CN105193803A - Ilepcimide sustained release preparation and preparation method thereof - Google Patents
Ilepcimide sustained release preparation and preparation method thereof Download PDFInfo
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- CN105193803A CN105193803A CN201410301465.0A CN201410301465A CN105193803A CN 105193803 A CN105193803 A CN 105193803A CN 201410301465 A CN201410301465 A CN 201410301465A CN 105193803 A CN105193803 A CN 105193803A
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- Prior art keywords
- ilepcimide
- slow releasing
- release material
- slow
- releasing preparation
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- BLPUOQGPBJPXRL-FNORWQNLSA-N Ilepcimide Chemical compound C=1C=C2OCOC2=CC=1/C=C/C(=O)N1CCCCC1 BLPUOQGPBJPXRL-FNORWQNLSA-N 0.000 title claims abstract description 50
- BLPUOQGPBJPXRL-UHFFFAOYSA-N (E)-1-[3',4'-(methylenedioxy)cinnamoyl]piperidine Natural products C=1C=C2OCOC2=CC=1C=CC(=O)N1CCCCC1 BLPUOQGPBJPXRL-UHFFFAOYSA-N 0.000 title claims abstract description 49
- 229950000956 ilepcimide Drugs 0.000 title claims abstract description 49
- 238000002360 preparation method Methods 0.000 title claims abstract description 40
- 239000003405 delayed action preparation Substances 0.000 title abstract 6
- 239000000463 material Substances 0.000 claims abstract description 54
- 239000000314 lubricant Substances 0.000 claims abstract description 16
- 239000011248 coating agent Substances 0.000 claims abstract description 13
- 238000000576 coating method Methods 0.000 claims abstract description 13
- 239000000945 filler Substances 0.000 claims abstract description 7
- 239000008187 granular material Substances 0.000 claims description 27
- 239000011230 binding agent Substances 0.000 claims description 15
- -1 hydroxypropyl Chemical group 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 10
- 238000012856 packing Methods 0.000 claims description 9
- 239000007779 soft material Substances 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 8
- 230000004584 weight gain Effects 0.000 claims description 8
- 235000019786 weight gain Nutrition 0.000 claims description 8
- 229920002125 Sokalan® Polymers 0.000 claims description 7
- 229920002472 Starch Polymers 0.000 claims description 6
- 239000008107 starch Substances 0.000 claims description 6
- 235000019698 starch Nutrition 0.000 claims description 6
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 4
- 229960001631 carbomer Drugs 0.000 claims description 4
- 239000008101 lactose Substances 0.000 claims description 4
- 235000019359 magnesium stearate Nutrition 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- 229920000881 Modified starch Polymers 0.000 claims description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 3
- 235000013539 calcium stearate Nutrition 0.000 claims description 3
- 239000008116 calcium stearate Substances 0.000 claims description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 3
- QWMVKSPSWWCSEK-UHFFFAOYSA-N ethene;pyrrolidin-2-one Chemical compound C=C.O=C1CCCN1 QWMVKSPSWWCSEK-UHFFFAOYSA-N 0.000 claims description 3
- 239000000499 gel Substances 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- 239000011159 matrix material Substances 0.000 claims description 3
- 239000004584 polyacrylic acid Substances 0.000 claims description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 claims description 3
- 239000003814 drug Substances 0.000 abstract description 23
- 229940079593 drug Drugs 0.000 abstract description 14
- 239000000853 adhesive Substances 0.000 abstract 1
- 230000001070 adhesive effect Effects 0.000 abstract 1
- 238000013268 sustained release Methods 0.000 abstract 1
- 239000012730 sustained-release form Substances 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 11
- 238000005516 engineering process Methods 0.000 description 9
- 230000003556 anti-epileptic effect Effects 0.000 description 8
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- 206010015037 epilepsy Diseases 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 239000012738 dissolution medium Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 231100000331 toxic Toxicity 0.000 description 4
- 230000002588 toxic effect Effects 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000002651 drug therapy Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 3
- 206010010904 Convulsion Diseases 0.000 description 2
- 241000790917 Dioxys <bee> Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010061334 Partial seizures Diseases 0.000 description 2
- 108010052164 Sodium Channels Proteins 0.000 description 2
- 102000018674 Sodium Channels Human genes 0.000 description 2
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 2
- 229960000623 carbamazepine Drugs 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 230000001037 epileptic effect Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 2
- 229960001848 lamotrigine Drugs 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- GXFZCDMWGMFGFL-KKXMJGKMSA-N (+)-Tubocurarine chloride hydrochloride Chemical compound [Cl-].[Cl-].C([C@H]1[N+](C)(C)CCC=2C=C(C(=C(OC3=CC=C(C=C3)C[C@H]3C=4C=C(C(=CC=4CC[NH+]3C)OC)O3)C=21)O)OC)C1=CC=C(O)C3=C1 GXFZCDMWGMFGFL-KKXMJGKMSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- ISNYUQWBWALXEY-UHFFFAOYSA-N Batrachotoxin Natural products C=1CC2(C3=CCC4C5(C)CCC(C4)(O)OC53C(O)C3)OCCN(C)CC32C=1C(C)OC(=O)C=1C(C)=CNC=1C ISNYUQWBWALXEY-UHFFFAOYSA-N 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 239000008709 Curare Substances 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- 241000758706 Piperaceae Species 0.000 description 1
- 208000033240 Progressive symmetric erythrokeratodermia Diseases 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 241001279009 Strychnos toxifera Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
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- 230000002397 epileptogenic effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
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- 231100000053 low toxicity Toxicity 0.000 description 1
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- MXXWOMGUGJBKIW-YPCIICBESA-N piperine Chemical class C=1C=C2OCOC2=CC=1/C=C/C=C/C(=O)N1CCCCC1 MXXWOMGUGJBKIW-YPCIICBESA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
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- 239000007974 sodium acetate buffer Substances 0.000 description 1
- BHZOKUMUHVTPBX-UHFFFAOYSA-M sodium acetic acid acetate Chemical compound [Na+].CC(O)=O.CC([O-])=O BHZOKUMUHVTPBX-UHFFFAOYSA-M 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 239000007939 sustained release tablet Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
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- 238000010998 test method Methods 0.000 description 1
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- ISNYUQWBWALXEY-OMIQOYQYSA-N tsg6xhx09r Chemical compound O([C@@H](C)C=1[C@@]23CN(C)CCO[C@]3(C3=CC[C@H]4[C@]5(C)CC[C@@](C4)(O)O[C@@]53[C@H](O)C2)CC=1)C(=O)C=1C(C)=CNC=1C ISNYUQWBWALXEY-OMIQOYQYSA-N 0.000 description 1
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- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention provides an ilepcimide sustained release preparation and a preparation method thereof. The ilepcimide sustained release preparation comprises the following components in mass percentage: 10-60% of ilepcimide, 30-85% of sustained-release material, 0-10% of adjusting drug release material, 0-3% of an adhesive, 5-20% of a filler, 0-2% of a lubricant and 0-5% of a coating material. The ilepcimide sustained release preparation can release a drug at a controlled rate to realize the purpose of releasing ilepcimide within about 24 hours by dosing the ilepcimide sustained release preparation once a day. The invention further discloses the preparation method of the ilepcimide sustained release preparation.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, particularly a kind of ilepcimide slow releasing preparation and preparation method thereof.
Background technology
Epilepsy is central nervous system's chronic disease, needs long-term drug therapy.The effective percentage of the antiepileptic used clinically at present only has 70% ~ 80%, and antiepileptic can not stop the formation of epileptogenic focus and the Progressive symmetric erythrokeratodermia of the course of disease, can only relief of symptoms.In addition, antiepileptic untoward reaction is more, relates to multiple systems of human body, common adverse reactions as erythra, dizziness, feel sick, poor appetite, mental act exception, Liver and kidney function exception, hormonal system dysfunction, lymphadenectasis etc.And epileptic often needs Long-term taking medicine or takes several antiepileptic simultaneously, this can increase the weight of the untoward reaction of medicine.Childhood period be important growth and development stage, therefore Patients with Epilepsy in Childhood treatment from adult different, it is very important that the antiepileptic that effect is remarkable, untoward reaction is few carries out treatment.Fructus Piperis belongs to dialypetalous flower plant, is the evergreen liana of Piperaceae.The folkd therapy that application Fructus Piperis controls epilepsy spreads to the sixties in last century in Yunnan Province of China Xishuangbanna always, found by the expert of Beijing Medical University and pay close attention to, developed effectively by unremitting effort, the Fructus Piperis bases new type domestic plant antuepileptic ilepcimide sheet of wide spectrum, low toxicity, for epileptic, especially child patient bring Gospel.
Ilepcimide is the chemical derivative of piperine, and also known as antiepilepsirine, by working to sodium channel, suppressing sodium current to produce, thus suppress the generation of epilepsy and the effect of development, is a kind of antiepileptic of new batrachotoxin.Its chemistry 3-(3 ', 4 ' secondary first dioxy phenyl)-acryloyl acyl piperidines by name or 3 ~ 4 first dioxy aryl pyrimidines, molecular formula is C
15h
17nO
3.Ilepcimide chemical constitution comprises two similar benzene ring structures split by 4 C-C or C-N singly-bounds.This structure and traditional antiepileptic carbamazepine and lamotrigine very similar, they also have two similar benzene ring structures of 1 or several C-C or C-N singly-bound segmentation, and the antiepileptic action of these two similar benzene ring structures to medicine serves important function.Because carbamazepine and lamotrigine can prevent generalized tonic-clonic from showing effect and epilepsy partial seizures by suppressing sodium channel high-frequency discharge, infer that ilepcimide may have suitable curative effect to epilepsy partial seizures.
Ilepcimide sheet is new type domestic plant Fructus Piperis bases antuepileptic, can be used for the treatment of various epilepsy.Research finds, is being less than half lethal dose TD
50dosage under, the rat and mouse that ilepcimide causes MES, MST, strychnine, Picroloxin and intracerebroventricular curare or glutamic acid is fainted from fear the antagonism all had in various degree, and can reduce the mortality rate of animal.In addition, through systematic study, NIH (NIH) also finds that ilepcimide can resist electrofit.And oral ilepcimide easily absorbs rapidly from gastrointestinal tract, blood level 4 ~ 6h peaks, and bioavailability reaches 93.9%.Drug main will be distributed in blood plasma and eliminate comparatively fast, and is distributed in rapidly in fat, liver, kidney and cerebral tissue, and the Ratio invariableness in blood plasma and cerebral tissue, through liver metabolism.
Slow releasing preparation grows a lot in recent years, slow releasing preparation compared with ordinary preparation, Drug therapy persistent, toxic and side effects is low, and times for spraying reduces, and blood drug level is steady, the blood drug level of medicine can be avoided to exceed therapeutic domain, and reduce the accumulated dose of medication, available minimum dose reaches maximum drug effect.
Commercialized product ilepcimide sheet one day twice, a 50 ~ 150mg.There is following shortcoming in it: (1) takes inconvenience, and patient compliance is poor; (2) Antiepileptic Drugs window is general all narrower, and ordinary tablet blood concentration fluctuation is large, and the too high especially patient of blood drug level is for existing larger toxic and side effects during child, and blood drug level is too low does not reach Preferred effects; (3) ordinary tablet takes medicine accumulated dose comparatively greatly, especially has a big risk to child patient potential hazard.Therefore, this problem is solved in the urgent need to finding a kind of better method.
Summary of the invention
The object of the present invention is to provide a kind of ilepcimide slow releasing preparation, medicine can be made to enter gastrointestinal tract with speed slowly, rationally, toxic and side effects is low, drug safety for said preparation composition, Drug therapy persistent, times for spraying reduces, and blood drug level is steady, and the blood drug level of medicine can be avoided to exceed therapeutic domain, reduce the accumulated dose of medication, available minimum dose reaches maximum drug effect.
Another object of the present invention is to the preparation method providing a kind of ilepcimide slow releasing preparation, the preparation method of ilepcimide slow releasing preparation of the present invention is convenient to produce, and product is easy to storage, can better reach the object of Co ntrolled release.
Object of the present invention is achieved through the following technical solutions:
A kind of ilepcimide slow releasing preparation, comprises following component by percentage to the quality: ilepcimide 10
-60%, slow-release material 30-85%, adjustment release material 0-10%, binding agent 0-3%, filler 5-20%, lubricant 0-2% and coating material 0-5%; Described slow-release material is hydrophilic gel matrix material, select hydroxypropyl emthylcellulose and polyoxyethylene wherein one or more; Described adjustment release material selection carbomer, polyacrylic acid and carboxymethyl starch sodium wherein one or more; Described filler select starch, pregelatinized Starch, lactose, mannitol wherein one or more; Described binding agent select ethanol, water, hydroxypropyl emthylcellulose, cross-linked ethylene ketopyrrolidine and polyvinylpyrrolidone wherein one or more; Described lubricant select magnesium stearate, Pulvis Talci, calcium stearate, zinc stearate and micropowder silica gel wherein one or more.
Slow-release material of the present invention is that hydrophilic gel matrix material comprises hydroxypropyl emthylcellulose and/or polyoxyethylene.In a preferred embodiment of the invention, hydroxypropyl emthylcellulose selects K4M and/or polyoxyethylene to select WSR-205.
Adjustment release material selection carbomer of the present invention, polyacrylic acid and carboxymethyl starch sodium wherein one or more.In a preferred embodiment of the invention, preferred carbomer 971NF.
Filler of the present invention select starch, pregelatinized Starch, lactose, mannitol wherein one or more.In a preferred embodiment of the invention, preferred lactose.
Binding agent of the present invention select ethanol, water, hydroxypropyl emthylcellulose, cross-linked ethylene ketopyrrolidine and polyvinylpyrrolidone wherein one or more.In a preferred embodiment of the invention, preferred 60% ethanol.
Lubricant of the present invention select magnesium stearate, Pulvis Talci, calcium stearate, zinc stearate and micropowder silica gel wherein one or more.In a preferred embodiment of the invention, preferred magnesium stearate.
In a preferred embodiment, the invention provides a kind of ilepcimide slow releasing preparation, ilepcimide 20-60%, slow-release material 30-84%, adjustment release material 1-10%, binding agent 0-10%, filler 5-20%, lubricant 0-2% and coating material 0-5%.
Slow releasing preparation of the present invention can be the dosage form such as tablet, capsule, preferred tablet.
Present invention also offers a kind of preparation method of ilepcimide slow releasing preparation, comprising:
All supplementary materials were pulverized 60-80 mesh sieve
By ilepcimide and slow-release material, adjustment release material, packing material mix homogeneously;
Add binding agent soft material, granulate, dry;
After dried granule granulate, preferably add lubricant again, mixing, tabletting;
Then wrap with moistureproof film-coat, dry.The object of wrapping moistureproof clothing film to improve the outward appearance of preparation, provides colour code simultaneously.This art for coating is known technology, does not repeat them here.
Advantage of the present invention: the impact that food absorbs it ilepcimide can be reduced, before or after meals all can be taken, effective blood drug concentration that can be stable for a long time, increase the curative effect of medicine, effective minimizing toxic and side effects, only need take medicine once for one day, an a slice, taking convenience, increases patient compliance.
Detailed description of the invention
Following examples are the present invention's preferably embodiment; but embodiments of the present invention are also not limited by the following examples; the change done under other any does not deviate from spirit of the present invention and principle, modification, substitute, combine, simplify, all should be the substitute mode of equivalence, be included within protection scope of the present invention.
Embodiment 1
Prescription (1000):
Preparation technology:
1) all supplementary materials were pulverized 60-80 mesh sieve
2) by ilepcimide and slow-release material, adjustment release material, packing material mix homogeneously;
3) add binding agent soft material, granulate, dry;
4) by after dried granule granulate, preferably lubricant is added again, mixing, tabletting;
5) then wrap with moistureproof film-coat, coating weight gain 2-3%, dry, both.
Embodiment 2
Prescription (1000):
Preparation technology:
1) all supplementary materials were pulverized 60-80 mesh sieve
2) by ilepcimide and slow-release material, adjustment release material, packing material mix homogeneously;
3) add binding agent soft material, granulate, dry;
4) by after dried granule granulate, preferably lubricant is added again, mixing, tabletting;
5) then wrap with moistureproof film-coat, coating weight gain 2-3%, dry, both.
Embodiment 3
Prescription (1000):
Preparation technology:
1) all supplementary materials were pulverized 60-80 mesh sieve
2) by ilepcimide and slow-release material, adjustment release material, packing material mix homogeneously;
3) add binding agent soft material, granulate, dry;
4) by after dried granule granulate, preferably lubricant is added again, mixing, tabletting;
5) then wrap with moistureproof film-coat, coating weight gain 2-3%, dry, both.
Embodiment 4
Prescription (1000):
Preparation technology:
1) all supplementary materials were pulverized 60-80 mesh sieve
2) by ilepcimide and slow-release material, adjustment release material, packing material mix homogeneously;
3) add binding agent soft material, granulate, dry;
4) by after dried granule granulate, preferably lubricant is added again, mixing, tabletting;
5) then wrap with moistureproof film-coat, coating weight gain 2-3%, dry, both.
Embodiment 5
Prescription (1000):
Preparation technology:
6) all supplementary materials were pulverized 60-80 mesh sieve
7) by ilepcimide and slow-release material, adjustment release material, packing material mix homogeneously;
8) add binding agent soft material, granulate, dry;
9) by after dried granule granulate, preferably lubricant is added again, mixing, tabletting;
10) then wrap with moistureproof film-coat, coating weight gain 2-3%, dry, both.
Embodiment 6
Prescription (1000):
Preparation technology:
1) all supplementary materials were pulverized 60-80 mesh sieve
2) by ilepcimide and slow-release material, adjustment release material, packing material mix homogeneously;
3) add binding agent soft material, granulate, dry;
4) by after dried granule granulate, preferably lubricant is added again, mixing, tabletting;
5) then wrap with moistureproof film-coat, coating weight gain 2-3%, dry, both.
Embodiment 7
Prescription (1000):
Preparation technology:
1) all supplementary materials were pulverized 60-80 mesh sieve
2) by ilepcimide and slow-release material, adjustment release material, packing material mix homogeneously;
3) add binding agent soft material, granulate, dry;
4) by after dried granule granulate, preferably lubricant is added again, mixing, tabletting;
5) then wrap with moistureproof film-coat, coating weight gain 2-3%, dry, both.
Embodiment 8
Under the dissolution medium condition of different pH, release test is carried out to tablet of the present invention.
The hydrochloric acid solution (pH=1.2) of (1) 0.5% sodium lauryl sulphate;
The Acetic acid-sodium acetate buffer (pH=4.5) of (2) 0.5% sodium lauryl sulphates;
(3) simulated intestinal fluid (pH6.8) not containing pancreatin of simulating.
The aqueous solution of (4) 0.5% sodium lauryl sulphates
Method of testing: according to drug release determination method (Chinese Pharmacopoeia 2010 editions two annex XD first methods), adopt the device of dissolution method (Chinese Pharmacopoeia 2010 editions two annex XC second methods), respectively with above-mentioned dissolution medium 900ml for solvent, rotating speed is 75 turns per minute, operates, 4 in accordance with the law, 8, within 12 and 16 hours, get solution 10ml respectively, filter, and the instant dissolution medium supplementing identical temperature, same volume in process container; Get subsequent filtrate 5ml, put in 25ml measuring bottle, with solvent dilution to scale, shake up, according to spectrophotography (Chinese Pharmacopoeia 2010 editions two annex IVA), measure trap respectively at the wavelength place of 326nm; Separately get ilepcimide reference substance and be about 10mg, accurately weighed, put in 50ml measuring bottle, add methanol 20ml, supersound process, make dissolving, with methanol dilution to scale, shake up; Precision measures above-mentioned solution 5ml, puts in 50ml measuring bottle, take dissolution medium as solvent, as stock solution, respectively with corresponding dissolution medium for solvent, by following dilution process, get a certain amount of stock solution and add appropriate solvent, be diluted to certain density ilepcimide reference substance solution:
Get contrast solution 1# respectively, 2#, 3#, 4#, 5#, 6# are measured in the same method trap, drawing standard curve.The burst size of every sheet at different time is calculated according to standard curve.The results are shown in Table 1
Table 1 ilepcimide dissolution of sustained-release tablets data (n=6)
Result of the test shows, release all conformance with standard requirements of preparation prepared by method provided by the invention.
It is the release curve of 100mg and 150mg sample and the release curve under different pH condition that the present invention have also been made pharmaceutical specifications simultaneously.The release curve of slow releasing tablet of the present invention under different pH condition illustrates that its absorption in human body of product of the present invention does not affect by pH value, effect stability.
Claims (8)
1. an ilepcimide slow releasing preparation, comprises following component by percentage to the quality: ilepcimide 10-60%, slow-release material 30-85%, adjustment release material 0-10%, binding agent 0-3%, filler 5-20%, lubricant 0-2% and coating material 0-5%.
2. ilepcimide slow releasing preparation according to claim 1, is characterized in that: described slow-release material is hydrophilic gel matrix material, select hydroxypropyl emthylcellulose and polyoxyethylene wherein one or more.
3. ilepcimide slow releasing preparation according to claim 1, is characterized in that: described adjustment release material selection carbomer, polyacrylic acid and carboxymethyl starch sodium wherein one or more.
4. ilepcimide slow releasing preparation according to claim 1, is characterized in that: described filler select starch, pregelatinized Starch, lactose, mannitol wherein one or more.
5. ilepcimide slow releasing preparation according to claim 1, wherein, described binding agent select ethanol, water, hydroxypropyl emthylcellulose, cross-linked ethylene ketopyrrolidine and polyvinylpyrrolidone wherein one or more.
6. ilepcimide slow releasing preparation according to claim 1, wherein, described lubricant select magnesium stearate, Pulvis Talci, calcium stearate, zinc stearate and micropowder silica gel wherein one or more.
7. ilepcimide slow releasing preparation according to claim 1, wherein, also may carry out bag moisture-proof film clothing after tabletting.
8. a preparation method for the ilepcimide slow releasing preparation any one of claim 1-7 described in claim, this preparation method comprises:
1) all supplementary materials were pulverized 60-80 mesh sieve;
2) by ilepcimide and slow-release material, adjustment release material, packing material mix homogeneously;
3) add binding agent soft material, granulate, dry;
4) by after dried granule granulate, preferably lubricant is added again, mixing, tabletting;
5) then wrap with moistureproof film-coat, coating weight gain 2-3%, dry, both.
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| CN105943537A (en) * | 2016-06-28 | 2016-09-21 | 顾万清 | Compound anisodamine and neostigmine sustained-release tablet and preparation method thereof |
| CN113521022A (en) * | 2021-06-24 | 2021-10-22 | 北京斯利安健康科技有限公司 | Sustained-release tablet containing alexidine and preparation method thereof |
| CN113577037A (en) * | 2021-06-24 | 2021-11-02 | 北京斯利安健康科技有限公司 | Controlled release tablet containing alexidine and preparation method and application thereof |
| CN114796127A (en) * | 2022-05-16 | 2022-07-29 | 北京斯利安药业有限公司 | Iloxamine sustained-release dry suspension and preparation method thereof |
| CN115590830A (en) * | 2021-07-08 | 2023-01-13 | 武汉熙瑞医药科技有限公司（Cn） | Broglitazone sustained-release preparation and preparation method thereof |
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| CN105193803B (en) | 2019-02-19 |
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