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公开(公告)号：WO2008088581A2
公开(公告)日：2008-07-24
申请号：PCT/US2007/075080
申请日：2007-08-02
Applicant: UNITED THERAPEUTICS CORPORATION , DWEK, Raymond, A. , NICHITA-BRANZA, Norica , PETRESCU, Stefana , POLLOCK, Stephanie , RUDD, Pauline , SCANLAN, Christopher , ZITZMANN, Nicole
Inventor： DWEK, Raymond, A. , NICHITA-BRANZA, Norica , PETRESCU, Stefana , POLLOCK, Stephanie , RUDD, Pauline , SCANLAN, Christopher , ZITZMANN, Nicole
CPC classification number: A61K31/70 , A61K9/1271 , A61K9/1272 , A61K38/212 , A61K47/6425 , A61K47/6911 , A61K2300/00
Abstract: One can treat a viral infection such as hepatitis B (HBV), hepatitis C (HCV), and bovine viral diarrhea virus (BVDV) infections via the delivery of pH sensitive liposomes directly into the endoplasmic reticulum (ER) membrane. Two exemplary liposome formulations are DOPE/CHEMS (DC liposomes) and DOPE/CHEMS/PEG-PE (DCPP liposomes). DC and DCPP liposomes can optimize the intracellular delivery of N -butyl deoxynojirimycin ( N B-DNJ), and consequently increase the in vivo activity of this iminosugar several orders of magnitude, and could be used in combination with other therapeutic agents such as interferon and/or ribavirin. The optimized release of N B-DNJ directly into the ER can be also applied for the treatment of other viruses, for which N B-DNJ is known to be an effective antiviral, such as human immunodeficiency virus (HIV).
Abstract translation: 通过将pH敏感的脂质体直接递送到内质网（ER）膜中，可以治疗乙型肝炎（HBV），丙型肝炎（HCV）和牛病毒性腹泻病毒（BVDV）感染的病毒感染。 两种示例性的脂质体制剂是DOPE / CHEMS（DC脂质体）和DOPE / CHEMS / PEG-PE（DCPP脂质体）。 DC和DCPP脂质体可以优化N-丁基脱氧野尻霉素（NB-DNJ）的细胞内递送，从而增加这种亚氨基二糖的体内活性几个数量级，并且可以与其它治疗剂如干扰素和/ 或利巴韦林。 NB-DNJ直接进入ER的优化释放也可以用于其他病毒的治疗，已知NB-DNJ是有效的抗病毒药物，如人类免疫缺陷病毒（HIV）。
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公开(公告)号：WO2008088581A3
公开(公告)日：2009-02-26
申请号：PCT/US2007075080
申请日：2007-08-02
Applicant: UNITED THERAPEUTICS CORP , DWEK RAYMOND A , NICHITA-BRANZA NORICA , PETRESCU STEFANA , POLLOCK STEPHANIE , RUDD PAULINE , SCANLAN CHRISTOPHER , ZITZMANN NICOLE
Inventor： DWEK RAYMOND A , NICHITA-BRANZA NORICA , PETRESCU STEFANA , POLLOCK STEPHANIE , RUDD PAULINE , SCANLAN CHRISTOPHER , ZITZMANN NICOLE
CPC classification number: A61K31/70 , A61K9/1271 , A61K9/1272 , A61K38/212 , A61K47/6425 , A61K47/6911 , A61K2300/00
Abstract: One can treat a viral infection such as hepatitis B (HBV), hepatitis C (HCV), and bovine viral diarrhea virus (BVDV) infections via the delivery of pH sensitive liposomes directly into the endoplasmic reticulum (ER) membrane. Two exemplary liposome formulations are DOPE/CHEMS (DC liposomes) and DOPE/CHEMS/PEG-PE (DCPP liposomes). DC and DCPP liposomes can optimize the intracellular delivery of N-butyl deoxynojirimycin (NB-DNJ), and consequently increase the in vivo activity of this iminosugar several orders of magnitude, and could be used in combination with other therapeutic agents such as interferon and/or ribavirin. The optimized release of NB-DNJ directly into the ER can be also applied for the treatment of other viruses, for which NB-DNJ is known to be an effective antiviral, such as human immunodeficiency virus (HIV).
Abstract translation: 通过将pH敏感的脂质体直接递送到内质网（ER）膜中，可以治疗乙型肝炎（HBV），丙型肝炎（HCV）和牛病毒性腹泻病毒（BVDV）感染的病毒感染。 两种示例性的脂质体制剂是DOPE / CHEMS（DC脂质体）和DOPE / CHEMS / PEG-PE（DCPP脂质体）。 DC和DCPP脂质体可以优化N-丁基脱氧野尻霉素（NB-DNJ）的细胞内递送，从而增加这种亚氨基二糖的体内活性几个数量级，并且可以与其它治疗剂如干扰素和/ 或利巴韦林。 NB-DNJ直接进入ER的优化释放也可以用于其他病毒的治疗，已知NB-DNJ是有效的抗病毒药物，如人类免疫缺陷病毒（HIV）。
