BIPHASIC RELEASE FORMULATIONS FOR LIPOPHILIC DRUGS

• Main Author: BARNWELL, STEPHEN GEORGE
• Format: Patent
• Language: English; Korean
• Published: 01.06.1999
• Edition: 6
• Subjects: HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

다음 성분으로 이루어지는 약학적 제제 (a) 올레산 또는 리놀레산과 같은, 포화 또는 모노-나 폴리-불포화된 C-C지방산 (b) 일반적으로 친유성이 약학적 활성물질 일부의 C-C지방산은 경구투약시에 비-지효성을 나타내고 일부의 C-C지방산과 최소한 일부의 약학적 활성물질은 경구투약시 지효성을 나타낸다. 약학적 활성물질은 프로프라놀올, 베라파밀, 니페디핀, 딜티아젬, 메토프롤올, 니카르디핀 또는 라베톨올과 같은 순화계용 약제가 있다. 이와같은 제제는 간 문맥 혈액공급에서 림프계로 활성물질의 흡수재 분포를 촉진하므로서 제일-통과 간 대사를 피한다. 이러한 형의 제제는 치료효능이 유지되고 더 낮은 화학량으로 달성되는 환자의 예정투약량 반응을 갖게 된다. PCT No. PCT/GB91/01824 Sec. 371 Date May 10, 1993 Sec. 102(e) Date May 10, 1993 PCT Filed Oct. 18, 1991 PCT Pub. No. WO92/06680 PCT Pub. Date Apr. 30, 1992.A pharmaceutical formulation comprises: (a) a C12-C24 fatty acid, which may be saturated or mono- or poly-unsaturated, such as oleic or linoleic acid; and (b) a generally lipophilic pharmaceutically active substance. A portion of the C12-C24 fatty acid is formulated for non-sustained release on non-parenteral administration and a portion of the C12-C24 fatty acid and at least a portion of the pharmaceutically active substance are formulated for sustained release on non-parenteral administration. The pharmaceutically active substance may be a cardiovascular drug such as propranolol, verapamil, nifedipine, diltiazem, metoprolol, nicardipine or labetolol. Such formulations promote absorption redistribution of the active substance(s) from the hepatic portal blood supply to the lymphatic system, thereby avoiding first-pass liver metabolism. Formulations of this type will have a predictable dose response in patients, achieved with a lower chemical load, with which therapeutic efficacy is maintained.