公开(公告)号：US4178376A

公开(公告)日：1979-12-11

申请号：US760859

申请日：1977-01-21

Applicant: Takeru Higuchi ,  Siegfried Lindenbaum

Inventor： Takeru Higuchi ,  Siegfried Lindenbaum

IPC: A61K47/12 ,  A61K31/47 ,  A61K9/42 ,  A61K31/135 ,  A61K31/44

CPC classification number: A61K47/12

Abstract: Rapid therapeutically effective antimalarial levels of a member selected from the group consisting of 6,8-Dichloro-.alpha.-(dibutyl-amino-methyl-2-(3',4'-dichlorophenyl-4-quinolinemethanol, 3-Dibutylamino-1-[2,6-bis(4-trifluoromethylphenyl)-4-pyridyl]propanol and 1,3-Dichloro-6-trifluoromethyl-9-[1-hydroxy-3-(dibutylamino) propyl]-phenanthrene are achieved by dissolving the same in an organic fatty acid of the formula: R-CCOH, wherein R represents a member selected from the group consisting of a saturated aliphatic hydrocarbon group of from seven to twenty carbon atoms and a mono-, di-, tri-, or tetra-unsaturated hydrocarbon group of from seven to twenty carbon atoms, and subsequently administering said acid containing the dissolved compound to a warm-blooded animal (e.g., human) afflicted with malaria.Because of the extremely poor solubility of the above-described antimalarial compounds, therapeutically effective antimalarial blood levels of the same have only been able to be achieved when such compounds are administered around the clock for extended periods of time. The method of this invention substantially enhances the bioavailability of these compounds and thus permits rapid therapeutically effective antimalarial blood levels of the same to be achieved.

Abstract translation: 选自6,8-二氯-α-（二丁基 - 氨基 - 甲基-2-（3'，4'-二氯苯基-4-喹啉甲醇，3-二丁基氨基-1- [2,6-双（4-三氟甲基苯基）-4-吡啶基]丙醇和1,3-二氯-6-三氟甲基-9- [1-羟基-3-（二丁基氨基）丙基] - 菲是通过将其 在下式的有机脂肪酸中：R-CCOH，其中R表示选自7至20个碳原子的饱和脂族烃基和一 - ，二 - ，三 - 或四 - 7至20个碳原子的不饱和烃基，然后将含有溶解的化合物的所述酸施用于患有疟疾的温血动物（例如人），由于上述抗疟疾化合物的溶解度极差， 有效的抗疟血液水平只能达到 d当这些化合物长时间地全天候给药时。 本发明的方法基本上增强了这些化合物的生物利用度，因此可以实现其快速治疗有效的抗疟血液水平。