of enol acetate phthalate ester is 2~3:1；The polyacrylic resin is selected from Eudragit L30D, Eudragit
One or more of L100, Eudragit S100 combination；The outer nuclear layer auxiliary material is superfine silica gel powder, magnesium stearate, talcum
The combination of one or more of powder, polyvinyl alcohol.
According to the second aspect of the invention, the present invention provides a kind of pharmaceutical composition of above-mentioned treatment cognition dysfunction
Preparation method, this method simple process are suitble to large-scale production.
An embodiment according to the present invention, the preparation method of the pharmaceutical composition of above-mentioned treatment cognition dysfunction,
It is characterized in that, the oxiracetam particle is prepared using following steps: the preparation of inner nuclear layer: by oxiracetam and kernel
Layer auxiliary material is uniformly mixed；The ethanol solution softwood of mass fraction 8-25% is pelletized, dry, and drying temperature is 45-65 DEG C, when
Between be 10-30min, obtain dry particl；The preparation of outer nuclear layer: outer core layer material and outer nuclear layer auxiliary material are uniformly mixed, with quality point
The ethyl alcohol that number is 50-95% dissolves, and the coating solution that mass fraction is 5-20% is made；Dry particl prepared by inner nuclear layer is put into stream
Change bed seed-coating machine, be coated with coating solution, after coating, dry, whole grain is to get oxiracetam particle of the present invention.
An embodiment according to the present invention, above-mentioned fluidized-bed coating machine set air blast flux 85-120L/min, atomization
Atmospheric pressure 0.3-0.5MPa, be coated flow quantity 80-120ml/min, 50-65 DEG C of stream temperature, time 15-30min.
An embodiment according to the present invention, in the preparation of above-mentioned outer nuclear layer, after coating in drying steps, dry temperature
Degree is 40-68 DEG C (preferably 40-60 DEG C), time 10-30min.
An embodiment according to the present invention, a kind of preparation method of pharmaceutical composition that treating cognition dysfunction,
Described pharmaceutical composition includes oxiracetam particle；The oxiracetam particle includes inner nuclear layer and outer nuclear layer；In described
Stratum nucleare includes oxiracetam and inner nuclear layer auxiliary material, and the outer nuclear layer includes outer core layer material and outer nuclear layer auxiliary material, wherein hydroxyl oxygen
Pyrrole vinegar amine 50-70%, inner nuclear layer auxiliary material 15-30%, outer core layer material 8-20%, outer nuclear layer auxiliary material 0.1-3%；The inner nuclear layer
Auxiliary material is xanthan gum, sodium alginate, methylcellulose, hydroxyethyl cellulose, chitin, microcrystalline cellulose, povidone or hydroxypropyl
Any one or a few composition in ylmethyl cellulose；The outer core layer material is polyacrylic resin and polyvinyl alcohol acetic acid
The mixture of phthalic acid ester, wherein the mass ratio of polyacrylic resin and polyvinyl acetate phthalate is 2~3:1；
The polyacrylic resin is selected from one or more of Eudragit L30D, Eudragit L100, Eudragit S100 group
It closes；The outer nuclear layer auxiliary material is the combination of one or more of superfine silica gel powder, magnesium stearate, talcum powder, polyvinyl alcohol；
Oxiracetam particle is prepared using following processing step:
The preparation of inner nuclear layer: oxiracetam and inner nuclear layer auxiliary material are uniformly mixed；The ethyl alcohol of mass fraction 8-25% is molten
Liquid softwood is pelletized, dry, and drying temperature is 45-65 DEG C, and time 10-30min obtains dry particl；The preparation of outer nuclear layer: will
Outer core layer material and outer nuclear layer auxiliary material are uniformly mixed, and are dissolved with the ethyl alcohol that mass fraction is 50-95%, and it is 5- that mass fraction, which is made,
20% coating solution；Cross colloid mill grinding；Then dry particl prepared by inner nuclear layer is put into fluidized-bed coating machine, with coating liquid stream
Change bed coating, seed-coating machine sets air blast flux 85-110L/min, atomization gas pressure 0.3-0.5MPa, is coated flow quantity 80-
120ml/min, 55-60 DEG C of stream temperature, time 15-30min, dry after coating, drying temperature is 40-60 DEG C, is done
The dry time be 10-30min, whole grain to get.
Pharmaceutical composition of the present invention can be above-mentioned oxiracetam particle and customary adjuvant (such as flavoring commonly used in the art
Agent, filler, adhesive, lubricant, corrigent etc.) tablet, capsule, granule, powder etc. through common process preparation is oral
Dosage form.
The utility model has the advantages that
The present invention provides a kind of pharmaceutical composition for treating cognition dysfunction, which is with oxiracetam
Active constituent uses the combination (2~3:1 of mass ratio) of special ratios polyacrylic resin and polyvinyl acetate phthalate
Less, the mainly disintegration release in intestinal juice is dissolved out in oxiracetam enteric coated particles stomach as the preparation of outer nuclear layer coating material,
Reduce oxiracetam dissolve out under one's belt brought by drug by gastric acid decompose and caused by side effect, bioavilability is high,
Toxic side effect is low, for preventing or treating memory dysfunction good effect；Particle also has good mobility, and particle simultaneously
Fine uniform, hardness is moderate, is suitble to capsule or powder packing.Invention oxiracetam particle is at 25 DEG C ± 2 of temperature
DEG C, place 24 months under the conditions of relative humidity 60% ± 10% after content and the release result of 60min change not compared with 0 day
Obviously, the release of 60min is greater than 80%, illustrates that oxiracetam particle acid-resistant strength of the present invention is strong, drug release rate stability
Well.Oxiracetam particle appearance prepared by the present invention is subsphaeroidal, and angle of repose is between 30-35 degree, good fluidity, particle compared with
Uniformly, uniformity of dosage units is good, is suitble to industrialized production.Preparation method of the present invention is simple, and material used, equipment are pharmaceutical preparation
Field conventional equipment, while the material being more toxic is not used, it is economic and environment-friendly, it is suitble to large-scale promotion.
Specific embodiment
The present invention is specifically described below by embodiment, it is necessary to which indicated herein is that following embodiment is only used
In invention is further explained, it should not be understood as limiting the scope of the invention, person skilled in art can
To make some nonessential modifications and adaptations to the present invention according to aforementioned present invention content.
Embodiment 1
The preparation method of oxiracetam particle
Prescription: oxiracetam 63g, hydroxypropyl methyl cellulose 16g, polyacrylic resin Eudragit L100 15g,
Polyvinyl acetate phthalate 5g, superfine silica gel powder 1g.
Preparation process: the preparation of inner nuclear layer: the hydroxypropyl methyl cellulose ethyl alcohol that appropriate concentration is 80% is dissolved, is matched
The hydroxypropyl methyl cellulose ethanol solution that mass fraction is 21% is made；Then hydroxypropyl methyl is added in oxiracetam
Cellulosic ethanol solution softwood, softwood cross sieve wet granular, dry, and drying temperature is 55 DEG C, drying time 20min,
Dry particl is made；The preparation of outer nuclear layer: by polyacrylic resin Eudragit L100, polyvinyl acetate phthalate and
Superfine silica gel powder is uniformly mixed, and is dissolved with the ethanol solution that mass fraction is 75%, and the coating solution that mass fraction is 12% is configured to,
Cross colloid mill grinding；Then dry particl prepared by inner nuclear layer is put into fluidized-bed coating machine, with coating solution fluidized bed coating, coating
Machine set air blast flux 102L/min, atomization gas pressure 0.4MPa, be coated flow quantity 100ml/min, 58 DEG C of stream temperature, the time
Dry after coating for 22min, drying temperature is 60 DEG C, drying time 15min, whole grain to get.
Embodiment 2
Prescription: oxiracetam 60g, methylcellulose 23g, polyacrylic resin Eudragit L30D 12g, polyethylene
Alcohol acetate phthalate ester 6g, magnesium stearate 1g.
Preparation process: the preparation of inner nuclear layer: the methylcellulose ethyl alcohol that appropriate concentration is 60% is dissolved, matter is configured to
Measure the methylcellulose ethanol solution that score is 10%；Then it is soft that methylcellulose ethanol solution system is added in oxiracetam
Material, softwood cross sieve wet granular, dry, and drying temperature is 45 DEG C, drying time 30min, and dry particl is made；Outer nuclear layer
Preparation: polyacrylic resin Eudragit L30D, polyvinyl acetate phthalate and magnesium stearate are uniformly mixed, and are used
The ethanol solution that mass fraction is 70% dissolves, and is configured to the coating solution that mass fraction is 15%, crosses colloid mill grinding；Then will
The dry particl of inner nuclear layer preparation is put into fluidized-bed coating machine, and with coating solution fluidized bed coating, seed-coating machine sets air blast flux 85L/
Min, atomization gas pressure 0.3MPa, be coated flow quantity 80ml/min, 55 DEG C of stream temperature, time 30min, after coating,
Dry, drying temperature is 40 DEG C, drying time 30min, whole grain to get.
Embodiment 3
Prescription: oxiracetam 50g, sodium alginate 28g, polyacrylic resin Eudragit S100 15g, polyvinyl alcohol
Acetate phthalate ester 5g, talcum powder 2g.
Preparation process: the preparation of inner nuclear layer: the sodium alginate ethyl alcohol that appropriate concentration is 50% is dissolved, quality is configured to
The sodium alginate ethanol solution that score is 8%；Then sodium alginate ethanol solution softwood, softwood are added in oxiracetam
Sieve wet granular is crossed, dry, drying temperature is 65 DEG C, drying time 10min, and dry particl is made；The preparation of outer nuclear layer: will
Polyacrylic resin Eudragit S100, polyvinyl acetate phthalate and talcum powder are uniformly mixed, and are with mass fraction
80% ethanol solution dissolution, is configured to the coating solution that mass fraction is 10%, crosses colloid mill grinding；Then it prepared by inner nuclear layer
Dry particl be put into fluidized-bed coating machine, with coating solution fluidized bed coating, seed-coating machine sets air blast flux 110L/min, atomization gas
Pressure 0.5MPa is coated flow quantity 120ml/min, 60 DEG C of stream temperature, time 15min, dry after coating, dry
Temperature be 60 DEG C, drying time 10min, whole grain to get.
Embodiment 4
Prescription: oxiracetam 70g, hydroxypropyl methyl cellulose 15g, polyacrylic resin Eudragit L30D 8g,
Polyvinyl acetate phthalate 4g, magnesium stearate 3g.
Preparation process: the preparation of inner nuclear layer: the hydroxypropyl methyl cellulose ethyl alcohol that appropriate concentration is 60% is dissolved, is matched
The hydroxypropyl methyl cellulose ethanol solution that mass fraction is 12% is made；Then hydroxypropyl methyl is added in oxiracetam
Cellulosic ethanol solution softwood, softwood cross sieve wet granular, dry, and drying temperature is 55 DEG C, drying time 22min,
Dry particl is made；The preparation of outer nuclear layer: by polyacrylic resin Eudragit L30D, polyvinyl acetate phthalate and
Magnesium stearate is uniformly mixed, and is dissolved with the ethanol solution that mass fraction is 75%, and the coating solution that mass fraction is 12% is configured to,
Cross colloid mill grinding；Then dry particl prepared by inner nuclear layer is put into fluidized-bed coating machine, with coating solution fluidized bed coating, coating
Machine set air blast flux 100L/min, atomization gas pressure 0.4MPa, be coated flow quantity 98ml/min, 58 DEG C of stream temperature, the time
Dry after coating for 20min, drying temperature is 50 DEG C, drying time 15min, whole grain to get.
Embodiment 5
Releasing result is investigated: referring to the relevant regulations of version Chinese Pharmacopoeia in 2015, by the oxiracetam of embodiment 1-4
Grain according to a certain amount of respectively loaded in HDPE bottles, transfer in 25 DEG C ± 2 DEG C of temperature, 60% ± 10% condition of relative humidity by sealing
Acid-resistant strength (being verified by medicament contg in acidproof rear enteric coated particles) after setting 24 months, after detection 0.1M HCl acidproof two hours
With the release of 60min in 6.8 buffer of pH, test result is as follows table 1.
1 acid-resistant strength of table and releasing result are investigated
The oxiracetam particle of 1-4 of embodiment of the present invention preparation is in 25 DEG C ± 2 DEG C of temperature, relative humidity 60% ± 10%
Under the conditions of place 24 months after content and the release result of 60min change compared with 0 day unobvious, the release of 60min is big
In 80%, illustrate that oxiracetam particle acid-resistant strength of the present invention is strong, drug release rate has good stability.Simultaneously according to Chinese Pharmacopoeia
Version two relevant regulations in 2015 investigate the mobility of particle of the present invention, as the result is shown the hydroxyl oxygen pyrrole vinegar of embodiment 1-4 preparation
Amine particle appearance is subsphaeroidal, and angle of repose is between 30-35 degree, and good fluidity, particle is more uniform, and uniformity of dosage units is good, is suitble to work
Industry metaplasia produces.
Claims (7)
1. a kind of pharmaceutical composition for treating cognition dysfunction, it is characterised in that: described pharmaceutical composition includes hydroxyl oxygen pyrrole vinegar
Amine enteric coated particles；The oxiracetam enteric coated particles include inner nuclear layer and outer nuclear layer；The inner nuclear layer includes oxiracetam
With inner nuclear layer auxiliary material, the outer nuclear layer includes outer core layer material and outer nuclear layer auxiliary material, wherein oxiracetam 50-70%, inner nuclear layer
Auxiliary material 15-30%, outer core layer material 8-20%, outer nuclear layer auxiliary material are 0.1-3%, by percentage to the quality；The oxiracetam intestines
The inner nuclear layer auxiliary material of molten particle is by xanthan gum, sodium alginate, methylcellulose, hydroxyethyl cellulose, chitin, microcrystalline cellulose
Any one or a few composition in element, povidone or hydroxypropyl methyl cellulose；Outside the oxiracetam enteric coated particles
Core layer material is the mixture of polyacrylic resin and polyvinyl acetate phthalate, wherein polyacrylic resin and poly- second
The mass ratio of enol acetate phthalate ester is 2~3:1；The outer nuclear layer auxiliary material be superfine silica gel powder, magnesium stearate, talcum powder,
The combination of one or more of polyvinyl alcohol.
2. a kind of pharmaceutical composition for treating cognition dysfunction, it is characterised in that: described pharmaceutical composition includes hydroxyl oxygen pyrrole vinegar
Amine particle；The oxiracetam particle includes inner nuclear layer and outer nuclear layer；The inner nuclear layer includes oxiracetam and inner nuclear layer
Auxiliary material, the outer nuclear layer include outer core layer material and outer nuclear layer auxiliary material, wherein oxiracetam 50-70%, inner nuclear layer auxiliary material 15-
30%, outer core layer material 8-20%, outer nuclear layer auxiliary material 0.1-3%；The inner nuclear layer auxiliary material is xanthan gum, sodium alginate, Methyl cellulose
Any one or a few in element, hydroxyethyl cellulose, chitin, microcrystalline cellulose, povidone or hydroxypropyl methyl cellulose
Composition；The outer core layer material is the mixture of polyacrylic resin and polyvinyl acetate phthalate, wherein polypropylene
The mass ratio of acid resin and polyvinyl acetate phthalate is 2~3:1；The polyacrylic resin is selected from Eudragit
One or more of L30D, Eudragit L100, Eudragit S100 combination；The outer nuclear layer auxiliary material be superfine silica gel powder,
The combination of one or more of magnesium stearate, talcum powder, polyvinyl alcohol.
3. the preparation method of the pharmaceutical composition for the treatment of cognition dysfunction as claimed in claim 1 or 2, which is characterized in that institute
It states oxiracetam particle to prepare using following steps: the preparation of inner nuclear layer: oxiracetam and inner nuclear layer auxiliary material be mixed equal
It is even；The ethanol solution softwood of mass fraction 8-25% is pelletized, dry, and drying temperature is 45-65 DEG C, time 10-30min,
Obtain dry particl；The preparation of outer nuclear layer: outer core layer material and outer nuclear layer auxiliary material are uniformly mixed, the second for being 50-95% with mass fraction
The coating solution that mass fraction is 5-20% is made in alcohol dissolution；Dry particl prepared by inner nuclear layer is put into fluidized-bed coating machine, with packet
Clothing liquid is coated, and after coating, dry, whole grain is to get oxiracetam particle of the present invention.
4. preparation method as claimed in claim 3, which is characterized in that the fluidized-bed coating machine sets air blast flux 85-
120L/min, atomization gas pressure 0.3-0.5MPa are coated flow quantity 80-120ml/min, and 50-65 DEG C of stream temperature, the time is
15-30min。
5. preparation method as claimed in claim 4, which is characterized in that in the outer nuclear layer preparation, dry step after coating
In rapid, drying temperature is 40-68 DEG C, time 10-30min.
6. preparation method as claimed in claim 5, which is characterized in that the fluidized-bed coating machine sets air blast flux 85-
110L/min, atomization gas pressure 0.3-0.5MPa are coated flow quantity 80-120ml/min, and 55-60 DEG C of stream temperature, the time is
15-30min；Dry after coating, drying temperature is 40-60 DEG C, time 10-30min.
7. a kind of preparation method for the pharmaceutical composition for treating cognition dysfunction, described pharmaceutical composition includes oxiracetam
Particle；The oxiracetam particle includes inner nuclear layer and outer nuclear layer；The oxiracetam particle includes inner nuclear layer and outer core
Layer；The inner nuclear layer includes oxiracetam and inner nuclear layer auxiliary material, and the outer nuclear layer includes outer core layer material and outer nuclear layer auxiliary material,
Wherein oxiracetam 50-70%, inner nuclear layer auxiliary material 15-30%, outer core layer material 8-20%, outer nuclear layer auxiliary material 0.1-3%；In described
Stratum nucleare auxiliary material be xanthan gum, sodium alginate, methylcellulose, hydroxyethyl cellulose, chitin, microcrystalline cellulose, povidone or
Any one or a few composition in hydroxypropyl methyl cellulose；The outer core layer material is polyacrylic resin and polyvinyl alcohol
The mixture of acetate phthalate ester, wherein the mass ratio of polyacrylic resin and polyvinyl acetate phthalate be 2~
3:1；The polyacrylic resin is selected from one of Eudragit L30D, Eudragit L100, Eudragit S100 or several
Kind combination；The outer nuclear layer auxiliary material is the combination of one or more of superfine silica gel powder, magnesium stearate, talcum powder, polyvinyl alcohol；
Oxiracetam particle: the preparation of inner nuclear layer is prepared using following processing step: by oxiracetam and inner nuclear layer auxiliary material
It is uniformly mixed；The ethanol solution softwood of mass fraction 8-25% is pelletized, dry, and drying temperature is 45-65 DEG C, time 10-
30min obtains dry particl；The preparation of outer nuclear layer: outer core layer material and outer nuclear layer auxiliary material are uniformly mixed, and are 50- with mass fraction
95% ethyl alcohol dissolution, is made the coating solution that mass fraction is 5-20%；Cross colloid mill grinding；Then by dry of inner nuclear layer preparation
Grain is put into fluidized-bed coating machine, and with coating solution fluidized bed coating, seed-coating machine sets air blast flux 85-110L/min, atomization air pressure
Power 0.3-0.5MPa is coated flow quantity 80-120 ml/min, and 55-60 DEG C of stream temperature, time 15-30min, coating terminates
Afterwards, dry, drying temperature is 40-60 DEG C, drying time 10-30min, whole grain to get.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710991470 | 2017-10-23 | ||
| CN2017109910788 | 2017-10-23 | ||
| CN201710991078 | 2017-10-23 | ||
| CN2017109914702 | 2017-10-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109692167A true CN109692167A (en) | 2019-04-30 |
Family
ID=66230069
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811188850.3A Pending CN109692167A (en) | 2017-10-23 | 2018-10-12 | The pharmaceutical composition and preparation method thereof for treating cognition dysfunction |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109692167A (en) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1682719A (en) * | 2005-03-01 | 2005-10-19 | 沈阳药科大学 | Enteric soluble coating slow releasing tablet containing huperzine A and preparing method |
| 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 |
| CN101766596A (en) * | 2009-01-04 | 2010-07-07 | 北京润德康医药技术有限公司 | Solid preparation with dextro-oxiracetam as active component |
| 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 |
| WO2016184381A1 (en) * | 2015-05-18 | 2016-11-24 | 重庆润泽医药有限公司 | Use of dextrorotatory oxiracetam in pharmaceutical field |
| CN106511311A (en) * | 2015-09-11 | 2017-03-22 | 重庆润泽医药有限公司 | Levo-oxiracetam sustained-release capsule with good particle mobility and preparation method of levo-oxiracetam sustained-release capsule |
| CN106619524A (en) * | 2015-10-27 | 2017-05-10 | 重庆润泽医药有限公司 | Good-stability sinistral oxiracetam and preparation method thereof |
-
2018
- 2018-10-12 CN CN201811188850.3A patent/CN109692167A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1682719A (en) * | 2005-03-01 | 2005-10-19 | 沈阳药科大学 | Enteric soluble coating slow releasing tablet containing huperzine A and preparing method |
| 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 |
| CN101766596A (en) * | 2009-01-04 | 2010-07-07 | 北京润德康医药技术有限公司 | Solid preparation with dextro-oxiracetam as active component |
| 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 |
| CN105125515A (en) * | 2013-12-06 | 2015-12-09 | 温州智创科技有限公司 | Levo-oxiracetam tablet and preparation method thereof |
| WO2016184381A1 (en) * | 2015-05-18 | 2016-11-24 | 重庆润泽医药有限公司 | Use of dextrorotatory oxiracetam in pharmaceutical field |
| CN106511311A (en) * | 2015-09-11 | 2017-03-22 | 重庆润泽医药有限公司 | Levo-oxiracetam sustained-release capsule with good particle mobility and preparation method of levo-oxiracetam sustained-release capsule |
| CN106619524A (en) * | 2015-10-27 | 2017-05-10 | 重庆润泽医药有限公司 | Good-stability sinistral oxiracetam and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| DEANGELIS, L: "THE EFFECTS OF ASCORBIC-ACID AND OXIRACETAM ON SCOPOLAMINE-INDUCED AMNESIA IN A HABITUATION TEST IN AGED MICE", 《NEUROBIOLOGY OF LEARNING AND MEMORY》 * |
| 孟胜男，胡容峰主编: "《药剂学》", 31 January 2016, 中国医药科技出版社 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1557179B2 (en) | Analgesic dosage forms that are unable to be inhaled or injected | |
| DE69934505T2 (en) | IN THE MUND DISSOLVING TABLET CONTAINING A BENZIMIDAZOLE | |
| TWI257311B (en) | Rapidly disintegrable solid preparation | |
| US20120321674A1 (en) | Technology for Preventing Abuse of Solid Dosage Forms | |
| CN104013592A (en) | Memantine hydrochloride slow-release pill and preparation method thereof | |
| JP2017509712A (en) | Abuse prevention immediate release coated reservoir solid dosage form | |
| CN104940301B (en) | A kind of antiviral oral pellet gel of Pudilan children and preparation method thereof | |
| CN103251572B (en) | Preparation method of theaflavin enteric microcapsule, as well as product prepared by preparation method and application of product | |
| CN101700227A (en) | Matrine colon targeted adhesive pellet and preparation method thereof | |
| CN112933059A (en) | Dry granulation process of brivaracetam tablets | |
| KR101562608B1 (en) | Compound chemical medicine acting on respiratory disease, preparation process and use thereof | |
| CN103520129B (en) | Montelukast sodium pulse release preparation | |
| CN105832671A (en) | Dry suspension for controlled-release of medicine and preparation method of dry suspension | |
| KR20170029604A (en) | Combination of Valerian Root Extract and Lavender Oil for Use in the Treatment of Sleep Disorders | |
| CN101991561B (en) | 3,4-dichlorophenyl-propenoyl-sec-butylamine composition | |
| CN101623280A (en) | Compound sustained release preparation for easing pain and preparation method thereof | |
| CN104434829B (en) | A kind of Essential Oil of Acorus tatarinowii oral quick disintegrating tablet and preparation method thereof | |
| CN103690506A (en) | Trospium chloride slow-release composition and preparation method thereof | |
| CN109692167A (en) | The pharmaceutical composition and preparation method thereof for treating cognition dysfunction | |
| CN104138376A (en) | A sustained release agent improving anoxia endurance | |
| CN100518721C (en) | Enteric quick-dissolving tablets containing aconitine, and preparation method thereof | |
| CN108014098A (en) | A kind of tolvaptan fast release micropill preparation, preparation method | |
| CN109718222A (en) | Oxiracetam enteric coated preparations and preparation method thereof | |
| CN108853376A (en) | The medicine for external application and preparation method thereof for treating canker sore | |
| CN104337783B (en) | A kind of capecitabine tablet and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190430 |