CN108904495A - A kind of levetiracetam medicinal composition and its preparation method and application - Google Patents
A kind of levetiracetam medicinal composition and its preparation method and application Download PDFInfo
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Abstract
The present invention relates to pharmaceutical technology field, a kind of levetiracetam medicinal composition and its preparation method and application is provided.The component of the levetiracetam medicinal composition includes 200-400 parts of Levetiracetam, 60-100 parts of microcrystalline cellulose, 60-100 parts of lactose, 6-12 parts of low-substituted hydroxypropyl methylcellulose and 1-4 parts of magnesium stearate according to parts by weight；Component further includes starch slurry 90-300ml, and the amount ratio of microcrystalline cellulose and starch slurry is 1g:1.5-5ml；Preparation method includes that each component is made to capsule or tablet after mixing.It is defined by the content to each component, enable drug slow release in vivo, reduce direct stimulation of the Levetiracetam to gastrointestinal tract, to reduce the generation of its side effect especially serious gastrointestinal reaction, the compliance and safety for improving patient medication, are conducive to long-term treatment.
Description
Technical field
The present invention relates to pharmaceutical technology fields, in particular to a kind of levetiracetam medicinal composition and its preparation
Methods and applications.
Background technique
Levetiracetam is antiepileptic, is clinically mainly used for the adult and partial hair of 4 years old or more Patients with Epilepsy in Childhood
The add-on of work.But the Levetiracetam of over much dosage will lead to few patients and diarrhea occur.Diarrhea daily more than 5 times or
When there is bloody diarrhea, it must generally reduce drug dose or stop chemical drug immediately and treat in time.After generally deactivated drug, meeting
Treatment is set to be difficult to go on smoothly, to influence to treat curative effect.
The main reason for receiving patient's diarrhea of chemical drug is the direct inhibition or destruction institute by drug to protection of intestinal mucosal barrier cells
It causes, while also related with many other factors such as enteron aisle secondary infection, nervous.The diarrhea of continuing vigorous can cause kidney function
Can not be complete, electrolyte disturbance, cardiovascular function is not complete, increases the incidence of Infective morbidity, there is the relevant septicemia of chemical drug,
Even threat to life.In addition to this quality of life of patient is also seriously affected.
Summary of the invention
The purpose of the present invention can be effectively improved left second and draw west for example including a kind of levetiracetam medicinal composition is provided
Alimentary canal side reaction caused by smooth.
The purpose of the present invention further includes providing a kind of preparation method of levetiracetam medicinal composition, and this method is simple,
Drug obtained can be effectively improved alimentary canal side reaction caused by Levetiracetam.
The purpose of the present invention further includes providing a kind of levetiracetam medicinal composition in preparation for mitigating by Zuo Yila
Application in the drug of western smooth caused diarrhea side effect.
To realize at least one above-mentioned purpose, the embodiment of the present invention uses following technical scheme：
A kind of levetiracetam medicinal composition, component includes 200-400 parts of Levetiracetam according to parts by weight, micro-
60-100 parts of crystalline cellulose, 60-100 parts of lactose, 6-12 parts of low-substituted hydroxypropyl methylcellulose and 1-4 parts of magnesium stearate；Component
It further include starch slurry 90-300ml, the amount ratio of microcrystalline cellulose and starch slurry is 1g:1.5-5ml；
Preferably, component includes 200-350 parts of Levetiracetam, 60-90 parts of microcrystalline cellulose, lactose according to parts by weight
60-90 parts, 6-10 parts of low-substituted hydroxypropyl methylcellulose and 1-3 parts of magnesium stearate；The amount ratio of microcrystalline cellulose and starch slurry
For 1g:1.5-4ml；
Preferably, component includes 250-350 parts of Levetiracetam, 70-90 parts of microcrystalline cellulose, lactose according to parts by weight
70-90 parts, 8-10 parts of low-substituted hydroxypropyl methylcellulose and 1-2 parts of magnesium stearate；The amount ratio of microcrystalline cellulose and starch slurry
For 1g:1.5-3ml.
A kind of levetiracetam medicinal composition, component include 250-300 parts of Levetiracetam, jade according to parts by weight
400-600 parts of peptide of rice；75-85 parts of microcrystalline cellulose, 75-85 parts of lactose, 8-9 parts of low-substituted hydroxypropyl methylcellulose and stearic acid
1-2 parts of magnesium；Component further includes starch slurry 90-300ml, and the amount ratio of microcrystalline cellulose and starch slurry is 1g:1.5-3ml；Zuo Yi
La Xitan and the amount ratio of corn peptide are 1:1.5-2.
A kind of preparation method of levetiracetam medicinal composition comprising by Levetiracetam, microcrystalline cellulose, lactose
It is uniformly mixed with low-substituted hydroxypropyl methylcellulose, adds starch slurry to pelletize, be subsequently added into magnesium stearate, be made after mixing
Capsule or tablet.
A kind of levetiracetam medicinal composition is used to mitigate the medicine of the diarrhea side effect caused by Levetiracetam in preparation
Application in object.
The beneficial effect of the embodiment of the present invention for example including：
By to Levetiracetam, microcrystalline cellulose, lactose, low-substituted hydroxypropyl methylcellulose and tristearin in the present embodiment
The content of sour magnesium is defined, and enables drug slow release in vivo, reduces Levetiracetam to the direct thorn of gastrointestinal tract
Swash, to reduce the generation of its side effect especially serious gastrointestinal reaction, maintains effective blood drug concentration, improve patient medication
Compliance and safety keep patient more easy-tolerated, are conducive to long-term treatment.The levetiracetam medicinal composition can promote stomach and intestine
Power promotes food digestion and absorption, can be effectively improved alimentary canal side reaction caused by Levetiracetam, improves patient's chemical drug
Compliance has good result to nauseous diarrhea, loss of appetite.
Specific embodiment
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
Understand, the following example is merely to illustrate the present invention, and is not construed as limiting the scope of the invention.It is not specified in embodiment specific
Condition person carries out according to conventional conditions or manufacturer's recommended conditions.Reagents or instruments used without specified manufacturer is
The conventional products that can be obtained by commercially available purchase.
Levetiracetam medicinal composition of the embodiment of the present invention and its preparation method and application is carried out specifically below
It is bright.
Levetiracetam is antiepileptic, is clinically mainly used for the adult and partial hair of 4 years old or more Patients with Epilepsy in Childhood
The add-on of work.Its gastral major side effects has common diarrhoea, indigestion, Nausea and vomiting.
Through inventor the study found that the daily defecation of normal person 1~2 time or 2~3 days defecations 1 time every, fecal nature is normal.
Not only times of defecation increases diarrhea patient, and property changes, in loose stools, watery stool even bloody diarrhea.
Diarrhea judgment basis to acquire excrement sample water content not less than 70%, it is shapeless subject to.Diarrhea can according to severity
To be divided into 5 grades.1 grade:Times of defecation increases<4 times/day, discharge object amount slightly increases；2 grades:Number of defecating increases by 4~6 times/day, row
Object amount moderate increases out, does not influence daily life；3 grades:Times of defecation increases>7 times/day, incontinence needs vein fluid infusion in 24 hours,
Hospitalization is needed, discharge object amount severe increases, and influences daily life；4 grades:Threat to life (such as haemodynamics failure)；5 grades:
It is dead.
Chemical drug causes diarrhea, and there are mainly two types of pathology：First is that caused by gastrointestinal motility；Second is that chemical drug causes intestinal mucosal lesion.
Diarrhea mechanism has the following：1. intestinal mucosal lesion, moisture absorption obstacle；2. enterocinesia is hyperfunction, make intestinal contents
Discharge rapidly；3. it is hyperfunction that intestinal mucosa secretes intestinal juice.
Small intestine has the functions such as wriggling and secretion digestive ferment, electrolyte, water and digestion and absorption.Colon receives the content of small intestine
Object absorbs moisture and electrolyte and stores excrement, wriggle 2~4 times daily, excrement is pushed to advance.There are about 9L liquid daily by adult
Body enters small intestine, and wherein 2L comes from food, and there are about 7L to come from saliva, gastric juice, pancreatic juice, bile and intestinal fluid.With food content object
Difference, these liquid can be hypertonic, isotonic or hypotonic, but to after ileum, that is, become isotonic solution, in favor of absorbing.One
As daily by jejunum absorb 3000~5000ml of liquid, 2000~4000ml of ileum, 1000~2000ml of colon.Daily defecation
200g or so, interior moisture content 75%.Small intestine is arranged intraperitoneal in wrinkle shape, and intestinal mucosa surface forms many villus and micro- suede
Hair, therefore the area of small intestinal mucosa is very big, is such as measured with microvillus, about 2,000,000 cm2, so, a large amount of liquid can be absorbed daily
Body.Contain invertase and maltose in microvillus, can specifically digest the sucrose and maltose in intestinal contents.Intestinal mucosa is thin
Born of the same parents' division growth speed is quickly, it is estimated that under normal circumstances, has 2,000 ten thousand~5,000 ten thousand epithelial cell turnovers to fall off per minute.
Quickly due to protection of intestinal mucosal barrier cells division growth speed, thus be subject to cell toxicity medicament it is direct inhibition or destruction,
Cause the atrophy of intestinal mucosa, intestinal villus is shortened or stripped off, and small intestine absorption area is reduced, and mucosal integrity is destroyed, and is caused:1. digesting
Obstacle, sucrose, maltose digestion are insufficient, ferment in intestinal tube, cause intestinal tympanites and enterospasm；2. malabsorption；3. secreting
Increase, undigested sucrose, maltose increase the osmotic pressure of intestinal contents, cause a large amount of extracellular matrix Liquid Penetrants to intestines
It is intracavitary.
The main reason for receiving patient's diarrhea of chemical drug is the direct inhibition or destruction institute by drug to protection of intestinal mucosal barrier cells
It causes, while also related with many other factors such as enteron aisle secondary infection, nervous.
In consideration of it, component is according to parts by weight the embodiment of the invention provides a kind of levetiracetam medicinal composition
Including 200-400 parts of Levetiracetam, 60-100 parts of microcrystalline cellulose, 60-100 parts of lactose, low-substituted hydroxypropyl methylcellulose 6-
12 parts and 1-4 parts of magnesium stearate；Component further includes starch slurry 90-300ml, and the amount ratio of microcrystalline cellulose and starch slurry is
1g:1-5ml；
Wherein, Levetiracetam is as main ingredient, and microcrystalline cellulose, lactose and low-substituted hydroxypropyl methylcellulose are as diluent
It is used with disintegrating agent, the weight of drug can be increased, convenient for its molding, so that capsule or tablet is made, while being conducive to be promoted
The disintegration ability of tablet.It should be understood that diluent includes but is not limited to the microcrystalline cellulose protected in the present embodiment.Lactose and low
Replace hydroxypropyl methylcellulose, such as in other embodiments of the invention, diluent can also include pregelatinized starch, sweet dew
One of alcohol, calcium monohydrogen phosphate, sorbierite, calcium monohydrogen phosphate and starch are a variety of.In the present embodiment, microcrystalline cellulose has good
Mobility, compressibility, self-lubricity and dry adhesive, and have preferable calving disaggregation.Lactose and low substitution simultaneously
Hydroxypropyl methylcellulose also has good compressibility, and microcrystalline cellulose, lactose and low-substituted hydroxypropyl methylcellulose are collectively as dilute
Agent and disintegrating agent are released, can be improved the compressibility of drug.Meanwhile microcrystalline cellulose, lactose and low-substituted hydroxypropyl methylcellulose energy
Enough be used as sustained release agent so that drug in vivo can slow release, maintain effective blood drug concentration, improve the compliance of patient medication
And safety.
Magnesium stearate is used cooperatively as lubricant with microcrystalline cellulose, improves the lubricity of drug, can be effective
The friction between tablet and punch die hole is avoided, guarantees the quality of drug.It should be understood that lubricant includes but is not limited in the present embodiment
The magnesium stearate protected, such as in other embodiments of the invention, lubricant can also include superfine silica gel powder and talcum
One of powder is a variety of.
Through inventor the study found that component includes that preferably, component includes left second according to parts by weight according to parts by weight
200-350 parts of La Xitan, 60-90 parts of microcrystalline cellulose, 60-90 parts of lactose, 6-10 parts of low-substituted hydroxypropyl methylcellulose and hard
1-3 parts of fatty acid magnesium；The amount ratio of microcrystalline cellulose and starch slurry is 1g:1-4ml；Preferably, component includes according to parts by weight
250-350 parts of Levetiracetam, 70-90 parts of microcrystalline cellulose, 70-90 parts of lactose, 8-10 parts of low-substituted hydroxypropyl methylcellulose with
And 1-2 parts of magnesium stearate；The amount ratio of microcrystalline cellulose and starch slurry is 1g:1.5-3ml.
It is further limited by the content to said components, enables drug slow release in vivo, reduced
Direct stimulation of the Levetiracetam to gastrointestinal tract maintains to reduce the generation of its side effect especially serious gastrointestinal reaction
Effective blood drug concentration improves the compliance and safety of patient medication, keeps patient more easy-tolerated, be conducive to long-term treatment.
In other embodiments of the invention, corn peptide 100-800 parts according to parts by weight of component；Preferably, corn
200-700 parts of peptide；Preferably, corn peptide 400-600 parts.Levetiracetam and the amount ratio of corn peptide are 1:0.5-2；Preferably
1:1-2；Preferably 1:1.5-2.
Corn peptide is small point that the protein extracted from corn is obtained by orientation digestion and specific small peptide isolation technics
Sub- peptide material.The composition glutamine content of corn peptide ammino acid is very high, and glutamine is the amino acid for constituting protein,
It is the nitrogen source of nucleic acid again, closely related with tissue growth, reparation, though being nonessential amino acid, it can improve body and exempt from
Epidemic disease power maintains intestinal mucosa normal configuration and function, improves the ability of organism adaptation external world destructive stimulus.As foregoing invention people
The study found that " the main reason for receiving patient's diarrhea of chemical drug is the direct inhibition or destruction due to drug to protection of intestinal mucosal barrier cells
It is caused ", in the present embodiment, by increasing corn peptide as one of main ingredient, Levetiracetam can be slowed down to gastrointestinal tract mucosa
Inhibit and destroy, and promote immunity of organisms, so that gastrointestinal tract mucosa is able to maintain that normal configuration.
In the present embodiment, by the way that Levetiracetam and corn peptide to be used cooperatively, corn peptide is able to suppress gastrointestinal absorption, and
And enhancing metabolism, direct stimulation of the Levetiracetam to gastrointestinal tract is reduced, to reduce its side effect especially serious gastrointestinal
The generation of reaction maintains effective blood drug concentration, improves the compliance and safety of patient medication, keep patient more easy-tolerated, favorably
In long-term treatment.
In addition, Levetiracetam and the amount ratio of corn peptide are 1 in the present embodiment:0.5-2 is conducive to drug molding, energy
The dosage of diluent or filler is enough reduced, and then reduces the calving disaggregation of diluent bring, so that drug slow release, effectively
Maintain blood concentration.
Further, levetiracetam medicinal composition provided in this embodiment can there are many dosage form, such as capsule or
Tablet.When levetiracetam medicinal composition is tablet, component includes 2-5 parts of coating agent according to parts by weight, preferably 2-3
Part；Preferably, coating agent is stomach dissolved film coating pre-mix dose.
Coating agent is stomach dissolved film coating pre-mix dose in the present embodiment, and levetiracetam medicinal composition collapses in stomach
Solution, but due to the effect of corn peptide, it is suppressed that absorption of the stomach to levetiracetam medicinal composition slows down Levetiracetam
Damage to gastrointestinal mucosa reaches higher blood concentration so that Levetiracetam is disintegrated in advance in blood, and is conducive to tie up
Hold the blood concentration.
In other embodiments of the invention, a kind of levetiracetam medicinal composition is provided, component is by weight
Number meter includes 250-300 parts of Levetiracetam, 400-600 parts of corn peptide；75-85 parts of microcrystalline cellulose, 75-85 parts of lactose,
8-9 parts of low-substituted hydroxypropyl methylcellulose and 1-2 parts of magnesium stearate；Component further includes starch slurry 90-300ml, microcrystalline cellulose
Amount ratio with starch slurry is 1g:1.5-3ml；Levetiracetam and the amount ratio of corn peptide are 1:1.5-2.
Second aspect, the embodiment of the invention also provides a kind of preparation method of levetiracetam medicinal composition, packets
Include following steps：
S1, Levetiracetam, microcrystalline cellulose, lactose and low-substituted hydroxypropyl methylcellulose are uniformly mixed, add starch slurry
It pelletizes.
It specifically includes：Levetiracetam is first crushed to 80-100 mesh, then by microcrystalline cellulose, lactose and low substitution hydroxyl
Third methylcellulose is uniformly mixed, and is uniformly mixed Levetiracetam with equal increments method, and the appropriate (microcrystalline cellulose of starch slurry is added
Amount ratio with starch slurry is 1g:1-5ml, the concentration of starch slurry are 5%), to be granulated 1-2 minutes.It is carried out with oscillating granulator wet
Whole grain, sieve mesh number are 20-22 mesh.Wet granular is set in HighefficientFluidbeddrier, is dried in 50-60 DEG C, and control pellet moisture exists
Between 1.5~6.5%.Particle after drying is set into whole grain in oscillating granulator, sieve mesh number is 16-18 mesh.It is stored after whole grain
It is spare in middle turning barrel.
When further including 100-700 parts of corn peptide in component；Corn peptide and microcrystalline cellulose, lactose and low-substituted hydroxypropyl first are fine
Dimension element mixes together.
S2, it is subsequently added into magnesium stearate, capsule or tablet is made after mixing.
The magnesium stearate for adding particle weight 0.8-0.9% after premixing is set in mixing machine, is mixed 5-6 minutes.Then into
Capsule or tablet is made in row.
When prepared as tablets, loading, piece thickness, tablet press machine speed, the hard 70~90N of control sheet, according to intermediate are adjusted
Grain content converting standard slice weight, tablet weight variation ± 4.5%.
The preparation of S3, coating agent：Appropriate purified water is added in liquid dispensing tank, starting stirring slurry agitation makes liquid level form whirlpool
Stomach dissolution type film coating powder is at the uniform velocity sprinkling upon on whirlpool liquid level by whirlpool, persistently stir 1 hour or more, coating powder dosage is plain piece weight
The 0.5~2.0% of amount, coating agent concentration are 10~15%.Adjustment air inlet, air output, control 40-50 DEG C of leaving air temp, make pot
Coating pan is added in 2~5pa, by plain piece in interior negative pressure, to plain piece preheating temperature to 34-40 DEG C, spray gun and it is unilateral it is best away from
It is off the pot with 2 revs/min from for 26~30cm, spray gun pipette tips are adjusted to starting hydrojet at lamella inclined-plane top 1/3.It is being coated
Pay attention to the spray pressure of spray gun should being adjusted as far as possible with spray angle to consistent in the process, while appropriate adjustment wriggling revolution speed,
Technique can have been reached and required ideal spray pattern.It is sprayed to film coating liquid, Film coated tablets is cooled down with air draft,
It is aluminum-plastic packaged.
In the present embodiment, after wet granulation, through whole grain overly moist, after dry, dry whole grain is carried out, and control wet whole grain
Grit number of crossing with dry whole grain is respectively 20-22 mesh and 16-18 mesh, so that the uniformity of the particle finally obtained is more preferably.
On the other hand, the embodiment of the invention also provides a kind of levetiracetam medicinal composition preparation for mitigate by
Application in the drug of diarrhea side effect caused by Levetiracetam.
It is further to levetiracetam medicinal composition of the invention and its preparation method and application with reference to embodiments
It is illustrated.
Embodiment 1
A kind of levetiracetam medicinal composition is present embodiments provided, preparation method is as follows：
S1, stock：It is Levetiracetam 200g, microcrystalline cellulose 60g, lactose 60g, low-substituted hydroxypropyl methylcellulose 10g, hard
Fatty acid magnesium 4g and starch slurry 300ml；
S2, granulation：Levetiracetam is crushed to 100 mesh；Then microcrystalline cellulose, lactose and low-substituted hydroxypropyl first is fine
Dimension element is uniformly mixed, and is uniformly mixed mixture with Levetiracetam with equal increments method, and starch slurry is added, and is granulated 1-2 minutes.
Wet whole grain is carried out with oscillating granulator, sieve mesh number is 20 mesh.Wet granular is placed in HighefficientFluidbeddrier, is first 70 with temperature
DEG C wind preheating 10min is carried out to drying machine, then at 60 DEG C dry to pellet moisture between 1.5~6.5%.It will dry
Particle afterwards sets whole grain in oscillating granulator, and sieve mesh number is 16 mesh.It is stored in after whole grain spare in middle turning barrel.It is subsequently added into hard
Fatty acid magnesium, mixture needed for obtaining capsule charge after mixing are hollow by loading loading by mixture needed for capsule charge
In capsule, content uniformity is controlled, the capsule preparations of levetiracetam medicinal composition are made.
Embodiment 2
A kind of levetiracetam medicinal composition is present embodiments provided, preparation method is as follows：
S1, stock：It is Levetiracetam 350g, microcrystalline cellulose 90g, lactose 90g, low-substituted hydroxypropyl methylcellulose 9g, hard
Fatty acid magnesium 2g, stomach dissolved film coating pre-mix dose 2g and starch slurry 300ml.
S2, granulation：Levetiracetam is crushed to 80 mesh；Then microcrystalline cellulose, lactose and low-substituted hydroxypropyl first is fine
Dimension element is uniformly mixed, and is uniformly mixed mixture with Levetiracetam with equal increments method, and starch slurry is added, and is granulated 1-2 minutes.
Wet whole grain is carried out with oscillating granulator, sieve mesh number is 22 mesh.Wet granular is placed in HighefficientFluidbeddrier, is first 60 with temperature
DEG C wind preheating 15min is carried out to drying machine, then at 50 DEG C dry to pellet moisture between 1.5~6.5%.It will dry
Particle afterwards sets whole grain in oscillating granulator, and sieve mesh number is 18 mesh.It is stored in after whole grain spare in middle turning barrel.It is subsequently added into hard
Capsule or tablet is made in fatty acid magnesium after mixing.
S3, coating：Appropriate purified water is added in liquid dispensing tank, starting stirring slurry agitation makes liquid level form whirlpool, will be soluble in the stomach
Type film coating powder is at the uniform velocity sprinkling upon on whirlpool liquid level, persistently stir 1 hour or more, coating powder dosage is the 0.5% of plain piece weight,
Coating agent concentration is 10%.Adjustment air inlet, air output, control 50 DEG C of leaving air temp, negative pressure in pot are added by plain piece in 5pa
Coating pan, it is off the pot with 2 revs/min to plain piece preheating temperature, to 40 DEG C, spray gun and unilateral optimum distance are 26cm, it will spray
Rifle pipette tips are adjusted to starting hydrojet at lamella inclined-plane top 1/3.Paying attention in coating process should be by the spray pressure of spray gun and spray
Fog horn degree is adjusted as far as possible to consistent, while appropriate adjustment wriggling revolution speed, can have been reached technique and required ideal spray pattern.To
Film coating liquid is sprayed, is cooled down with air draft to Film coated tablets, aluminum-plastic packaged, and levetiracetam medicinal composition is made
Tablet.
Embodiment 3
A kind of levetiracetam medicinal composition is present embodiments provided, preparation method is as follows：
S1, stock：Levetiracetam 300g, corn peptide 100g, microcrystalline cellulose 80g, lactose 80g, low-substituted hydroxypropyl first
Cellulose 9g, magnesium stearate 1.5g, stomach dissolved film coating pre-mix dose 3g and starch slurry 240ml；
S2, granulation：Levetiracetam is crushed to 80 mesh；Then microcrystalline cellulose, lactose and low-substituted hydroxypropyl first is fine
Dimension element is uniformly mixed, and is uniformly mixed mixture with Levetiracetam with equal increments method, and starch slurry is added, and is granulated 1-2 minutes.
Wet whole grain is carried out with oscillating granulator, sieve mesh number is 20 mesh.Wet granular is placed in HighefficientFluidbeddrier, is first 65 with temperature
DEG C wind preheating 10min is carried out to drying machine, then at 60 DEG C dry to pellet moisture between 1.5~6.5%.It will dry
Particle afterwards sets whole grain in oscillating granulator, and sieve mesh number is 18 mesh.It is stored in after whole grain spare in middle turning barrel.It is subsequently added into hard
Plain piece is made in fatty acid magnesium after mixing.
S3, coating：Appropriate purified water is added in liquid dispensing tank, starting stirring slurry agitation makes liquid level form whirlpool, will be soluble in the stomach
Type film coating powder is at the uniform velocity sprinkling upon on whirlpool liquid level, persistently stir 1 hour or more, coating powder dosage is the 1.0% of plain piece weight,
Coating agent concentration is 12%.Adjustment air inlet, air output, control 45 DEG C of leaving air temp, negative pressure in pot are added by plain piece in 3pa
Coating pan, it is off the pot with 2 revs/min to plain piece preheating temperature, to 35 DEG C, spray gun and unilateral optimum distance are 28cm, it will spray
Rifle pipette tips are adjusted to starting hydrojet at lamella inclined-plane top 1/3.Paying attention in coating process should be by the spray pressure of spray gun and spray
Fog horn degree is adjusted as far as possible to consistent, while appropriate adjustment wriggling revolution speed, can have been reached technique and required ideal spray pattern.To
Film coating liquid is sprayed, is cooled down with air draft to Film coated tablets, aluminum-plastic packaged, and levetiracetam medicinal composition is made
Tablet.
Embodiment 4-6
The preparation method for the levetiracetam medicinal composition that embodiment 4-6 is provided is roughly the same with embodiment 1, distinctive points
It is, component is different.
In embodiment 4, the component of levetiracetam medicinal composition includes Levetiracetam 350g, corn peptide 700g, micro-
Crystalline cellulose 70g, lactose 70g, low-substituted hydroxypropyl methylcellulose 10g, magnesium stearate 1g, stomach dissolved film coating pre-mix dose 2g with
And starch slurry 210ml；
In embodiment 5, the component of levetiracetam medicinal composition includes Levetiracetam 300g, corn peptide 450g, micro-
Crystalline cellulose 80g, lactose 80g, low-substituted hydroxypropyl methylcellulose 8g, magnesium stearate 2g, stomach dissolved film coating pre-mix dose 3g with
And starch slurry 160ml；
In embodiment 6, the component of levetiracetam medicinal composition includes Levetiracetam 400g, corn peptide 800g, micro-
Crystalline cellulose 100g, lactose 100g, low-substituted hydroxypropyl methylcellulose 5g, magnesium stearate 1g, stomach dissolved film coating pre-mix dose 2g
And starch slurry 300ml.
One, zoopery
The medicine group that the embodiment of the present invention 1~6, test example 1-3 and comparative example 1-3 are provided below with reference to animal experiment
Effect of the object caused by improving because of Levetiracetam in terms of digestive tract reaction is closed to be evaluated.
1, composition forms
Test example 1-3：The content of corn peptide in embodiment 3 is replaced with into 200g, 400g and 600g by 550g, remaining with
Embodiment 3 is identical.
Comparative example 1-3：Corn peptide in test example 1-3 is replaced with into starch, content is constant.
2, influence of the present composition to pigeon diarrhea situation
Pigeon 120 for choosing 200~300g of weight, half male and half female is randomly divided into 12 groups, every group 10.Prohibit before experiment
Food can't help water for 24 hours, and each composition of stomach-filling (Examples 1 to 6, test example 1-3 and comparative example 1-3) is administered in pigeon, convert into left second
La Xitan is 300mg/, and the diarrhea number and number of elements of pigeon in 12h are recorded after administration, and experimental result carries out comparison among groups, sees
Table 1：
1. pigeon diarrhea situation of table
By 1 result of table as it can be seen that Examples 1 to 6, test example 1-3 group pigeon diarrhea number of elements and average diarrhea number are obviously few
In the pigeon of comparative example 1-3 group.It can be seen that the ratio of the dosage when Levetiracetam and corn peptide from above-mentioned test example 1-3
1:When between 0.5-2, it can be effectively improved alimentary canal side reaction caused by Levetiracetam, and with the dosage of corn peptide
Increase, improvement is more preferably obvious, and diarrhea number of elements and diarrhea number are significantly reduced.
By above-mentioned animal experiment, pharmaceutical composition according to the present invention can promote gastroenteritic power, promote food digestion
And absorption, it can be effectively improved alimentary canal side reaction caused by Levetiracetam, the compliance of patient's chemical drug is improved, to nauseous abdomen
It rushes down, loss of appetite has good result.
Two, the selection of granulating process
Comparative example 4：Omit the dressing step in embodiment 3；Comparative example 5：Omit the dry finishing step in embodiment 3.
The degree for deviateing labelled amount according to the product that different granulating process obtains is calculated, limit is in ± 15% range, uniformly
Degree meets regulation.Experimental result please refers to table 2.
Influence of the different granulating process of table 2. to the product uniformity
| Example | Preparation process | The product uniformity |
| Embodiment 3 | Wet granulation+wet whole grain+drying+dry whole grain | + 6% |
| Comparative example 4 | Wet granulation+drying+dry whole grain | + 11% |
| Comparative example 5 | Wet granulation+wet whole grain+drying | + 9% |
From table 2 it can be seen that, through whole grain overly moist, after dry, carrying out dry whole grain by after wet granulation, finally obtaining
Particle and the departure degree of labelled amount are minimum, and uniformity is more preferably.
In conclusion in the present embodiment, by fine to Levetiracetam, microcrystalline cellulose, lactose and low-substituted hydroxypropyl first
Dimension element and the content of magnesium stearate are defined, and enable drug slow release in vivo, reduce Levetiracetam to stomach
The direct stimulation of enteron aisle maintains effective blood drug concentration, mentions to reduce the generation of its side effect especially serious gastrointestinal reaction
The compliance and safety of high patient medication, keep patient more easy-tolerated, are conducive to long-term treatment.Corn peptide is especially added as master
One of medicine can slow down inhibition and destruction of the Levetiracetam to gastrointestinal tract mucosa, and promote immunity of organisms, so that
Gastrointestinal tract mucosa is able to maintain that normal configuration.Pharmaceutical composition according to the present invention can promote gastroenteritic power, and food is promoted to disappear
Change and absorb, there is preventing or arresting vomiting effect, alimentary canal side reaction caused by Levetiracetam can be effectively improved, improves patient and put chemical drug
Compliance has good result to nauseous diarrhea, loss of appetite.
These are only the preferred embodiment of the present invention, is not intended to restrict the invention, for those skilled in the art
For member, the invention may be variously modified and varied.All within the spirits and principles of the present invention, it is made it is any modification,
Equivalent replacement, improvement etc., should all be included in the protection scope of the present invention.
Claims (10)
1. a kind of levetiracetam medicinal composition, which is characterized in that its component includes Levetiracetam according to parts by weight
200-400 parts, 60-100 parts of microcrystalline cellulose, 60-100 parts of lactose, 6-12 parts of low-substituted hydroxypropyl methylcellulose and stearic acid
1-4 parts of magnesium；The components also include starch slurry 90-300ml, the amount ratio of the microcrystalline cellulose and the starch slurry is 1g:
1.5-5ml；
Preferably, the component includes 200-350 parts of Levetiracetam, 60-90 parts of microcrystalline cellulose, lactose according to parts by weight
60-90 parts, 6-10 parts of low-substituted hydroxypropyl methylcellulose and 1-3 parts of magnesium stearate；The microcrystalline cellulose and the starch slurry
Amount ratio be 1g:1.5-4ml；
Preferably, the component includes 250-350 parts of Levetiracetam, 70-90 parts of microcrystalline cellulose, lactose according to parts by weight
70-90 parts, 8-10 parts of low-substituted hydroxypropyl methylcellulose and 1-2 parts of magnesium stearate；The microcrystalline cellulose and the starch slurry
Amount ratio be 1g:1.5-3ml.
2. levetiracetam medicinal composition according to claim 1, which is characterized in that the component is according to parts by weight
Including 100-800 parts of corn peptide；The Levetiracetam and the amount ratio of the corn peptide are 1:0.5-2；
Preferably, the component includes 200-700 parts of corn peptide according to parts by weight；The Levetiracetam and the corn peptide
Amount ratio be 1:1-2；
Preferably, the component includes 400-600 parts of corn peptide according to parts by weight；The Levetiracetam and the corn peptide
Amount ratio be 1:1.5-2.
3. levetiracetam medicinal composition according to claim 1, which is characterized in that the levetiracetam pharmaceutical group
Closing object is capsule or tablet；
Preferably, the levetiracetam medicinal composition is tablet, and the component includes coating agent 2-5 according to parts by weight
Part, preferably 2-3 parts；Preferably, the coating agent is stomach dissolved film coating pre-mix dose.
4. a kind of levetiracetam medicinal composition, which is characterized in that its component includes Levetiracetam according to parts by weight
250-300 parts, 400-600 parts of corn peptide；75-85 parts of microcrystalline cellulose, 75-85 parts of lactose, low-substituted hydroxypropyl methylcellulose 8-9
Part and 1-2 parts of magnesium stearate；The components also include starch slurry 90-300ml, the microcrystalline cellulose and the starch slurry
Amount ratio is 1g:1.5-3ml；The Levetiracetam and the amount ratio of the corn peptide are 1:1.5-2.
5. a kind of preparation method of levetiracetam medicinal composition as described in claim 1, which is characterized in that it includes will
The Levetiracetam, the microcrystalline cellulose, the lactose and the low-substituted hydroxypropyl methylcellulose are uniformly mixed, and are added described
Starch slurry is pelletized, and the magnesium stearate is subsequently added into, and capsule or tablet are made after mixing.
6. the preparation method of levetiracetam medicinal composition according to claim 5, which is characterized in that the component is pressed
Parts by weight meter further includes 100-700 parts of corn peptide；
Preferably, first the microcrystalline cellulose, the lactose, the low-substituted hydroxypropyl methylcellulose and the corn peptide are mixed
Uniformly, then mixture is uniformly mixed with the Levetiracetam in the method for equal increments,
Preferably, before the Levetiracetam is added, the Levetiracetam is first crushed to 80-100 mesh.
7. the preparation method of levetiracetam medicinal composition according to claim 5, which is characterized in that granulation includes first
Wet granulation is carried out, wet whole grain is then carried out, crosses 20-22 mesh, then drying at 50-60 DEG C to pellet moisture is 1.5%-
6.5%, the particle after drying is subjected to dry whole grain, crosses 16-18 mesh.
8. the preparation method of levetiracetam medicinal composition according to claim 7, which is characterized in that particle to be placed in
Before being dried in drying machine, preheating 10-15min first is carried out to the drying machine with the wind that temperature is 60-70 DEG C, is then carried out
Drying at room temperature.
9. the preparation method of levetiracetam medicinal composition according to claim 6, which is characterized in that the component is pressed
Parts by weight meter includes 2-5 parts of coating agent, and coating powder is configured to the coating agent that concentration is 10-15%, is carried out to plain piece
It is preheated to 34-40 DEG C, the coating agent is then sprayed to the surface of the plain piece, tablet is cooled down after the completion of sprinkling.
10. a kind of levetiracetam medicinal composition according to any one of claims 1-4 or such as claim 5-9 are any
Levetiracetam medicinal composition made from the preparation method of levetiracetam medicinal composition described in is in preparation for subtracting
The gently application caused by Levetiracetam in the drug of diarrhea side effect.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101422442A (en) * | 2008-12-09 | 2009-05-06 | 沈阳药科大学 | Levetiracetam osmotic pump controlled release tablet and preparation method thereof |
| US20150079170A1 (en) * | 2007-05-30 | 2015-03-19 | Girish Kumar Jain | Novel tablet dosage form |
| CN104922075A (en) * | 2015-05-31 | 2015-09-23 | 黑龙江佰彤儿童药物研究有限公司 | Solid preparation for treating pediatric epilepsy and preparation method thereof |
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2018
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150079170A1 (en) * | 2007-05-30 | 2015-03-19 | Girish Kumar Jain | Novel tablet dosage form |
| CN101422442A (en) * | 2008-12-09 | 2009-05-06 | 沈阳药科大学 | Levetiracetam osmotic pump controlled release tablet and preparation method thereof |
| CN104922075A (en) * | 2015-05-31 | 2015-09-23 | 黑龙江佰彤儿童药物研究有限公司 | Solid preparation for treating pediatric epilepsy and preparation method thereof |
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