CN1608623A - Enteric coated donepezil hydrochloride tablet and its perpn process - Google Patents
Enteric coated donepezil hydrochloride tablet and its perpn process Download PDFInfo
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Abstract
The present invention discloses enteric coated Donepezil hydrochloride tablet and its preparation process. The enteric coated Donepezil hydrochloride tablet is prepared with Donepezil hydrochloride as material medicine and proper amount of supplementary material. The enteric coated Donepezil hydrochloride tablet is used in treating light and medium degree senile dementia, and compared with gastric coated Donepezil hydrochloride tablet, the enteric coated Donepezil hydrochloride tablet has less side effects, no irritation to stomach and other advantages. Taking Donepezil regularly is beneficial to light and medium degree senile dementia patient.
Description
Technical field: the present invention relates to a kind of donepezil hydrochloride enteric coatel tablets and preparation method thereof, be applicable to, belong to technical field of medicaments to treatment slight or moderate dementia of the Alzheimer type symptom.
Background technology: dementia is a modal disease of geratic period.(Alzheimer AD), is a kind of chronic brain degeneration disease to alzheimer disease.Clinical manifestation is progressive memory disorder, and the decline of analytical judgment ability, mood change, behavioral disorder even confusion die of pneumonia or urinary tract infection at last.According to statistics: U.S. alzheimer disease patient is 200-400 ten thousand, and global 1700-2500 ten thousand is after heart disease, tumor and apoplexy in western countries' alzheimer disease, comes the 4th the dead disease that causes.
From the medication history of treatment, physostigmine is used to improve senile dementia disease man memory power and cognitive function already.In long-term and short-term comparative study, physostigmine can improve memory and cognitive really, but because this medicine t
1/2Short (only 30min) causes its clinical value to baffle greatly.More recent alternative medicine is a tacrine, but need use dosage and genotoxic potential thereof because many patients can not tolerate it, makes it in use to have only 10%～30% patient's cognitive function to make moderate progress.In can the patient of tolerate higher doses, its effective percentage also reaches 30%～50% only, because this medical instrument has liver toxicity, the drug withdrawal midway of having to sometimes.
Donepezil hydrochloride is that unique a kind of while is by the new drug light, the moderate AD symptomatic treatment that is used for of U.S. FDA and Britain MCA approval listing.Donepezil hydrochloride is first kind of reversibility acetylcholinesteraseinhibitors inhibitors.Compare with tacrine, the neuron acetylcholinesterase is had the selective inhibitory of higher degree, also have gratifying pharmacodynamics, pharmacokinetics and safety indexes, better tolerance, convenient drug administration.Clinical practice proves that donepezil hydrochloride can be used as the alternative medicine treatment alzheimer disease of tacrine.In sum, donepezil is as the cholinesterase inhibitor of a new generation treatment alzheimer disease, is effective for the improvement of mild to moderate alzheimer disease patient's clinical symptoms.Little, the long half time, safe of acetylcholine esterase selectivity, dosage of height does not find that importantly it has liver toxicity, for the clinical practice of donepezil provides important basis.In the prior art donepezil hydrochloride is prepared into gastric soluble tablet, the technology of donepezil hydrochloride being made drop pill is also arranged recently, as: Chinese patent application: 02110065.9, name is called: donepezil hydrochloride dripping pills; Be used for treatment slight or moderate dementia of the Alzheimer type symptom.But, we find in the use: the disintegrate under one's belt of common donepezil hydrochloride gastric soluble tablet, stimulation to stomach is bigger, cause nausea easily, untoward reaction such as vomiting, anorexia, diarrhoea, especially to the patient who suffers from ulcer, the dangerous increase of patient of taking nonsteroidal antiinflammatory drug, gastric soluble tablet causes active constituent content to reduce easily by stomach acids destroy simultaneously, affects the treatment; And drop pill is except that the shortcoming with gastric soluble tablet, also because the too fast Cmax that causes easily of drug release rate is too high, cause cholinesterase activity to suppress stronger easily, it is strong excessively to cause intending the choline effect easily, occur bradycardia, epilepsy, bladder urinate be obstructed, side reaction such as hypotension, respiration inhibition, collapse, convulsions; That is to say that existing these preparation formulations can not satisfy the instructions for use of doctor and patient fully, have the comparison critical limitations.
Summary of the invention: the object of the present invention is to provide a kind of donepezil hydrochloride enteric coatel tablets and preparation method thereof, the advantage of this enteric dosage form is: medicine does not dissolve under one's belt, can not cause stimulation, the patient who suffers from ulcer, the patient who takes nonsteroidal antiinflammatory drug are safe from danger stomach; Product dissolves in small intestinal, and release is steady, blood drug level is steady, intends a little less than the choline effect, and side reaction is less, and slightly suitable or moderate dementia of the Alzheimer type patient takes for a long time.
The present invention is achieved through the following technical solutions: the donepezil hydrochloride enteric coatel tablets: it is mainly made by donepezil hydrochloride crude drug and suitable adjuvant.Specifically: calculate according to components by weight percent, it is prepared from by donepezil hydrochloride 3-8g, water soluble starch 20-30g, dextrin 8-12g, little smart cellulose 20-30g, low-substituted hydroxypropyl methylcellulose 3-8g, magnesium stearate 1-5g, 1.0% hypromellose 40-100 milliliter, Pulvis Talci 2.0-10g, titanium dioxide 1.0-8.0g, polyacrylic resin II1.0-6.0g, polyacrylic resin III2.0-6.0g, 50-100ml50% alcoholic solution, Tween 80 1-6g.Say accurately: calculate according to weight, it is prepared from by donepezil hydrochloride 5g, water soluble starch 25g, dextrin 10g, little smart cellulose 25g, low-substituted hydroxypropyl methylcellulose 5g, magnesium stearate 2g, 1.0% hypromellose aqueous solution 40ml, Pulvis Talci 1.6g, titanium dioxide 0.8g, polyacrylic resin II1.2g, polyacrylic resin III1.2g, 50% alcoholic solution 80ml, tween 80 2g.For this product, following prescription has also obtained success through experiment: it is prepared from by donepezil hydrochloride crude drug 3-8g, amylum pregelatinisatum 20-30g, lactose 8-10g, sodium carboxymethyl cellulose 3-8g, hypromellose 1-3g, carboxymethyl starch sodium 1-3g, Polyethylene Glycol 1-5g, 1.0% hypromellose aqueous solution 40-100ml, polyacrylic resin II1-6g, Pulvis Talci 2.0-10g, titanium dioxide 1.0-8.0g, 50% alcoholic solution 50-100ml.
The preparation method of described donepezil hydrochloride enteric coatel tablets: get donepezil hydrochloride and sieve, water soluble starch, dextrin, little smart cellulose, low-substituted hydroxypropyl methylcellulose sieve mixing respectively, with the preparation soft material, after make granule, drying, granulate adds the magnesium stearate mix homogeneously, tabletting; The preparation enteric coating liquid is standby; Spray bag by the coating routine, drying, packing, packing.Concrete method is: donepezil hydrochloride is crossed the 80-100 mesh sieve, and water soluble starch, dextrin, little smart cellulose, low-substituted hydroxypropyl methylcellulose are crossed the 60-80 mesh sieve respectively..Take by weighing supplementary material by recipe quantity, mixing, 40ml-100ml prepares soft material with 1.0%-2.0% hypromellose aqueous solution, 20-40 mesh sieve system granule, 60-65 ℃ dry 2-3 hour, 18-20 mesh sieve granulate adds the magnesium stearate mix homogeneously, tabletting.The preparation method of coating solution for get hypromellose, polyacrylic resin II, polyacrylic resin III join in 50% ethanol, make its dissolving of expanding, and add medicinal Pulvis Talci and titanium dioxide, tween 80 then, fully stir evenly, and be standby.Spray bag by the coating routine, drying, packing, packing.Method is more accurately: donepezil hydrochloride 5g crosses 80 mesh sieves, and water soluble starch 25g, dextrin 10g, little smart cellulose 25g, low-substituted hydroxypropyl methylcellulose 5g cross 60 mesh sieves respectively..Take by weighing supplementary material by recipe quantity, mixing adds the preparation soft material with 1.0% hypromellose aqueous solution 40ml, and with 20 mesh sieve system granules, drying is 2 hours under 60 ℃, carries out granulate later with 18 mesh sieves sieve, adds the magnesium stearate mix homogeneously behind the granulate, tabletting.The preparation method of coating solution is: get hypromellose 2.4g, polyacrylic resin II1.2g, polyacrylic resin III1.2g joins in the 80ml50% ethanol, make its dissolving of expanding, add 1.6g medicinal Pulvis Talci and 0.8g titanium dioxide, tween 80 2g then, fully stir evenly, standby.Spray bag by the coating routine, drying, packing, packing.Method with following adjuvant preparation: donepezil hydrochloride 5g crosses 80 mesh sieves, amylum pregelatinisatum 25g, lactose 8g, sodium carboxymethyl cellulose 5g, carboxymethyl starch sodium 1.5g, Polyethylene Glycol 2g cross 60 mesh sieves respectively, prepare soft material with 1.0% hypromellose aqueous solution 60ml, with 20 mesh sieve system granules, drying is 2 hours under 65 ℃, later carry out granulate with 18 mesh sieves sieve, carry out tabletting behind the granulate.The preparation method of coating solution is: gets hypromellose 1.2g polyacrylic resin II1.2g and adds among the 50% alcoholic solution 50ml, make its dissolving of expanding, add the 2g medicinal Pulvis Talci then and the 1.6g titanium dioxide fully stirs evenly, and standby.Spray bag by the coating routine, drying, packing, packing.
This product is a salt, have certain draw moist, and mildly bitter flavor, outward appearance is chosen to be coating solution and makees film coating, reaches to cover bitterness, reduces to draw wetly, increases medicine stability, improves the purpose of tablet appearance.Simultaneously because the side effect that this medical instrument has gastric mucosa to stimulate, so add enteric coating adding on the basis of film-coat, make medicine disintegrate in small intestinal, stimulate to reduce gastric mucosa, the utilization rate of raising medicine.
The prescription screening of these enteric coatel tablets is divided into two stages to carry out, and the phase I mainly is to select supplementary product kind and binding agent, and second stage adopts orthogonal design method that prescription is optimized screening.Discover in the prescription screening process that the granulation of employing 2% hypromellose aqueous solution is big because of viscosity, it is inhomogeneous to make granule, fine powder is more, adopts 5% hypromellose aqueous solution granulation viscosity deficiency, and adopts 1.0% hypromellose aqueous solution granulation viscosity comparatively suitable.
| Medicine | Time | Cognitive function improves | Memory is improved | The daily behavior activity | Feel sick, side effect such as vomiting |
| Donepezil hydrochloride enteric coatel tablets (5mg) | 15 weeks | Significantly improve | Significantly improve | Significantly improve | Do not have |
| Donepezil hydrochloride enteric coatel tablets (10mg) | 30 weeks | Significantly improve | Significantly improve | Significantly improve | Do not have |
| Donepezil hydrochloride gastric soluble tablet (5mg) | 15 weeks | Significantly improve | Significantly improve | Significantly improve | Have |
| Donepezil hydrochloride gastric soluble tablet (10mg) | 30 weeks | Significantly improve | Significantly improve | Significantly improve | Have |
| Placebo (5mg) | 15 weeks | Not having work improves | Do not have significantly and improve | Do not have significantly and improve | Do not have |
| Placebo (10mg) | 30 weeks | Do not have significantly and improve | Do not have significantly and improve | Do not have significantly and improve | Do not have |
Orthogonal design is on the basis of above-mentioned research, with starch-dextrin, lactose, microcrystalline Cellulose and disintegrating agent is four factors, and three levels of getting are carried out orthogonal design, is leading indicator with disintegration of tablet speed, dissolution, consider that simultaneously uniform particles degree and sheet are heavy, obtain determining prescription at last.The results are shown in Table 2,3,4,5.
Table 2 orthogonal design factor level table
Hydric factor
Flat starch: dextrin-A microcrystalline Cellulose B lactose-C disintegrating agent-D
1 25: 10 35 10 low-substituted hydroxypropyl cellulose 5mg
2 20: 15 30 15 low-substituted hydroxypropyl cellulose 5mg
3. 30: 5 25 20 carboxymethylstach sodium 5mg
Table 3 orthonormal design of experiments result and date processing table (n=3)
Experiment A B C D disintegration time (second) dissolution (15 minutes, %)
1?????????1?????????1????1????1????109?????????????97.4
2?????????1?????????2????2????2????106?????????????99.7
3?????????1?????????3????3????3????98??????????????98.3
4?????????2?????????1????2????3????116?????????????98.9
5?????????2?????????2????3????1????108?????????????97.6
6?????????2?????????3????1????2????97??????????????99.3
7?????????3?????????1????3????2????116?????????????98.2
8?????????3?????????2????1????3????113?????????????97.6
9?????????3?????????3????2????1????107?????????????98.7
Table 4 disintegration time extreme difference check result
Factor A B C D
I??????313????341????319????324
II?????321????327????329????319
III????336????302????322????327
I’???????????104.3??113.7??106.3??108.0
II’?????????107.0??109.0??109.7??106.3
III’???????336????302????322????327
MAX????112.0??113.7??109.7??109.0
MIN????104.3??100.7??106.3??106.3
Extreme difference R 7.7 13.0 3.3 2.7
Table 5 dissolution extreme difference check result
Factor A B C D
I?????295.4????295.4????294.3????293.7
II????295.8????294.9????297.3????297.2
III???294.5????296.3????294.1????294.8
I’?????????98.5?????98.2?????98.1?????97.9
II’???????98.6?????98.3?????99.1?????99.1
III’?????98.2?????98.8?????98.0?????97.9
MAX???98.6?????98.8?????99.1?????99.1
MIN???98.2?????98.2?????98.0?????97.9
Extreme difference R 0.4 0.6 1.1 1.2
I, II, III are respectively first, second and third horizontal score sum, and I ', II ', III ' are averages, and R is the extreme difference between the level, and extreme difference is big more, show that the difference between the level is also big.
According to donepezil hydrochloride enteric coatel tablets disintegration time and dissolution extreme difference check result as can be seen: A, B, four kinds of factors of C, D are respectively 7.7,13.0,3.3 and 2.7 to the disintegration time extreme difference of this tablet, extreme difference to dissolution is respectively 0.4,0.6,1.1 and 1.2, promptly four factors are B → A → C → D to the size order that influences of disintegration time, and best prescription is B1A3C1D2; It is D → C → B → A that dissolution is influenced size order.Best prescription is D2C2B3A2.
Take all factors into consideration fine powder what, tablet weight that the particulate all even back of granulating produces, determine that starch and dextrin ratio are 25: 10, lactose consumption 10, microcrystalline Cellulose consumption are 25, and the low-substituted hydroxypropyl cellulose consumption is 5.Promptly adopt the effect of each component of prescription in prescription as follows:
The donepezil hydrochloride principal agent
Starch filled dose, diluent
The amylum pregelatinisatum filler
Dextrin diluent, binding agent
The lactose diluent
Little smart cellulose diluent, disintegrating agent
The low-substituted hydroxypropyl cellulose disintegrating agent
Magnesium
1.0% hypromellose solution adhesive
Sodium carboxymethyl cellulose wetting agent, binding agent
The carboxymethyl starch sodium disintegrating agent
The Polyethylene Glycol lubricant
The hypromellose coating is used
The Pulvis Talci coating is used
The titanium dioxide coating is used
Polyacrylic resin II enteric coating is used
Polyacrylic resin III enteric coating is used
50% ethanol coating is used
The tween 80 wetting agent
Pharmacokinetics test of the present invention shows that medicine mainly absorbs in the human small intestine, its relative bioavailability is 40-100%, food does not influence absorption rate and degree, reached peak serum concentration in about 3-4 hour, eliminate about 70 hours of half-life, behind the multiple dosing, accumulating of blood plasma reaches 4-7 doubly, reaches stable state in 15 days.Mainly discharge by the former medicine of liver metabolism by urine.
Clinical research of the present invention shows: the donepezil hydrochloride enteric coatel tablets are used for mild to moderate AD patient's treatment.Because the half-life of this medicine is longer, taking medicine every day can reach the treatment requirement 1 time.Adopt the method for placebo and donepezil hydrochloride gastric soluble tablet matched group that the III clinical trial phase has been carried out in the drug effect and the safety of donepezil 2 times, therapeutic dose is 5mg and 10mg.Test period was respectively for 15 and 30 weeks.Clinical effectiveness mainly adopts cognitive scale (ADAS-Cog) and clinicist that impression assessment (CIBIC-Plus) scale that improves is estimated.In addition, other scale also comprises simple intelligent status checkout (MMSE) etc.; Clinical comparison the results are shown in following table:
| Medicine | Time | Cognitive function improves | Memory is improved | The daily behavior activity | Feel sick, side effect such as vomiting |
| Donepezil hydrochloride enteric coatel tablets (5mg) | 15 weeks | Significantly improve | Significantly improve | Significantly improve | Do not have |
| Donepezil hydrochloride enteric coatel tablets (10mg) | 30 weeks | Significantly improve | Significantly improve | Significantly improve | Do not have |
| Donepezil hydrochloride gastric soluble tablet (5mg) | 15 weeks | Significantly improve | Significantly improve | Significantly improve | Have |
| Donepezil hydrochloride gastric soluble tablet (10mg) | 30 weeks | Significantly improve | Significantly improve | Significantly improve | Have |
| Placebo (5mg) | 15 weeks | Not having work improves | Do not have significantly and improve | Do not have significantly and improve | Do not have |
| Placebo (10mg) | 30 weeks | Do not have significantly and improve | Do not have significantly and improve | Do not have significantly and improve | Do not have |
By above clinical observation as can be seen: donepezil hydrochloride enteric coatel tablets provided by the invention are effective and safe for the improvement of the mild to moderate alzheimer disease patient's clinical symptoms of treatment, compare with the donepezil hydrochloride gastric soluble tablet have side reaction few, to advantages such as stomach are non-stimulated.Taking donepezil for a long time is useful to mild to moderate alzheimer disease patient.
Specific embodiment:
Embodiments of the invention 1: donepezil hydrochloride 5g crosses 80 mesh sieves, and water soluble starch 25g, dextrin 10g, little smart cellulose 25g, low-substituted hydroxypropyl methylcellulose 5g cross 60 mesh sieves respectively.Take by weighing supplementary material by recipe quantity, mixing adds the preparation soft material with 1.0% hypromellose aqueous solution 40ml, and with 20 mesh sieve system granules, drying is 2 hours under 60 ℃, carries out granulate later with 18 mesh sieves sieve, adds the magnesium stearate mix homogeneously behind the granulate, tabletting.The preparation method of coating solution is: get hypromellose 2.4g, polyacrylic resin II1.2g, polyacrylic resin III1.2g joins in the 80ml50% ethanol, make its dissolving of expanding, add 1.6g medicinal Pulvis Talci and 0.8g titanium dioxide, tween 80 2g then, fully stir evenly, standby.Spray bag by the coating routine, drying, packing, packing.
Embodiments of the invention 2: donepezil hydrochloride 5g crosses 80 mesh sieves, amylum pregelatinisatum 25g, lactose 8g, sodium carboxymethyl cellulose 5g, carboxymethyl starch sodium 1.5g, Polyethylene Glycol 2g cross 60 mesh sieves respectively, prepare soft material with 1.0% hypromellose aqueous solution 60ml, with 20 mesh sieve system granules, drying is 2 hours under 65 ℃, later carry out granulate with 18 mesh sieves sieve, carry out tabletting behind the granulate.The preparation method of coating solution is: gets hypromellose 1.2g polyacrylic resin II1.2g and adds among the 50% alcoholic solution 50ml, make its dissolving of expanding, add the 2g medicinal Pulvis Talci then and the 1.6g titanium dioxide fully stirs evenly, and standby.Spray bag by the coating routine, drying, packing, packing.
Embodiments of the invention 3: it is prepared from according to following method by donepezil hydrochloride 3g, water soluble starch 20g, dextrin 8g, little smart cellulose 20g, low-substituted hydroxypropyl methylcellulose 3g, magnesium stearate 1g, 40 milliliters of 1.0% hypromelloses, Pulvis Talci 2.0g, titanium dioxide 1.0g, polyacrylic resin II1.0g, polyacrylic resin III2.0g, 50ml50% alcoholic solution, Tween 80 1g: donepezil hydrochloride is crossed 80 mesh sieves, and water soluble starch, dextrin, little smart cellulose, low-substituted hydroxypropyl methylcellulose are crossed 60 mesh sieves respectively..Take by weighing supplementary material by recipe quantity, mixing prepares soft material with 1.0% hypromellose aqueous solution 40ml, 20 mesh sieve system granules, and 60 ℃ of dryings 2 hours, 18 mesh sieve granulate add the magnesium stearate mix homogeneously, tabletting.The preparation method of coating solution for get hypromellose, polyacrylic resin II, polyacrylic resin III join in 50% ethanol, make its dissolving of expanding, and add medicinal Pulvis Talci and titanium dioxide, tween 80 then, fully stir evenly, and be standby.Spray bag by the coating routine, drying, packing, packing.
Embodiments of the invention 4: it is prepared from as follows by donepezil hydrochloride 8g, water soluble starch 30g, dextrin 12g, little smart cellulose 30g, low-substituted hydroxypropyl methylcellulose 8g, magnesium stearate 5g, 100 milliliters of 1.0% hypromelloses, Pulvis Talci 10g, titanium dioxide 8.0g, polyacrylic resin II6.0g, polyacrylic resin III6.0g, 100ml50% alcoholic solution, Tween 80 6g: donepezil hydrochloride is crossed 100 mesh sieves, and water soluble starch, dextrin, little smart cellulose, low-substituted hydroxypropyl methylcellulose are crossed 80 mesh sieves respectively..Take by weighing supplementary material by recipe quantity, mixing prepares soft material with 2.0% hypromellose aqueous solution 100ml, 40 mesh sieve system granules, and 65 ℃ of dryings 3 hours, 20 mesh sieve granulate add the magnesium stearate mix homogeneously, tabletting.The preparation method of coating solution for get hypromellose, polyacrylic resin II, polyacrylic resin III join in 50% ethanol, make its dissolving of expanding, and add medicinal Pulvis Talci and titanium dioxide, tween 80 then, fully stir evenly, and be standby.Spray bag by the coating routine, drying, packing, packing.
Embodiments of the invention 5: get donepezil hydrochloride and sieve, water soluble starch, dextrin, little smart cellulose, low-substituted hydroxypropyl methylcellulose sieve respectively, mixing, with the preparation soft material, after make granule, drying, granulate adds the magnesium stearate mix homogeneously, tabletting; The preparation enteric coating liquid is standby: spray bag by the coating routine, and drying, packing, packing.
Embodiments of the invention 6: it is by donepezil hydrochloride crude drug 8g, amylum pregelatinisatum 30g, lactose 10g, sodium carboxymethyl cellulose 8g, hypromellose 3g, carboxymethyl starch sodium 3g, Polyethylene Glycol 5g, 1.0% hypromellose aqueous solution 100ml, polyacrylic resin II6g, Pulvis Talci 10g, titanium dioxide 8.0g, 50% alcoholic solution 100ml preparation: donepezil hydrochloride is crossed 80 mesh sieves, amylum pregelatinisatum, lactose, sodium carboxymethyl cellulose, carboxymethyl starch sodium, Polyethylene Glycol is crossed 60 mesh sieves respectively, prepare soft material with 1.0% hypromellose aqueous solution 60ml, with 20 mesh sieve system granules, drying is 2 hours under 65 ℃, carry out later granulate with 18 mesh sieves sieve, carry out tabletting behind the granulate, the preparation method of coating solution is: get hypromellose, polyacrylic resin II adds in 50% alcoholic solution, make its dissolving of expanding, add medicinal Pulvis Talci then and titanium dioxide fully stirs evenly, standby, spray bag by the coating routine, dry, packing, packing.
Embodiments of the invention 7: it is by donepezil hydrochloride crude drug 3g, amylum pregelatinisatum 20g, lactose 8g, sodium carboxymethyl cellulose 3g, hypromellose 1g, carboxymethyl starch sodium 1g, Polyethylene Glycol 1g, 1.0% hypromellose aqueous solution 40ml, polyacrylic resin II1g, Pulvis Talci 2.0g, titanium dioxide 1.0g, 50% alcoholic solution 50ml preparation: donepezil hydrochloride is crossed 80 mesh sieves, amylum pregelatinisatum, lactose, sodium carboxymethyl cellulose, carboxymethyl starch sodium, Polyethylene Glycol is crossed 60 mesh sieves respectively, prepare soft material with 1.0% hypromellose aqueous solution 60ml, with 20 mesh sieve system granules, drying is 2 hours under 65 ℃, carry out later granulate with 18 mesh sieves sieve, carry out tabletting behind the granulate, the preparation method of coating solution is: get hypromellose, polyacrylic resin II adds in 50% alcoholic solution, make its dissolving of expanding, add medicinal Pulvis Talci then and titanium dioxide fully stirs evenly, standby, spray bag by the coating routine, dry, packing, packing.
Claims (4)
1.[document source] electronic application
2.[the message in-coming date] 2004-11-5
3.[application number]
4.[claim item]
[claim 1] donepezil hydrochloride enteric coatel tablets is characterized in that: it is mainly made by donepezil hydrochloride crude drug and suitable adjuvant.
[claim 2] is according to the described donepezil hydrochloride enteric coatel tablets of claim 1, it is characterized in that: calculate according to components by weight percent, it is prepared from by donepezil hydrochloride 3-8g, water soluble starch 20-30g, dextrin 8-12g, little smart cellulose 20-30g, low-substituted hydroxypropyl methylcellulose 3-8g, magnesium stearate 1-5g, 1.0% hypromellose 40-100 milliliter, Pulvis Talci 2.0-10g, titanium dioxide 1.0-8.0g, polyacrylic resin II 1.0-6.0g, polyacrylic resin III 2.0-6.0g, 50-100ml 50% alcoholic solution, Tween 80 1-6g.
[claim 3] is according to claim 1 or 2 described donepezil hydrochloride enteric coatel tablets, it is characterized in that: calculate according to weight, it is prepared from by donepezil hydrochloride 5g, water soluble starch 25g, dextrin 10g, little smart cellulose 25g, low-substituted hydroxypropyl methylcellulose 5g, magnesium stearate 2g, 1.0% hypromellose aqueous solution 40ml, Pulvis Talci 1.6g, titanium dioxide 0.8g, polyacrylic resin II 1.2g, polyacrylic resin III 1.2g, 50% alcoholic solution 80ml, tween 80 2g.
[claim 4] is characterized in that according to claims 1 described donepezil hydrochloride enteric coatel tablets: it is prepared from by donepezil hydrochloride crude drug 3-8g, amylum pregelatinisatum 20-30g, lactose 8-10g, sodium carboxymethyl cellulose 3-8g, hypromellose 1-3g, carboxymethyl starch sodium 1-3g, Polyethylene Glycol 1-5g, 1.0% hypromellose aqueous solution 40-100ml, polyacrylic resin II 1-6g, Pulvis Talci 2.0-10g, titanium dioxide 1.0-8.0g, 50% alcoholic solution 50-100ml.
Is [claim 5] as claim 1? in the preparation method of any described donepezil hydrochloride enteric coatel tablets, it is characterized in that: get donepezil hydrochloride and sieve, water soluble starch, dextrin, little smart cellulose, low-substituted hydroxypropyl methylcellulose sieve respectively, mixing, with the preparation soft material, after make granule, dry, granulate adds the magnesium stearate mix homogeneously, tabletting; The preparation enteric coating liquid is standby; Spray bag by the coating routine, drying, packing, packing.
[claim 6] is according to the preparation method of the described donepezil hydrochloride enteric coatel tablets of claim 5, it is characterized in that: donepezil hydrochloride is crossed the 80-100 mesh sieve, and water soluble starch, dextrin, little smart cellulose, low-substituted hydroxypropyl methylcellulose are crossed the 60-80 mesh sieve respectively..Take by weighing supplementary material by recipe quantity, mixing, 40ml-100ml prepares soft material with 1.0%-2.0% hypromellose aqueous solution, 20-40 mesh sieve system granule, 60-65 ℃ dry 2-3 hour, 18-20 mesh sieve granulate adds the magnesium stearate mix homogeneously, tabletting.The preparation method of coating solution for get hypromellose, polyacrylic resin II, polyacrylic resin III join in 50% ethanol, make its dissolving of expanding, and add medicinal Pulvis Talci and titanium dioxide, tween 80 then, fully stir evenly, and be standby.Spray bag by the coating routine, drying, packing, packing.
[claim 7] is according to the preparation method of claim 5 or 6 described donepezil hydrochloride enteric coatel tablets, it is characterized in that: donepezil hydrochloride 5g crosses 80 mesh sieves, water soluble starch 25g, dextrin 10g, little smart cellulose 25g, low-substituted hydroxypropyl methylcellulose 5g crosses 60 mesh sieves respectively, take by weighing supplementary material by recipe quantity, mixing, add the preparation soft material with 1.0% hypromellose aqueous solution 40ml, with 20 mesh sieve system granules, drying is 2 hours under 60 ℃, carry out later granulate with 18 mesh sieves sieve, add the magnesium stearate mix homogeneously behind the granulate, tabletting, the preparation method of coating solution is: get hypromellose 2.4g, polyacrylic resin II1.2g, polyacrylic resin III 1.2g joins in 80ml 50% ethanol, make its dissolving of expanding, add 1.6g medicinal Pulvis Talci and 0.8g titanium dioxide then, tween 80 2g fully stirs evenly, and is standby, spray bag by the coating routine, drying, packing, packing.
The preparation method of [claim 8] donepezil hydrochloride enteric coatel tablets described in claim 1 or 4, it is characterized in that: donepezil hydrochloride 5g crosses 80 mesh sieves, amylum pregelatinisatum 25g, lactose 8g, sodium carboxymethyl cellulose 5g, carboxymethyl starch sodium 1.5g, Polyethylene Glycol 2g crosses 60 mesh sieves respectively, prepare soft material with 1.0% hypromellose aqueous solution 60ml, with 20 mesh sieve system granules, drying is 2 hours under 65 ℃, carry out later granulate with 18 mesh sieves sieve, carry out tabletting behind the granulate, the preparation method of coating solution is: get hypromellose 1.2g polyacrylic resin II 1.2g and add among the 50% alcoholic solution 50ml, make its dissolving of expanding, add the 2g medicinal Pulvis Talci then and the 1.6g titanium dioxide fully stirs evenly, standby, spray bag by the coating routine, drying, packing, packing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410155435 CN1608623A (en) | 2004-11-05 | 2004-11-05 | Enteric coated donepezil hydrochloride tablet and its perpn process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410155435 CN1608623A (en) | 2004-11-05 | 2004-11-05 | Enteric coated donepezil hydrochloride tablet and its perpn process |
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| Publication Number | Publication Date |
|---|---|
| CN1608623A true CN1608623A (en) | 2005-04-27 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410155435 Pending CN1608623A (en) | 2004-11-05 | 2004-11-05 | Enteric coated donepezil hydrochloride tablet and its perpn process |
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| CN (1) | CN1608623A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2213278A1 (en) * | 2009-01-28 | 2010-08-04 | Labtec GmbH | Pharmaceutical preparation with improved stability of the active agent |
| CN102309465A (en) * | 2010-06-30 | 2012-01-11 | 天津药物研究院 | Sustained release tablet containing donepezil hydrochloride active component as well as preparation method and application thereof |
| EP1832298A4 (en) * | 2004-12-27 | 2012-12-12 | Eisai R&D Man Co Ltd | Matrix-type controlled release preparation comprising basic substance or salt thereof, and process for production of the same |
| CN106727371A (en) * | 2016-12-08 | 2017-05-31 | 江苏豪森药业集团有限公司 | Doneppezil Hydrochloride pharmaceutical composition and preparation method thereof |
| CN109364096A (en) * | 2018-12-25 | 2019-02-22 | 浙江华康药业股份有限公司 | A kind of xylitol enteric coatel tablets and its preparation method and application |
-
2004
- 2004-11-05 CN CN 200410155435 patent/CN1608623A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1832298A4 (en) * | 2004-12-27 | 2012-12-12 | Eisai R&D Man Co Ltd | Matrix-type controlled release preparation comprising basic substance or salt thereof, and process for production of the same |
| EP2213278A1 (en) * | 2009-01-28 | 2010-08-04 | Labtec GmbH | Pharmaceutical preparation with improved stability of the active agent |
| CN102309465A (en) * | 2010-06-30 | 2012-01-11 | 天津药物研究院 | Sustained release tablet containing donepezil hydrochloride active component as well as preparation method and application thereof |
| CN102309465B (en) * | 2010-06-30 | 2015-04-22 | 天津药物研究院 | Sustained release tablet containing donepezil hydrochloride active component as well as preparation method and application thereof |
| CN106727371A (en) * | 2016-12-08 | 2017-05-31 | 江苏豪森药业集团有限公司 | Doneppezil Hydrochloride pharmaceutical composition and preparation method thereof |
| CN109364096A (en) * | 2018-12-25 | 2019-02-22 | 浙江华康药业股份有限公司 | A kind of xylitol enteric coatel tablets and its preparation method and application |
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