CN1255332A - Release-controlled micropill for treating benign prostatic hyperplasis and its preparing process - Google Patents
Release-controlled micropill for treating benign prostatic hyperplasis and its preparing process Download PDFInfo
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- CN1255332A CN1255332A CN 99117214 CN99117214A CN1255332A CN 1255332 A CN1255332 A CN 1255332A CN 99117214 CN99117214 CN 99117214 CN 99117214 A CN99117214 A CN 99117214A CN 1255332 A CN1255332 A CN 1255332A
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- controlled release
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Abstract
A release-controlled micropill for treating benign prostatic hyperplastic is prepared from Aipuliete, pill core, ethylenecellulose, acrylic resin, surfactant, plasticizer and hydroxypropyl methylcellulose agonist. Its preparing process is also disclosed. Its advantages are high durability up to more than 12 hrs, and high curative effect.
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; to the treatment benign prostatic hyperplasis have good curative effect (Sun Zuyue, slaughter 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%～1 7.5% 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 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 (15)
1, a kind of controlled release micro pill for the treatment of benign prostatic hyperplasis 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%
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, controlled release micro pill as claimed in claim 1 is characterized in that each component forms celphere, pastille confining bed, not pastille confining bed, controlled release clothing layer and seal-coat layer from inside to outside.
8, controlled release micro pill as claimed in claim 7 is characterized in that the pastille confining bed is made up of following component: epristeride 85%～95% hydroxypropyl emthylcellulose 4%～10% antiplastering aid 1%～5%
9, controlled release micro pill as claimed in claim 7 is characterized in that the pastille confining bed is not made up of following component: hydroxypropyl emthylcellulose 60%～80% antiplastering aid 20%～40%
10, controlled release micro pill as claimed in claim 7 is characterized in that controlled release clothing layer is made up of following component: ethyl cellulose 50%～90% acrylic resin 1%～8% surfactant 3%～16% plasticizer 6%～26%
11, controlled release micro pill as claimed in claim 7 is characterized in that the seal-coat layer is made up of following component: hydroxypropyl emthylcellulose 55%～90% antiplastering aid 10%～45%
12, 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.
13, preparation method as claimed in claim 12 is characterized in that antiplastering aid 200 mesh sieves excessively.
14, preparation method as claimed in claim 12 is characterized in that spray coating carries out in ebullated bed coating machine.
15, preparation method as claimed in claim 12, 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 true CN1255332A (en) | 2000-06-07 |
| CN1094347C CN1094347C (en) | 2002-11-20 |
Family
ID=5279854
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| 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 |
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| CN (1) | CN1094347C (en) |
Families Citing this family (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 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09323926A (en) * | 1996-03-15 | 1997-12-16 | Nikken Chem Co Ltd | Sustained release tablet of sodium valproate |
| US5910319A (en) * | 1997-05-29 | 1999-06-08 | Eli Lilly And Company | Fluoxetine enteric pellets and methods for their preparation and use |
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1999
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| CN1094347C (en) | 2002-11-20 |
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