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1. 发明授权

US07776312B2 Method of treating Alzheimer's disease comprising administering deferoxamine (DFO) to the upper one-third of the nasal cavity 有权
标题翻译：治疗阿尔茨海默氏病的方法包括将去铁胺（DFO）施用于鼻腔上三分之一
公开(公告)号：US07776312B2
公开(公告)日：2010-08-17
申请号：US11580366
申请日：2006-10-13
申请人： William H. Frey, II , Samuel Scott Panter , Leah Ranae Bresin Hanson , Annina Roeytenberg
发明人： William H. Frey, II , Samuel Scott Panter , Leah Ranae Bresin Hanson , Annina Roeytenberg
IPC分类号： A61K49/00 , A01K31/00 , A01K9/00
CPC分类号： A61K9/0043 , A61K31/165 , A61K31/195 , A61K38/1841 , A61K38/2006 , A61K38/28 , A61K38/30 , A61K45/06 , A61K2800/522
摘要： Methods and pharmaceutical compositions for preconditioning and/or providing neuroprotection to the animal central nervous system against the effects of neurological disorders involving ischemia, trauma, metal poisoning and neurodegeneration, including the associated cognitive, behavioral and physical impairments. In one embodiment, the method is accomplished by stimulating and/or stabilizing hypoxia-inducible factor-1α (HIF-1α). HIF-1α is known to provide a neuroprotective benefit under ischemic conditions. In another embodiment, the method is accomplished by differentially reducing, inhibiting or preventing the increased expression of selected genes caused by neurological disorders. Patients at risk for certain diseases or disorders that are associated with risk for cerebral ischemia may benefit, e.g., those at risk for Alzheimer's disease, Parkinson's disease, Wilson's disease, Huntington's disease, thalassemia or stroke, or those patients having head or spinal cord injury. Patients undergoing certain medical procedures that may result in ischemia may also benefit. Initially, the possibility of ischemia or neurodegeneration is recognized. Intranasal therapeutic agents are administered to the upper third of the nasal cavity to bypass the blood-brain barrier and access the central nervous system directly to avoid unwanted and potentially lethal side effects. Therapeutic agents include those substances that interact with iron and/or copper such as iron chelators, copper chelators, and antioxidants. Particular examples of such therapeutic agents are the iron chelators deferoxamine (DFO) and deferasirox. Intranasal administration of DFO is known to stimulate and/or stabilize HIF-1α and provides an efficient and safe method for pre-conditioning the brain to protect against cerebral ischemia.
摘要翻译：用于预处理和/或向动物中枢神经系统提供神经保护作用的方法和/或药物组合物抵抗涉及缺血，创伤，金属中毒和神经变性的神经障碍的影响，包括相关的认知，行为和身体损伤。在一个实施方案中，该方法通过刺激和/或稳定缺氧诱导因子-1α（HIF-1α）来实现。已知HIF-1α在缺血条件下提供神经保护作用。在另一个实施方案中，该方法通过差异性降低，抑制或预防由神经障碍引起的所选基因的表达增加来实现。与某些与脑缺血风险有关的疾病或病症有风险的患者可能会受益，例如阿尔茨海默病，帕金森病，威尔逊氏症，亨廷顿舞蹈病，地中海贫血或中风危险的患者，或患有头部或脊髓损伤的患者。患有可能导致缺血的某些医疗程序的患者也可能受益。最初认识到缺血或神经变性的可能性。将鼻内治疗剂施用于鼻腔的上三分之一以绕过血脑屏障，并直接进入中枢神经系统，以避免不必要的和可能致命的副作用。治疗剂包括与铁和/或铜相互作用的那些物质，例如铁螯合剂，铜螯合剂和抗氧化剂。这些治疗剂的具体实例是铁螯合剂去铁胺（DFO）和去铁素。已知DFO的鼻内给药可以刺激和/或稳定HIF-1α，并提供了一种预防大脑预防脑缺血的有效和安全的方法。

2. 发明申请

US20100267834A1 METHODS AND PHARMACEUTICAL COMPOSITIONS FOR DIFFERENTIALLY ALTERING GENE EXPRESSION TO PROVIDE NEUROPROTECTION FOR THE ANIMAL CENTRAL NERVOUS SYSTEM AGAINST THE EFFECTS OF ISCHEMIA, NEURODEGENERATION, TRAUMA AND METAL POISONING 审中-公开
标题翻译：方法和药物组合物，用于不同程度地改变基因表达，为动物中枢神经系统提供神经保护，防止ISCHEMIA，神经细胞凋亡，TRAUMA和金属毒素的作用
公开(公告)号：US20100267834A1
公开(公告)日：2010-10-21
申请号：US12829844
申请日：2010-07-02
申请人： William H. Frey, II , Samuel Scott Panter , Leah Ranae Bresin Hanson , Annina Roeytenberg
发明人： William H. Frey, II , Samuel Scott Panter , Leah Ranae Bresin Hanson , Annina Roeytenberg
IPC分类号： A61K31/164 , C07C237/06 , A61P25/28
CPC分类号： A61K9/0043 , A61K31/165 , A61K31/195 , A61K38/1841 , A61K38/2006 , A61K38/28 , A61K38/30 , A61K45/06 , A61K2800/522
摘要： Pharmaceutical compositions for treating and/or pre-treating or preconditioning the animal central nervous system against the effects of Alzheimer's Disease including the associated neurodegeneration and cognitive, behavioral and physical impairments. In one embodiment, an effective dose of deferoxamine (DFO) is administered to the upper one-third of the subject patient's nasal cavity to effectively bypass the blood-brain barrier, thereby allowing application of the DFO dose directly to the central nervous system.
摘要翻译：用于治疗和/或预处理或预处理动物中枢神经系统的药物组合物抵抗阿尔茨海默病的影响，包括相关的神经变性和认知，行为和身体损伤。在一个实施方案中，将有效剂量的去铁胺（DFO）施用于受试患者鼻腔的上三分之一，以有效地绕过血脑屏障，从而允许将DFO剂量直接施用于中枢神经系统。

3. 发明授权

US09351927B2 Pharmaceutical compositions for treatment of patients with neurodegeneration following ischemic insult 有权
标题翻译：用于治疗缺血性侮辱后神经变性患者的药物组合物
公开(公告)号：US09351927B2
公开(公告)日：2016-05-31
申请号：US12829844
申请日：2010-07-02
申请人： William H. Frey, II , Samuel Scott Panter , Leah Ranae Bresin Hanson , Annina Roeytenberg
发明人： William H. Frey, II , Samuel Scott Panter , Leah Ranae Bresin Hanson , Annina Roeytenberg
IPC分类号： A61K9/00 , A61K31/165 , A61K38/16 , A61K38/28 , A61K31/195 , A61K38/18 , A61K38/20 , A61K38/30 , A61K45/06
CPC分类号： A61K9/0043 , A61K31/165 , A61K31/195 , A61K38/1841 , A61K38/2006 , A61K38/28 , A61K38/30 , A61K45/06 , A61K2800/522
摘要： Pharmaceutical compositions for treating and/or pre-treating or preconditioning the animal central nervous system against the effects of Alzheimer's Disease including the associated neurodegeneration and cognitive, behavioral and physical impairments. In one embodiment, an effective dose of deferoxamine (DFO) is administered to the upper one-third of the subject patient's nasal cavity to effectively bypass the blood-brain barrier, thereby allowing application of the DFO dose directly to the central nervous system.
摘要翻译：用于治疗和/或预处理或预处理动物中枢神经系统的药物组合物抵抗阿尔茨海默病的影响，包括相关的神经变性和认知，行为和身体损伤。在一个实施方案中，将有效剂量的去铁胺（DFO）施用于受试患者鼻腔的上三分之一，以有效地绕过血脑屏障，从而允许将DFO剂量直接施用于中枢神经系统。

4. 发明授权

US08568691B2 Methods for providing neuroprotection for the animal central nervous system against the effects of ischemia, neurodegeneration, trauma, and metal poisoning 有权
标题翻译：为动物中枢神经系统提供神经保护以防止缺血，神经变性，创伤和金属中毒的作用的方法
公开(公告)号：US08568691B2
公开(公告)日：2013-10-29
申请号：US12619009
申请日：2009-11-16
申请人： William H. Frey, II , Samuel Scott Panter , Leah Ranae Bresin Hanson
发明人： William H. Frey, II , Samuel Scott Panter , Leah Ranae Bresin Hanson
IPC分类号： A61K49/14 , A61K38/44 , A61K9/10
CPC分类号： A61K31/16 , A61K9/0043 , A61K31/165 , A61K31/195 , A61K38/1841 , A61K38/2006 , A61K38/28 , A61K38/30 , A61K45/06
摘要： Methods and pharmaceutical compositions for providing neuroprotection to the animal central nervous system against the effects of ischemia, and neurodegeneration. Patients at risk for certain diseases or disorders that are associated with cerebral ischemia may benefit, e.g., those at risk for Alzheimer's disease, Parkinson's disease, Wilson's disease or stroke or those patients having head or spinal cord injury. Patients undergoing certain medical procedures that may result in ischemia may also benefit. Initially, the possibility of ischemia or neurodegeneration is recognized. Intranasal therapeutic agents are administered to the upper third of the nasal cavity to bypass the blood-brain barrier and access the central nervous system directly to avoid unwanted and potentially lethal side effects. Therapeutic agents include those substances that interact with iron and/or copper such as iron chelators and copper chelators. A particular example of such therapeutic agents is the iron chelator deferoxamine (DFO). Intranasal administration of DFO provides an effective method for pre-conditioning the brain to protect against cerebral ischemia.
摘要翻译：用于向动物中枢神经系统提供神经保护以抵抗缺血和神经变性的作用的方法和药物组合物。与脑缺血相关的某些疾病或病症有风险的患者可能有益于例如阿尔茨海默病，帕金森病，威尔逊病或中风危险的患者或患有头部或脊髓损伤的患者。患有可能导致缺血的某些医疗程序的患者也可能受益。最初认识到缺血或神经变性的可能性。将鼻内治疗剂施用于鼻腔的上三分之一以绕过血脑屏障，并直接进入中枢神经系统，以避免不必要的和可能致命的副作用。治疗剂包括与铁和/或铜相互作用的那些物质，例如铁螯合剂和铜螯合剂。这种治疗剂的具体实例是铁螯合剂去铁胺（DFO）。 DFO的鼻内给药提供了预处理脑部以防止脑缺血的有效方法。

5. 发明授权

US08592485B2 Methods and pharmaceutical compositions for treating the animal central nervous system for psychiatric disorders 有权
标题翻译：用于治疗动物中枢神经系统用于精神疾病的方法和药物组合物
公开(公告)号：US08592485B2
公开(公告)日：2013-11-26
申请号：US13161934
申请日：2011-06-16
申请人： Leah Ranae Bresin Hanson , William H. Frey, II
发明人： Leah Ranae Bresin Hanson , William H. Frey, II
IPC分类号： A61K31/13 , A61K31/131 , A61K31/16
CPC分类号： A61K31/16 , A61K31/19 , A61K33/00 , A61K45/06 , C07C259/06 , A61K2300/00
摘要： The present invention comprises methods and pharmaceutical compositions for intranasal delivery of effective amounts of DFO directly to the CNS, in particular the brain treatments that inhibit GSK3b in patients with psychiatric disorders including, but not limited to, bipolar disorder, depression, ADHD and schizophrenia. In addition a treatment composition is disclosed which comprises DFO and in certain embodiments combines DFO with one or more of the psychotropic drug types, i.e., antipsychotics, mood stabilizers and antidepressants. Moreover, a treatment for treating impairment of neural plasticity through inhibition of GSK3b is provided as well as prevention of apoptosis of cells through inhibition of GSK3b.
摘要翻译：本发明包括用于将有效量的DFO直接递送至CNS的方法和药物组合物，特别是抑制精神病学障碍（包括但不限于双相情感障碍，抑郁，ADHD和精神分裂症）的患者中的GSK3b的脑治疗。此外，公开了包含DFO的治疗组合物，并且在某些实施方案中将DFO与一种或多种精神药物类型（即抗精神病药，情绪稳定剂和抗抑郁药）组合。此外，通过抑制GSK3b治疗神经可塑性的损伤，并通过抑制GSK3b来预防细胞凋亡。

6. 发明授权

US09808509B2 Pharmaceutical compositions and methods for enhancing targeting of therapeutic compounds to the central nervous system 有权
公开(公告)号：US09808509B2
公开(公告)日：2017-11-07
申请号：US12134385
申请日：2008-06-06
申请人： William H. Frey, II , Leah Ranae Bresin Hanson , Shyeilla V. Dhuria
发明人： William H. Frey, II , Leah Ranae Bresin Hanson , Shyeilla V. Dhuria
IPC分类号： A61K38/20 , A61K9/00 , A61K31/16 , A61K33/24 , A61K38/18 , A61K38/19 , A61K38/28 , A61K38/30 , A61K45/06
CPC分类号： A61K38/2006 , A61K9/0043 , A61K31/16 , A61K33/24 , A61K38/1841 , A61K38/191 , A61K38/28 , A61K38/30 , A61K45/06 , Y02A50/421 , A61K2300/00
摘要： Pharmaceutical compositions and methods for enhancing targeting of therapeutic compounds to, inter alia, the CNS applied via intranasal administration while reducing non-target exposure are provided. In certain embodiments, at least one vasoconstrictor is provided intranasally prior to intranasal administration of at least one therapeutic compound. In other embodiments, the vasoconstrictor(s) and therapeutic compound(s) are combined in a pharmaceutical composition and delivered intranasally. The present invention substantially increases targeting of the therapeutic compound(s) to, inter alia, the CNS while substantially reducing unwanted and potentially harmful systemic exposure. The preferred administration of the invention applies the vasoconstrictor(s) and/or therapeutic compound(s) to the upper third of the nasal cavity, though application to the lower two-thirds of the nasal cavity is also within the scope of the invention.

7. 发明授权

US07618615B2 Methods for providing neuroprotection for the animal central nervous system against neurodegeneration caused by ischemia 有权
标题翻译：为动物中枢神经系统提供神经保护以防止由缺血引起的神经变性的方法
公开(公告)号：US07618615B2
公开(公告)日：2009-11-17
申请号：US11200898
申请日：2005-08-10
申请人： William H. Frey, II , Samual Scott Panter , Leah Ranae Bresin Hanson
发明人： William H. Frey, II , Samual Scott Panter , Leah Ranae Bresin Hanson
IPC分类号： A61K49/00 , A61K9/08
CPC分类号： A61K31/16 , A61K9/0043 , A61K31/165 , A61K31/195 , A61K38/1841 , A61K38/2006 , A61K38/28 , A61K38/30 , A61K45/06
摘要： Methods and pharmaceutical compositions for preconditioning and/or providing neuroprotection to the animal central nervous system against the effects of ischemia, trauma, metal poisoning and neurodegeneration, including the associated cognitive, behavioral and physical impairments. In one embodiment, the method is accomplished by stimulating and stabilizing hypoxia-inducible factor-1α (HIF-1α). HIF-1α is known to provide a neuroprotective benefit under ischemic conditions. Patients at risk for certain diseases or disorders that are associated with risk for cerebral ischemia may benefit, e.g., those at risk for Alzheimer's disease, Parkinson's disease, Wilson's disease or stroke or those patients having head or spinal cord injury. Patients undergoing certain medical procedures that may result in ischemia may also benefit. Initially, the possibility of ischemia or neurodegeneration is recognized. Intranasal therapeutic agents are administered to the upper third of the nasal cavity to bypass the blood-brain barrier and access the central nervous system directly to avoid unwanted and potentially lethal side effects. Therapeutic agents include those substances that interact with iron and/or copper such as iron chelators, copper chelators, and antioxidants. A particular example of such therapeutic agents is the iron chelator deferoxamine (DFO). Intranasal administration of DFO is known to stimulate and/or stabilize HIF-1α and provides an efficient and safe method for pre-conditioning the brain to protect against cerebral ischemia. Moreover, DFO is shown to decrease weight loss in subjects when administered pre and/or post stroke.
摘要翻译：用于预处理和/或向动物中枢神经系统提供神经保护以防止缺血，创伤，金属中毒和神经变性的影响的方法和药物组合物，包括相关的认知，行为和身体损伤。在一个实施方案中，该方法通过刺激和稳定缺氧诱导因子-1α（HIF-1α）来实现。已知HIF-1α在缺血条件下提供神经保护益处。与某些与脑缺血风险有关的疾病或病症有风险的患者可能会受益，例如阿尔茨海默病，帕金森病，威尔逊病或中风危险的患者或患有头部或脊髓损伤的患者。患有可能导致缺血的某些医疗程序的患者也可能受益。最初认识到缺血或神经变性的可能性。将鼻内治疗剂施用于鼻腔的上三分之一以绕过血脑屏障，并直接进入中枢神经系统，以避免不必要的和可能致命的副作用。治疗剂包括与铁和/或铜相互作用的那些物质，例如铁螯合剂，铜螯合剂和抗氧化剂。这种治疗剂的具体实例是铁螯合剂去铁胺（DFO）。已知DFO的鼻内施用可以刺激和/或稳定HIF-1α，并提供了一种有效和安全的预处理脑保护脑缺血的方法。此外，DFO被证明可减轻受试者在卒中前和/或卒中时的体重减轻。

8. 发明申请

US20080305077A1 PHARMACEUTICAL COMPOSITIONS AND METHODS FOR ENHANCING TARGETING OF THERAPEUTIC COMPOUNDS TO THE CENTRAL NERVOUS SYSTEM 有权
标题翻译：药物组合物和将治疗化合物靶向中央神经系统的方法
公开(公告)号：US20080305077A1
公开(公告)日：2008-12-11
申请号：US12134385
申请日：2008-06-06
申请人： William H. Frey, II , Leah Ranae Bresin Hanson , Shyeilla V. Dhuria
发明人： William H. Frey, II , Leah Ranae Bresin Hanson , Shyeilla V. Dhuria
IPC分类号： A61K38/20 , A61K38/28 , A61K33/24 , A61K31/225 , A61P31/00 , A61P25/00 , A61K31/16 , A61P25/28 , A61P37/00 , A61P35/00 , A61K31/22 , A61K38/18
CPC分类号： A61K38/2006 , A61K9/0043 , A61K31/16 , A61K33/24 , A61K38/1841 , A61K38/191 , A61K38/28 , A61K38/30 , A61K45/06 , Y02A50/421 , A61K2300/00
摘要： Pharmaceutical compositions and methods for enhancing targeting of therapeutic compounds to, inter alia, the CNS applied via intranasal administration while reducing non-target exposure are provided. In certain embodiments, at least one vasoconstrictor is provided intranasally prior to intranasal administration of at least one therapeutic compound. In other embodiments, the vasoconstrictor(s) and therapeutic compound(s) are combined in a pharmaceutical composition and delivered intranasally. The present invention substantially increases targeting of the therapeutic compound(s) to, inter alia, the CNS while substantially reducing unwanted and potentially harmful systemic exposure. The preferred administration of the invention applies the vasoconstrictor(s) and/or therapeutic compound(s) to the upper third of the nasal cavity, though application to the lower two-thirds of the nasal cavity is also within the scope of the invention.
摘要翻译：提供了用于增强治疗性化合物靶向的药物组合物和方法，特别是通过鼻内给药施用的CNS，同时减少非目标暴露。在某些实施方案中，在鼻内施用至少一种治疗化合物之前鼻内提供至少一种血管收缩剂。在其它实施方案中，血管收缩剂和治疗化合物在药物组合物中组合并且被鼻内递送。本发明显着地增加治疗性化合物的靶向特别是CNS，同时显着减少不必要的和可能有害的全身暴露。本发明的优选给药将血管收缩剂和/或治疗化合物应用于鼻腔的上三分之一，尽管施用于鼻腔的下三分之二也在本发明的范围内。

9. 发明申请

US20110311654A1 METHODS AND PHARMACEUTICAL COMPOSITIONS FOR TREATING THE ANIMAL CENTRAL NERVOUS SYSTEM FOR PSYCHIATRIC DISORDERS 有权
标题翻译：用于治疗动物中心神经系统的心理疾病的方法和药物组合物
公开(公告)号：US20110311654A1
公开(公告)日：2011-12-22
申请号：US13161934
申请日：2011-06-16
申请人： Leah Ranae Bresin Hanson , William H. Frey, II
发明人： Leah Ranae Bresin Hanson , William H. Frey, II
IPC分类号： A61K31/16 , A61K33/00 , A61P25/18 , A61P25/00 , A61P25/24 , A61K31/19 , C07C259/06
CPC分类号： A61K31/16 , A61K31/19 , A61K33/00 , A61K45/06 , C07C259/06 , A61K2300/00
摘要： The present invention comprises methods and pharmaceutical compositions for intranasal delivery of effective amounts of DFO directly to the CNS, in particular the brain treatments that inhibit GSK3b in patients with psychiatric disorders including, but not limited to, bipolar disorder, depression, ADHD and schizophrenia. In addition a treatment composition is disclosed which comprises DFO and in certain embodiments combines DFO with one or more of the psychotropic drug types, i.e., antipsychotics, mood stabilizers and antidepressants. Moreover, a treatment for treating impairment of neural plasticity through inhibition of GSK3b is provided as well as prevention of apoptosis of cells through inhibition of GSK3b.
摘要翻译：本发明包括用于将有效量的DFO直接递送至CNS的方法和药物组合物，特别是抑制精神病学障碍（包括但不限于双相情感障碍，抑郁，ADHD和精神分裂症）的患者中的GSK3b的脑治疗。此外，公开了包含DFO的治疗组合物，并且在某些实施方案中将DFO与一种或多种精神药物类型（即抗精神病药，情绪稳定剂和抗抑郁药）组合。此外，通过抑制GSK3b治疗神经可塑性的损伤，并通过抑制GSK3b来预防细胞凋亡。

10. 发明授权

US09445991B2 Methods, pharmaceutical compositions and articles of manufacture for administering therapeutic cells to the animal central nervous system 有权
标题翻译：用于向动物中枢神经系统施用治疗细胞的方法，药物组合物和制品
公开(公告)号：US09445991B2
公开(公告)日：2016-09-20
申请号：US15082210
申请日：2016-03-28
申请人： William H. Frey, II , Lusine Danielyan , Christoph H. Gleiter
发明人： William H. Frey, II , Lusine Danielyan , Christoph H. Gleiter
IPC分类号： A61K35/30 , A61K9/00 , A61K35/28
CPC分类号： A61K9/0043 , A61K35/28 , A61K35/30 , A61K38/47 , A61K2300/00
摘要： Methods and compositions for preventing and treating the damaged and/or degenerating CNS experiencing loss or death of CNS cells. Various embodiments of the invention transport a therapeutically effective amount of, inter alia at least one therapeutic cell to the CNS by intranasal application to the upper-third of the nasal cavity, thereby bypassing the blood-brain barrier. A pharmaceutical composition according to the invention may comprise at least one therapeutic cell, at least one delivery-enhancement agent, at least one antibiotic, at least one regulatory factor and/or at least one immunosuppressive agent, wherein the composition is delivered to the upper-third of the nasal cavity. The therapeutic cells, once delivered to the CNS, migrate preferentially to the area of damage or degeneration or injury.
摘要翻译：用于预防和治疗CNS细胞损伤或死亡的损伤和/或退化的CNS的方法和组合物。本发明的各种实施方案通过鼻内施用到鼻腔上三分之一，从而绕过血脑屏障，将治疗有效量的尤其是至少一种治疗细胞转运至CNS。根据本发明的药物组合物可以包含至少一种治疗细胞，至少一种递送增强剂，至少一种抗生素，至少一种调节因子和/或至少一种免疫抑制剂，其中所述组合物被递送至上三分之一的鼻腔。一旦递送到CNS的治疗细胞优先迁移到损伤或退化或损伤的区域。

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