ALMARSSON, ORN,艾尔马森 欧恩,艾爾馬森 歐恩,BLUMBERG, LAURA COOK,布朗柏格 劳拉C,布朗柏格 勞拉C,REMENAR, JULIUS F.,雷米纳 朱利奥斯F,雷米納 朱利奧斯F
申请号：
TW105104821
公开号：
TWI623325B
申请日:
2010.12.27
申请国别(地区):
TW
年份:
2018
代理人:
摘要：
The invention provides a method of sustained delivery of a tertiary amine-containing parent drug comprising administering to a patient an effective amount of a prodrug compound of the invention wherein upon administration to the patient, release of the parent drug from the prodrug is sustained release. Prodrug compounds suitable for use in the methods of the invention are labile quaternary ammonium salts of tertiary amine-containing parent drugs (or tertiary imine-containing parent drugs) that are derivatized through aldehyde-linked prodrug moieties that reduce the solubility of the prodrug compound at a reference pH as compared to the parent drug. The physical, chemical and solubility properties of these derivatives can be further modulated by the choice of counterion X-. In one embodiment, the present invention provides a prodrug compound of Formula I: where R1-R5 are defined in the written description of the invention. The prodrug compounds of the invention can be used to treat any condition for which the tertiary amine-containing parent drug or tertiary imine-containing parent drug is useful as a treatment.本發明提供一種持續傳遞含三級胺原藥的方法,包括將一有效量之本發明的前藥化合物投予至患者,其中在投予至患者後,從前藥釋放出原藥係持續釋放。合適於使用在本發明之方法中的前藥化合物為含三級胺原藥(或含三級亞胺原藥)之不穩定的四級銨鹽,其透過醛鏈結的前藥部分衍生,其減低前藥化合物在參考pH的溶解度(如與原藥比較)。這些衍生物的物理、化學及溶解度性質可藉由抗衡離子X-之選擇進一步調變。在一個具體實例中,本發明提供式I之前藥化合物:其中R1-R5係在發明的書面說明中定義。本發明的前藥化合物可使用來治療該含三級胺原藥或含三級亞胺原藥有用作為治療之任何症狀。
