CN100551369C - A kind of slow releasing preparation that contains cilostazol and preparation method thereof - Google Patents
A kind of slow releasing preparation that contains cilostazol and preparation method thereof Download PDFInfo
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- CN100551369C CN100551369C CNB2007100204738A CN200710020473A CN100551369C CN 100551369 C CN100551369 C CN 100551369C CN B2007100204738 A CNB2007100204738 A CN B2007100204738A CN 200710020473 A CN200710020473 A CN 200710020473A CN 100551369 C CN100551369 C CN 100551369C
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- RRGUKTPIGVIEKM-UHFFFAOYSA-N cilostazol Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCCC1=NN=NN1C1CCCCC1 RRGUKTPIGVIEKM-UHFFFAOYSA-N 0.000 title claims abstract description 38
- 229960004588 cilostazol Drugs 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
- 230000003578 releasing effect Effects 0.000 title claims abstract description 15
- 239000000463 material Substances 0.000 claims abstract description 11
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 8
- -1 polyethylene Polymers 0.000 claims description 14
- 239000002775 capsule Substances 0.000 claims description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
- 239000001856 Ethyl cellulose Substances 0.000 claims description 8
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 8
- 230000001476 alcoholic effect Effects 0.000 claims description 8
- 229920001249 ethyl cellulose Polymers 0.000 claims description 8
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 8
- 239000000314 lubricant Substances 0.000 claims description 6
- 229920002472 Starch Polymers 0.000 claims description 5
- 239000008187 granular material Substances 0.000 claims description 5
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 5
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 5
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 5
- 235000019359 magnesium stearate Nutrition 0.000 claims description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 5
- 239000008107 starch Substances 0.000 claims description 5
- 235000019698 starch Nutrition 0.000 claims description 5
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 4
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 239000000945 filler Substances 0.000 claims description 4
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 4
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 4
- 229920002125 Sokalan® Polymers 0.000 claims description 3
- 235000000346 sugar Nutrition 0.000 claims description 3
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- 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 2
- 239000004375 Dextrin Substances 0.000 claims description 2
- 229920001353 Dextrin Polymers 0.000 claims description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 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 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- 239000004698 Polyethylene Substances 0.000 claims description 2
- 239000004743 Polypropylene Substances 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 2
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- NKWPZUCBCARRDP-UHFFFAOYSA-L calcium bicarbonate Chemical compound [Ca+2].OC([O-])=O.OC([O-])=O NKWPZUCBCARRDP-UHFFFAOYSA-L 0.000 claims description 2
- 229910000020 calcium bicarbonate Inorganic materials 0.000 claims description 2
- 235000011132 calcium sulphate Nutrition 0.000 claims description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 235000010980 cellulose Nutrition 0.000 claims description 2
- 239000004568 cement Substances 0.000 claims description 2
- 238000004132 cross linking Methods 0.000 claims description 2
- 235000019425 dextrin Nutrition 0.000 claims description 2
- 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 2
- 239000008103 glucose Substances 0.000 claims description 2
- 235000001727 glucose Nutrition 0.000 claims description 2
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 229920000573 polyethylene Polymers 0.000 claims description 2
- 229920001155 polypropylene Polymers 0.000 claims description 2
- 229920001296 polysiloxane Polymers 0.000 claims description 2
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 claims description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 2
- 239000000741 silica gel Substances 0.000 claims description 2
- 229910002027 silica gel Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 11
- 229940079593 drug Drugs 0.000 abstract description 6
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 7
- 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 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000007500 overflow downdraw method Methods 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- OJPDDTMYEPHDAJ-UHFFFAOYSA-N 1-butoxy-3,4-dihydroquinolin-2-one Chemical class C(CCC)ON1C(CCC2=CC=CC=C12)=O OJPDDTMYEPHDAJ-UHFFFAOYSA-N 0.000 description 1
- WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229920000219 Ethylene vinyl alcohol Polymers 0.000 description 1
- 206010017577 Gait disturbance Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 230000006502 antiplatelets effects Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 229940082484 carbomer-934 Drugs 0.000 description 1
- 229920003086 cellulose ether Polymers 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 229960001123 epoprostenol Drugs 0.000 description 1
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229960005152 pentetrazol Drugs 0.000 description 1
- 239000002957 persistent organic pollutant Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000001196 vasorelaxation Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Abstract
The present invention relates to field of pharmaceutical preparations, be specifically related to the slow releasing preparation of cilostazol, slow released cilostazol preparation of the present invention is by containing 35～60% cilostazols, other pharmaceutic adjuvant of 10～60% slow-release materials and surplus is formed, slow release cilostazol preparation of the present invention enters drug slow release in back in the body, can take once in one day.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of slow releasing preparation that contains cilostazol and preparation method thereof.
Background technology
Cilostazol (cilostazol) chemistry 6-[4-by name (1-cyclohexyl-1H-pentylenetetrazole (5 ')] butoxy-3,4-dihydro-1H quinolinones (2 '), it is a kind of novel anti platelet aggregation drugs, by phosphodiesterase activity in inhibition platelet and the vascular smooth muscle, thus the interior cAMP concentration of platelet increasing and smooth muscle, performance antiplatelet effects and vasorelaxation action.This product suppresses platelet initial stage, the second phase of ADP, epinephrine, collagen and arachidonic acid-induction and assembles and release reaction, and be dosage correlation.The oral 100mg of cilostazol to the inhibition of platelet aggregation in vitro than respective amount aspirin strong 7～78 times (it is invalid that aspirin was assembled the platelet initial stage).This product is not disturbed vascular endothelial cell synthetic vessel protectiveness prostacyclin; to the chronic arteria occlusion patient; adopt plethysmography to show that this product can increase tissue blood flow's amount at foot, gastrocnemius position; make the rising of lower limb blood pressure index, SkBF increase and the temperature rise of extremity skin, and improve intermittent limping.
At present clinical use mainly be the cilostazol ordinary tablet, in addition, the report of other dosage form is arranged also, as: CN1562018A discloses the solid dispersion of cilostazol; CN1403083A discloses the fast disintegrating tablet of cilostazol.The oral back disintegrate rapidly of these quick releasing formulations discharges a large amount of unnecessary cilostazols at short notice in vivo, therefore can produce such as headache, serious head and not accommodate the side effect of pain.In order to overcome these defectives, CN1168102A discloses a kind of resin particle that can discharge the cilostazol of aequum a segment length in the time in vivo continuously, it is by mixing cilostazol in the ethylene-vinyl alcohol copolymer to realize continuing the purpose of release, it mainly adopts the fusion method preparation, but when preparing, need use fusion method organic solvents such as chloroform, the residual meeting of these solvents causes side effect to the patient, in addition, cilostazol and copolymer are easily oxidized in fusion and the forming process, and these unfavorable factors have all restricted its production and use.
Summary of the invention
The invention discloses a kind of slow releasing preparation of cilostazol, it contains as the cilostazol of active component and slow-release material, slow released cilostazol preparation of the present invention is taken the back medicine and is slowly discharged in vivo, medicine is the long period drug level of remaining valid in vivo, thereby reach the minimizing drug dose, improve drug effect, the good effect of prolong drug action time and minimizing adverse effect.
Slow released cilostazol preparation of the present invention is by containing 35～60% cilostazols, and other pharmaceutic adjuvant of 10～60% slow-release materials and surplus is formed, and above-mentioned percentage ratio is weight percentage.
Preferred percentage by weight is a cilostazol 45～60%, slow-release material 15～50%, and surplus is other pharmaceutic adjuvant.
In above-mentioned described slow-release material preference card POP, ethyl cellulose, methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, stearic acid, glyceryl monostearate, octadecanol, polyethylene, polypropylene, the polysiloxanes one or more.
Slow-release material is one or more in carbopol, hydroxypropyl methylcellulose, the ethyl cellulose more preferably.
Above-mentioned described other pharmaceutic adjuvant is one or more in pharmaceuticss such as filler, disintegrating agent, binding agent, lubricant adjuvant commonly used preferably.
In the preferred sugar of above-mentioned filler, sucrose, starch, pregelatinized Starch, cellulose, Icing Sugar, dextrin, glucose, mannitol, calcium sulfate, the calcium bicarbonate one or more; In disintegrating agent preferable methyl Starch Sodium, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, the cross-linking sodium carboxymethyl cellulose one or more; In the water of the alcoholic solution of binding agent preferred alcohols, polyvinylpyrrolidone, ethyl cellulose, starch slurry, cellulose ethers or alcoholic solution, the rubber cement one or more; In the preferred magnesium stearate of lubricant, Pulvis Talci, micropowder silica gel, sodium lauryl sulphate or the Stepanol MG one or more.
Slow releasing preparation of the present invention, preferred dosage form is tablet or capsule.
Slow releasing preparation preparation technology of the present invention is simple, and concrete grammar is: will granulate behind cilostazol, slow-release material, other pharmaceutic adjuvant mixing, tabletting or be filled into capsule again.
Slow releasing preparation of the present invention has changed the release form of original dosage form, discharges 10-30% in two hours taking medicine, and takes medicine to discharge 45～75% in eight hours, continues drug effect thereby produce.The invention provides a kind of drug reservoir form, the medicine that contains cilostazol can slowly be discharged.Slow releasing pharmaceutical of the present invention can be taken once in one day.
The specific embodiment
Embodiment 1
The slow released cilostazol sheet is by 1000
Composition weight (g)
Cilostazol 200
Hydroxypropyl emthylcellulose K4M 70
Lactose 100
Magnesium stearate 3.5
Polyvinyl pyrrolidone alcoholic solution K-30 q.s
Preparation method:
The supplementary material crushing screening, behind the mixing with mix lubricant, tabletting.
Embodiment 2
Slow released cilostazol sheet: by 1000
Composition weight (g)
Cilostazol 200
Hydroxypropyl emthylcellulose Methocl K4M 40
Hydroxypropyl emthylcellulose Methocl 100cp 40
Lactose 100
Magnesium stearate 3.5
Polyvinyl pyrrolidone alcoholic solution q.s
Preparation method:
The supplementary material crushing screening by above-mentioned recipe quantity difference mixing, is made granule, and oven dry is sieved, then with the mix lubricant tabletting.
Embodiment 3
Slow released cilostazol sheet: by 1000
Composition weight (g)
Cilostazol 200
Hydroxypropyl emthylcellulose Methocl K4M 120
Microcrystalline Cellulose PH101 30
Lactose 50
Magnesium stearate 4
Hypromellose alcoholic solution (100cp) q.s
Preparation method is with embodiment 2.
Embodiment 4
Slow released cilostazol capsule: by 1000 capsules
Composition weight (g)
Cilostazol 200
Hydroxypropyl emthylcellulose K10M 120
Lactose 30
Amidin q.s
Preparation method:
The supplementary material crushing screening by above-mentioned recipe quantity difference mixing, is made granule, oven dry, and granulate is poured in the capsule.
Embodiment 5
Slow released cilostazol capsule: by 1000 capsules
Composition weight (g)
Cilostazol 200
Hydroxypropyl emthylcellulose 120
Ethyl cellulose 30
Ethyl cellulose alcoholic solution q.s
Preparation method is with embodiment 4.
Embodiment 6
Slow released cilostazol capsule: by 1000 capsules
Composition weight (g)
Cilostazol 200
Hydroxypropyl emthylcellulose 120
Carbomer 934 20
Lactose 20
Polyvinyl pyrrolidone alcoholic solution q.s
Preparation method is with embodiment 4.
Embodiment 7
External dissolution test
Dissolution medium: 0.45% lauryl sodium sulfate aqueous solution, 100 rev/mins of commentaries on classics basket methods
The different time cumulative in vitro stripping value of prepared slow released cilostazol preparation sees Table among the embodiment 1 to 6:
Last table as seen, slow released cilostazol preparation of the present invention can slowly discharge, and has reached ideal releasing effect.
Claims (4)
1, a kind of slow releasing preparation of cilostazol, it is characterized in that: by containing 45～60 weight % cilostazols, other pharmaceutic adjuvant of 15～50 weight % slow-release materials and surplus is formed, to granulate behind cilostazol, slow-release material and other pharmaceutic adjuvant mixing, tabletting or be filled into capsule promptly again, wherein slow-release material is selected from one or more in carbopol, ethyl cellulose, methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, stearic acid, glyceryl monostearate, octadecanol, polyethylene, polypropylene, the polysiloxanes.
2, the slow releasing preparation of claim 1, wherein slow-release material is selected from one or more in carbopol, hydroxypropyl methylcellulose, the ethyl cellulose.
3, the slow releasing preparation of claim 1, wherein other pharmaceutic adjuvant is selected from one or more in filler, disintegrating agent, binding agent, the lubricant.
4, the slow releasing preparation of claim 3, wherein filler is selected from one or more in sucrose, starch, cellulose, Icing Sugar, dextrin, glucose, mannitol, calcium sulfate, the calcium bicarbonate; Disintegrating agent is selected from one or more in methyl starch sodium, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, the cross-linking sodium carboxymethyl cellulose; Binding agent is selected from the alcoholic solution of polyvinylpyrrolidone, ethyl cellulose, in the rubber cement one or more; Lubricant is selected from one or more in magnesium stearate, Pulvis Talci, micropowder silica gel, the sodium lauryl sulphate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007100204738A CN100551369C (en) | 2007-03-02 | 2007-03-02 | A kind of slow releasing preparation that contains cilostazol and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007100204738A CN100551369C (en) | 2007-03-02 | 2007-03-02 | A kind of slow releasing preparation that contains cilostazol and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101015536A CN101015536A (en) | 2007-08-15 |
| CN100551369C true CN100551369C (en) | 2009-10-21 |
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| CNB2007100204738A Active CN100551369C (en) | 2007-03-02 | 2007-03-02 | A kind of slow releasing preparation that contains cilostazol and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9180198B2 (en) * | 2009-09-23 | 2015-11-10 | Korea United Pharm, Inc. | Slow-release cilostazol tablet having an improved elution rate and minimal side effects |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101006990A (en) * | 2005-09-26 | 2007-08-01 | 刘凤鸣 | Slow release preparation of cilostazol |
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2007
- 2007-03-02 CN CNB2007100204738A patent/CN100551369C/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101006990A (en) * | 2005-09-26 | 2007-08-01 | 刘凤鸣 | Slow release preparation of cilostazol |
Non-Patent Citations (2)
| Title |
|---|
| 药物辅料手册. [英]R.C.罗 P.J.韦勒,[美]P.J.舍斯基编,郑俊民主译，343，化学工业出版社. 2005 |
| 药物辅料手册. [英]R.C.罗 P.J.韦勒,[美]P.J.舍斯基编,郑俊民主译，343，化学工业出版社. 2005 * |
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| CN101015536A (en) | 2007-08-15 |
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