DINITROSYL IRON COMPLEX, PHARMACEUTICAL COMPOSITION COMPRISING THE SAME, COMPOSITE MATERIAL COMPRISING THE SAME, AND USES THEREOF

專利類型

發明

專利國別 (專利申請國家)

美國

專利申請案號

15/413,428

專利證號

US 10,538,545 B2

專利獲證名稱

DINITROSYL IRON COMPLEX, PHARMACEUTICAL COMPOSITION COMPRISING THE SAME, COMPOSITE MATERIAL COMPRISING THE SAME, AND USES THEREOF

專利所屬機關 (申請機關)

中原大學

獲證日期

2020/01/21

技術說明

本發明係利用雙亞硝基鐵錯合物作為新穎一氧化氮的載體，經由設計並改變此錯合物結構，達成一氧化氮或次硝酸(Nitroxyl)的傳遞或釋放，且具有自半小時至一天相當廣的反應半衰期，以解決過去一氧化氮提供試劑釋放速率極快導致局部一氧化氮濃度過高、毒性高、結構不穩定不易保存等缺點。本發明揭示此錯合物的合成方法，以及其傳遞一氧化氮並延長線蟲壽命、延緩線蟲老化、刺激斑馬魚心肌鬆弛、及強化斑馬魚心肌收縮力。除此之外，利用金屬有機骨架材料的孔洞性以及結構可調控性，進一步將雙亞硝基鐵錯合物修飾於金屬有機骨架材料上，並利用管餵方式將藥物投遞於小鼠，發現可大幅增加口服給藥後的生物可利用率。此發明進一步可應用於一氧化氮相關的研究、生物應用以及醫藥應用。另外，也可將金屬有機骨架材料作為一口服藥物的藥物載體。 This invention relates to the utilization of dinitrosyl iron complexes (DNICs) as a novel prodrug for the delivery of nitric oxide. Through the design and modification of this complex, DNIC can transfer and release nitric oxide and nitroxyl with a wide range of reaction half-life between 0.5 h to 1 day. This NO-transfer reactivity of DNICs is contrast to the traditional NO-donor which features fast NO-release kinetics and high local concentration of nitric oxide, high toxicity, and poor stability. This article covers the demonstration of synthesis and NO-transfer reactivity of DNICs which extends the lifespan of C. elegans, delays the aging process in C. elegans, and triggers the vasodilation and myocardial inotropic effect in zebrafish. Through oral gavage of the conjugated dinitrosyl iron complex with metal-organic framework material in mouse, the bioavailability of dinitrosyl iron complex via oral administration is significantly enhanced.

備註

本會(收文號1110060137)同意該校111年9月26日原產字第1110003412號函申請終止維護專利(中原大學)

連絡單位 (專責單位/部門名稱)

產學合作暨專利技轉中心

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