CN1094347C - A kind of controlled-release pellets for treating benign prostatic hyperplasia and preparation method thereof - Google Patents
A kind of controlled-release pellets for treating benign prostatic hyperplasia and preparation method thereof Download PDFInfo
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- CN1094347C CN1094347C CN99117214A CN99117214A CN1094347C CN 1094347 C CN1094347 C CN 1094347C CN 99117214 A CN99117214 A CN 99117214A CN 99117214 A CN99117214 A CN 99117214A CN 1094347 C CN1094347 C CN 1094347C
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- 238000002360 preparation method Methods 0.000 title claims abstract description 50
- 238000013270 controlled release Methods 0.000 title claims abstract description 41
- 239000008188 pellet Substances 0.000 title abstract 5
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 title abstract 2
- 208000004403 Prostatic Hyperplasia Diseases 0.000 title abstract 2
- 239000004925 Acrylic resin Substances 0.000 claims abstract description 21
- 229920000178 Acrylic resin Polymers 0.000 claims abstract description 21
- VAPSMQAHNAZRKC-PQWRYPMOSA-N Epristeride Chemical compound C1C=C2C=C(C(O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)NC(C)(C)C)[C@@]1(C)CC2 VAPSMQAHNAZRKC-PQWRYPMOSA-N 0.000 claims abstract description 12
- 229950009537 epristeride Drugs 0.000 claims abstract description 12
- 235000019325 ethyl cellulose Nutrition 0.000 claims abstract description 10
- 229920001249 ethyl cellulose Polymers 0.000 claims abstract description 10
- 239000004014 plasticizer Substances 0.000 claims abstract description 9
- 239000004094 surface-active agent Substances 0.000 claims abstract description 9
- 239000001856 Ethyl cellulose Substances 0.000 claims abstract description 5
- 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 abstract description 5
- 239000000725 suspension Substances 0.000 claims description 35
- 238000005507 spraying Methods 0.000 claims description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- 238000001035 drying Methods 0.000 claims description 20
- 239000011248 coating agent Substances 0.000 claims description 19
- 238000000576 coating method Methods 0.000 claims description 19
- 239000006187 pill Substances 0.000 claims description 19
- 235000010603 pastilles Nutrition 0.000 claims description 18
- 238000003756 stirring Methods 0.000 claims description 15
- 239000012153 distilled water Substances 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- -1 hydroxypropyl Chemical group 0.000 claims description 9
- 206010013786 Dry skin Diseases 0.000 claims description 5
- 229920002472 Starch Polymers 0.000 claims description 5
- 229930006000 Sucrose Natural products 0.000 claims description 5
- 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 5
- 238000007654 immersion Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 239000008107 starch Substances 0.000 claims description 5
- 235000019698 starch Nutrition 0.000 claims description 5
- 239000005720 sucrose Substances 0.000 claims description 5
- ZFOZVQLOBQUTQQ-UHFFFAOYSA-N Tributyl citrate Chemical compound CCCCOC(=O)CC(O)(C(=O)OCCCC)CC(=O)OCCCC ZFOZVQLOBQUTQQ-UHFFFAOYSA-N 0.000 claims description 4
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 claims description 4
- 239000005995 Aluminium silicate Substances 0.000 claims description 3
- PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 0.000 claims description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical group [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 3
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical group CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 3
- 235000012211 aluminium silicate Nutrition 0.000 claims description 3
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 claims description 3
- 239000004816 latex Substances 0.000 claims description 3
- 229920000126 latex Polymers 0.000 claims description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 3
- 239000001069 triethyl citrate Substances 0.000 claims description 3
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 3
- 235000013769 triethyl citrate Nutrition 0.000 claims description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 2
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 claims description 2
- KMZHZAAOEWVPSE-UHFFFAOYSA-N 2,3-dihydroxypropyl acetate Chemical compound CC(=O)OCC(O)CO KMZHZAAOEWVPSE-UHFFFAOYSA-N 0.000 claims description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
- 239000005642 Oleic acid Substances 0.000 claims description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 2
- MOVRNJGDXREIBM-UHFFFAOYSA-N aid-1 Chemical compound O=C1NC(=O)C(C)=CN1C1OC(COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)CO)C(O)C1 MOVRNJGDXREIBM-UHFFFAOYSA-N 0.000 claims description 2
- 238000000889 atomisation Methods 0.000 claims description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 2
- 239000000344 soap Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 13
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 abstract description 5
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 abstract description 5
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 abstract description 5
- 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 abstract description 5
- 239000008280 blood Substances 0.000 abstract description 4
- 210000004369 blood Anatomy 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 2
- 238000000338 in vitro Methods 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 239000011162 core material Substances 0.000 abstract 1
- 238000012423 maintenance Methods 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 229920001577 copolymer Polymers 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- TYSYCALJZQGVLT-UHFFFAOYSA-N 3-acetyl-3,4-dihydroxy-4-(hydroxymethyl)hexane-2,5-dione Chemical class CC(=O)C(O)(CO)C(O)(C(C)=O)C(C)=O TYSYCALJZQGVLT-UHFFFAOYSA-N 0.000 description 1
- 239000002677 5-alpha reductase inhibitor Substances 0.000 description 1
- 229920003138 Eudragit® L 30 D-55 Polymers 0.000 description 1
- 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 description 1
- 235000010407 ammonium alginate Nutrition 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000036967 uncompetitive effect Effects 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The invention discloses a controlled release pellet for treating benign prostatic hyperplasia, which consists of epristeride, a blank pellet core, ethyl cellulose, acrylic resin, a surfactant, a plasticizer and a hydroxypropyl methyl cellulose anti-sticking agent. The invention also discloses a preparation method of the controlled release pellet. The controlled release pellet can be effectively maintained for more than 12 hours in vitro tests, can properly control the release rate of the medicament compared with epristeride, can prolong the maintenance of the effective concentration of the medicament in the blood of the elderly and improve the treatment effect of the medicament.
Description
The present invention relates to a kind of pharmaceutical composition for the treatment of benign prostatic hyperplasis and preparation method thereof, particularly a kind of controlled release micro pill for the treatment of benign prostatic hyperplasis and preparation method thereof.
Epristeride (Epristeride) (17 β-(the N-tert-butyl group-amino-formoxyl)-androstane-3; 5-diene-3-carboxylic acid) is a kind of 5-alpha-reductase inhibitors of uncompetitive; the treatment benign prostatic hyperplasis had good curative effect (Sun Zuyue, Tu Ceng Hong " pharmacy progress " 1995,19 (4) P211～215).But the result of study of the old human body single-dose of epristeride pharmacokinetics shows that the biological half-life of this medicine is t
1/2Therefore=5.095h can not keep this medicine for a long time in blood in human body in medicine valid density, influences the therapeutic effect of this medicine.
The object of the present invention is to provide a kind of micropill with treatment benign prostatic hyperplasis of control-release function, it can keep epristeride for a long time in old blood in human body in medicine valid density.
Another object of the present invention is to provide the preparation method of this controlled release micro pill.
Treatment benign prostatic hyperplasis controlled release micro pill of the present invention contains following component (following all be weight percentage): epristeride 2.5%～3.5% blank pill core 70.0%～82.5% ethyl cellulose 9.5%～17.5% acrylic resin 0.5%～1.0% surfactant 1.3%～2.5% plasticizer 2.2%～4.1% hydroxypropyl methylcellulose 0.5%～1.1% antiplastering aid 0.2%～0.4%
Above-mentioned each component is formed celphere, pastille confining bed, not pastille confining bed, controlled release clothing layer and seal-coat layer from inside to outside. wherein pastille confining bed is made up of following component: epristeride 85%～95% hydroxypropyl methylcellulose 4%～10% antiplastering aid 1%～5% not pastille confining bed is made up of following component: hydroxypropyl methylcellulose 60%～80% antiplastering aid 20%～40% controlled release clothing layer is made up of following component: ethyl cellulose 50%～90% acrylic resin 1%～8% surfactant 3%～16% plasticizer 6%～26% seal-coat layer is made up of following component: hydroxypropyl methylcellulose 55%～90% antiplastering aid 10%～45%
Wherein celphere is mixed by 30%～70% starch and 30%～70% sucrose, surfactant is a sodium lauryl sulphate, hexadecanol, monovalence ammonium soaps or their mixture, antiplastering aid is Pulvis Talci or Kaolin, plasticizer is a triethyl citrate, dibutyl sebacate, diethyl phthalate, the acetic acid monoglyceride, tributyl citrate, Oleum Ricini, triacetyl glycerine, cochin oil or oleic acid, the preferred enteric solubility I of acrylic resin acrylic resin latex, enteric solubility II acrylic resin, enteric solubility III acrylic resin, their structural formula is:
Wherein enteric solubility I acrylic resin latex is a methacrylic acid--butyl acrylate copolymer (polymer monomers n
1: n
2=1: 1, R
1Be H, R
2Be C
4H
9, M
w=2.5 * 10
5), enteric solubility II acrylic resin is methacrylic acid-methylmethacrylate copolymer (polymer monomers n
1: n
2=1: 1, R
1Be CH
3, R
2Be CH
3, M
w=1.35 * 10
5), enteric solubility III acrylic resin is methacrylic acid-methylmethacrylate copolymer (polymer monomers n
1: n
2=1: 2, R
1Be CH
3, R
2Be CH
3, M
w=1.35 * 10
5).
The preparation method of treatment benign prostatic hyperplasis controlled release micro pill of the present invention is made up of following steps: the preparation of (one) coating suspension successively
(1) preparation of suspension: 2～10 gram hydroxypropyl emthylcelluloses in 20～120ml80～90 ℃ distilled water immersion 2～8 hours, are added 0.2～10 gram antiplastering aid and 100～180ml95% ethanol then, stir, 200 mesh sieves filter.
(2) preparation of coating suspension: 2～6.5 gram epristerides are added 55～160ml95% dissolve with ethanol, add 6.0～47ml suspension again, stir.(2) preparation of controlled release coat liquid
13～65 gram ethyl celluloses, 1.3～3.3 gram acrylic resins, 3.8～17 gram plasticizers, 1.8～9.2 gram surfactants, 181～240ml distilled water are mixed, stir, filter with 200 mesh sieves.(3) preparation of pastille confining bed
After celphere 50～150 gram dryings, that 63～215ml coating suspension spray coating is in celphere, and then dry.(4) the not preparation of pastille confining bed
Continue spray coating, drying with 5～18ml suspension.(5) preparation of controlled release clothing layer
With 80～180ml controlled release coat liquid, continue spray coating, drying.(6) preparation of seal-coat layer
Continue spray coating, drying with 5～18ml suspension.
Wherein antiplastering aid has been crossed 200 mesh sieves, and spray coating carries out in ebullated bed coating machine, and the working condition of ebullated bed coating machine is 40～60 ℃ of baking temperatures, and atomisation pressure is 0.8～3.0bar, and the wriggling pump speed is 0.2～5ml/min.
The present invention treats the controlled release micro pill of benign prostatic hyperplasis and can effectively keep more than 12 hours in vitro tests, compare with epristeride, can suitably control the rate of release of medicament, can prolong this medicine, improve the therapeutic effect of this medicine the keeping of old blood in human body in medicine valid density.
The preparation of embodiment 1 (one) coating suspension
(1) preparation of suspension: 2 gram hydroxypropyl emthylcelluloses in 20ml80 ℃ of distilled water immersion 2 hours, are added 0.2 gram then and crossed 200 mesh sieve Pulvis Talci and 100ml95% ethanol, stir, 200 mesh sieves filter.
(2) preparation of coating suspension: 2 gram epristerides are added the 60ml95% dissolve with ethanol, add the 6.0ml suspension again, stir.(2) preparation of controlled release coat liquid
13 gram ethyl celluloses, 1.3 gram enteric solubility II acrylic resins, 3.8ml triethyl citrate, 1.8 gram sodium lauryl sulphates, 181ml distilled water are mixed, stir, filter with 200 mesh sieves.(3) preparation of pastille confining bed
After 50 ℃ of following dryings of celphere that 50% starch and 50% sucrose mix, 50 grams, that 63ml coating suspension spray coating is in celphere, and then dry.(4) the not preparation of pastille confining bed
Continue spray coating, drying with the 5ml suspension.(5) preparation of controlled release clothing layer
With 80ml controlled release coat liquid, continue spray coating, drying.(6) preparation of seal-coat layer
Continue spray coating, drying with the 5ml suspension.Promptly get white spherical piller, treat the controlled release micro pill of benign prostatic hyperplasis for the present invention.
The preparation of embodiment 2 (one) coating suspensions
(1) preparation of suspension: 5 gram hydroxypropyl emthylcelluloses in 60ml85 ℃ of distilled water immersion 4 hours, are added 2 grams then and crossed 200 mesh sieve Kaolin and 140ml95% ethanol, stir, 200 mesh sieves filter.
(2) preparation of coating suspension: 3.5 gram epristerides are added the 100ml95% dissolve with ethanol, add the 11ml suspension again, stir.(2) preparation of controlled release coat liquid
36.5 ethyl celluloses, 1.9 gram enteric solubility III acrylic resins, 9 gram dibutyl sebacates, 5.5 gram hexadecanol, 212ml distilled water are mixed, stir, filter with 200 mesh sieves.(3) preparation of pastille confining bed
After 50 ℃ of following dryings of celphere that 30% starch and 70% sucrose mix, 90 grams, that 114ml coating suspension spray coating is in celphere, and then dry.(4) the not preparation of pastille confining bed
Continue spray coating, drying with the 10ml suspension.(5) preparation of controlled release clothing layer
With 120ml controlled release coat liquid, continue spray coating, drying.(6) preparation of seal-coat layer
Continue spray coating, drying with the 13ml suspension.Promptly get white spherical piller, treat the controlled release micro pill of benign prostatic hyperplasis for the present invention.
The preparation of embodiment 3 (one) coating suspensions
(1) preparation of suspension: 10 gram hydroxypropyl emthylcelluloses in 120ml90 ℃ of distilled water immersion 8 hours, are added 10 grams then and crossed 200 mesh sieve Pulvis Talci and 180ml95% ethanol, stir, 200 mesh sieves filter.
(2) preparation of coating suspension: 8 gram epristerides are added the 160ml95% dissolve with ethanol, add the 47ml suspension again, stir.(2) preparation of controlled release coat liquid
Eudragit L30 D-55 acrylic resin, 17 gram triacetyl glycerines, 2 gram hexadecanol, 3 gram ammonium alginates, the 240ml distilled water of 65 ethyl celluloses, 3.3 gram Shanghai Romo Co.,Ltd are mixed, stir, filter with 200 mesh sieves.(3) preparation of pastille confining bed
After 50 ℃ of following dryings of celphere that 70% starch and 30% sucrose mix, 150 grams, that 200ml coating suspension spray coating is in celphere, and then dry.(4) the not preparation of pastille confining bed
Continue spray coating, drying with the 18ml suspension.(5) preparation of controlled release clothing layer
With 180ml controlled release coat liquid, continue spray coating, drying.(6) preparation of seal-coat layer
Continue spray coating, drying with the 18ml suspension.Promptly get white spherical piller, treat the controlled release micro pill of benign prostatic hyperplasis for the present invention.
The test of embodiment 4 releases
Get embodiment 1,2, the controlled release micro pill that makes in 3, be numbered sample 1, sample 2, sample 3, according to drug release determination method (two appendix XD first methods of Chinese Pharmacopoeia nineteen ninety-five version), adopt dissolution method second subtraction unit, 800ml is a solvent with sodium hydroxide solution (0.001mol/L), rotating speed is that per minute 80 changes, operation in accordance with the law, through 1,2, in the time of 4 and 8 hours, get solution 10ml respectively, and replenish uniform temp simultaneously, the sodium hydroxide solution of equal volume (0.001mol/L), filter, get subsequent filtrate,, measure trap at the wavelength place of 266nm according to spectrophotography (the 18th page of two appendix IVA of Chinese Pharmacopoeia nineteen ninety-five version); Other gets epristeride 15mg, puts in the 100ml volumetric flask, and the about 60ml of hydro-oxidation sodium solution (0.001mol/L) ultrasonicly makes whole dissolvings, is cooled to room temperature, and (0.001mol/L) is diluted to scale with sodium hydroxide solution, shakes up, and filters; Precision is measured subsequent filtrate 2ml, puts in the 50ml volumetric flask, and (0.001mol/L) is diluted to scale with sodium hydroxide solution, shakes up, and measures with method.Measurement result is as shown in table 1.
Table 1 controlled release micro pill release test of the present invention
| Sample time (hour) | Average accumulated discharges percentage ratio (%) | |
| 1 2 4 8 | Sample number into spectrum | 1 2 3 |
| 19.29 17.13 16.73 30.50 30.69 28.27 53.98 52.36 51.98 83.30 83.59 82.80 | ||
Claims (10)
1, a kind of controlled release micro pill for the treatment of benign prostatic hyperplasis, contain following component (following all be weight percentage): epristeride 2.5%～3.5% celphere 70.0%～82.5% ethyl cellulose 9.5%～17.5% acrylic resin 0.5%～1.0% surfactant 1.3%～2.5% plasticizer 2.2%～4.1% hydroxypropyl emthylcellulose 0.5%～1.1% antiplastering aid 0.2%～0.4% wherein each component is formed celphere from inside to outside, the pastille confining bed, pastille confining bed not, controlled release clothing layer and seal-coat layer, the pastille confining bed is made up of following component: epristeride 85%～95% hydroxypropyl emthylcellulose 4%～10% antiplastering aid 1%～5% not pastille confining bed is made up of following component: hydroxypropyl emthylcellulose 60%～80% antiplastering aid 20%～40% controlled release clothing layer is made up of following component: ethyl cellulose 50%～90% acrylic resin 1%～8% surfactant 3%～16% plasticizer 6%～26% seal-coat layer is made up of following component: hydroxypropyl emthylcellulose 55%～90% antiplastering aid 10%～45%
2, controlled release micro pill as claimed in claim 1 is characterized in that celphere is mixed by 30%～70% starch and 30%～70% sucrose.
3, controlled release micro pill as claimed in claim 1 is characterized in that the preferred enteric solubility I of acrylic resin acrylic resin latex, enteric solubility II acrylic resin, enteric solubility III acrylic resin.
4, controlled release micro pill as claimed in claim 1 is characterized in that surfactant is sodium lauryl sulphate, hexadecanol, monovalence ammonium soaps or their mixture.
5, controlled release micro pill as claimed in claim 1 is characterized in that antiplastering aid is Pulvis Talci or Kaolin.
6, controlled release micro pill as claimed in claim 1 is characterized in that plasticizer is triethyl citrate, dibutyl sebacate, diethyl phthalate, acetic acid monoglyceride, tributyl citrate, Oleum Ricini, triacetyl glycerine, cochin oil or oleic acid.
7, a kind of method for preparing the described controlled release micro pill of claim 1 is made up of following steps: the preparation of (one) coating suspension successively
(1) preparation of suspension: 2～10 gram hydroxypropyl emthylcelluloses in 20～120ml80～90 ℃ distilled water immersion 2～8 hours, are added 0.2～10 gram antiplastering aid and 100～180ml95% ethanol then, stir, 200 mesh sieves filter.
(2) preparation of coating suspension: 2～6.5 gram epristerides are added 55～160ml95% dissolve with ethanol, add 6.0～47ml suspension again, stir.(2) preparation of controlled release coat liquid
13～65 gram ethyl celluloses, 1.3～3.3 gram acrylic resins, 3.8～17 gram plasticizers, 1.8～9.2 gram surfactants, 181～240ml distilled water are mixed, stir, filter with 200 mesh sieves.(3) preparation of pastille confining bed
After celphere 50～150 gram dryings, that 63～215ml coating suspension spray coating is in celphere, and then dry.(4) the not preparation of pastille confining bed
Continue spray coating, drying with 5～18ml suspension.(5) preparation of controlled release clothing layer
With 80～180ml controlled release coat liquid, continue spray coating, drying.(6) preparation of seal-coat layer
Continue spray coating, drying with 5～18ml suspension.
8, preparation method as claimed in claim 7 is characterized in that antiplastering aid 200 mesh sieves excessively.
9, preparation method as claimed in claim 7 is characterized in that spray coating carries out in ebullated bed coating machine.
10, preparation method as claimed in claim 7, the working condition that it is characterized in that ebullated bed coating machine are 40～60 ℃ of baking temperatures, and atomisation pressure is 0.8～3.0bar, and the wriggling pump speed is 0.2～5ml/min.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN99117214A CN1094347C (en) | 1999-11-15 | 1999-11-15 | A kind of controlled-release pellets for treating benign prostatic hyperplasia and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN99117214A CN1094347C (en) | 1999-11-15 | 1999-11-15 | A kind of controlled-release pellets for treating benign prostatic hyperplasia and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1255332A CN1255332A (en) | 2000-06-07 |
| CN1094347C true CN1094347C (en) | 2002-11-20 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN99117214A Expired - Fee Related CN1094347C (en) | 1999-11-15 | 1999-11-15 | A kind of controlled-release pellets for treating benign prostatic hyperplasia and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1094347C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100421666C (en) * | 2006-07-27 | 2008-10-01 | 江苏联环药业股份有限公司 | Epristeride slow release preparation |
| CN101602865B (en) * | 2009-03-13 | 2011-08-31 | 王懋 | Ethylcellulose mixed suspension liquid and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1200924A (en) * | 1997-05-29 | 1998-12-09 | 伊莱利利公司 | Fluoxetine enteric micropills |
| CN1213301A (en) * | 1996-03-15 | 1999-04-07 | 日研化学株式会社 | Sustained-release metal valproate tablets |
-
1999
- 1999-11-15 CN CN99117214A patent/CN1094347C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1213301A (en) * | 1996-03-15 | 1999-04-07 | 日研化学株式会社 | Sustained-release metal valproate tablets |
| CN1200924A (en) * | 1997-05-29 | 1998-12-09 | 伊莱利利公司 | Fluoxetine enteric micropills |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100421666C (en) * | 2006-07-27 | 2008-10-01 | 江苏联环药业股份有限公司 | Epristeride slow release preparation |
| CN101602865B (en) * | 2009-03-13 | 2011-08-31 | 王懋 | Ethylcellulose mixed suspension liquid and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1255332A (en) | 2000-06-07 |
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