| 摘要 |
<p>#CMT# #/CMT# Solid, orally administrable pharmaceutical drug delivery system (A) comprises 5-chloro-N ({(5S)- 2-oxo-3-[4-(3-oxo-4-morpholinyl)- phenyl]-1,3-oxazolidine-5-yl}-methyl)-2-thiophene carboxamide (I) with a fast release of the active substance, where the active substance (I) is in amorphous form and 80% of the active substance (I) is released within less than 2 hours, according to United State Pharmacopeial drug release procedure with apparatus 2 (Paddle). #CMT# : #/CMT# Independent claims are included for: (1) a method for the preparation of (A) comprising preparing the active substance (I) containing a mixture by a melt process, mixing the obtained mixture in powder form with further auxiliary materials and subsequently filling the mixture as sachet or capsules, or after mixing with tableting additives, preferably by direct tableting and press-molding to tablets, which is subsequently polished; (2) a mutli-particulate pharmaceutical drug delivery system; (3) a pharmaceutical drug delivery system comprising the multi-particulate pharmaceutical drug delivery system; (4) a method for the preparation of multi-particulate pharmaceutical drug delivery system comprising preparing active substance (I) with an extrudate by melt extrusion process and cutting the obtained mixture; and (5) a method for prophylaxis, secondary prophylaxis and/or treatment of thromboembolic diseases comprising administering (A). #CMT#ACTIVITY : #/CMT# Thrombolytic; Cardiant; Antianginal; Vasotropic; Cerebroprotective; Anticoagulant. #CMT#MECHANISM OF ACTION : #/CMT# Factor Xa inhibitor. #CMT#USE : #/CMT# (I) is useful for the preparation of a medicament to prophylaxis, secondary prophylaxis and/or treating diseases such as thromboembolic diseases, myocardial infarction, Angina Pectoris, reocclusion, restenosis after angioplasty or aortocoronary bypass, stroke, transient ischemic attacks, peripheral arterial block disease, pulmonary embolism and deep vein thrombosis (claimed). #CMT#ADVANTAGE : #/CMT# (A) exhibits an improved bioavailability. The bioavailability of (I) (in the solid form) was tested in beagle dogs. The result showed that (I) exhibited the maximum observed concentration of 7.54 mg/l, when compared with the micronized crystalline active substance (2.22 mg/l). #CMT#PHARMACEUTICALS : #/CMT# Preferred Components: 80% of the active substance (I) is released at a maximum of 1 hour. The release quantity of the active substance (I) by (A) is at least higher by a factor of 1.5 in comparison with 20 mg micronized crystalline active substance (I) in modification (I) at 1 hour. The active substance (I) is in amorphous form by the melting process, preferably melt extrusion process. (A) further contains one or more suitable auxiliary materials, preferably polyethylene glycol, which is used in melting process, and the amount of the active substance (I) in mixture after the melting process is 0.1-30%. A polymer is used in the melt extrusion process. The amount of the polymer and (I) in the melt extrusion process is at least 40% and 0.1-20%, respectively. (A) further comprises a suitable material (0.2-40%) is added as softener for the polymer and/or for reducing the melt temperature of the active substance (I). The suitable additive material is a sugar alcohol. The active substance (I) contains the melt extrudate. The particle diameter of the multi-particulate drug delivery system is 0.5-3 mm. The molded article obtained from the extrudate is cut in spherical form, and is lacquered. #CMT#POLYMERS : #/CMT# Preferred Components: The polymer is hydroxypropyl cellulose or polyvinyl pyrrolidone. #CMT#ADMINISTRATION : #/CMT# Administration of (I) is 20 mg, in the form of capsule, sachet or tablet (claimed).</p> |
