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1. 发明授权

US5484584A Therapeutic and diagnostic use of modified polymeric microcapsules 失效
标题翻译：改性聚合物微胶囊的治疗和诊断用途
公开(公告)号：US5484584A
公开(公告)日：1996-01-16
申请号：US916348
申请日：1992-07-17
申请人： Sidney Wallace , David Yang , Michael Wallace , Chun Li , Li-Ren Kuang
发明人： Sidney Wallace , David Yang , Michael Wallace , Chun Li , Li-Ren Kuang
IPC分类号： A61K9/50 , A61K9/16 , A61K31/135 , A61K31/28 , A61K31/565 , A61K31/70 , A61K47/34 , A61K47/48 , A61K49/04 , A61K51/12 , A61P35/00 , B01J13/12 , B01J13/20 , A61K51/00 , B01J13/02 , B32B5/16
CPC分类号： A61K9/1647 , A61K47/48869 , A61K49/048 , A61K51/1251 , A61K9/1641 , A61K9/1652 , A61K9/167 , A61K9/1694 , B01J13/125 , B01J13/20 , A61K2123/00 , Y10T428/2985
摘要： The present invention relates to a highly efficient method of preparing modified microcapsules exhibiting selective targeting. These microcapsules are suitable for encapsulation surface attachment of therapeutic and diagnostic agents. In one aspect of the invention, surface charge of the polymeric material is altered by conjugation of an amino acid ester to the providing improved targeting of encapsulated agents to specific tissue cells. Examples include encapsulation of radiodiagnostic agents in 1 .mu.m capsules to provide improved opacification and encapsulation of cytotoxic agents in 100 .mu.m capsules for chemoembolization procedures. The microcapsules are suitable for attachment of a wide range of targeting agents, including antibodies, steroids and drugs, which may be attached to the microcapsule polymer before or after formation of suitably sized microcapsules. The invention also includes microcapsules surface modified with hydroxyl groups. Various agents such as estrone may be attached to the microcapsules and effectively targeted to selected organs.
摘要翻译：本发明涉及一种制备显示出选择性靶向的改性微胶囊的高效方法。这些微胶囊适用于治疗和诊断剂的包封表面附着。在本发明的一个方面，聚合物材料的表面电荷通过氨基酸酯的缀合改变，从而提供包封的试剂对特定组织细胞的改进的靶向。实例包括将1毫米胶囊中的放射诊断剂包封，以提供100微米胶囊中的细胞毒性剂的改善的不透明和包封以用于化学栓塞过程。微胶囊适合于连接广泛范围的靶向剂，包括抗体，类固醇和药物，其可在形成适当大小的微胶囊之前或之后附着于微胶囊聚合物。本发明还包括用羟基表面改性的微胶囊。可以将诸如雌酮的各种试剂连接到微胶囊上并且有效地靶向选定的器官。

2. 发明申请

US20060287220A1 Water soluble paclitaxel prodrugs 有权
标题翻译：水溶性紫杉醇前药
公开(公告)号：US20060287220A1
公开(公告)日：2006-12-21
申请号：US11513390
申请日：2006-08-31
申请人： Chun Li , Sidney Wallace , Dong-Fang Yu , David Yang
发明人： Chun Li , Sidney Wallace , Dong-Fang Yu , David Yang
IPC分类号： A61K38/16 , A61K31/337
CPC分类号： A61K41/0038 , A61K31/337 , A61K31/4375 , A61K38/13 , A61K47/547 , A61K47/59 , A61K47/60 , A61K47/645 , A61K51/0497 , A61K51/065 , A61K2121/00 , A61K2123/00 , A61L31/10 , A61L31/16 , A61L2300/416 , A61L2300/606 , C08G73/1092
摘要： Disclosed are water soluble compositions of paclitaxel and docetaxel formed by conjugating the paclitaxel or docetaxel to a water soluble polymer such as poly-glutamic acid, poly-aspartic acid or poly-lysine. Also disclosed are methods of using the compositions for treatment of tumors, auto-immune disorders such as rheumatoid arthritis. Other embodiments include the coating of implantable stents for prevention of restenosis.
摘要翻译：公开了通过将紫杉醇或多西他赛与水溶性聚合物如聚谷氨酸，聚天冬氨酸或聚赖氨酸缀合而形成的紫杉醇和多西他赛的水溶性组合物。还公开了使用组合物治疗肿瘤，自身免疫疾病如类风湿性关节炎的方法。其他实施方案包括用于预防再狭窄的可植入支架的涂层。

3. 发明授权

US07135496B2 Water soluble paclitaxel derivatives 有权
公开(公告)号：US07135496B2
公开(公告)日：2006-11-14
申请号：US10282490
申请日：2002-10-28
申请人： Chun Li , Sidney Wallace , Dong-Fang Yu , David Yang
发明人： Chun Li , Sidney Wallace , Dong-Fang Yu , David Yang
IPC分类号： A01N37/00 , A61K31/21
CPC分类号： A61K41/0038 , A61K31/337 , A61K31/4375 , A61K38/13 , A61K47/547 , A61K47/59 , A61K47/60 , A61K47/645 , A61K51/0497 , A61K51/065 , A61K2121/00 , A61K2123/00 , A61L31/10 , A61L31/16 , A61L2300/416 , A61L2300/606 , C08G73/1092
摘要： Disclosed are water soluble compositions of paclitaxel and docetaxel formed by conjugating the paclitaxel or docetaxel to a water soluble polymer such as poly-glutamic acid, poly-aspartic acid or poly-lysine. Also disclosed are methods of using the compositions for treatment of tumors, auto-immune disorders such as rheumatoid arthritis. Other embodiments include the coating of implantable stents for prevention of restenosis.

4. 发明申请

US20060111273A1 Water soluble paclitaxel derivatives 审中-公开
标题翻译：水溶性紫杉醇衍生物
公开(公告)号：US20060111273A1
公开(公告)日：2006-05-25
申请号：US11253810
申请日：2005-10-20
申请人： Chun Li , Sidney Wallace , Dong-Fang Yu , David Yang
发明人： Chun Li , Sidney Wallace , Dong-Fang Yu , David Yang
IPC分类号： A61K38/16
CPC分类号： A61K41/0038 , A61K31/337 , A61K31/4375 , A61K38/13 , A61K47/547 , A61K47/59 , A61K47/60 , A61K47/645 , A61K51/0497 , A61K51/065 , A61K2121/00 , A61K2123/00 , A61L31/10 , A61L31/16 , A61L2300/416 , A61L2300/606 , C08G73/1092
摘要： Disclosed are water soluble compositions of paclitaxel and docetaxel formed by conjugating the paclitaxel or docetaxel to a water soluble polymer such as polyglutamic acid, poly-aspartic acid or poly-lysine. Also disclosed are methods of using the compositions for treatment of tumors, auto-immune disorders such as rheumatoid arthritis. Other embodiments include the coating of implantable stents for prevention of restenosis.
摘要翻译：公开了通过将紫杉醇或多西他赛与水溶性聚合物如聚谷氨酸，聚天冬氨酸或聚赖氨酸缀合而形成的紫杉醇和多西他赛的水溶性组合物。还公开了使用组合物治疗肿瘤，自身免疫疾病如类风湿性关节炎的方法。其他实施方案包括用于预防再狭窄的可植入支架的涂层。

5. 发明申请

US20060135404A1 Water soluble paclitaxel derivatives 审中-公开
公开(公告)号：US20060135404A1
公开(公告)日：2006-06-22
申请号：US11285392
申请日：2005-11-23
申请人： Chun Li , Sidney Wallace , Dong-Fang Yu , David Yang
发明人： Chun Li , Sidney Wallace , Dong-Fang Yu , David Yang
IPC分类号： A61K38/16
CPC分类号： A61K41/0038 , A61K31/337 , A61K31/4375 , A61K38/13 , A61K47/547 , A61K47/59 , A61K47/60 , A61K47/645 , A61K51/0497 , A61K51/065 , A61K2121/00 , A61K2123/00 , A61L31/10 , A61L31/16 , A61L2300/416 , A61L2300/606 , C08G73/1092
摘要： Disclosed are water soluble compositions of paclitaxel and docetaxel formed by conjugating the paclitaxel or docetaxel to a water soluble polymer such as poly-glutamic acid, poly-aspartic acid or poly-lysine. Also disclosed are methods of using the compositions for treatment of tumors, auto-immune disorders such as rheumatoid arthritis. Other embodiments include the coating of implantable stents for prevention of restenosis.

6. 发明授权

US06730699B2 Water soluble paclitaxel derivatives 有权
公开(公告)号：US06730699B2
公开(公告)日：2004-05-04
申请号：US10300031
申请日：2002-11-20
申请人： Chun Li , Sidney Wallace , Dong-Fang Yu , David Yang
发明人： Chun Li , Sidney Wallace , Dong-Fang Yu , David Yang
IPC分类号： A61K31335
CPC分类号： A61K41/0038 , A61K31/337 , A61K31/4375 , A61K38/13 , A61K47/547 , A61K47/59 , A61K47/60 , A61K47/645 , A61K51/0497 , A61K51/065 , A61K2121/00 , A61K2123/00 , A61L31/10 , A61L31/16 , A61L2300/416 , A61L2300/606 , C08G73/1092
摘要： Disclosed are water soluble compositions of paclitaxel and docetaxel formed by conjugating the paclitaxel or docetaxel to a water soluble polymer such as poly-glutamic acid, poly-aspartic acid or poly-lysine. Also disclosed are methods of using the compositions for treatment of tumors, auto-immune disorders such as rheumatoid arthritis. Other embodiments include the coating of implantable stents for prevention of restenosis.

7. 发明授权

US06515017B1 Water soluble paclitaxel derivatives 有权
公开(公告)号：US06515017B1
公开(公告)日：2003-02-04
申请号：US10153818
申请日：2002-05-24
申请人： Chun Li , Sidney Wallace , Dong-Fang Yu , David Yang
发明人： Chun Li , Sidney Wallace , Dong-Fang Yu , David Yang
IPC分类号： A61K31335
CPC分类号： A61K41/0038 , A61K31/337 , A61K31/4375 , A61K38/13 , A61K47/547 , A61K47/59 , A61K47/60 , A61K47/645 , A61K51/0497 , A61K51/065 , A61K2121/00 , A61K2123/00 , A61L31/10 , A61L31/16 , A61L2300/416 , A61L2300/606 , C08G73/1092
摘要： Disclosed are water soluble compositions of paclitaxel and docetaxel formed by conjugating the paclitaxel or docetaxel to a water soluble polymer such as poly-glutamic acid, poly-aspartic acid or poly-lysine. Also disclosed are methods of using the compositions for treatment of tumors, auto-immune disorders such as rheumatoid arthritis. Other embodiments include the coating of implantable stents for prevention of restenosis.

8. 发明授权

US5238714A Efficient microcapsule preparation and method of use 失效
标题翻译：有效的微生物制备和使用方法
公开(公告)号：US5238714A
公开(公告)日：1993-08-24
申请号：US592020
申请日：1990-10-02
申请人： Sidney Wallace , David Yang , Michael Wallace
发明人： Sidney Wallace , David Yang , Michael Wallace
IPC分类号： A61K9/50 , A61K9/16 , A61K47/48 , A61K49/04 , A61K51/12 , B01J13/12 , B01J13/20
CPC分类号： A61K49/048 , A61K47/48315 , A61K51/1251 , A61K9/1641 , A61K9/1647 , A61K9/1652 , A61K9/167 , A61K9/1694 , B01J13/125 , B01J13/20 , A61K2123/00
摘要： The present invention relates to a method of preparing microcapsules suitable for encapsulation of therapeutic and diagnostic agents. The capsular coats are prepared from biodegradable polymers. In a particular aspect of the invention, surface charge of the polymeric material is altered by conjugation of an amino acid ester to the polymer, providing targeting to specific tissue cells. Encapsulation of hydrophilic radiodiagnostic agents in 1 .mu.m capsules provides improved opacification. Encapsulation of cytotoxic agents in 100 .mu.m capsules is useful in chemoembolization procedures.
摘要翻译：本发明涉及一种制备适于封闭治疗和诊断剂的微胶囊的方法。荚膜由可生物降解的聚合物制成。在本发明的特定方面，聚合物材料的表面电荷通过氨基酸酯与聚合物的缀合而改变，从而提供靶向特定的组织细胞。亲水性放射诊断剂在1微米胶囊中的封装提供了改善的不透明度。细胞毒素在100μm胶囊中的包封可用于化疗栓塞手术。

9. 发明授权

US6096874A High affinity tamoxifen derivatives 失效
标题翻译：高亲和力他莫昔芬衍生物
公开(公告)号：US6096874A
公开(公告)日：2000-08-01
申请号：US477525
申请日：1995-06-07
申请人： Sidney Wallace , David Yang , E. Delpassand , A. Cherif , S. Quadri
发明人： Sidney Wallace , David Yang , E. Delpassand , A. Cherif , S. Quadri
IPC分类号： C07B59/00 , C07C217/18 , C07C233/18 , C07C237/10 , C07F13/00 , C07C211/00 , C07C221/00 , C07F5/00
CPC分类号： C07B59/001 , C07C217/18 , C07C233/18 , C07C237/10
摘要： The synthesis of tamoxifen derivatives, most particularly halo, halo alkyl, hydroxy, and amino tamoxifen derivatives is disclosed. The native tamoxifen molecule includes a substituted chemical group positioned on the aliphatic chain of the tamoxifen molecule. Particular tamoxifen derivatives of the invention include chloro, bromo, iodo, fluoro, amino and DTPA tamoxifen derivatives, and corresponding lower alkyl halogenated forms. The halogenated tamoxifen derivatives possess superior binding affinities for estrogen receptor rich tissues, such as uterine tissue and breast tissue, relative to unsubstituted native tamoxifen. Radiolabeled forms of the tamoxifen derivatives may be used as highly specific imaging agents for estrogen receptor rich tissues. The fluoro and bromo tamoxifen derivatives are particularly useful for imaging estrogen receptors by PET whereas the iodinated tamoxifens are particularly useful in imaging estrogen receptors by SPECT. Rapid and efficient methods of preparing the tamoxifen derivatives having high specific activity (>6 Ci/.mu.mol) are also disclosed. Aliphatic chain substituted tamoxifen derivatives are shown to possess greater estrogen receptor binding affinity and more potent tumor cell inhibition than tamoxifen or tamoxifen derivatives substituted at other locations on the molecule (i.e., non-aliphatic chain substituted tamoxifen). The tanioxifen derivatives of the present invention may advantageously be used as anti-cancer therapeutic agents to halt estrogen-receptor positive tumors, such as those of breast and uterine tissue. The present invention also provides a hydrophilic DTPA-tamnoxifen analogue, and uses thereof in imaging estrogen receptor positive ER+ lesions.
摘要翻译：公开了三苯氧胺衍生物，特别是卤素，卤代烷基，羟基和氨基三苯氧胺衍生物的合成。天然的三苯氧胺分子包括位于他莫昔芬分子脂族链上的取代的化学基团。本发明的特定的他莫昔芬衍生物包括氯，溴，碘，氟，氨基和DTPA三苯氧胺衍生物，以及相应的低级烷基卤化形式。相对于未取代的天然三苯氧胺，卤代三苯氧胺衍生物对于富含雌激素受体的组织如子宫组织和乳腺组织具有优异的结合亲和力。他莫昔芬衍生物的放射性标记形式可用作富含雌激素受体的组织的高度特异性成像剂。氟代和溴三苯氧胺衍生物特别适用于通过PET成像雌激素受体，而碘化的三苯氧胺特别可用于通过SPECT成像雌激素受体。还公开了制备具有高比活性（> 6Ci /μmol）的他莫昔芬衍生物的快速和有效的方法。脂肪族链取代的他莫昔芬衍生物显示出比分子上其他位置（即非脂肪链状取代的三苯氧胺）上取代的他莫昔芬或他莫昔芬衍生物具有更大的雌激素受体结合亲和力和更有效的肿瘤细胞抑制。本发明的季戊四醇衍生物可有利地用作抗癌治疗剂，以阻止雌激素受体阳性肿瘤，例如乳腺和子宫组织的肿瘤。本发明还提供了亲水性DTPA-他莫昔芬类似物及其在成像雌激素受体阳性ER +损伤中的用途。

10. 发明申请

US20120317786A1 METHOD AND APPARATUS FOR JOINING MULTIPLE COMPONENTS 有权
标题翻译：用于接合多个组件的方法和装置
公开(公告)号：US20120317786A1
公开(公告)日：2012-12-20
申请号：US13162625
申请日：2011-06-17
申请人： Pei-Chung Wang , David Yang , Jeff Wang , Blair E. Carlson
发明人： Pei-Chung Wang , David Yang , Jeff Wang , Blair E. Carlson
IPC分类号： B23P11/00 , B21D39/00
CPC分类号： B21D39/031
摘要： A method of joining multiple components includes stacking the components vertically. Each component includes two opposite substantially planar surfaces that are arranged in a column when the components are stacked. The method also includes placing the stacked components in a clinch-crimping apparatus having a first punch, a second punch, and a crimping element. The method also includes displacing a section of the substantially planar surfaces of the stacked components by driving the first punch in a first direction that is substantially perpendicular to the surfaces. The method additionally includes retracting the first punch from the displaced section and crimping the displaced section by the crimping element to form a crush initiator. The method additionally includes disengaging the crimping element from the crimped, displaced section. Furthermore, the method includes clinching the crimped, displaced section by driving the second punch in a second direction that is opposite to the first direction.
摘要翻译：连接多个组件的方法包括垂直堆叠组件。每个部件包括两个相对的基本平坦的表面，当组件堆叠时，该表面布置成一列。该方法还包括将堆叠的部件放置在具有第一冲头，第二冲头和压接元件的夹紧压接装置中。该方法还包括通过沿基本上垂直于表面的第一方向驱动第一冲头来移动堆叠部件的基本平坦的表面的一部分。该方法另外包括从移位部分缩回第一冲头并且通过压接元件压接位移部分以形成挤压引发器。该方法另外包括使压接元件从卷曲的位移部分脱离。此外，该方法包括通过沿与第一方向相反的第二方向驱动第二冲头来夹紧卷曲的移位部分。

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