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1. 发明授权

US06899731B2 Controlled delivery of therapeutic agents by insertable medical devices 失效
标题翻译：通过可插入的医疗设备控制治疗剂的输送
公开(公告)号：US06899731B2
公开(公告)日：2005-05-31
申请号：US09750779
申请日：2001-01-02
申请人： Weiping Li , Hai-Quan Mao , Kam W. Leong
发明人： Weiping Li , Hai-Quan Mao , Kam W. Leong
IPC分类号： A61L29/16 , A61L31/16 , A61F2/06 , A61K48/00
CPC分类号： A61L31/16 , A61L29/16 , A61L2300/258 , A61L2300/416 , A61L2300/602 , A61L2300/608 , A61L2300/802
摘要： A medical device and method for transportation and release of a therapeutic agent into a mammalian body are disclosed. The medical device is coated with alternating layers of a negatively charged therapeutic agent and a cationic polyelectrolyte, following a controlled adsorption technique. The method is simple, with minimal perturbation to the therapeutic agent and uses clinically acceptable biopolymers such as human serum albumin. The amount of the therapeutic agent that can be delivered by this technique is optimized by the number of the layers of the therapeutic agent adsorbed on the surface of medical device. There is a washing step between alternate layers of the therapeutic agent and cationic polyelectrolyte carrier, so that the amount of the therapeutic agent on the insertable medical device represents the portion that is stably entrapped and adsorbed on to the medical device. The insertable medical device and method according to this invention are capable of reproducibly delivering therapeutic agent to a site in a mammalian body, and allow for a highly reproducible and controllable release kinetics of the therapeutic agent.
摘要翻译：公开了用于将哺乳动物体内的治疗剂输送和释放的医疗装置和方法。在受控吸附技术之后，医疗装置涂覆有带负电的治疗剂和阳离子聚电解质的交替层。该方法简单，对治疗剂的扰动最小，并且使用临床可接受的生物聚合物例如人血清白蛋白。通过该技术可以递送的治疗剂的量通过吸收在医疗装置表面上的治疗剂的层数来优化。在治疗剂和阳离子聚电解质载体的交替层之间存在洗涤步骤，使得可插入医疗装置上的治疗剂的量表示稳定地截留并吸附到医疗装置上的部分。根据本发明的可插入医疗装置和方法能够将治疗剂可再现地递送到哺乳动物体内的部位，并且允许治疗剂的高度可重现和可控的释放动力学。

2. 发明授权

US06376644B1 Biodegradable polymers chain-extended by phosphates, compositions, articles and methods for making and using the same 有权
标题翻译：通过磷酸盐，组合物，制品和制造和使用它们的方法延伸的可生物降解的聚合物
公开(公告)号：US06376644B1
公开(公告)日：2002-04-23
申请号：US09654326
申请日：2000-09-01
申请人： Hai-Quan Mao , Kam W. Leong , Zhong Zhao , James P. English
发明人： Hai-Quan Mao , Kam W. Leong , Zhong Zhao , James P. English
IPC分类号： C08G7904
CPC分类号： A61K9/0024 , A61K9/1647 , A61L17/12 , A61L26/0019 , A61L27/18 , C08G63/6922 , C08G63/912 , Y10S623/924 , C08L85/02
摘要： Biodegradable polymers are described comprising the recurring monomeric units shown in formula I or II: wherein X is —O— or —NR′—, where R′ is H or alkyl; L is a branched or straight chain aliphatic group having from 1-20 carbon atoms; M1 and M2 are each independently (1) a branched or straight chain aliphatic group having from 1-20 carbon atoms; or (2) a branched or straight chain, oxy-, carboxy- or amino-aliphatic group having from 1-20 carbon atoms; Y is —O—, —S— or —NR′—, where R′ is H or alkyl; R is H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy; the molar ratio of x:y is about 1; the molar ratio n:(x or y) is between about 200:1 and 1:200; and the molar ratio q:r is between about 1:99 and 99:1; wherein said biodegradable polymer is biocompatible before and upon biodegradat. Processes for preparing the polymers, compositions containing the polymers and biologically active substances, articles useful for implantation or injection into the body fabricated from the compositions, and methods for controllably releasing biologically active substances using the polymers, are also described.
摘要翻译：描述包含式I或II所示的重复单体单元的生物可降解聚合物：其中X是-O-或-NR'-，其中R'是H或烷基; L是具有1-20个碳原子的支链或直链脂族基团; M1和M2各自独立地为（1）具有1-20个碳原子的支链或直链脂族基团; 或（2）具有1-20个碳原子的支链或直链，氧基，羧基或氨基 - 脂族基团; Y是-O - ， - S-或-NR'-，其中R'是H或烷基; R是H，烷基，烷氧基，芳基，芳氧基，杂环或杂环氧基; x：y的摩尔比为约1; 摩尔比n：（x或y）在约200:1和1:200之间; 并且摩尔比q：r在约1:99和99:1之间; 其中所述可生物降解聚合物在生物降解之前和之后是生物相容的。还描述了制备聚合物的方法，含有聚合物和生物活性物质的组合物，用于植入或注射到由组合物制造的身体中的制品，以及使用该聚合物可控地释放生物活性物质的方法。

3. 发明授权

US06600010B2 Biodegradable terephthalate polyester-poly (phosphate) polymers, compositions, articles, and methods for making and using the same 有权
标题翻译：可生物降解的对苯二甲酸酯聚酯 - 聚（磷酸酯）聚合物，组合物，制品及其制备和使用方法
公开(公告)号：US06600010B2
公开(公告)日：2003-07-29
申请号：US09921297
申请日：2001-08-02
申请人： Hai-Quan Mao , Kam W. Leong , Wenbin Dang , Hungnan Lo , Zhong Zhao , David P. Nowotnik , James P. English
发明人： Hai-Quan Mao , Kam W. Leong , Wenbin Dang , Hungnan Lo , Zhong Zhao , David P. Nowotnik , James P. English
IPC分类号： C08G7902
CPC分类号： C08G63/6926 , A61K9/1647 , A61L17/12 , A61L26/0019 , A61L27/18 , Y10T428/2938 , Y10T442/3545 , C08L85/02
摘要： Biodegradable terephthalate polymers are described comprising the recurring monomeric units shown in formula I: wherein R is a divalent organic moiety; R′ is an aliphatic, aromatic or heterocyclic residue; x is ≧1; and n is 0-5,000, wherein the biodegradable polymer is biocompatible before and upon biodegradation. Processes for preparing the polymers, compositions containing the polymers and biologically active substances, articles useful for implantation or injection into the body fabricated from the compositions, and methods for controllably releasing biologically active substances using the polymers, are also described.
摘要翻译：描述了可生物降解的对苯二甲酸酯聚合物，其包含式I所示的重复单体单元：其中R是二价有机部分; R'是脂族，芳族或杂环残基; x是> = 1; andn为0-5,000，其中生物可降解聚合物在生物降解之前和之后是生物相容的。还描述了制备聚合物的方法，含有聚合物和生物活性物质的组合物，用于植入或注射到由组合物制造的身体中的制品，以及使用该聚合物可控地释放生物活性物质的方法。

4. 发明授权

US6166173A Biodegradable polymers chain-extended by phosphates, compositions, articles and methods for making and using the same 失效
标题翻译：通过磷酸盐，组合物，制品和制造和使用它们的方法延伸的可生物降解的聚合物
公开(公告)号：US6166173A
公开(公告)日：2000-12-26
申请号：US53649
申请日：1998-04-02
申请人： Hai-Quan Mao , Kam W. Leong , Zhong Zhao , James P. English
发明人： Hai-Quan Mao , Kam W. Leong , Zhong Zhao , James P. English
IPC分类号： A61L27/00 , A61K9/00 , A61K9/16 , A61L17/10 , A61L17/12 , A61L24/00 , A61L26/00 , A61L27/14 , A61L27/18 , C08G63/692 , C08G63/91 , C08G69/42 , C08G79/04 , C08L67/00 , C08L77/00 , C08L85/02 , C08L101/16 , A61K31/80
CPC分类号： A61K9/0024 , A61K9/1647 , A61L17/12 , A61L26/0019 , A61L27/18 , C08G63/6922 , C08G63/912 , Y10S623/924 , C08L85/02
摘要： Biodegradable polymers are described comprising the recurring monomeric units shown in formula I or II: wherein X is --O-- or --NR'--, where R' is H or alkyl; L is a branched or straight chain aliphatic group having from 1-20 carbon atoms; M.sub.1 and M.sub.2 are each independently (1) a branched or straight chain aliphatic group having from 1-20 carbon atoms; or (2) a branched or straight chain, oxy-, carboxy- or amino-aliphatic group having from 1-20 carbon atoms; Y is --O--, --S-- or --NR'--, where R' is H or alkyl; R is H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy; the molar ratio of x:y is about 1; the molar ratio n:(x or y) is between about 200:1 and 1:200; and the molar ratio q:r is between about 1:99 and 99:1; wherein said biodegradable polymer is biocompatible before and upon biodegradat.Processes for preparing the polymers, compositions containing the polymers and biologically active substances, articles useful for implantation or injection into the body fabricated from the compositions, and methods for controllably releasing biologically active substances using the polymers, are also described.
摘要翻译：描述包含式I或II所示的重复单体单元的生物可降解聚合物：其中X是-O-或-NR'-，其中R'是H或烷基; L是具有1-20个碳原子的支链或直链脂族基团; M1和M2各自独立地为（1）具有1-20个碳原子的支链或直链脂族基团; 或（2）具有1-20个碳原子的支链或直链，氧基，羧基或氨基 - 脂族基团; Y是-O - ， - S-或-NR'-，其中R'是H或烷基; R是H，烷基，烷氧基，芳基，芳氧基，杂环或杂环氧基; x：y的摩尔比为约1; 摩尔比n：（x或y）在约200:1和1:200之间; 并且摩尔比q：r在约1:99和99:1之间; 其中所述可生物降解聚合物在生物降解之前和之后是生物相容的。还描述了制备聚合物的方法，含有聚合物和生物活性物质的组合物，用于植入或注射到由组合物制造的身体中的制品，以及使用该聚合物可控地释放生物活性物质的方法。

5. 发明授权

US06805876B2 Phosphate based biodegradable polymers 有权
标题翻译：磷酸盐生物降解聚合物
公开(公告)号：US06805876B2
公开(公告)日：2004-10-19
申请号：US09803358
申请日：2001-03-10
申请人： Kam W. Leong , Wen Jie , Ren-Xi Zhuo , Hai-Quan Mao
发明人： Kam W. Leong , Wen Jie , Ren-Xi Zhuo , Hai-Quan Mao
IPC分类号： A61F202
CPC分类号： A61K9/0024 , A61K9/1647 , A61L27/18 , A61L27/58 , A61L31/16 , A61L2300/604 , C08G79/04 , C08L85/02
摘要： Featured are biodegradable polymers comprising repeat units derived from cyclic phosphate monomers and optionally further comprising repeat units derived from lactide or caprolactone monomers. Also featured are methods for preparing the biodegradable polymers of the invention and biodegradable polymer compositions comprising a biologically active substance and a biodegradable polymer. Additionally featured are articles and microspheres prepared from biodegradable polymers and polymer compositions of the invention. Further, methods for the controlled release of a biologically active substance using the biodegradable polymers of the invention are also described.
摘要翻译：特别是包含衍生自环状磷酸酯单体的重复单元的生物可降解聚合物，任选地还包含衍生自丙交酯或己内酯单体的重复单元。还特征在于制备本发明的可生物降解的聚合物的方法和包含生物活性物质和可生物降解的聚合物的可生物降解的聚合物组合物。另外特征是由本发明的可生物降解聚合物和聚合物组合物制备的制品和微球。此外，还描述了使用本发明的可生物降解聚合物控制释放生物活性物质的方法。

6. 发明授权

US08361502B2 Compositions and methods for the expansion and differentiation of stem cells 有权
标题翻译：干细胞扩增和分化的组成和方法
公开(公告)号：US08361502B2
公开(公告)日：2013-01-29
申请号：US11975492
申请日：2007-10-18
申请人： Hai-Quan Mao , Kam W. Leong , Kian-Ngiap Chua , Seeram Ramakrishna
发明人： Hai-Quan Mao , Kam W. Leong , Kian-Ngiap Chua , Seeram Ramakrishna
IPC分类号： A61K9/14
CPC分类号： C12N5/0075 , B82Y5/00 , B82Y30/00 , C12N5/0641 , C12N2533/30
摘要： The instant invention provides methods and compositions for the expansion and differentiation of stem cells.
摘要翻译：本发明提供了用于扩增和分化干细胞的方法和组合物。

7. 发明授权

US06548302B1 Polymers for delivery of nucleic acids 有权
标题翻译：用于递送核酸的聚合物
公开(公告)号：US06548302B1
公开(公告)日：2003-04-15
申请号：US09336390
申请日：1999-06-18
申请人： Hai-Quan Mao , Kevin Y. Lin , Bart S. Hendriks , Kam W. Leong , Michael F. Haller
发明人： Hai-Quan Mao , Kevin Y. Lin , Bart S. Hendriks , Kam W. Leong , Michael F. Haller
IPC分类号： A61K4800
CPC分类号： C08J9/00 , A61K9/1641 , A61K9/1647 , A61K48/00 , A61K2039/55555 , C08J2399/00 , C12N15/88 , Y10S977/906
摘要： The present invention relates to compositions and methods for delivery of nucleic acids. In particular, the invention provides a polymeric delivery formulation including a nucleic acid to be transfected into a host cell, formulated in a biodegradable polymer having phosphorous-based linkages.
摘要翻译：本发明涉及递送核酸的组合物和方法。特别地，本发明提供了一种包含待转染宿主细胞的核酸的聚合递送制剂，其配制在具有磷基连接的可生物降解的聚合物中。

8. 发明授权

US06322797B1 Biodegradable terephthalate polyester-poly (phosphate) polymers, compositions, articles, and methods for making and using the same 失效
标题翻译：可生物降解的对苯二甲酸酯聚酯 - 聚（磷酸酯）聚合物，组合物，制品及其制备和使用方法
公开(公告)号：US06322797B1
公开(公告)日：2001-11-27
申请号：US09053648
申请日：1998-04-02
申请人： Hai-Quan Mao , Kam W. Leong , Wenbin Dang , Hungnan Lo , Zhong Zhao , David P. Nowotnik , James P. English
发明人： Hai-Quan Mao , Kam W. Leong , Wenbin Dang , Hungnan Lo , Zhong Zhao , David P. Nowotnik , James P. English
IPC分类号： C08G7902
CPC分类号： C08G63/6926 , A61K9/1647 , A61L17/12 , A61L26/0019 , A61L27/18 , Y10T428/2938 , Y10T442/3545 , C08L85/02
摘要： Biodegradable terephthalate polymers are described comprising the recurring monomeric units shown in formula I: wherein R is a divalent organic moiety; R′ is an aliphatic, aromatic or heterocyclic residue; x is ≧1; and n is 0-5,000, wherein the biodegradable polymer is biocompatible before and upon biodegradation. Processes for preparing the polymers, compositions containing the polymers and biologically active substances, articles useful for implantation or injection into the body fabricated from the compositions, and methods for controllably releasing biologically active substances using the polymers, are also described.
摘要翻译：描述了可生物降解的对苯二甲酸酯聚合物，其包含式I所示的重复单体单元：其中R是二价有机部分; R'是脂族，芳族或杂环残基; x是> = 1; andn为0-5,000，其中生物可降解聚合物在生物降解之前和之后是生物相容的。用于制备聚合物的方法，含有聚合物和生物活性物质的组合物，用于植入或注射到由组合物制造的身体中的制品，以及可控制的方法还使用聚合物释放生物活性物质。

9. 发明授权

US06238687B1 Biodegradable polymers, compositions, articles and methods for making and using the same 失效
标题翻译：可生物降解的聚合物，组合物，制品及其制备和使用方法
公开(公告)号：US06238687B1
公开(公告)日：2001-05-29
申请号：US09286713
申请日：1999-04-05
申请人： Hai-Quan Mao , Kam W. Leong
发明人： Hai-Quan Mao , Kam W. Leong
IPC分类号： A61F202
CPC分类号： C08G79/04 , A61K9/204 , A61L15/26 , A61L17/10 , A61L26/0019 , A61L27/18 , A61L27/34 , A61L29/06 , A61L31/06 , C08L85/02
摘要： Biodegradable polymer compositions that degrade in vivo into non-toxic residues are described. In part, the present invention is directed to such polymers containing phosphorus and desaminotyrosyl L-tyrosine linkages in the polymer backbone. Processes for preparing such polymers, compositions containing such polymers and biologically active substances, articles useful for implantation or injection into the body fabricated from the compositions, and methods for controllably releasing biologically active substances using the polymers, are also described.
摘要翻译：描述了将体内降解为无毒残留物的生物可降解聚合物组合物。部分地，本发明涉及在聚合物主链中含有磷和脱氨基酪氨酰L-酪氨酸键的这种聚合物。还描述了制备这种聚合物的方法，含有这种聚合物和生物活性物质的组合物，用于植入或注射到由组合物制造的身体中的制品，以及使用该聚合物可控地释放生物活性物质的方法。

10. 发明授权

US5972707A Gene delivery system 失效
标题翻译：基因传递系统
公开(公告)号：US5972707A
公开(公告)日：1999-10-26
申请号：US890599
申请日：1997-07-09
申请人： Krishnendu Roy , Hai-Quan Mao , Vu L. Truong , Thomas August , Kam W. Leong
发明人： Krishnendu Roy , Hai-Quan Mao , Vu L. Truong , Thomas August , Kam W. Leong
IPC分类号： C12N15/09 , A61K9/16 , A61K9/51 , A61K47/48 , A61K48/00 , C12N15/88 , C12N15/00
CPC分类号： A61K9/5161 , A61K47/4823 , A61K47/48238 , A61K47/48292 , A61K47/48561 , A61K47/48876 , A61K9/167 , A61K9/5169 , A61K9/5192 , B82Y5/00 , C12N15/88 , A61K48/00 , Y10S977/808 , Y10S977/906 , Y10S977/915 , Y10S977/916 , Y10S977/92
摘要： A gene delivery system is made of enzymatically degradable polymeric cation and nucleic acid (DNA or RNA) nanospheres optionally with a linking moiety or a targeting ligand attached to the surface. The delivery system can be made by a simple method of coacervation. Targeting ligands can be attached to the nanosphere directly or via a linking moiety. The linkage design allows the attachment of any molecule onto the nanosphere surface including antibodies, cell adhesion molecules, hormones and other cell-specific ligands.
摘要翻译：基因递送系统由可酶降解的聚合阳离子和核酸（DNA或RNA）纳米球制成，任选地具有连接部分或连接到表面的靶向配体。输送系统可以通过简单的凝聚方法制成。靶向配体可以直接或通过连接部分连接到纳米球。连接设计允许将任何分子附着到纳米球表面，包括抗体，细胞粘附分子，激素和其他细胞特异性配体。

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