公开(公告)号：US08034270B2

公开(公告)日：2011-10-11

申请号：US10835926

申请日：2004-04-30

申请人： David P. Martin ,  Said Rizk ,  Ajay Ahuja ,  Simon F. Williams

发明人： David P. Martin ,  Said Rizk ,  Ajay Ahuja ,  Simon F. Williams

IPC分类号： D01D5/088 ,  D01D5/16 ,  D01F6/62 ,  D02G3/02

CPC分类号： A61F2/0063 ,  A61F2002/0068 ,  A61L27/18 ,  A61L27/48 ,  A61L31/06 ,  B29C47/0004 ,  B29C47/0014 ,  B29C71/0072 ,  B29K2067/00 ,  B29L2031/753 ,  D01D5/088 ,  D01D5/098 ,  D01D5/16 ,  D01F6/62 ,  D01F6/625 ,  D01F6/84 ,  D02G3/02 ,  Y10T428/1362 ,  Y10T428/1369 ,  Y10T428/249922 ,  Y10T442/10 ,  Y10T442/183 ,  Y10T442/184 ,  Y10T442/2525 ,  C08L67/04

摘要： Absorbable polyester fibers, braids, and surgical meshes with prolonged strength retention have been developed. These devices are preferably derived from biocompatible copolymers or homopolymers of 4-hydroxybutyrate. These devices provide a wider range of in vivo strength retention properties than are currently available, and could offer additional benefits such as anti-adhesion properties, reduced risks of infection or other post-operative problems resulting from absorption and eventual elimination of the device, and competitive cost. The devices may also be particularly suitable for use in pediatric populations where their absorption should not hinder growth, and provide in all patient populations wound healing with long-term mechanical stability. The devices may additionally be combined with autologous, allogenic and/or xenogenic tissues to provide implants with improved mechanical, biological and handling properties.

摘要翻译： 已经开发了具有延长的强度保持性的可吸收聚酯纤维，辫子和外科网。 这些装置优选衍生自生物相容性共聚物或4-羟基丁酸酯的均聚物。 这些装置提供比目前可获得的更广泛的体内强度保留性能，并且可以提供额外的益处，例如抗粘附性能，降低的感染风险或由吸收和最终消除装置而产生的其他手术后问题，以及 有竞争力的成本。 这些装置还可以特别适用于儿科人群，其吸收不应阻碍生长，并在所有患者群体中提供长期机械稳定性的伤口愈合。 所述装置可以另外与自体，同种异体和/或异种组织组合，以提供具有改进的机械，生物和处理性质的植入物。

公开(公告)号：US08027718B2

公开(公告)日：2011-09-27

申请号：US11370967

申请日：2006-03-07

申请人： Robert J. Spinner ,  David P. Martin ,  Timothy R. Conrad

发明人： Robert J. Spinner ,  David P. Martin ,  Timothy R. Conrad

IPC分类号： A61N1/30 ,  A61N1/00

CPC分类号： A61M19/00 ,  A61B18/02 ,  A61B2018/0212 ,  A61N1/36017 ,  A61N1/36021

摘要： A method and apparatus are disclosed for anesthetizing a region of a patient's body. The method includes identifying a target nerve which, upon activation, anesthetizes a region of a patient's body including a surgical site. The target nerve is located and an active site of a nerve blocking apparatus is placed in proximity to the nerve. The nerve blocking apparatus is activated to block neural propagation along the nerve. The activation of the nerve blocking apparatus is maintained during a surgical procedure at the surgical site.

摘要翻译： 公开了用于麻醉患者身体区域的方法和装置。 该方法包括识别目标神经，其在激活时麻醉患者身体的包括手术部位的区域。 定位目标神经，将神经阻滞装置的活动部位置于神经附近。 神经阻断装置被激活以阻断沿着神经的神经传播。 在手术部位的手术过程中，保持神经阻滞装置的活化。

公开(公告)号：US20100093043A1

公开(公告)日：2010-04-15

申请号：US11735888

申请日：2007-04-16

申请人： Gjalt W. Huisman ,  Frank Skraly ,  David P. Martin ,  Oliver P. Peoples

发明人： Gjalt W. Huisman ,  Frank Skraly ,  David P. Martin ,  Oliver P. Peoples

IPC分类号： C12P13/04 ,  C12N1/12 ,  C12N15/74

CPC分类号： C12N9/0008 ,  C08G63/06 ,  C12N9/1029 ,  C12N9/1096 ,  C12N15/8243 ,  C12P7/625

摘要： The gene encoding a 4-hydroxybutyryl-Co A transferase has been isolated from bacteria and integrated into the genome of bacteria also expressing a polyhydroxyalkanoate synthase, to yield an improved production process for 4HB-containing polyhydroxyalkanoates using transgenic organisms, including both bacteria and plants. The new pathways provide means for producing 4HB containing PHAs from cheap carbon sources such as sugars and fatty acids, in high yields, which are stable. Useful strains are obtaining by screening strains having integrated into their genomes a gene encoding a 4HB-CoA transferase and/or PHA synthase, for polymer production. Processes for polymer production use recombinant systems that can utilize cheap substrates. Systems are provided which can utilize amino acid degradation pathways, α-ketoglutarate, or succinate as substrate.

摘要翻译： 已经从细菌中分离出编码4-羟基丁酰-CoA转移酶的基因，并整合到也表达聚羟基链烷酸酯合酶的细菌的基因组中，以使用包括细菌和植物在内的转基因生物来产生含4HB的聚羟基链烷酸酯的改进的生产方法。 新途径提供了从低廉的碳源（如糖和脂肪酸）生产含有PHB的4HB的方法，其产率高，稳定。 有用的菌株是通过筛选在其基因组中整合了编码4HB-CoA转移酶和/或PHA合成酶的基因的聚合物生产获得的菌株。 用于聚合物生产的方法使用可以利用廉价底物的重组体系。 提供可以利用氨基酸降解途径的系统，α-酮戊二酸或琥珀酸作为底物。

公开(公告)号：US07268205B2

公开(公告)日：2007-09-11

申请号：US11623593

申请日：2007-01-16

申请人： Simon F. Williams ,  David P. Martin ,  Frank A. Skraly

发明人： Simon F. Williams ,  David P. Martin ,  Frank A. Skraly

IPC分类号： C08G63/08

CPC分类号： A61L27/58 ,  A61F2/07 ,  A61F2210/0004 ,  A61K31/715 ,  A61L17/12 ,  A61L27/18 ,  A61L31/06 ,  A61L31/148 ,  A61L31/16 ,  A61L2300/00 ,  C08G63/06 ,  C08J9/26 ,  C08J2201/0444 ,  C08J2201/0482 ,  C08J2367/04 ,  C08K5/0033 ,  C08L67/04 ,  C12P7/625 ,  Y10S606/911

摘要： Devices formed of or including biocompatible polyhydroxyalkanoates are provided with controlled degradation rates, preferably less than one year under physiological conditions. Preferred devices include sutures, suture fasteners, meniscus repair devices, rivets, tacks, staples, screws (including interference screws), bone plates and bone plating systems, surgical mesh, repair patches, slings, cardiovascular patches, orthopedic pins (including bone filling augmentation material), adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, nerve guides, tendon repair devices, atrial septal defect repair devices, pericardial patches, bulking and filling agents, vein valves, bone marrow scaffolds, meniscus regeneration devices, ligament and tendon grafts, ocular cell implants, spinal fusion cages, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, and hemostats. The polyhydroxyalkanoates can contain additives, be formed of mixtures of monomers or include pendant groups or modifications in their backbones, or can be chemically modified, all to alter the degradation rates. The polyhydroxyalkanoate compositions also provide favorable mechanical properties, biocompatibility, and degradation times within desirable time frames under physiological conditions.

公开(公告)号：US06867248B1

公开(公告)日：2005-03-15

申请号：US10403244

申请日：2003-03-28

申请人： David P. Martin ,  Frank Skraly ,  Simon F. Williams

发明人： David P. Martin ,  Frank Skraly ,  Simon F. Williams

IPC分类号： A61K9/16 ,  A61K47/48 ,  A61L15/26 ,  A61L17/10 ,  A61L17/12 ,  A61L24/00 ,  A61L26/00 ,  A61L27/18 ,  A61L27/34 ,  A61L27/58 ,  A61L29/06 ,  A61L31/06 ,  A61L31/14 ,  C08G63/06 ,  C08G63/64 ,  C08G63/685 ,  C08G63/688 ,  C08G63/91 ,  C08K5/00 ,  C12N5/00 ,  C12P7/62 ,  C08L67/04

CPC分类号： C12P7/625 ,  A61K9/1647 ,  A61K47/593 ,  A61K47/6957 ,  A61L15/26 ,  A61L17/10 ,  A61L17/12 ,  A61L24/0042 ,  A61L26/0019 ,  A61L26/009 ,  A61L27/18 ,  A61L27/34 ,  A61L27/58 ,  A61L29/06 ,  A61L31/06 ,  A61L31/148 ,  C08G63/06 ,  C08G63/64 ,  C08G63/6852 ,  C08G63/6882 ,  C08G63/912 ,  C08K5/0033 ,  C12N5/0068 ,  C12N2533/30 ,  C08L67/04

摘要： Biocompatible polyhydroxyalkanoate compositions with controlled degradation rates have been developed. In one embodiment, the polyhydroxyalkanoates contain additives to alter the degradation rates. In another embodiment, the polyhydroxyalkanoates are formed of mixtures of monomers or include pendant groups or modifications in their backbones to alter their degradation rates. In still another embodiment, the polyhydroxyalkanoates are chemically modified. Methods for manufacturing the devices which increase porosity or exposed surface area can be used to alter degradability. For example, as demonstrated by the examples, porous polyhydroxyalkanoates can be made using methods that creates pores, voids, or interstitial spacing, such as an emulsion or spray drying technique, or which incorporate leachable or lyophilizable particles within the polymer. Examples describe poly(4HB) compositions including foams, coatings, meshes, and microparticles. As demonstrated by the examples, these polyhydroxyalkanoate compositions have extremely favorable mechanical properties, as well as are biocompatible and degrade within desirable time frames under physiological conditions. These polyhydroxyalkanoate materials provide a wider range of polyhydroxyalkanoate degradation rates than are currently available. Methods for processing these materials, particularly for therapeutic, prophylactic or diagnostic applications, or into devices which can be implanted or injected, are also described.

摘要翻译： 已经开发了具有受控降解速率的生物相容性聚羟基链烷酸酯组合物。 在一个实施方案中，聚羟基链烷酸酯含有改变降解速率的添加剂。 在另一个实施方案中，聚羟基链烷酸酯由单体的混合物形成或包括侧链基团或其主链中的修饰以改变其降解速率。 在另一个实施方案中，聚羟基链烷酸酯被化学改性。 用于制造增加孔隙率或暴露表面积的装置的方法可用于改变降解性。 例如，如通过实施例所证明的，多孔聚羟基链烷酸酯可以使用产生孔，空隙或间隙的方法，例如乳液或喷雾干燥技术，或者在聚合物内含有可浸出或可冷冻干燥的颗粒。 实例描述了包括泡沫，涂层，网格和微粒的聚（4HB）组合物。 如实施例所示，这些聚羟基链烷酸酯组合物在生理条件下在期望的时间范围内具有非常有利的机械性能以及生物相容性和降解性。 这些聚羟基链烷酸酯材料提供比目前可获得的更广泛的聚羟基链烷酸酯降解速率。 还描述了用于处理这些材料的方法，特别是用于治疗，预防或诊断应用，或可植入或注射的装置。

公开(公告)号：US06867247B2

公开(公告)日：2005-03-15

申请号：US10136499

申请日：2002-05-01

申请人： Simon F. Williams ,  David P. Martin ,  Frank A. Skraly

发明人： Simon F. Williams ,  David P. Martin ,  Frank A. Skraly

IPC分类号： A61B17/58 ,  A61F2/84 ,  A61K45/00 ,  A61L15/64 ,  A61L17/00 ,  A61L17/12 ,  A61L27/00 ,  A61L27/18 ,  A61L27/58 ,  A61L31/06 ,  A61L31/14 ,  C08G63/06 ,  C08K5/00 ,  C12P7/62 ,  C08L67/04

CPC分类号： A61L27/58 ,  A61F2/07 ,  A61F2210/0004 ,  A61K31/715 ,  A61L17/12 ,  A61L27/18 ,  A61L31/06 ,  A61L31/148 ,  A61L31/16 ,  A61L2300/00 ,  C08G63/06 ,  C08J9/26 ,  C08J2201/0444 ,  C08J2201/0482 ,  C08J2367/04 ,  C08K5/0033 ,  C08L67/04 ,  C12P7/625 ,  Y10S606/911

摘要： Devices formed of or including biocompatible polyhydroxyalkanoates are provided with controlled degradation rates, preferably less than one year under physiological conditions. Preferred devices include sutures, suture fasteners, meniscus repair devices, rivets, tacks, staples, screws (including interference screws), bone plates and bone plating systems, surgical mesh, repair patches, slings, cardiovascular patches, orthopedic pins (including bone filling augmentation material), adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, nerve guides, tendon repair devices, atrial septal defect repair devices, pericardial patches, bulking and filling agents, vein valves, bone marrow scaffolds, meniscus regeneration devices, ligament and tendon grafts, ocular cell implants, spinal fusion cages, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, and hemostats. The polyhydroxyalkanoates can contain additives, be formed of mixtures of monomers or include pendant groups or modifications in their backbones, or can be chemically modified, all to alter the degradation rates. The polyhydroxyalkanoate compositions also provide favorable mechanical properties, biocompatibility, and degradation times within desirable time frames under physiological conditions.

公开(公告)号：US06689589B2

公开(公告)日：2004-02-10

申请号：US10006915

申请日：2001-11-09

申请人： Gjalt W. Huisman ,  Frank Skraly ,  David P. Martin ,  Oliver P. Peoples

发明人： Gjalt W. Huisman ,  Frank Skraly ,  David P. Martin ,  Oliver P. Peoples

IPC分类号： C12P762

CPC分类号： C12N9/0008 ,  C08G63/06 ,  C12N9/1029 ,  C12N9/1096 ,  C12N15/8243 ,  C12P7/625

摘要： The gene encoding a 4-hydroxybutyryl-Co A transferase has been isolated from bacteria and integrated into the genome of bacteria also expressing a polyhydroxyalkanoate synthase, to yield an improved production process for 4HB-containing polyhydroxyalkanoates using transgenic organisms, including both bacteria and plants. The new pathways provide means for producing 4HB containing PHAs from cheap carbon sources such as sugars and fatty acids, in high yields, which are stable. Useful strains are obtaining by screening strains having integrated into their genomes a gene encoding a 4HB-CoA transferase and/or PHA synthase, for polymer production. Processes for polymer production use recombinant systems that can utilize cheap substrates. Systems are provided which can utilize amino acid degradation pathways, &agr;-ketoglutarate, or succinate as substrate.

公开(公告)号：US06610764B1

公开(公告)日：2003-08-26

申请号：US09218575

申请日：1998-12-22

申请人： David P. Martin ,  Frank Skraly ,  Simon F. Williams

发明人： David P. Martin ,  Frank Skraly ,  Simon F. Williams

IPC分类号： C08L6704

CPC分类号： C08G63/912 ,  A61K9/1647 ,  A61K47/593 ,  A61K47/6957 ,  A61L15/26 ,  A61L17/10 ,  A61L17/12 ,  A61L24/0042 ,  A61L26/0019 ,  A61L26/009 ,  A61L27/18 ,  A61L27/34 ,  A61L27/58 ,  A61L29/06 ,  A61L31/06 ,  A61L31/148 ,  C08G63/06 ,  C08G63/64 ,  C08G63/6852 ,  C08G63/6882 ,  C08J9/26 ,  C08J2201/0444 ,  C08J2201/0482 ,  C08J2367/04 ,  C08K5/0033 ,  C12N5/0068 ,  C12N2533/30 ,  C12P7/625 ,  C08L67/04

摘要： Biocompatible polyhydroxyalkanoate compositions with controlled degradation rates have been developed. In one embodiment, the polyhydroxyalkanoates contain additives to alter the degradation rates. In another embodiment, the polyhydroxyalkanoates are formed of mixtures of monomers or include pendant groups or modifications in their backbones to alter their degradation rates. In still another embodiment, the polyhydroxyalkanoates are chemically modified. Methods for manufacturing the devices which increase porosity or exposed surface area can be used to alter degradability. For example, as demonstrated by the examples, porous polyhydroxyalkanoates can be made using methods that creates pores, voids, or interstitial spacing, such as an emulsion or spray drying technique, or which incorporate leachable or lyophilizable particles within the polymer. Examples describe poly(4HB) compositions including foams, coatings, meshes, and microparticles. As demonstrated by the examples, these polyhydroxyalkanoate compositions have extremely favorable mechanical properties, as well as are biocompatible and degrade within desirable time frames under physiological conditions. These polyhydroxyalkanoate materials provide a wider range of polyhydroxyalkanoate degradation rates than are currently available. Methods for processing these materials, particularly for therapeutic, prophylactic or diagnostic applications, or into devices which can be implanted or injected, are also described.

摘要翻译： 已经开发了具有受控降解速率的生物相容性聚羟基链烷酸酯组合物。 在一个实施方案中，聚羟基链烷酸酯含有改变降解速率的添加剂。 在另一个实施方案中，聚羟基链烷酸酯由单体的混合物形成或包括侧链基团或其主链中的修饰以改变其降解速率。 在另一个实施方案中，聚羟基链烷酸酯被化学改性。 用于制造增加孔隙率或暴露表面积的装置的方法可用于改变降解性。 例如，如通过实施例所证明的，多孔聚羟基链烷酸酯可以使用产生孔，空隙或间隙的方法，例如乳液或喷雾干燥技术，或者在聚合物内含有可浸出或可冷冻干燥的颗粒。 实例描述了包括泡沫，涂层，网格和微粒的聚（4HB）组合物。 如实施例所示，这些聚羟基链烷酸酯组合物在生理条件下在期望的时间范围内具有非常有利的机械性能以及生物相容性和降解性。 这些聚羟基链烷酸酯材料提供比目前可获得的更广泛的聚羟基链烷酸酯降解速率。 还描述了用于处理这些材料的方法，特别是用于治疗，预防或诊断应用，或可植入或注射的装置。

公开(公告)号：US06555123B2

公开(公告)日：2003-04-29

申请号：US10123951

申请日：2002-04-16

申请人： Simon F. Williams ,  David P. Martin

发明人： Simon F. Williams ,  David P. Martin

IPC分类号： A61F200

CPC分类号： C12P7/625 ,  A61L27/18 ,  C08L67/04

摘要： Polyhydroxyalkanoate materials are provided which are suitable for repair of soft tissue, augmentation, and as viscosupplements in animals, particularly humans. The materials comprise liquid polyhydroxyalkanoate polymer compositions or polyhydroxyalkanoate microdispersions. Devices also are provided for storage and delivery of the polyhydroxyalkanoate compositions in vivo. Methods are provided for repairing or augmenting soft tissue in animals using the materials. In a preferred embodiment, the method include the steps of (a) selecting the animal soft tissue to be repaired or augmented; and (b) placing an injectable, liquid polyhydroxyalkanoate polymer or a polyhydroxyalkanoate microdispersion into the animal soft tissue, preferably using a minimally-invasive method such as injection. In another embodiment, the liquid polyhydroxyalkanoate polymer compositions or polyhydroxyalkanoate microdispersions are used as viscosupplements.

公开(公告)号：US08753555B2

公开(公告)日：2014-06-17

申请号：US13084388

申请日：2011-04-11

申请人： Said Rizk ,  David P. Martin ,  Kicherl Ho ,  Simon F. Williams

发明人： Said Rizk ,  David P. Martin ,  Kicherl Ho ,  Simon F. Williams

IPC分类号： B29C55/04 ,  B29C55/12 ,  A61L27/18 ,  A61L27/58 ,  C08L67/04 ,  C08G63/08

CPC分类号： A61L27/34 ,  A61L27/18 ,  A61L31/10 ,  B29C55/005 ,  B29C55/04 ,  B29C55/12 ,  B29K2067/00 ,  B29K2067/046 ,  B29K2995/006 ,  C08L67/04

摘要： Continuous processing methods for making absorbable polymeric films with one or more of the following properties: high toughness, low modulus, high tensile strength, and thickness less than 10 mm, more preferably less than 1 mm, and more preferably less than 100 μm, have been developed. In the preferred embodiment, the polymer is a polyhydroxyalkanoate, and in the most preferred embodiment, the polymer comprises 4-hydroxybutyrate. A particularly preferred embodiment is a film of poly-4-hydroxybutyrate or copolymer thereof, wherein the film has a tensile strength greater than 5.5 kgf/mm2, tensile modulus less than 181 kgf/mm2, and elongation at break from 10-500%, wherein the film is derived by a continuous process such as melt extrusion or solvent casting, followed by orientation to more than 25% of the film's original length in one or more directions. These can be used for a variety of purposes including fabrication of medical devices.

摘要翻译： 用于制造具有以下特性中的一种或多种的可吸收聚合物膜的连续加工方法：高韧性，低模量，高拉伸强度和小于10mm，更优选小于1mm，更优选小于100μm的厚度具有 已经开发 在优选的实施方案中，聚合物是聚羟基链烷酸酯，并且在最优选的实施方案中，聚合物包含4-羟基丁酸酯。 特别优选的实施方案是聚-4-羟基丁酸酯或其共聚物的膜，其中所述膜的拉伸强度大于5.5kgf / mm 2，拉伸模量小于181kgf / mm 2，断裂伸长率为10-500％ 其中所述膜通过连续方法如熔体挤出或溶剂浇铸得到，然后在一个或多个方向上定向至超过膜的原始长度的25％。 这些可以用于各种目的，包括制造医疗器械。