公开(公告)号：US09408884B2

公开(公告)日：2016-08-09

申请号：US14406198

申请日：2013-06-03

Applicant: Ronald E. Betts ,  John Dang Nguyen

Inventor： Ronald E. Betts ,  John Dang Nguyen

IPC: C07D498/18 ,  C08L67/04 ,  A61K36/68 ,  A61L31/10 ,  A61L31/16 ,  A61K31/685 ,  A61K38/16 ,  A61K38/17 ,  A61K47/26 ,  A61K47/46

CPC classification number: A61L31/16 ,  A61K31/685 ,  A61K36/68 ,  A61K38/168 ,  A61K38/1709 ,  A61K47/26 ,  A61K47/46 ,  A61L31/10 ,  A61L2300/416 ,  A61L2300/606 ,  A61L2300/608 ,  C07D498/18 ,  C08L67/04

Abstract: A new class of rapamycin 40-O-cyclic hydrocarbon esters is disclosed. The 40-O position of the rapamycin ester has the form 40-O—R, where R is C(O)—(CH2)n-X, n is 0, 1 or 2, and X is a cyclic hydrocarbon having 3-8 carbons, optionally containing one or more unsaturated bonds, and one or more linear (CH2)n) and/or cyclic (X) carbon atoms may have an OH or halide group. Also disclosed are therapeutic compositions and methods that employ the novel analogs.

Abstract translation: 公开了一类新型雷帕霉素40-O-环烃酯。 雷帕霉素酯的40-O位具有40-O-R形式，其中R是C（O） - （CH 2）n X，n是0,1或2，X是具有3-8个碳原子的环状烃 ，任选地含有一个或多个不饱和键，以及一个或多个线性（CH 2）n）和/或环状（X）的碳原子可以具有OH或卤化物基团。 还公开了使用新型类似物的治疗组合物和方法。

公开(公告)号：US08871292B2

公开(公告)日：2014-10-28

申请号：US13556893

申请日：2012-07-24

Applicant: Douglas R. Savage ,  Ronald E. Betts

Inventor： Douglas R. Savage ,  Ronald E. Betts

IPC: B05D3/12 ,  B05D3/10 ,  A61L33/00 ,  A61F2/06 ,  A61L31/16 ,  A61F2/91

CPC classification number: A61L31/16 ,  A61F2/91 ,  A61L2300/416

Abstract: A radially expandable, endovascular stent designed for placement at a site of vascular injury, for inhibiting restenosis at the site, a method of using, and a method of making the stent. The stent includes a radially expandable body formed of one or more metallic filaments and a liquid-infusible mechanical anchoring layer attached to or formed in outer surface of the filaments. A drug coating in the stent is composed of a substantially polymer-free composition of an anti-restenosis drug, and has a substratum infused in the anchoring layer and a substantially continuous surface stratum of drug that is brought into direct contact with the vessel walls at the vascular site. Thus, the rate of release of the anti-restenosis drug from the surface stratum into said vascular site is determined solely by the composition of said drug coating.

Abstract translation: 设计用于放置在血管损伤部位，用于抑制现场再狭窄的径向可扩张的血管内支架，使用方法和制造支架的方法。 该支架包括由一个或多个金属细丝形成的径向可扩张体，以及附着于细丝的外表面或形成于细丝的外表面的液体不可渗透的机械锚定层。 支架中的药物涂层由基本上无聚合物的抗再狭窄药物组合物组成，并且具有输注在锚定层中的基质和药物的基本上连续的表面层，其与血管壁直接接触 血管部位。 因此，抗再狭窄药物从表层到所述血管部位的释放速率仅由所述药物包衣的组成确定。

公开(公告)号：US20130035754A1

公开(公告)日：2013-02-07

申请号：US13647977

申请日：2012-10-09

Applicant: John E. SHULZE ,  Ronald E. BETTS ,  Douglas R. SAVAGE

Inventor： John E. SHULZE ,  Ronald E. BETTS ,  Douglas R. SAVAGE

IPC: A61F2/06

CPC classification number: A61L31/16 ,  A61F2/90 ,  A61F2/91 ,  A61F2/915 ,  A61F2002/072 ,  A61F2002/91533 ,  A61F2002/91575 ,  A61F2230/0054 ,  A61F2240/001 ,  A61F2250/0067 ,  A61K9/0024 ,  A61L31/022 ,  A61L31/06 ,  A61L31/10 ,  A61L2300/416 ,  A61L2300/602 ,  A61L2300/606 ,  A61L2420/08 ,  C08L29/04 ,  C08L67/04

Abstract: An intravascular stent and method for inhibiting restenosis, following vascular injury, is disclosed. The stent has an expandable, linked-filament body and a drug-release coating formed on the stent-body filaments, for contacting the vessel injury site when the stent is placed in-situ in an expanded condition. The coating releases, for a period of at least 4 weeks, a restenosis-inhibiting amount of a monocyclic triene immunosuppressive compound having an alkyl group substituent at carbon position 40 in the compound. The stent, when used to treat a vascular injury, gives good protection against clinical restenosis, even when the extent of vascular injury involves vessel overstretching by more than 30% diameter. Also disclosed is a stent having a drug-release coating composed of (i) 10 and 60 weight percent poly-dl-Iactide polymer substrate and (ii) 40-90 weight percent of an anti-restenosis compound, and a polymer undercoat having a thickness of between 1-5 microns.

Abstract translation: 公开了血管内支架和用于抑制血管损伤后再狭窄的方法。 支架具有可扩张的连接长丝体和形成在支架体细丝上的药物释放涂层，用于当支架在扩张状态下原位放置时接触血管损伤部位。 该涂层释放至少4周的再狭窄抑制量的化合物中在碳位置40具有烷基取代基的单环三烯免疫抑制化合物。 当支架用于治疗血管损伤时，即使在血管损伤程度超过30％直径的血管破裂的情况下，也能对抗临床再狭窄提供良好的保护。 还公开了一种支架，其具有由（i）10重量％和60重量％的聚-DL-酰胺聚合物基材和（ii）40-90重量％的抗再狭窄化合物组成的药物释放包衣，以及聚合物底涂层，其具有 厚度介于1-5微米之间。

公开(公告)号：US20120330406A1

公开(公告)日：2012-12-27

申请号：US13554296

申请日：2012-07-20

Applicant: Douglas R. Savage ,  John E. Shulze ,  Ronald E. Betts ,  Sepehr Fariabi ,  Shih-Horng Su

Inventor： Douglas R. Savage ,  John E. Shulze ,  Ronald E. Betts ,  Sepehr Fariabi ,  Shih-Horng Su

IPC: A61F2/82 ,  B05D7/14

CPC classification number: A61L31/16 ,  A61F2/82 ,  A61F2/848 ,  A61F2/89 ,  A61F2/91 ,  A61F2/915 ,  A61F2002/825 ,  A61F2002/91541 ,  A61F2002/91566 ,  A61F2210/0004 ,  A61F2210/0014 ,  A61F2220/0025 ,  A61F2230/0013 ,  A61F2240/001 ,  A61F2250/0023 ,  A61F2250/0025 ,  A61F2250/0026 ,  A61F2250/0036 ,  A61F2250/0037 ,  A61F2250/0051 ,  A61F2250/0067 ,  A61F2250/0068 ,  A61F2250/0096 ,  A61L31/022 ,  A61L31/10 ,  A61L2300/416 ,  A61L2300/606 ,  A61L2420/02

Abstract: An improvement in drug-eluting stents, and method of their making, are disclosed. The surface of a metal stent is roughened to have a surface roughness of at least about 20 μin (0.5 μm) and a surface roughness range of between about 300-700 μin (7.5-17.5 μm). The roughened stent surface is covered with a polymer-free coating of a limus drug, to a coating thickness greater than the range of surface roughness of the roughened stent surface.

Abstract translation: 披露了药物洗脱支架的改进及其制作方法。 金属支架的表面被粗糙化以具有至少约20μin（0.5μm）的表面粗糙度和在约300-700μin（7.5-17.5μm）之间的表面粗糙度范围。 粗糙化的支架表面覆盖有无聚合物的斜肌药物涂层，涂层厚度大于粗糙化支架表面的表面粗糙度范围。

公开(公告)号：US20110123704A1

公开(公告)日：2011-05-26

申请号：US13023312

申请日：2011-02-08

Applicant: Douglas R. Savage ,  Ronald E. Betts

Inventor： Douglas R. Savage ,  Ronald E. Betts

IPC: B05D5/00 ,  A61L33/00

CPC classification number: A61L31/16 ,  A61F2/91 ,  A61L2300/416

Abstract: A radially expandable, endovascular stent designed for placement at a site of vascular injury, for inhibiting restenosis at the site, a method of using, and a method of making the stent. The stent includes a radially expandable body formed of one or more metallic filaments and a liquid-infusible mechanical anchoring layer attached to or formed in outer surface of the filaments. A drug coating in the stent is composed of a substantially polymer-free composition of an anti-restenosis drug, and has a substratum infused in the anchoring layer and a substantially continuous surface stratum of drug that is brought into direct contact with the vessel walls at the vascular site. Thus, the rate of release of the anti-restenosis drug from the surface stratum into said vascular site is determined solely by the composition of said drug coating.

Abstract translation: 设计用于放置在血管损伤部位，用于抑制现场再狭窄的径向可扩张的血管内支架，使用方法和制造支架的方法。 该支架包括由一个或多个金属细丝形成的径向可扩张体，以及附着于细丝的外表面或形成于细丝的外表面的液体不可渗透的机械锚定层。 支架中的药物涂层由基本上无聚合物的抗再狭窄药物组合物组成，并且具有注入锚固层中的基质和药物的基本连续的表面层，其与血管壁直接接触 血管部位。 因此，抗再狭窄药物从表层到所述血管部位的释放速率仅由所述药物包衣的组成确定。

公开(公告)号：US5338435A

公开(公告)日：1994-08-16

申请号：US905255

申请日：1992-06-26

Applicant: Ronald E. Betts ,  Douglas R. Savage ,  Richard J. Koerner ,  Matthew J. Leader ,  Kee V. Sin ,  Jeffrey A. Graves ,  Marshall L. Sherman

Inventor： Ronald E. Betts ,  Douglas R. Savage ,  Richard J. Koerner ,  Matthew J. Leader ,  Kee V. Sin ,  Jeffrey A. Graves ,  Marshall L. Sherman

IPC: G01N27/26 ,  A61B5/00 ,  A61B5/15 ,  B01L3/00 ,  G01N1/00 ,  G01N27/27 ,  G01N27/28 ,  G01N33/487 ,  G01N33/49

CPC classification number: G01N33/4925 ,  A61B5/14539 ,  A61B5/14542 ,  A61B5/1468 ,  A61B5/1473 ,  A61B5/15003 ,  A61B5/150251 ,  A61B5/150305 ,  A61B5/150786 ,  A61B5/153 ,  A61B5/157 ,  A61B2562/08 ,  B01L3/502

Abstract: A plastic covered nonconducting substrate with an electrical circuit means is secured to the extent to withstand the presence of liquids in contact with the substrate. The covered substrate can have the substrate with one or more fluid preconditionable electrical components, a housing secured to the substrate to maintain contact of the preconditioning fluid with the electrical component like a sensor, and moisture impervious seals to cover openings in the housing for the disposition of the preconditioning fluid in the housing for contact with the electrical component on the substrate. The housing can have one or more parts and have one or more channels for containing the preconditioning fluid.The electrical component can be an improved electronic wiring board having a thermistor and at least one blood gas sensor supported, in close relation, one to the other, on one side of the board and a heater supported on the other side of the board to provide heat in response to temperature sensed by the thermistor, to at least the region where the thermistor and the blood gas sensor are positioned on the board to control the temperature of the region of the board within a narrow distribution of temperatures.

Abstract translation: 具有电路装置的塑料覆盖的非导电基板被固定到能够承受与基板接触的液体的存在的程度。 被覆盖的基板可以具有一个或多个流体预调节电气部件的基板，固定到基板的壳体，以保持预处理流体与电气部件如传感器的接触，以及防潮密封件，以覆盖外壳中的开口用于处置 的壳体中的预处理流体与衬底上的电气部件接触。 壳体可以具有一个或多个部件并且具有用于容纳预处理流体的一个或多个通道。 电气部件可以是具有热敏电阻和至少一个血液传感器的改进的电子布线板，所述至少一个血液传感器在板的一侧彼此相对地相互支撑，并且加热器支撑在板的另一侧上以提供 至少热敏电阻和血液气体传感器位于板上的区域，以控制板的区域在较窄的温​​度分布范围内的温度。

公开(公告)号：US5284570A

公开(公告)日：1994-02-08

申请号：US721028

申请日：1991-06-26

Applicant: Douglas R. Savage ,  Ronald E. Betts ,  Richard J. Koerner ,  Douglas R. Hillier

Inventor： Douglas R. Savage ,  Ronald E. Betts ,  Richard J. Koerner ,  Douglas R. Hillier

IPC: A61B5/00 ,  A61B5/15 ,  G01N33/487 ,  G01N33/49 ,  G01N27/26

CPC classification number: G01N33/4925 ,  A61B5/14539 ,  A61B5/14542 ,  A61B5/1468 ,  A61B5/157 ,  A61B5/15003

Abstract: A fluid sample collector, sensing, and calibration device contains a collector like a syringe, with one or more analyte sensors, and a calibrator for calibrating the sensor. These can be pre-assembled and are particularly adapted to be disposable after a single use; the analyte sensor may be connected to a self-contained monitoring instrument or analyzer which processes the signals from the sensor and displays the information to the operator.

Abstract translation: 流体样品收集器，感测和校准装置包含诸如注射器的收集器，具有一个或多个分析物传感器，以及用于校准传感器的校准器。 这些可以预先组装，并且特别适于在一次使用之后是一次性的; 分析物传感器可以连接到独立的监测仪器或分析器，其处理来自传感器的信号并将信息显示给操作者。

公开(公告)号：US4748121A

公开(公告)日：1988-05-31

申请号：US677108

申请日：1984-11-30

Applicant: Richard P. Beaver ,  Ronald E. Betts ,  Lin-Chang Chiang ,  George V. Sanzero

Inventor： Richard P. Beaver ,  Ronald E. Betts ,  Lin-Chang Chiang ,  George V. Sanzero

IPC: C03C3/06 ,  C03C3/089 ,  C03C11/00 ,  C03C13/00 ,  C03C25/68 ,  C07K17/14 ,  C12M1/40 ,  C12N5/00 ,  C12N11/14 ,  C12N11/00 ,  G01N33/552

CPC classification number: C03C11/005 ,  C03C13/00 ,  C12M21/18 ,  C12M25/10 ,  C12N11/14 ,  C12N5/0068 ,  C12N2533/12 ,  Y10S530/811

Abstract: Biochemically active material is immobilized on porous silica-rich glass fibers having a diameter of about 3 to 150 microns, a length of about 0.03 inch to continuous fiber length, a mean pore diameter in the range of about 10 to 3000 angstroms, a pore volume of about 0.5 to 1.5 cc/gm and a surface area of about 10 to 600 m.sup.2 /gm. The porous glass fibers are preferably formed from a composition containing greater than 35 up to 60 weight percent B.sub.2 O.sub.3, about 1 to 10 weight percent alkali metal oxides, about 30 to 65 weight percent SiO.sub.2, up to about 5 weight percent ZrO.sub.2, and up to about 4 weight percent Al.sub.2 O.sub.3. Fibers having the composition are heated to cause phase separation into a boron-rich phase and a silica-rich phase, and are then treated by water and acid leaching to produce the porous glass fibers. A biochemically active material is attached to the fibers by absorption or by covalent bonding with a linking agent.

Abstract translation: 将生物活性材料固定在直径为约3至150微米，长度为约0.03英寸至连续纤维长度的多孔二氧化硅玻璃纤维上，平均孔径在约10至3000埃范围内，孔体积 约0.5至1.5cc / gm，表面积为约10至600m 2 / gm。 多孔玻璃纤维优选由含有大于35重量％至60重量％B 2 O 3，约1至10重量％碱金属氧化物，约30至65重量％SiO 2，至多约5重量％ZrO 2的组合物形成， 约4重量％的Al 2 O 3。 将具有该组成的纤维加热以引起相分离成富硼相和富含二氧化硅的相，然后用水和酸浸法处理以产生多孔玻璃纤维。 生物化学活性材料通过吸收或与连接剂的共价键连接在纤维上。

公开(公告)号：US20120290076A1

公开(公告)日：2012-11-15

申请号：US13556893

申请日：2012-07-24

Applicant: Douglas R. SAVAGE ,  Ronald E. BETTS

Inventor： Douglas R. SAVAGE ,  Ronald E. BETTS

IPC: A61F2/82

CPC classification number: A61L31/16 ,  A61F2/91 ,  A61L2300/416

Abstract: A radially expandable, endovascular stent designed for placement at a site of vascular injury, for inhibiting restenosis at the site, a method of using, and a method of making the stent. The stent includes a radially expandable body formed of one or more metallic filaments and a liquid-infusible mechanical anchoring layer attached to or formed in outer surface of the filaments. A drug coating in the stent is composed of a substantially polymer-free composition of an anti-restenosis drug, and has a substratum infused in the anchoring layer and a substantially continuous surface stratum of drug that is brought into direct contact with the vessel walls at the vascular site. Thus, the rate of release of the anti-restenosis drug from the surface stratum into said vascular site is determined solely by the composition of said drug coating.

Abstract translation: 设计用于放置在血管损伤部位，用于抑制现场再狭窄的径向可扩张的血管内支架，使用方法和制造支架的方法。 该支架包括由一个或多个金属细丝形成的径向可扩张体，以及附着于细丝的外表面或形成于细丝的外表面的液体不可渗透的机械锚定层。 支架中的药物涂层由基本上无聚合物的抗再狭窄药物组合物组成，并且具有输注在锚定层中的基质和药物的基本连续的表面层，其与血管壁直接接触 血管部位。 因此，抗再狭窄药物从表层到所述血管部位的释放速率仅由所述药物包衣的组成确定。

公开(公告)号：US08252047B2

公开(公告)日：2012-08-28

申请号：US13023312

申请日：2011-02-08

Applicant: Douglas R. Savage ,  Ronald E. Betts

Inventor： Douglas R. Savage ,  Ronald E. Betts

IPC: A61F2/82

CPC classification number: A61L31/16 ,  A61F2/91 ,  A61L2300/416

Abstract: A radially expandable, endovascular stent designed for placement at a site of vascular injury, for inhibiting restenosis at the site, a method of using, and a method of making the stent. The stent includes a radially expandable body formed of one or more metallic filaments and a liquid-infusible mechanical anchoring layer attached to or formed in outer surface of the filaments. A drug coating in the stent is composed of a substantially polymer-free composition of an anti-restenosis drug, and has a substratum infused in the anchoring layer and a substantially continuous surface stratum of drug that is brought into direct contact with the vessel walls at the vascular site. Thus, the rate of release of the anti-restenosis drug from the surface stratum into said vascular site is determined solely by the composition of said drug coating.

Abstract translation: 设计用于放置在血管损伤部位，用于抑制现场再狭窄的径向可扩张的血管内支架，使用方法和制造支架的方法。 该支架包括由一个或多个金属细丝形成的径向可扩张体，以及附着于细丝的外表面或形成于细丝的外表面的液体不可渗透的机械锚定层。 支架中的药物涂层由基本上无聚合物的抗再狭窄药物组合物组成，并且具有输注在锚定层中的基质和药物的基本连续的表面层，其与血管壁直接接触 血管部位。 因此，抗再狭窄药物从表层到所述血管部位的释放速率仅由所述药物包衣的组成确定。