CN104027311A - Dimethyl fumarate-containing enteric slow-release pellet - Google Patents
Dimethyl fumarate-containing enteric slow-release pellet Download PDFInfo
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- CN104027311A CN104027311A CN201410194551.6A CN201410194551A CN104027311A CN 104027311 A CN104027311 A CN 104027311A CN 201410194551 A CN201410194551 A CN 201410194551A CN 104027311 A CN104027311 A CN 104027311A
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Abstract
The invention relates to a dimethyl fumarate-containing enteric slow-release pellet for treating multiple sclerosis. The dimethyl fumarate-containing enteric slow-release pellet is characterized in that the pellet is subjected to coating, one layer gives play to enteric effect, and one layer gives play to slow-release effect, so that the pellet is controlled to slowly release active substances according to a certain rate after arriving at intestinal tracts.
Description
Technical field
The present invention relates to a kind of pharmaceutical preparation that is used for the treatment of the dimethyl fumarate enteric sustained-release pellet of multiple sclerosis, it has two regulation and control layers, there is respectively enteric effect and slow releasing function, can control micropill after arriving intestinal according to the slow release of active agent of certain speed.
Background technology
Dimethyl fumarate enteric-soluble controlled-release capsule is a kind of medicine that is used for the treatment of multiple sclerosis (MS).The Tecfidera of Biogen Idec company (dimethyl fumarate slow releasing capsule) ratifies by FDA, is used for the treatment of multiple sclerosis.
Multiple sclerosis (MS) is a kind of central nervous system disease, and it is chronic or intermittent that typical evolution is, and on the impact of human body, can be developed to by less body worry the forfeiture of larger major function.Dimethyl fumarate enteric-soluble controlled-release capsule has adopted a kind of new MS treatment approach---and by activating nuclear factor (red is derivative)-2 sample paths, play a role, this path makes cells in vivo have the ability to resist to follow the diseases such as MS and the inflammation come and the injury of oxidative stress.
Dimethyl fumarate is mainly used in antiseptic at present, and does not have at home enterprise that dimethyl fumarate slow releasing capsule is declared and produced successfully.Apply planet mixer herein and carry out the preparation of soft material, effectively avoided each component of ball core to mix inhomogeneous, and the appearance of the easy agglomerating caking phenomenon of soft material, it is even containing pill core particle size distribution that dimethyl fumarate prepared by spheronization is extruded in application, surface rounding is smooth, is conducive to control by the method for coating the release of medicine.And the present invention is by the mode of coating enteric controlled-release layer and slow release controlled release layer and the method that two kinds of slow-release materials of application combine strengthen medicine in the controllability of intestinal rate of release respectively.
Summary of the invention
The object of the invention is to provide a kind of enteric sustained-release pellet that contains dimethyl fumarate, and it comprises enteric regulation and control layer and slowly-releasing regulation and control layer.Containing the contained component of pill core, there is following weight percent: dimethyl fumarate 27-32%, microcrystalline Cellulose 28-42%, silicified microcrystalline cellulose 16-24%, cross-linking sodium carboxymethyl cellulose 5-8%, PVP K30 is 4-6%, silica sol 2.5-3.5%.
The contained component of enteric regulation and control layer coating solution of enteric sustained-release pellet as herein described has following weight percent: especially strange L100 is 10-15%, sodium lauryl sulphate 0.80-1.20%, Pulvis Talci 2.50-3.50%, triethyl citrate 1.00-1.50%, tween 80 is 1.00-1.50%, 95% (volume fraction) ethanol 78.00-84.00%.
The contained component of slowly-releasing regulation and control layer coating solution of enteric sustained-release pellet as herein described has following weight percent: Eudragit RL 30D is 9.00-13.00%, Eudragit RS 30D is 24.00-33.00%, triethyl citrate 1.10-1.60%, sodium lauryl sulphate 0.70-110%, tween 80 is 1.30-1.70%, Pulvis Talci 2.70-3.30%, simethicone 0.67-0.91%, water 48.00-53.00%.
The preparation method of enteric sustained-release pellet described herein comprises the steps: that dimethyl fumarate is put into planet mixer with other component of ball core mixs homogeneously, the binding agent mix homogeneously that adds recipe quantity, adds the soft material preparing to extrude and in round as a ball comminutor, carries out the preparation of ball core; Ball core fluid bed drying, will use spray coated slow release regulation and control layer at the bottom of fluid bed through the micropill of granulate, be dried to moisture and carry out enteric layer coating after qualified, be dried to the micropill fill capsule of moisture after qualified.
The specific embodiment
By following examples, the present invention is done further and illustrated, but be not limited in following instance.
Enforcement vitro release test: use the II type digestion instrument (oar formula) with 1000mL stripping rotor.Bathe temperature and be set as 37 ℃ ± 0.5 ℃, oar speed is set as 100rpm.One capsules is placed in to the stripping rotor 2 hours that 750ml0.1N HCl (pH1.2) is housed.Then add 220ml0.2M sodium phosphate buffer to make pH become 6.8.Each sampling time point gathers 1.5ml sample, with HPLC, analyzes dimethyl fumarate.HPLC parameter setting is as follows: chromatographic column Phenomenex Luna C18,50 * 4.6mm, 3 μ m; 30 ℃ of column oven temperature; Mobile phase: methanol: 20mM phosphate buffer pH3.0 (35: 65V/V), volume injected: 5 μ l, flow velocity: 0.8ml/min, detector wavelength: 210nm, running time 5min.
Embodiment 1:
Ball core prescription:
Enteric regulation and control layer coating fluid prescription:
Slowly-releasing regulation and control layer coating fluid prescription:
Embodiment 2:
Ball core prescription:
Enteric regulation and control layer coating fluid prescription:
Slowly-releasing regulation and control layer coating fluid prescription:
Embodiment 3:
Ball core prescription:
Enteric regulation and control layer coating fluid prescription:
Slowly-releasing regulation and control layer coating fluid prescription:
Preparation technology:
Take each component in ball core prescription and put into planet mixer mix homogeneously, the binding agent mix homogeneously that adds recipe quantity, 50% ethanol (mass fraction) the solution soft material processed that adds 10%PVP k30, adds the soft material preparing to extrude and in round as a ball comminutor, carries out the preparation of ball core; 40 ℃ of micropill fluid beds are dry, will use through the micropill of granulate spray coated slow release regulation and control layer at the bottom of fluid bed, and weightening finish reaches requirement, are dried to moisture and carry out enteric layer coating after qualified, and weightening finish reaches requirement, are dried to the micropill fill capsule of moisture after qualified.
Embodiment 1～3 release data:
Known from result: the micropill that the method makes can obtain good release.
Embodiment 1～4 accelerated test related substance result comparison:
From result, learn: after the method makes micropill and incapsulates, the related substance of sample is more stable.
Claims (5)
1. an enteric sustained-release pellet that is used for the treatment of the dimethyl fumarate of multiple sclerosis, comprises enteric regulation and control layer and slowly-releasing regulation and control layer.
2. enteric sustained-release pellet according to claim 1, it is characterized in that the described composition containing pill core has following weight percent: dimethyl fumarate 27-32%, microcrystalline Cellulose 28-42%, silicified microcrystalline cellulose 16-24%, cross-linking sodium carboxymethyl cellulose 5-8%, PVP K30 is 4-6%, silica sol 2.5-3.5%.
3. enteric sustained-release pellet as claimed in claim 1, it is characterized in that the contained component of described enteric regulation and control layer coating solution has following weight percent: especially strange L100 is 10-15%, sodium lauryl sulphate 0.80-1.20%, Pulvis Talci 2.50-3.50%, triethyl citrate 1.00-1.50%, tween 80 is 1.00-1.50%, 95%(volume fraction) ethanol 78.00-84.00%.
4. enteric sustained-release pellet as claimed in claim 1, it is characterized in that the contained component of described slowly-releasing regulation and control layer coating solution has following weight percent: Eudragit RL 30D is 9.00-13.00%, Eudragit RS 30D is 24.00-33.00%, triethyl citrate 1.10-1.60%, sodium lauryl sulphate 0.70-1.10%, tween 80 is 1.30-1.70%, Pulvis Talci 2.70-3.30%, simethicone 0.67-0.91%, water 48.00-53.00%.
5. enteric sustained-release pellet as claimed in claim 1, is characterized in that preparation method comprises the steps:
Dimethyl fumarate is put into planet mixer with other component of ball core and mix homogeneously, add the binding agent mix homogeneously of recipe quantity, the soft material preparing is added to extrude and in round as a ball comminutor, carry out the preparation of ball core; Micropill application fluid bed drying, will use spray coated slow release regulation and control layer at the bottom of fluid bed through the micropill of granulate, be dried to moisture and carry out enteric layer coating after qualified, and qualified micropill incapsulates to be dried to moisture.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201410194551.6A CN104027311A (en) | 2014-05-09 | 2014-05-09 | Dimethyl fumarate-containing enteric slow-release pellet |
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| CN201410194551.6A CN104027311A (en) | 2014-05-09 | 2014-05-09 | Dimethyl fumarate-containing enteric slow-release pellet |
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| CN201410194551.6A Pending CN104027311A (en) | 2014-05-09 | 2014-05-09 | Dimethyl fumarate-containing enteric slow-release pellet |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104490849A (en) * | 2014-11-24 | 2015-04-08 | 广东东阳光药业有限公司 | High-density dimethyl fumarate enteric-coated granules and preparation method thereof |
| CN104523602A (en) * | 2014-12-12 | 2015-04-22 | 广东东阳光药业有限公司 | Dimethyl fumarate enteric-coated pellet and preparation method thereof |
| CN104352441B (en) * | 2014-10-16 | 2017-06-09 | 山东百诺医药股份有限公司 | A kind of dimethyl fumarate enteric-coated micro-pill and preparation method thereof |
| CN107205937A (en) * | 2014-11-19 | 2017-09-26 | 比奥根Ma公司 | Pharmaceutical beads preparation comprising dimethyl fumarate |
| CN107205985A (en) * | 2015-02-08 | 2017-09-26 | 阿尔科米斯制药爱尔兰有限公司 | Monomethyl fumarate prodrug compositions |
| WO2018077479A1 (en) * | 2016-10-25 | 2018-05-03 | Pharmathen S.A. | Pharmaceutical compositions comprising a fumaric acid ester and method for the preparation thereof |
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Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104352441B (en) * | 2014-10-16 | 2017-06-09 | 山东百诺医药股份有限公司 | A kind of dimethyl fumarate enteric-coated micro-pill and preparation method thereof |
| CN107205937A (en) * | 2014-11-19 | 2017-09-26 | 比奥根Ma公司 | Pharmaceutical beads preparation comprising dimethyl fumarate |
| CN113521029A (en) * | 2014-11-19 | 2021-10-22 | 比奥根Ma公司 | Pharmaceutical bead formulations comprising dimethyl fumarate |
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| CN104490849A (en) * | 2014-11-24 | 2015-04-08 | 广东东阳光药业有限公司 | High-density dimethyl fumarate enteric-coated granules and preparation method thereof |
| CN104523602A (en) * | 2014-12-12 | 2015-04-22 | 广东东阳光药业有限公司 | Dimethyl fumarate enteric-coated pellet and preparation method thereof |
| CN104523602B (en) * | 2014-12-12 | 2018-06-05 | 广东东阳光药业有限公司 | A kind of dimethyl fumarate enteric microplate and preparation method thereof |
| CN107205985A (en) * | 2015-02-08 | 2017-09-26 | 阿尔科米斯制药爱尔兰有限公司 | Monomethyl fumarate prodrug compositions |
| WO2018077479A1 (en) * | 2016-10-25 | 2018-05-03 | Pharmathen S.A. | Pharmaceutical compositions comprising a fumaric acid ester and method for the preparation thereof |
| US20200046670A1 (en) * | 2016-10-25 | 2020-02-13 | Pharmathen S.A. | Pharmaceutical compositions comprising a fumaric acid ester and method for the preparation thereof |
| US10894026B2 (en) | 2016-10-25 | 2021-01-19 | Pharmathen S.A. | Pharmaceutical compositions comprising a fumaric acid ester and method for the preparation thereof |
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Application publication date: 20140910 |