公开(公告)号：US07837913B2

公开(公告)日：2010-11-23

申请号：US11200982

申请日：2005-08-10

申请人： Jeff S. Sakamoto ,  James R. Weiss ,  Jean-Pierre Fleurial ,  Adam Kisor ,  Mark Tuszynski ,  Shula Stokols ,  Todd Edward Holt ,  David James Welker ,  Christopher David Breckon

发明人： Jeff S. Sakamoto ,  James R. Weiss ,  Jean-Pierre Fleurial ,  Adam Kisor ,  Mark Tuszynski ,  Shula Stokols ,  Todd Edward Holt ,  David James Welker ,  Christopher David Breckon

IPC分类号： B29B17/00 ,  B29B44/04 ,  B01D24/00

CPC分类号： A61L27/56 ,  A61L31/14 ,  Y10S977/896 ,  Y10T428/249964 ,  Y10T428/29

摘要： Millimeter to nano-scale structures manufactured using a multi-component polymer fiber matrix are disclosed. The use of dissimilar polymers allows the selective dissolution of the polymers at various stages of the manufacturing process. In one application, biocompatible matrixes may be formed with long pore length and small pore size. The manufacturing process begins with a first polymer fiber arranged in a matrix formed by a second polymer fiber. End caps may be attached to provide structural support and the polymer fiber matrix selectively dissolved away leaving only the long polymer fibers. These may be exposed to another product, such as a biocompatible gel to form a biocompatible matrix. The polymer fibers may then be selectively dissolved leaving only a biocompatible gel scaffold with the pores formed by the dissolved polymer fibers.

摘要翻译： 公开了使用多组分聚合物纤维基质制造的毫米至纳米级结构。 使用不同的聚合物允许在制造过程的各个阶段选择性地溶解聚合物。 在一个应用中，可以形成具有长孔长度和小孔径的生物相容性基质。 制造过程从布置在由第二聚合物纤维形成的基体中的第一聚合物纤维开始。 可以连接端盖以提供结构支撑，并且聚合物纤维基质选择性地溶解掉，仅留下长的聚合物纤维。 这些可能暴露于另一种产品，例如生物相容性凝胶，以形成生物相容性基质。 然后可以选择性地溶解聚合物纤维，仅留下具有由溶解的聚合物纤维形成的孔的生物相容的凝胶支架。

公开(公告)号：US20100055144A1

公开(公告)日：2010-03-04

申请号：US11200982

申请日：2005-08-10

申请人： Jeff S. Sakamoto ,  James R. Weiss ,  Jean-Pierre Fleurial ,  Adam Kisor ,  Mark Tuszynski ,  Shula Stokols ,  Todd Edward Holt ,  David James Welker ,  Christopher David Breckon

发明人： Jeff S. Sakamoto ,  James R. Weiss ,  Jean-Pierre Fleurial ,  Adam Kisor ,  Mark Tuszynski ,  Shula Stokols ,  Todd Edward Holt ,  David James Welker ,  Christopher David Breckon

IPC分类号： A61F2/28 ,  C23F1/00 ,  A61F2/02

CPC分类号： A61L27/56 ,  A61L31/14 ,  Y10S977/896 ,  Y10T428/249964 ,  Y10T428/29

摘要： Millimeter to nano-scale structures manufactured using a multi-component polymer fiber matrix are disclosed. The use of dissimilar polymers allows the selective dissolution of the polymers at various stages of the manufacturing process. In one application, biocompatible matrixes may be formed with long pore length and small pore size. The manufacturing process begins with a first polymer fiber arranged in a matrix formed by a second polymer fiber. End caps may be attached to provide structural support and the polymer fiber matrix selectively dissolved away leaving only the long polymer fibers. These may be exposed to another product, such as a biocompatible gel to form a biocompatible matrix. The polymer fibers may then be selectively dissolved leaving only a biocompatible gel scaffold with the pores formed by the dissolved polymer fibers.

公开(公告)号：US20070037768A1

公开(公告)日：2007-02-15

申请号：US11582618

申请日：2006-10-17

申请人： Mark Tuszynski

发明人： Mark Tuszynski

IPC分类号： A61K48/00

CPC分类号： A61K48/005 ,  A61K38/185 ,  A61K48/00 ,  A61K48/0075 ,  A61K48/0083 ,  C07K14/475 ,  C12N15/86 ,  C12N15/867 ,  C12N2740/16043 ,  C12N2799/021 ,  C12N2799/027

摘要： A specific clinical protocol for use toward therapy of defective, diseased and damaged neurons in the mammalian brain, of particular usefulness for treatment of neurodegenerative conditions such as Parkinson's disease and Alzheimer's disease. The protocol is practiced by delivering a definite concentration of recombinant neurotrophin, such as glial cell-derived neurotrophic factor), into a targeted region of the brain (such as the substantia nigra) using a lentiviral expression vector. The neurotrophin is delivered to, or within close proximity of, identified defective, diseased or damaged brain cells. The concentration of neurotrophin delivered as part of a neurotrophic composition varies from 1010 to 1015 neurotrophin encoding viral particles/ml of composition fluid. Each delivery site receives from 2.5 μl to 25 μl of neurotrophic composition, delivered slowly, as in over a period of time ranging upwards of 10 minutes/delivery site. Each delivery site is at, or within 500 μm of, a targeted cell, and no more than about 10 mm from another delivery site. The method stimulates growth of targeted neurons, and reversal of functional deficits associated with the neurodegenerative disease being treated.

摘要翻译： 用于治疗哺乳动物脑中有缺陷，患病和受损神经元的特定临床方案，对于治疗神经变性疾病如帕金森病和阿尔茨海默氏病尤其有用。 通过使用慢病毒表达载体将确定浓度的重组神经营养因子（例如神经胶质细胞衍生的神经营养因子）递送至脑的靶向区域（例如黑质）来实施该方案。 神经营养蛋白被递送到或者在非常接近的识别的有缺陷的，患病的或受损的脑细胞中。 作为神经营养组合物的一部分递送的神经营养因子的浓度从编码病毒颗粒/ ml的组合物流体的10 10至10 15神经营养因子变化。 每个送货站点从2.5毫升到25毫升的神经营养组合物，缓慢递送，如超过10分钟/送货地点的一段时间。 每个递送部位在目标细胞的500μm以下，距离另一个递送部位不超过约10mm。 该方法刺激靶向神经元的生长，并与正在治疗的神经变性疾病相关的功能性逆转逆转。

公开(公告)号：US20060051322A1

公开(公告)日：2006-03-09

申请号：US10332306

申请日：2001-05-17

申请人： Mark Tuszynski

发明人： Mark Tuszynski

IPC分类号： A61K48/00

CPC分类号： C12N15/86 ,  A61K38/185 ,  A61K48/00 ,  C12N2750/14143 ,  C12N2750/14171

摘要： A specific clinical protocol for use toward therapy of defective, diseased and damaged cholinergic neurons in the mammalian brain, of particular usefulness for treatment of neurodegenerative conditions such as Alzheimer's disease. The protocol is practiced by delivering a definite concentration of recombinant neurotrophin into, or within close proximity of, identified defective, diseased or damaged brain cells. Using a viral vector, the concentration of neurotrophin delivered as part of a neurotrophic composition varies from 1010 to 1015 neurotrophin encoding viral particles/ml of composition fluid. Each delivery site receives form 2.5 μl to 25 μl of neurotrophic composition, delivered slowly, as in over a period of time ranging upwards of 10 minutes/delivery site. Each delivery site is at, or within 500 μm of, a targeted cell, and no more than about 10 mm from another delivery site. Stable in situ neurotrophin expression can be achieved for 12 months, or longer.

摘要翻译： 用于治疗哺乳动物脑中有缺陷的，患病的和受损的胆碱能神经元的特定临床方案，对于治疗神经变性疾病如阿尔茨海默氏病尤其有用。 通过将确定的重组神经营养因子浓度递送到或者非常接近于鉴定的有缺陷的，患病的或受损的脑细胞来实施该方案。 使用病毒载体，作为神经营养组合物的一部分递送的神经营养因子的浓度在编码病毒颗粒/ ml组合物流体的10 10 10 10 15神经营养因子中变化。 每个送货地点接收2.5至25毫克的神经营养组合物，缓慢递送，如超过10分钟/送货地点的一段时间。 每个递送部位在目标细胞的500μm以下，距离另一个递送部位不超过约10mm。 稳定的原位神经营养蛋白表达可以达到12个月或更长时间。

公开(公告)号：US20050123516A1

公开(公告)日：2005-06-09

申请号：US10986259

申请日：2004-11-09

申请人： Mark Tuszynski

发明人： Mark Tuszynski

IPC分类号： A61K38/18 ,  A61K48/00 ,  C07K14/475 ,  C12N15/867

CPC分类号： A61K48/005 ,  A61K38/185 ,  A61K48/00 ,  A61K48/0075 ,  A61K48/0083 ,  C07K14/475 ,  C12N15/86 ,  C12N15/867 ,  C12N2740/16043 ,  C12N2799/021 ,  C12N2799/027

摘要： A specific clinical protocol for use toward therapy of defective, diseased and damaged neurons in the mammalian brain, of particular usefulness for treatment of neurodegenerative conditions such as Parkinson's disease and Alzheimer's disease. The protocol is practiced by delivering a definite concentration of recombinant neurotrophin, such as glial cell-derived neurotrophic factor), into a targeted region of the brain (such as the substantia nigra) using a lentiviral expression vector. The neurotrophin is delivered to, or within close proximity of, identified defective, diseased or damaged brain cells. The concentration of neurotrophin delivered as part of a neurotrophic composition varies from 1010 to 1015 neurotrophin encoding viral particles/ml of composition fluid. Each delivery site receives from 2.5 μl to 25 μl of neurotrophic composition, delivered slowly, as in over a period of time ranging upwards of 10 minutes/delivery site. Each delivery site is at, or within 500 μm of, a targeted cell, and no more than about 10 mm from another delivery site. The method stimulates growth of targeted neurons, and reversal of functional deficits associated with the neurodegenerative disease being treated.

摘要翻译： 用于治疗哺乳动物脑中有缺陷，患病和受损神经元的特定临床方案，对于治疗神经变性疾病如帕金森病和阿尔茨海默氏病尤其有用。 通过使用慢病毒表达载体将确定浓度的重组神经营养因子（例如神经胶质细胞衍生的神经营养因子）递送至脑的靶向区域（例如黑质）来实施该方案。 神经营养蛋白被递送到或者在非常接近的识别的有缺陷的，患病的或受损的脑细胞中。 作为神经营养组合物的一部分递送的神经营养因子的浓度从编码病毒颗粒/ ml的组合物流体的10 10至10 15神经营养因子变化。 每个送货站点从2.5毫升到25毫升的神经营养组合物，缓慢递送，如超过10分钟/送货地点的一段时间。 每个递送部位在目标细胞的500μm以下，距离另一个递送部位不超过约10mm。 该方法刺激靶向神经元的生长，并与正在治疗的神经变性疾病相关的功能性逆转逆转。

公开(公告)号：US20060222631A1

公开(公告)日：2006-10-05

申请号：US11431436

申请日：2006-05-10

申请人： Mark Tuszynski

发明人： Mark Tuszynski

IPC分类号： A61K48/00 ,  A61K38/18 ,  C12N15/867

CPC分类号： A61K38/185

摘要： A protocol for use of growth factors to stimulate neuronal cell growth and activity in trkB receptor containing cortical tissues, including the entorhinal and hippocampal cortices. The method introduces exogenous growth factor, such as BDNF, NT-4/5 and NT-3, into the EC. The method is useful in therapy of defective, diseased and damaged neurons in the mammalian brain, of particular usefulness for treatment of neurodegenerative conditions such as Alzheimer's disease or for normal aging.

公开(公告)号：US20090202605A1

公开(公告)日：2009-08-13

申请号：US12203068

申请日：2008-09-02

申请人： Jeff S. Sakamoto ,  Mark Tuszynski ,  Thomas Gros

发明人： Jeff S. Sakamoto ,  Mark Tuszynski ,  Thomas Gros

IPC分类号： A61K9/70 ,  A61P25/00

CPC分类号： A61K9/0024 ,  A61K9/0092 ,  A61K47/32 ,  A61K47/34

摘要： Millimeter to nano-scale structures manufactured using a multi-component polymer fiber matrix are disclosed. The use of dissimilar polymers allows the selective dissolution of the polymers at various stages of the manufacturing process. In one application, biocompatible matrixes may be formed with long pore length and small pore size. The manufacturing process begins with a first polymer fiber arranged in a matrix formed by a second polymer fiber. End caps may be attached to provide structural support and the polymer fiber matrix selectively dissolved away leaving only the long polymer fibers. These may be exposed to another product, such as a biocompatible gel to form a biocompatible matrix. The polymer fibers may then be selectively dissolved leaving only a biocompatible gel scaffold with the pores formed by the dissolved polymer fibers. The scaffolds may be used in, among other applications, the repair of central and peripheral nerves. Scaffolds for the repair of peripheral nerves may include a reservoir for the sustained release of nerve growth factor. The scaffolds may also include a multifunctional polyelectrolyte layer for the sustained release of nerve growth factor and enhance biocompatibility.

摘要翻译： 公开了使用多组分聚合物纤维基质制造的毫米至纳米级结构。 使用不同的聚合物允许在制造过程的各个阶段选择性地溶解聚合物。 在一个应用中，可以形成具有长孔长度和小孔径的生物相容性基质。 制造过程从布置在由第二聚合物纤维形成的基体中的第一聚合物纤维开始。 可以连接端盖以提供结构支撑，并且聚合物纤维基质选择性地溶解掉，仅留下长的聚合物纤维。 这些可能暴露于另一种产品，例如生物相容性凝胶，以形成生物相容性基质。 然后可以选择性地溶解聚合物纤维，仅留下具有由溶解的聚合物纤维形成的孔的生物相容的凝胶支架。 除了其他应用之外，支架可用于修复中枢神经和周围神经。 用于修复周围神经的支架可以包括用于持续释放神经生长因子的储库。 支架还可以包括用于持续释放神经生长因子并增强生物相容性的多功能聚电解质层。

公开(公告)号：US20070249554A1

公开(公告)日：2007-10-25

申请号：US11702936

申请日：2007-02-05

申请人： Mark Tuszynski

发明人： Mark Tuszynski

IPC分类号： A61K31/7052 ,  A61P25/28

CPC分类号： C12N15/86 ,  A61K38/185 ,  A61K48/00 ,  C12N2750/14143 ,  C12N2750/14171

摘要： A specific clinical protocol for use toward therapy of defective, diseased and damaged cholinergic neurons in the mammalian brain, of particular usefulness for treatment of neurodegenerative conditions such as Alzheimer's disease. The protocol is practiced by delivering a definite concentration of recombinant neurotrophin into, or within close proximity of, identified defective, diseased or damaged brain cells. Using a viral vector, the concentration of neurotrophin delivered as part of a neurotrophic composition varies from 1010 to 1015 neurotrophin encoding viral particles/ml of composition fluid. Each delivery site receives form 2.5 μl to 25 μl of neurotrophic composition delivered slowly, as in over a period of time ranging upward of 10 minutes/delivery site. Each delivery site is at, or within 500 μm of, a targeted cell, and no more than about 10 mm from another delivery site. Stable in situ neurotrophin expression can be achieved for 12 months, or longer.

摘要翻译： 用于治疗哺乳动物脑中有缺陷的，患病的和受损的胆碱能神经元的特定临床方案，对于治疗神经变性疾病如阿尔茨海默氏病尤其有用。 通过将确定的重组神经营养因子浓度递送到或者非常接近于鉴定的有缺陷的，患病的或受损的脑细胞来实施该方案。 使用病毒载体，作为神经营养组合物的一部分递送的神经营养因子的浓度在编码病毒颗粒/ ml组合物流体的10 10 10 10 15神经营养因子中变化。 每个递送站点接收到2.5个月至25个月的神经营养物质缓慢递送的形式，如在超过10分钟/递送部位的时间段内。 每个递送部位在目标细胞的500μm以下，距离另一个递送部位不超过约10mm。 稳定的原位神经营养蛋白表达可以达到12个月或更长时间。