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    • 1. 发明授权
    • Photoactivatable compounds comprising benzochlorin and furocoumarin
    • 包含苯并二氢卟酚和呋喃香豆素的可光活化化合物
    • US6008211A
    • 1999-12-28
    • US508238
    • 1995-07-27
    • Byron RobinsonAlan R. MorganHugh L. Narciso, Jr.
    • Byron RobinsonAlan R. MorganHugh L. Narciso, Jr.
    • A61K31/366A61K31/407A61K31/409A61K31/4375A61K41/00A61P9/10A61P17/06A61P27/06A61P35/00C07D487/22C07D493/04C07D519/00A61K31/40
    • C07D493/04A61K41/0066A61K41/0071
    • A broad class of photosensitive compounds having enhanced in vivo target tissue selectivity and versatility in photodynamic therapy. Many furocoumarin compounds, such as psoralens, exhibit cytostatic activity when photoactivated but exhibit little in vivo specificity for selectively accumulating in any particular target tissue such as atheromatous plaques. Reactive Oxygen Producing Photosensitizers ("ROPPs") are photoactivatable compounds having an affinity for hyperproliferating cells (such as atheromatous plaque cells), which when photoactivated, produce cytotoxic reaction products. The photoactivity of a ROPP, such as a porphyrin, may be reduced by metalating the porphyrin while the selective affinity of the metalized ROPP for hyperproliferating tissue remains substantially unchanged. By linking a furocoumarin compound to a ROPP to form a F-ROPP, the cytostatic properties of the furocoumarin portion of the F-ROPP can be exploited while the selective affinity of the ROPP portion of the compound for hyperproliferating cells such as atheromatous plaque provides enhanced tissue selectivity without cytotoxicity. In vivo, certain F-ROPPs may be forced to selectively accumulate in a target tissue by illuminating only the target tissue with light having a wavelength operable for photoactivating the F portion of the F-ROPP thereby causing the F-ROPP to either form a monoadduct with or crosslink the cellular DNA in the target tissue. Light of a second wavelength can then be delivered to the target tissue to photoactivate the ROPP portion causing further interference with cellular activity.
    • 广泛的光敏化合物具有增强的体内靶组织选择性和光动力疗法的多功能性。 许多呋喃香豆素化合物,如补骨脂素,当光活化时表现出细胞抑制活性,但是在任何特定靶组织如动脉粥样硬化斑块中选择性积累,但体内特异性较小。 活性氧生产光敏剂(“ROPP”)是具有对过度增殖细胞(如动脉粥样硬化斑块细胞)的亲和力的光活化化合物,其在光活化时产生细胞毒性反应产物。 可以通过金属化卟啉来减少ROPP如卟啉的光活性,同时金属化ROPP对过度增殖组织的选择性亲和性基本上保持不变。 通过将呋喃香豆素化合物与ROPP连接以形成F-ROPP,可以利用F-ROPP的呋喃香豆素部分的细胞生长抑制性能,而化合物的ROPP部分对过度增殖细胞如动脉粥样硬化斑块的选择性亲和力提高 组织选择性没有细胞毒性。 在体内,某些F-ROPP可能被迫通过用具有可激活F-ROPP的F部分的光波长的光照射目标组织而选择性地累积在靶组织中,从而使F-ROPP形成单加合物 与目标组织中的细胞DNA交联或交联。 然后可以将第二波长的光递送到目标组织以激活ROPP部分,导致进一步干扰细胞活性。
    • 2. 发明授权
    • Compounds and method for PDT of intimal hyperplasia and other diseases
    • PDT内膜增生等疾病的化合物和方法
    • US06054449A
    • 2000-04-25
    • US801829
    • 1997-02-14
    • Byron RobinsonAlan R. MorganHugh L. Narciso, Jr.
    • Byron RobinsonAlan R. MorganHugh L. Narciso, Jr.
    • A61K31/366A61K31/407A61K31/409A61K31/4375A61K41/00A61P9/10A61P17/06A61P27/06A61P35/00C07D487/22C07D493/04C07D519/00A61K31/41C09B47/00C07D478/22
    • C07D493/04A61K41/0066A61K41/0071
    • A broad class of photosensitive compounds having enhanced in vivo target tissue selectivity and versatility in photodynamic therapy. Many furocoumarin compounds, such as psoralens, exhibit cytostatic activity when photoactivated but exhibit little in vivo specificity for selectively accumulating in any particular target tissue such as atheromatous plaques. Reactive Oxygen Producing Photosensitizers ("ROPPs") are photoactivatable compounds having an affinity for hyperproliferating cells (such as atheromatous plaque cells), which when photoactivated, produce cytotoxic reaction products. The photoactivity of a ROPP, such as a porphyrin, may be reduced by metalating the porphyrin while the selective affinity of the metalized ROPP for hyperproliferating tissue remains substantially unchanged. By linking a furocoumarin compound to a ROPP to form a F-ROPP, the cytostatic properties of the furocoumarin portion of the F-ROPP can be exploited while the selective affinity of the ROPP portion of the compound for hyperproliferating cells such as atheromatous plaque provides enhanced tissue selectivity without cytotoxicity. In vivo, certain F-ROPPs may be forced to selectively accumulate in a target tissue by illuminating only the target tissue with light having a wavelength operable for photoactivating the F portion of the F-ROPP thereby causing the F-ROPP to either form a monoadduct with or crosslink the cellular DNA in the target tissue. Light of a second wavelength can then be delivered to the target tissue to photoactivate the ROPP portion causing further interference with cellular activity.
    • 广泛的光敏化合物具有增强的体内靶组织选择性和光动力疗法的多功能性。 许多呋喃香豆素化合物,如补骨脂素,当光活化时表现出细胞抑制活性,但是在任何特定靶组织如动脉粥样硬化斑块中选择性积累,但体内特异性较小。 活性氧生产光敏剂(“ROPP”)是具有对过度增殖细胞(如动脉粥样硬化斑块细胞)的亲和力的光活化化合物,其在光活化时产生细胞毒性反应产物。 可以通过金属化卟啉来减少ROPP如卟啉的光活性,同时金属化ROPP对过度增殖组织的选择性亲和性基本上保持不变。 通过将呋喃香豆素化合物与ROPP连接以形成F-ROPP,可以利用F-ROPP的呋喃香豆素部分的细胞生长抑制性能,而化合物的ROPP部分对过度增殖细胞如动脉粥样硬化斑块的选择性亲和力提高 组织选择性没有细胞毒性。 在体内,某些F-ROPP可能被迫通过用具有可激活F-ROPP的F部分的光波长的光照射目标组织而选择性地累积在靶组织中,从而使F-ROPP形成单加合物 与目标组织中的细胞DNA交联或交联。 然后可以将第二波长的光递送到目标组织以激活ROPP部分,导致进一步干扰细胞活性。
    • 3. 发明授权
    • Photoactivatable compositions and to methods for the diagnosis and
treating medical conditions
    • 与用于进行PDT的DNA形成和加合的组合物
    • US5773609A
    • 1998-06-30
    • US801831
    • 1997-02-14
    • Byron RobinsonAlan R. MorganHugh L. Narciso, Jr.
    • Byron RobinsonAlan R. MorganHugh L. Narciso, Jr.
    • A61K31/366A61K31/407A61K31/409A61K31/4375A61K41/00A61P9/10A61P17/06A61P27/06A61P35/00C07D487/22C07D493/04C07D519/00A61K31/35
    • C07D493/04A61K41/0066A61K41/0071
    • A broad class of photosensitive compounds having enhanced in vivo target tissue selectivity and versatility in photodynamic therapy. Many furocoumarin compounds, such as psoralens, exhibit cytostatic activity when photoactivated but exhibit little in vivo specificity for selectively accumulating in any particular target tissue such as atheromatous plaques. Reactive Oxygen Producing Photosensitizers ("ROPPs") are photoactivatable compounds having an affinity for hyperproliferating cells (such as atheromatous plaque cells), which when photoactivated, produce cytotoxic reaction products. The photoactivity of a ROPP, such as a porphyrin, may be reduced by metalating the porphyrin while the selective affinity of the metalized ROPP for hyperproliferating tissue remains substantially unchanged. By linking a furocoumarin compound to a ROPP to form a F-ROPP, the cytostatic properties of the furocoumarin portion of the F-ROPP can be exploited while the selective affinity of the ROPP portion of the compound for hyperproliferating cells such as atheromatous plaque provides enhanced tissue selectivity without cytotoxicity. In vivo, certain F-ROPPs may be forced to selectively accumulate in a target tissue by illuminating only the target tissue with light having a wavelength operable for photoactivating the F portion of the F-ROPP thereby causing the F-ROPP to either form a monoadduct with or crosslink the cellular DNA in the target tissue. Light of a second wavelength can then be delivered to the target tissue to photoactivate the ROPP portion causing further interference with cellular activity.
    • 广泛的光敏化合物具有增强的体内靶组织选择性和光动力疗法的多功能性。 许多呋喃香豆素化合物,如补骨脂素,当光活化时表现出细胞抑制活性,但是在任何特定靶组织如动脉粥样硬化斑块中选择性积累,但体内特异性较小。 活性氧生产光敏剂(“ROPP”)是具有对过度增殖细胞(如动脉粥样硬化斑块细胞)的亲和力的光活化化合物,其在光活化时产生细胞毒性反应产物。 可以通过金属化卟啉来减少ROPP如卟啉的光活性,同时金属化ROPP对过度增殖组织的选择性亲和性基本上保持不变。 通过将呋喃香豆素化合物与ROPP连接以形成F-ROPP,可以利用F-ROPP的呋喃香豆素部分的细胞生长抑制性能,而化合物的ROPP部分对过度增殖细胞如动脉粥样硬化斑块的选择性亲和力提高 组织选择性没有细胞毒性。 在体内,某些F-ROPP可能被迫通过用具有可激活F-ROPP的F部分的光波长的光照射目标组织而选择性地累积在靶组织中,从而使F-ROPP形成单加合物 与目标组织中的细胞DNA交联或交联。 然后可以将第二波长的光递送到目标组织以激活ROPP部分,导致进一步干扰细胞活性。
    • 4. 发明授权
    • Surface illuminator for photodynamic therapy
    • 用于光动力疗法的表面照明器
    • US5835648A
    • 1998-11-10
    • US813680
    • 1997-03-07
    • Hugh L. Narciso, Jr.Christine J. RadaskyDaniel R. DoironSteven C. Anderson
    • Hugh L. Narciso, Jr.Christine J. RadaskyDaniel R. DoironSteven C. Anderson
    • A61N5/06F21V8/00G02B6/24G02B6/26
    • G02B6/241A61N5/062G02B6/0008A61N2005/0644A61N2005/0666
    • A device for delivering phototherapeutic light to uniformly illuminate a tissue surface. The device is a bowl-shaped shell with a more-or-less parabolic profile and having an open end and an apex. The inner surface of the shell is adapted to diffusely reflect light with very low absorption by the shell material. A light output end of a fiber optic is introduced into the interior of the shell through a fiber optic port in the shell wall near the apex. The light output end of the fiber is positioned such that light emanating therefrom impinges upon the inner surface of the shell. The shape of the shell causes greater than 60 percent of the light emanating from the fiber to intercept the shell's surface and be diffusely reflected. The diffusely reflected light may then undergo further diffuse reflection within the shell prior to reaching the treatment surface adjacent to the open end of the shell to provide more uniform illumination of the treatment surface than the fiber could otherwise provide. A highly reflective coating is applied to the outer surface of the shell to prevent loss of treatment light from the device. In addition, treatment light which is reflected from the tissue surface and normally lost is captured by the interior surface of the shell and re-reflected to reenter the tissue surface. Thus, little or no treatment light is lost due to reflection or scattering from tissue providing improved efficiency. The shell preferably includes a laterally extending flange around a portion of the open end which can be affixed to the tissue surface thereby preventing relative motion between the illuminator and tissue surface during treatment enabling accurate dosimetry.
    • 一种用于传送光治疗光以均匀地照射组织表面的装置。 该装置是具有或多或少抛物面轮廓并具有开口端和顶点的碗状壳体。 外壳的内表面适用于通过外壳材料以非常低的吸收扩散地反射光。 光纤的光输出端通过靠近顶点的壳壁中的光纤端口引入壳体的内部。 纤维的光输出端定位成使得其发出的光撞击到壳体的内表面上。 壳的形状导致从纤维发出的光的大于60%拦截壳的表面并被漫反射。 然后漫反射光可以在到达壳体的开口端处的处理表面之前在壳体内进一步的漫反射,以提供处理表面比纤维另有提供的更均匀的照明。 将高反射涂层施加到外壳的外表面以防止来自该装置的处理光的损失。 此外,由组织表面反射并且正常损失的处理光被壳体的内表面捕获并重新反射以重新进入组织表面。 因此,由于来自组织的反射或散射,治疗光很少或不会丧失,从而提高了效率。 壳体优选地包括围绕开口端的一部分的横向延伸的凸缘,其可以固定到组织表面,从而防止在治疗期间照明器和组织表面之间的相对运动,使得能够进行精确的剂量测定。
    • 5. 发明授权
    • Method for treating cardiovascular disease through adjunctive
photodynamic therapy
    • 通过辅助光动力治疗治疗心血管疾病的方法
    • US5298018A
    • 1994-03-29
    • US930860
    • 1992-08-14
    • Hugh L. Narciso, Jr.
    • Hugh L. Narciso, Jr.
    • A61K31/555A61N5/06A61N1/30
    • A61N5/062A61K31/555A61N5/0601
    • Photodynamic Therapy (PDT) is used as an adjunctive or stand alone procedure for the treatment of cardiovascular disease. When used as an adjunctive therapy to Percutaneous Transluminal Coronary Angioplasty, laser angioplasty, atherectomy, stenting, or any other interventional or surgical procedure, it has been found that the treatment timing is critical to the success of the combined therapies. A photosensitizer is administered prior to the surgical or interventional procedure and then readministered after the procedure to maintain the photosensitizer concentration level in the atheromatous plaque and smooth muscle cells in the vicinity of the lesion for a period of about 5-18 days, the period in which cell proliferation can occur. The photosensitizer inhibits smooth muscle cell proliferation and, thus, minimizes or eliminates the possibility of re-stenosis. The photosensitizer is then illuminated at the end of this period, thereby lysing the atheromatous plaque and smooth muscles. The photosensitizer inhibits atheromatic smooth muscle cell proliferation.
    • 光动力疗法(PDT)用作治疗心血管疾病的辅助或独立手术。 当用作经皮冠状动脉冠状动脉成形术,激光血管成形术,粥样斑块切除术,支架置入术或任何其他介入或外科手术的辅助治疗时,已经发现治疗时机对于联合治疗的成功至关重要。 在手术或介入手术之前施用光敏剂,然后在手术后重新施用,以维持病变附近的动脉粥样硬化斑块和平滑肌细胞中的光敏剂浓度水平,持续约5-18天, 哪些细胞增殖可能发生。 光敏剂抑制平滑肌细胞增殖,从而使再狭窄的可能性最小化或消除。 然后在此期间结束时照射光敏剂,从而裂解动脉粥样硬化斑块和平滑肌肉。 光敏剂抑制无神经平滑肌细胞增殖。
    • 6. 发明授权
    • Optical fiber microlens
    • 光纤微透镜
    • US5231684A
    • 1993-07-27
    • US902674
    • 1992-06-22
    • Hugh L. Narciso, Jr.Daniel R. Doiron
    • Hugh L. Narciso, Jr.Daniel R. Doiron
    • A61B18/22G02B6/32G02B6/38
    • G02B6/32A61B2018/2266G02B6/3861
    • A microlens assembly for use with an optical fiber or fiber bundle that requires no crimping or mechanical distortion of the optical fiber. The microlens assembly has a front lens mounting portion and a rear portion. The rear portion is a cylindrical tube which is bonded to the sheath and cladding of the optical fiber or fiber bundle by means of suitable adhesive. The front lens mounting portion which houses the output lens is also tubular, having an inner diameter greater than the outer diameter of the rear portion. The front lens mounting portion is slid over the rear portion until the desired distribution of light emanating from the lens is achieved. The front lens mounting portion is then locked into position by bonding it to the rear portion by means of an appropriate adhesive. The adhesives are stable at high temperature and have an index of refractions suitable for preventing refractive loss of light from the lateral walls of the fiber core. In one embodiment, the cylindrical space in the microlens assembly between the output lens and the tip of the optical fiber or fiber bundle is filled with an optically transparent fluid or elastomer such as silicone. The filling excludes body fluids from entering the microlens assembly.
    • 用于光纤或光纤束的微透镜组件,其不需要光纤的卷曲或机械变形。 微透镜组件具有前透镜安装部分和后部部分。 后部是圆柱形管,其通过合适的粘合剂结合到光纤或纤维束的护套和包层。 容纳输出透镜的前透镜安装部分也是管状的,其内径大于后部的外径。 前透镜安装部分在后部部分上滑动,直到实现从透镜发出的光的期望分布。 然后通过适当的粘合剂将前透镜安装部分通过将其固定到后部而被锁定到位。 粘合剂在高温下是稳定的,并且具有适合于防止来自纤维芯侧壁的光的折射损失的折射率。 在一个实施例中,在输出透镜和光纤或纤维束的尖端之间的微透镜组件中的圆柱形空间填充有光学透明的流体或弹性体,例如硅树脂。 填充物不包括体液进入微透镜组件。
    • 7. 发明授权
    • Device and method for intra-vascular optical radial imaging
    • 用于血管内光学径向成像的装置和方法
    • US5217456A
    • 1993-06-08
    • US840478
    • 1992-02-24
    • Hugh L. Narciso, Jr.
    • Hugh L. Narciso, Jr.
    • A61B5/00
    • A61B1/00177A61B1/043A61B5/0071A61B5/0084
    • An intra-vascular optical radial imaging system comprising an intra-vascular guidewire-compatible catheter, a source of illumination and a synchronous fluorescence detector. The catheter is inserted into a blood vessel until the tip is adjacent to a section of vessel to be imaged. A narrow beam of light emanating radially from an aperture underlying the segment to be imaged repetitively illuminates segments of the wall of the vessel in a scanning or sweeping manner with the light of a wavelength that induces fluorescence in molecules in the tissue. Fluorescence from molecules in the illuminated tissue enters the catheter through the aperture and is conveyed to a spectral analyzer. Properties of the fluorescence signal are characteristic of the particular tissue and may be used to differentiate healthy tissue from atherosclerotic plaque. The method yields not only the longitudinal position of a lesion along a vessel but also the cylindrical coordinates by determining the circular or angular position of the lesion on the interior wall of the vessel.
    • 一种血管内光学径向成像系统,其包括血管内导丝相容导管,照明源和同步荧光检测器。 将导管插入血管,直到尖端与要成像的血管的一部分相邻。 从被成像的片下面的孔径向辐射的窄光束以扫描或扫描方式以在组织中的分子中诱导荧光的波长的光重复地照射血管壁。 来自照射组织中的分子的荧光通过孔进入导管并被传送到光谱分析仪。 荧光信号的特性是特定组织的特征,可用于区分健康组织与动脉粥样硬化斑块。 该方法不仅产生沿着血管的病变的纵向位置,而且通过确定血管内壁上的病变的圆形或角位置来产生圆柱坐标。
    • 8. 发明授权
    • Continuous gradient cylindrical diffusion tip for optical fibers and
method for making
    • 用于光纤的连续梯度圆柱形扩散尖端和制造方法
    • US5196005A
    • 1993-03-23
    • US799047
    • 1991-11-26
    • Daniel R. DoironHugh L. Narciso, Jr.Paul Paspa
    • Daniel R. DoironHugh L. Narciso, Jr.Paul Paspa
    • A61B18/22A61N5/06
    • A61B18/22A61N5/0601A61B2018/2261
    • A cylindrical diffuser tip for use with an optical fiber is described. The diffuser tip comprises a silicone core containing scattering centers embedded therein abutted to the terminus of the conventional optical core of an optical fiber, and an outer protective plastic tube to provide controlled stiffness or rigidity to the silicone diffuser tip while maintaining a flexibility comparable to that of the optical fiber. The scattering centers embedded in the silicone core are distributed to provide a gradient that increases continuously in a direction perpendicular from the terminus face of the optical fiber. The tip provides a substantially uniform distribution of radiance along its length and is particularly useful for laser radiation treatment of tumors. The stiffness of the diffuser tip can be varied by choosing a protective tube of varying wall thickness and durometer. The diffuser tip is useful for providing uniform cylindrical illumination of target tissue in remote areas of the body and is particularly useful in such areas as Photodynamic Therapy of tumors, phototherapy of atheromas and hyperthermia.
    • 描述了与光纤一起使用的圆柱形扩散器尖端。 扩散器末端包括含有嵌入其中的散射中心的硅芯芯,其邻接于光纤的常规光学核心的末端,以及外部保护塑料管,以提供与硅胶扩散器尖端的受控的刚度或刚度,同时保持与之相当的灵活性 的光纤。 嵌入在硅芯中的散射中心被分配以提供在与光纤的终端面垂直的方向上连续增加的梯度。 尖端沿其长度提供基本均匀的辐射分布,并且对于肿瘤的激光辐射治疗特别有用。 可以通过选择不同壁厚和硬度的保护管来改变扩散器尖端的刚度。 扩散器尖端可用于在身体的偏远地区提供均匀的圆柱形照射目标组织,并且特别适用于诸如肿瘤的光动力治疗,动脉粥样化光疗和高热疗等领域。
    • 10. 发明授权
    • Intraluminal shunt and methods of use
    • 管腔内分流及使用方法
    • US6095997A
    • 2000-08-01
    • US034849
    • 1998-03-04
    • Fritz FrenchHugh L. Narciso, Jr.Troy ChapmanMike Hogendijk
    • Fritz FrenchHugh L. Narciso, Jr.Troy ChapmanMike Hogendijk
    • A61B17/00A61M39/02A61M39/10A61M5/00A61F2/04A61M5/178A61M11/00A61M29/00
    • A61M1/3653A61M39/02A61B17/00234
    • The present invention is directed to intraluminal shunt devices and methods of their use for delivering a drug or other fluid to a target vessel of a patient while also maintaining perfusion of blood through the vessel to reduce ischemia downstream of the vessel. The intraluminal shunt devices may generally include a primary elongate tubular member that is sized and dimensioned to be inserted into the target vessel, such as the right coronary artery. The primary tubular member includes at least one inner lumen which permits blood perfusion through the vessel. At least one secondary tubular member is provided which is in fluid communication with the primary tubular member. The secondary tubular member may be configured for drug or fluid delivery through the primary tubular member and into the vessel in either an anterograde or retrograde direction. Methods of using shunt devices are also described which generally include making an incision in the target vessel, inserting the proximal and distal ends of the primary tubular member into the target vessel via the incision, and selectively delivering the drug or fluid in either an anterograde or retrograde direction through the primary tubular member and into the vessel.
    • 本发明涉及腔内分流装置及其用于将药物或其它流体递送至患者的靶容器的方法,同时还保持血液通过血管的灌注以减少血管下游的缺血。 管腔内分流装置通常可以包括主细长管状构件,其尺寸和尺寸被设计成插入目标血管,例如右冠状动脉。 主管状构件包括允许血液灌注通过血管的至少一个内腔。 提供至少一个次级管状构件,其与主管状构件流体连通。 次级管状构件可以被配置用于通过主管状构件的药物或流体输送并且以顺行或逆行方向进入容器。 还描述了使用分流装置的方法,其通常包括在靶容器中进行切口,通过切口将初级管状构件的近端和远端插入靶容器中,并且选择性地将药物或流体递送到顺行或顺行 逆行方向通过主管状构件并进入血管。