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1. 发明申请

US20080260834A1 VITAMIN D3 ANALOG LOADED POLYMER FORMULATIONS FOR CANCER AND NEURODEGENERATIVE DISORDERS 审中-公开
标题翻译： VITAMIN D3模拟装载聚合物制剂用于癌症和神经损伤性疾病
公开(公告)号：US20080260834A1
公开(公告)日：2008-10-23
申请号：US12165036
申请日：2008-06-30
申请人： Martin Burke , Maria-Christina White , Mark C. Watts , Jae Kyoo Lee , Betty M. Tyler , Gary H. Posner , Henry Brem
发明人： Martin Burke , Maria-Christina White , Mark C. Watts , Jae Kyoo Lee , Betty M. Tyler , Gary H. Posner , Henry Brem
IPC分类号： A61K31/59 , A61K9/10 , A61P35/00 , A61P25/28
CPC分类号： A61K9/0024 , A61K9/0085 , A61K9/1641
摘要： Localized delivery of 1,25 D3 directly to a target area using biodegradable polymeric matrices maximizes the efficacy of this drug while minimizing systemic exposure and toxicity. Anticalcemic analogs of 1,25 D3 have also been incorporated into controlled release polymer formulations to achieve efficacious intracranial concentrations of 1,25 D3 analogs for the treatment of intracranial tumors as well as neurodegenerative disorders such as Alzheimer's disease as well as to maximize the efficacy of these analogs in the treatment of systemic malignancies. The therapeutic efficacy of these formulations was demonstrated through a variety of studies in vitro and in vivo. Hybrid analogs of 1,25 D3 were incorporated into biodegradable polymer wafers composed of a polyanhydride copolymer of 1,3-bis(p-carboxyphenoxy)propane (CPP) and sebacic acid (SA) in a 20:80 molar ratio. In addition to providing improved treatments for malignancies and neurodegenerative disorders, the spatial localization and high reproducibility of this controlled delivery methodology presents a unique opportunity to study in vivo the poorly understood mechanisms of 1,25 D3's antiangiogenic, antiproliferative, and transcriptional regulating activities.
摘要翻译：使用可生物降解的聚合物基质直接向目标区域局部递送1,25 D 3 N使该药物的功效最大化，同时使全身暴露和毒性最小化。 1,25 D 3 N的类似物也被并入控释聚合物制剂中，以实现颅内肿瘤治疗的有效颅内浓度1,25D 3 N 3类似物以及神经变性疾病如阿尔茨海默病，以及使这些类似物在治疗全身性恶性肿瘤中的功效最大化。通过体外和体内的各种研究证实了这些制剂的治疗功效。将1,25 D 3 N的混合类似物掺入到由20重量份的1,3-双（对羧基苯氧基）丙烷（CPP）和癸二酸（SA）的聚酐共聚物组成的可生物降解的聚合物晶片中：80摩尔比。除了为恶性肿瘤和神经变性疾病提供改进的治疗之外，这种受控递送方法的空间定位和高重现性提供了一个独特的机会，可以在体内研究一个不太了解的1,25 D 3 抗血管生成，抗增殖和转录调节活性。

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