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    • 7. 发明申请
    • Neuroprotective Effects of Gly-Pro-Glu Following Intravenous Infusion
    • 静脉注射后Gly-Pro-Glu的神经保护作用
    • US20070224165A1
    • 2007-09-27
    • US10574280
    • 2004-10-22
    • Jian GuanGregory ThomasDavid BatchelorPeter Gluckman
    • Jian GuanGregory ThomasDavid BatchelorPeter Gluckman
    • A61K38/06
    • A61K38/06A61K2300/00
    • Gly-Pro-Glu (GPE) is rapidly metabolized in vivo. We found that GPE infusion elicits potent and consistent neuroprotection in all brain regions examined, and in certain embodiments, the effects were greater than those of a bolus injection followed by infusion (“loading dose/infusion”). GPE reduced apoptosis in the hippocampus and inhibited microglial proliferation and prevented the injury-induced loss of astrocytes and improved long-term somatofunction. GPE after infusion showed a broad effective dose range (0.3-30 mg/kg/h) and had a surprisingly extended window of treatment efficacy, permitting its use from 1 to at least as late as 24 h after neural injury. We also found that neuroprotective effects of acute GPE administration were prolonged and therefore capable of being used effectively to treat a variety of neurodegenerative conditions, even when administered after a neural injury. Thus, GPE can be an effective neuroprotective agent used either alone or co-administered along with other neuroprotective agents, antiinflammatory agents or peptidase or protease inhibitors. Compositions of GPE and protease and/or peptidase inhibitors are provided.
    • Gly-Pro-Glu(GPE)在体内迅速代谢。 我们发现GPE输注在所检查的所有脑区域中引起有效和一致的神经保护作用,并且在某些实施方案中,效果大于进行推注,随后输注(“加载剂量/输注”)的效果。 GPE减少海马细胞凋亡并抑制小胶质细胞增殖,并防止损伤诱导的星形胶质细胞的丧失和改善长期的生物功能。 输注后的GPE显示广泛的有效剂量范围(0.3-30mg / kg / h),并且具有惊人的延长的治疗效果窗口,允许其在神经损伤后至少至迟24小时使用。 我们还发现,急性GPE给药的神经保护作用延长,因此即使在神经损伤后施用,也能有效地用于治疗各种神经退行性疾病。 因此,GPE可以是单独使用或与其它神经保护剂,抗炎剂或肽酶或蛋白酶抑制剂一起使用的有效的神经保护剂。 提供GPE和蛋白酶和/或肽酶抑制剂的组合物。
    • 8. 再颁专利
    • IGF-1 to improve neural outcome
    • IGF-1改善神经结局
    • USRE43982E1
    • 2013-02-05
    • US10606745
    • 2003-06-27
    • Peter GluckmanKaroly Nikolich
    • Peter GluckmanKaroly Nikolich
    • A61K38/30
    • A method of treating injuries to or diseases of the central nervous system that predominantly effects glia and/or non-cholinergic neuronal cells characterized in that it comprises the step of increasing the active concentration(s) of insulin-like growth factor 1 and/or analogues thereof in the central nervous system of the patient. The present invention also provides therapeutic compositions comprising insulin-like growth factor 1 and/or analogues thereof for administration to a patient at or following a neural insult, which compositions are useful in minimizing damage to the central nervous system that would otherwise occur following the insult.
    • 治疗主要影响神经胶质细胞和/或非胆碱能神经细胞的中枢神经系统的损伤或疾病的方法,其特征在于其包括增加胰岛素样生长因子1和/或 在患者的中枢神经系统中的类似物。 本发明还提供包含胰岛素样生长因子1和/或其类似物的治疗组合物,用于在神经损伤或神经损伤时向患者施用,所述组合物可用于最小化在侮辱之后发生的对中枢神经系统的损伤 。
    • 9. 发明授权
    • GPE analogs
    • GPE类似物
    • US07112570B2
    • 2006-09-26
    • US10362266
    • 2001-08-24
    • Peter GluckmanTajrena Alexi
    • Peter GluckmanTajrena Alexi
    • A61K38/06C07K5/083
    • C07K5/0819A61K38/00A61K47/60C07K5/0806
    • The invention relates to GPE analogs, particularly GPE analogs capable of inducing an equivalent physiological effect to GPE within a patient. Such GPE analogs include peptides where the Gly of Gly-Pro-Glu is replaced by any of Ala, Ser, Thr, or Pro; where the Pro of Gly-Pro-Glu is replaced by any of Ala, Ser, Thr, or Gly; and where the Glu of Gly-Pro-Glu is replaced by any of Asn, Asp, or Gln. The GPE analogs of the invention have application in any method of therapy or prophylaxis in which GPE has application. These applications include the treatment of acute brain injury and neurodegenerative disease, including but not limited to injury or disease in the CNS. The GPE analogs will normally be administered as part of a pharmaceutical composition or preparation.
    • 本发明涉及GPE类似物,特别是GPE类似物,其能够诱导患者内GPE的等效生理作用。 这样的GPE类似物包括其中Gly-Pro-Glu的Gly被Ala,Ser,Thr或Pro中的任一个替代的肽; 其中Gly-Pro-Glu的Pro被Ala,Ser,Thr或Gly中的任一个替代; 并且其中Gly-Pro-Glu的Glu被Asn,Asp或Gln中的任一个替代。 本发明的GPE类似物可应用于GPE具有应用的任何治疗或预防方法。 这些应用包括治疗急性脑损伤和神经变性疾病,包括但不限于CNS中的损伤或疾病。 GPE类似物通常作为药物组合物或制剂的一部分施用。