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1. 发明授权

US5494682A Ionically cross-linked polymeric microcapsules 失效
标题翻译：离子交联聚合物微胶囊
公开(公告)号：US5494682A
公开(公告)日：1996-02-27
申请号：US210018
申请日：1994-03-18
申请人： Smadar Cohen , Carmen Bano , Karyn B. Visscher , Marie Chow , Harry R. Allcock , Robert S. Langer
发明人： Smadar Cohen , Carmen Bano , Karyn B. Visscher , Marie Chow , Harry R. Allcock , Robert S. Langer
IPC分类号： A61K9/127 , A61K9/16 , A61K9/50 , A61K31/70 , A61K31/708 , A61K31/715 , A61K35/12 , A61K38/00 , A61K47/02 , A61K47/30 , A61K47/32 , A61K47/34 , A61K49/22 , A61K51/12 , B01J13/02 , B01J13/10 , B01J13/14 , C08G79/02 , C12N11/04
CPC分类号： A61K49/223 , A61K49/225 , A61K49/226 , A61K51/1258 , A61K9/1271 , A61K9/1641 , A61K9/5031 , B01J13/14 , C08G79/025 , C12N11/04 , A61K2123/00 , Y10T428/2984 , Y10T428/2985 , Y10T428/2987
摘要： A method for encapsulating biologically-labile materials such as proteins, liposomes, bacteria and eucaryotic cells within a synthetic polymeric capsule, and the product thereof, are disclosed. The method is based on the use of a water-soluble polymer with charged side chains that are crosslinked with multivalent ions of the opposite charge to form a gel encapsulating biological material, that is optionally further stabilized by interactions with multivalent polyions of the same charge as those used to form the gel. In the preferred embodiment, hydrolytically stable polyphosphazenes are formed of monomers having carboxylic acid side groups that are crosslinked by divalent or trivalent cations such as Ca.sup.2+ or Al.sup.3+, then stabilized with a polycation such as poly-L-lysine. A variety of different compositions can be formed from the crosslinked polymer. In a preferred embodiment, microcapsules are made by spraying an aqueous solution of polyphosphazene and material to be encapsulated into a calcium chloride solution.
摘要翻译：公开了一种将生物不稳定材料如蛋白质，脂质体，细菌和真核细胞包封在合成聚合物胶囊内的方法及其产品。该方法基于使用具有带电侧链的水溶性聚合物，其与相反电荷的多价离子交联以形成包封生物材料的凝胶，其可任选地通过与相同电荷的多价离子的相互作用进一步稳定用于形成凝胶的那些。在优选的实施方案中，水解稳定的聚磷腈由具有羧酸侧基的单体形成，其通过二价或三价阳离子如Ca 2+或Al 3+交联，然后用聚阳离子如聚-L-赖氨酸稳定。可以从交联聚合物形成各种不同的组合物。在优选的实施方案中，通过将聚磷腈的水溶液和待包封的材料喷雾到氯化钙溶液中来制备微胶囊。

2. 发明授权

US5149543A Ionically cross-linked polymeric microcapsules 失效
标题翻译：离子交联聚合物微球
公开(公告)号：US5149543A
公开(公告)日：1992-09-22
申请号：US593684
申请日：1990-10-05
申请人： Smadar Cohen , Carmen Bano , Karyn B. Visscher , Marie Chow , Harry R. Allcock , Robert S. Langer
发明人： Smadar Cohen , Carmen Bano , Karyn B. Visscher , Marie Chow , Harry R. Allcock , Robert S. Langer
IPC分类号： A61K9/127 , A61K9/16 , A61K9/50 , A61K31/70 , A61K31/708 , A61K31/715 , A61K35/12 , A61K38/00 , A61K47/02 , A61K47/30 , A61K47/32 , A61K47/34 , A61K49/22 , A61K51/12 , B01J13/02 , B01J13/10 , B01J13/14 , C08G79/02 , C12N11/04
CPC分类号： A61K49/223 , A61K49/225 , A61K49/226 , A61K51/1258 , A61K9/1271 , A61K9/1641 , A61K9/5031 , B01J13/14 , C08G79/025 , C12N11/04 , A61K2123/00 , Y10T428/2984 , Y10T428/2985 , Y10T428/2987
摘要： A method for encapsulating biologically-labile materials such as proteins, liposomes, bacteria and eucaryotic cells within a synthetic polymeric capsule, and the product thereof, are disclosed. The method is based on the use of a water-soluble polymer with charged side chains that are crosslinked with multivalent ions of the opposite charge to form a gel encapsulating biological material, that is optionally further stabilized by interactions with multivalent polyions of the same charge as those used to form the gel. In the preferred embodiment, hydrolytically stable polyphosphazenes are formed of monomers having carboxylic acid side groups that are crosslinked by divalent or trivalent cations such as Ca.sup.2+ or Al.sup.3+, then stabilized with a polycation such as poly-L-lysine. A variety of different compositions can be formed from the crosslinked polymer. In a preferred embodiment, microcapsules are made by spraying an aqueous solution of polyphosphazene and material to be encapsulated into a calcium chloride solution. A semipermeable membrane is formed on the microspheres by complexation of the surface carboxylate groups with poly(L-lysine).
摘要翻译：公开了一种将生物不稳定材料如蛋白质，脂质体，细菌和真核细胞包封在合成聚合物胶囊内的方法及其产品。该方法基于使用具有带电侧链的水溶性聚合物，其与相反电荷的多价离子交联以形成包封生物材料的凝胶，其任选通过与相同电荷的多价离子的相互作用进一步稳定用于形成凝胶的那些。在优选的实施方案中，水解稳定的聚磷腈由具有羧酸侧基的单体形成，其通过二价或三价阳离子如Ca 2+或Al 3+交联，然后用聚阳离子如聚-L-赖氨酸稳定。可以从交联聚合物形成各种不同的组合物。在优选的实施方案中，通过将聚磷腈的水溶液和待包封的材料喷雾到氯化钙溶液中来制备微胶囊。通过表面羧酸酯基与聚（L-赖氨酸）的络合，在微球上形成半透膜。

3. 发明授权

US5308701A Ionically cross-linked polymeric microcapsules 失效
标题翻译：离子交联聚合物微胶囊
公开(公告)号：US5308701A
公开(公告)日：1994-05-03
申请号：US880248
申请日：1992-05-08
申请人： Smadar Cohen , Carmen Bano , Karyn B. Visscher , Marie B. Chow , Harry R. Allcock , Robert S. Langer
发明人： Smadar Cohen , Carmen Bano , Karyn B. Visscher , Marie B. Chow , Harry R. Allcock , Robert S. Langer
IPC分类号： A61K9/127 , A61K9/16 , A61K9/50 , A61K31/70 , A61K31/708 , A61K31/715 , A61K35/12 , A61K38/00 , A61K47/02 , A61K47/30 , A61K47/32 , A61K47/34 , A61K49/22 , A61K51/12 , B01J13/02 , B01J13/10 , B01J13/14 , C08G79/02 , C12N11/04
CPC分类号： A61K49/223 , A61K49/225 , A61K49/226 , A61K51/1258 , A61K9/1271 , A61K9/1641 , A61K9/5031 , B01J13/14 , C08G79/025 , C12N11/04 , A61K2123/00 , Y10T428/2984 , Y10T428/2985 , Y10T428/2987
摘要： A method for encapsulating biologically-labile materials such as proteins, liposomes, bacteria and eucaryotic cells within a synthetic polymeric capsule, and the product thereof, are disclosed. The method is based on the use of a water-soluble polymer with charged side chains that are crosslinked with multivalent ions of the opposite charge to form a gel encapsulating biological material, that is optionally further stabilized by interactions with multivalent polyions of the same charge as those used to form the gel. In the preferred embodiment, hydrolytically stable polyphosphazenes are formed of monomers having carboxylic acid side groups that are crosslinked by divalent or trivalent cations such as Ca.sup.2+ or Al.sup.3+, then stabilized with a polycation such as poly-L-lysine. A variety of different compositions can be formed from the crosslinked polymer. In a preferred embodiment, microcapsules are made by spraying an aqueous solution of polyphosphazene and material to be encapsulated into a calcium chloride solution. A semi-permeable membrane is formed on the microspheres by complexation of the surface carboxylate groups with poly(L-lysine).
摘要翻译：公开了一种将生物不稳定材料如蛋白质，脂质体，细菌和真核细胞包封在合成聚合物胶囊内的方法及其产品。该方法基于使用具有带电侧链的水溶性聚合物，其与相反电荷的多价离子交联以形成包封生物材料的凝胶，其任选通过与相同电荷的多价离子的相互作用进一步稳定用于形成凝胶的那些。在优选的实施方案中，水解稳定的聚磷腈由具有羧酸侧基的单体形成，其通过二价或三价阳离子如Ca 2+或Al 3+交联，然后用聚阳离子如聚-L-赖氨酸稳定。可以从交联聚合物形成各种不同的组合物。在优选的实施方案中，通过将聚磷腈的水溶液和待包封的材料喷雾到氯化钙溶液中来制备微胶囊。通过表面羧酸酯基与聚（L-赖氨酸）的络合，在微球上形成半透膜。

4. 发明授权

US5562099A Polymeric microparticles containing agents for imaging 失效
标题翻译：含有成像剂的聚合物微粒
公开(公告)号：US5562099A
公开(公告)日：1996-10-08
申请号：US292522
申请日：1994-08-18
申请人： Smadar Cohen , Alexander K. Andrianov , Margaret Wheatley , Harry R. Allcock , Robert S. Langer
发明人： Smadar Cohen , Alexander K. Andrianov , Margaret Wheatley , Harry R. Allcock , Robert S. Langer
IPC分类号： A61K9/127 , A61K9/16 , A61K9/50 , A61K49/22 , A61K51/12 , B01J13/14 , C08G79/02 , C12N11/04 , A61K49/00
CPC分类号： B82Y5/00 , A61K49/223 , A61K49/225 , A61K49/226 , A61K51/1258 , A61K9/1271 , A61K9/1641 , A61K9/5031 , B01J13/14 , C08G79/025 , C12N11/04 , A61K2123/00 , Y10S977/753
摘要： Compositions, methods for preparing and methods of using contrast agent-filled polymeric microparticles for imaging are disclosed. In a preferred embodiment, air-encapsulating microparticles are formed by ionotropically gelling synthetic polyelectrolytes such as poly(carboxylatophenoxy)phosphazene, poly(acrylic acid), poly(methacrylic acid) and methacrylic acid copolymers (Eudragit's) by contact with multivalent ions such as calcium ions. In the preferred embodiment, the average size of the microparticles is less than seven .mu.m so that they are suitable for injection intravenously. The polymeric microparticles are stable to imaging and display high echogenicity, both in vitro and in vivo. Due to their in vivo stability their potential application is extended beyond vascular imaging to liver and renal diseases, fallopian tube diseases, detecting and characterizing tumor masses and tissues, and measuring peripheral blood velocity. The microparticles can optionally be linked with ligands that minimize tissue adhesion or that target the microparticles to specific regions.
摘要翻译：公开了组合物，制备方法和使用造影剂填充的聚合物微粒用于成像的方法。在一个优选的实施方案中，空气封装的微粒通过与多价离子例如钙的接触通过离子交换胶凝合成聚合电解质如聚（羧基苯氧基）磷腈，聚（丙烯酸），聚（甲基丙烯酸）和甲基丙烯酸共聚物（Eudragit's）离子。在优选的实施方案中，微粒的平均尺寸小于7μm，使得它们适于静脉内注射。聚合物微粒对于成像是稳定的，并且在体外和体内均显示出高回波性。由于其体内稳定性，其潜在应用范围超出血管成像，肝肾疾病，输卵管疾病，检测和表征肿瘤块和组织，并测量外周血速度。微粒可任选地与使组织粘附最小化或将微粒靶向特定区域的配体连接。

5. 发明授权

US5487390A Gas-filled polymeric microbubbles for ultrasound imaging 失效
标题翻译：用于超声成像的气体填充聚合物微泡
公开(公告)号：US5487390A
公开(公告)日：1996-01-30
申请号：US182216
申请日：1994-01-14
申请人： Smadar Cohen , Alexander K. Andrianov , Margaret Wheatley , Harry R. Allcock , Robert S. Langer
发明人： Smadar Cohen , Alexander K. Andrianov , Margaret Wheatley , Harry R. Allcock , Robert S. Langer
IPC分类号： A61K9/127 , A61K9/16 , A61K9/50 , A61K49/22 , A61K51/12 , B01J13/14 , C08G79/02 , C12N11/04 , A61B8/14
CPC分类号： A61K9/1271 , A61K49/223 , A61K49/225 , A61K49/226 , A61K51/1258 , A61K9/1641 , A61K9/5031 , B01J13/14 , C08G79/025 , C12N11/04 , A61K2123/00 , Y10S977/753 , Y10S977/929 , Y10T428/2987
摘要： Compositions, methods for preparing and methods of using air-filled polymeric microcapsules for ultrasound imaging are disclosed. Air-encapsulating microcapsules are formed by ionotropically gelling synthetic polyelectrolytes such as poly(carboxylatophenoxy)phosphazene, poly(acrylic acid), poly(methacrylic acid) and methacrylic acid copolymers (Eudragit's) by contact with multivalent ions such as calcium ions. In the preferred embodiment, the average size of the microcapsules is less than seven .mu.m so that they are suitable for injection intravenously. The polymeric microcapsules are stable to imaging and display high echogenicity, both in vitro and in vivo. Due to their in vivo stability their potential application is extended beyond vascular imaging to liver and renal diseases, fallopian tube diseases, detecting and characterizing tumor masses and tissues, and measuring peripheral blood velocity. The microcapsules can optionally be linked with ligands that minimize tissue adhesion or that target the microcapsules to specific regions.
摘要翻译：公开了组合物，制备方法和使用空气填充的聚合物微胶囊用于超声成像的方法。通过与多价离子如钙离子接触，通过离子交换胶凝聚合电解质如聚（羧基苯氧基）磷腈，聚（丙烯酸），聚（甲基丙烯酸）和甲基丙烯酸共聚物（Eudragit's））形成空气封装的微胶囊。在优选的实施方案中，微胶囊的平均尺寸小于7μm，使得它们适合静脉内注射。聚合物微胶囊在体外和体内都能稳定成像并显示高回波性。由于其体内稳定性，其潜在应用范围超出血管成像，肝肾疾病，输卵管疾病，检测和表征肿瘤块和组织，并测量外周血速度。微胶囊可以任选地与使组织粘附最小化或将微胶囊靶向特定区域的配体连接。

6. 发明授权

US5762904A Oral delivery of vaccines using polymerized liposomes 失效
标题翻译：使用聚合脂质体口服输送疫苗
公开(公告)号：US5762904A
公开(公告)日：1998-06-09
申请号：US786617
申请日：1997-01-17
申请人： Junichi Okada , Smadar Cohen , Robert S. Langer
发明人： Junichi Okada , Smadar Cohen , Robert S. Langer
IPC分类号： A61K9/127 , A61K39/00 , A61M36/12
CPC分类号： A61K9/1273 , Y10S424/812 , Y10T428/2984
摘要： Polymerized liposomes, methods of preparing the polymerized liposomes and incorporating biologically active substances within the polymerized liposomes, and methods of administering polymerized liposomes containing a biologically active substance to be delivered to a patient are disclosed. The polymerized liposomes are prepared by polymerizing double bond-containing liposomes. The polymerization can be initiated with a source of radiation and/or a free radical initiator. Biologically active substances can be incorporated into both the hydrophilic and hydrophobic layers of the liposomes, either during or after polymerization. The polymerized liposomes can be administered orally to a patient in need of the biologically active substance to be delivered. Examples demonstrate enhanced stability.
摘要翻译：聚合的脂质体，制备聚合的脂质体并将生物活性物质并入聚合的脂质体内的方法，以及施用含有待递送给患者的生物活性物质的聚合脂质体的方法。通过聚合含双键的脂质体制备聚合的脂质体。可以用辐射源和/或自由基引发剂引发聚合。在聚合过程中或之后，生物活性物质可以并入脂质体的亲水层和疏水层中。聚合的脂质体可以口服给予需要递送的生物活性物质的患者。实例表明增强的稳定性。

7. 发明授权

US5330768A Controlled drug delivery using polymer/pluronic blends 失效
标题翻译：使用聚合物/ pluronic混合物控制药物递送
公开(公告)号：US5330768A
公开(公告)日：1994-07-19
申请号：US726349
申请日：1991-07-05
申请人： Tae G. Park , Smadar Cohen , Robert S. Langer
发明人： Tae G. Park , Smadar Cohen , Robert S. Langer
IPC分类号： A61K9/16 , A61K9/70
CPC分类号： A61K9/7007 , A61K9/1641 , A61K9/1647 , Y10S514/963 , Y10S514/964
摘要： A new series of degradable polymeric matrices were prepared by blending polymers that degrade by hydrolysis such as poly(L-lactic acid)(PLA), and nonionic Pluronic.TM. surfactants, block copolymers of polyethyleneoxide (PEO) and polypropyleneoxide (PPO). The water content of the polymer blend films was controlled by mixing different types of block copolymers and by adjusting their amount. In aqueous solution, the blends revealed the typical liquid-crystalline phase transition of Pluronic.TM. polymers, suggesting the formation of a gel-like structure within the polymer skeleton. Poly(lactic acid) degradation rates were not affected by the blending procedure, although the hydration degree in these matrices was higher. When used as drug-releasing matrices, these blends extended protein release and minimized the initial protein burst, as compared to the pure polymer.
摘要翻译：通过混合通过水解降解的聚合物如聚（L-乳酸）（PLA）和非离子Pluronic TM表面活性剂，聚环氧乙烷（PEO）和聚环氧丙烷（PPO）的嵌段共聚物）来制备新的可降解聚合物基质系列。通过混合不同类型的嵌段共聚物并通过调节它们的量来控制聚合物共混物膜的含水量。在水溶液中，共混物显示Pluronic TM聚合物的典型液晶相变，表明在聚合物骨架内形成凝胶状结构。尽管这些基质中的水合度较高，但聚（乳酸）降解速率不受共混程序的影响。当用作药物释放基质时，与纯聚合物相比，这些共混物延长了蛋白质释放并使初始蛋白质爆发最小化。

8. 发明授权

US09387222B2 Alginate biomaterials for the treatment of hepatic disorders 有权
标题翻译：藻酸盐生物材料用于治疗肝脏疾病
公开(公告)号：US09387222B2
公开(公告)日：2016-07-12
申请号：US12744512
申请日：2008-11-27
申请人： Yaron Ilan , Gadi Lalazar , Eyal Shteyer , Ami Ben-Yaakov , Smadar Cohen , Tsiona Elkayam
发明人： Yaron Ilan , Gadi Lalazar , Eyal Shteyer , Ami Ben-Yaakov , Smadar Cohen , Tsiona Elkayam
IPC分类号： A61K9/00 , A61K9/10 , A61K38/02 , A61P1/16 , A61K31/734 , A61K31/738 , A61L27/20 , A61L31/04
CPC分类号： A61K31/738 , A61K31/734 , A61L27/20 , A61L31/042 , A61P1/16 , C08L5/04
摘要： The present invention relates to methods for the treatment of hepatic disorders in a subject in need thereof. More specifically, the methods of the invention are based on the administration, preferably, systemic administration, of a therapeutically effective amount of at least one biocompatible alginate biomaterial, any modification thereof and any combination thereof. The invention further provides methods for sustaining serum albumin levels, and/or reducing serum AST and ALT, in subjects suffering from hepatic disorder. Still further, the invention provides methods for reducing apoptosis and inducing cell proliferation in a damaged liver tissue of a subject suffering of hepatic disorder, using the alginate biomaterial described by the invention.
摘要翻译：本发明涉及在有需要的受试者中治疗肝脏疾病的方法。更具体地，本发明的方法基于治疗有效量的至少一种生物相容性藻酸盐生物材料，其任何修饰以及它们的任何组合，优选全身施用。本发明还提供了在患有肝脏障碍的受试者中维持血清白蛋白水平和/或降低血清AST和ALT的方法。此外，本发明提供了使用本发明描述的藻酸盐生物材料减少患有肝脏疾病的受试者的损伤的肝组织中细胞凋亡和诱导细胞增殖的方法。

9. 发明授权

US08461132B2 Injectable cross-linked polymeric preparations and uses thereof 有权
公开(公告)号：US08461132B2
公开(公告)日：2013-06-11
申请号：US13430020
申请日：2012-03-26
申请人： Smadar Cohen , Jonathan Leor
发明人： Smadar Cohen , Jonathan Leor
IPC分类号： A01N43/04
CPC分类号： A61K35/33 , A61K9/0024 , A61K31/734 , A61K31/738 , A61K35/12 , A61K35/34 , A61K45/06 , A61L27/20 , A61L27/52 , A61L2400/06 , A61L2430/20 , C08L5/04
摘要： A therapeutic composition for treatment of a body tissue which includes an aqueous solution of a cross-linked polymer being capable of: (i) maintaining a liquid state in storage at room temperature for at least 24 hours; and (ii) assuming a gel state following deposition within the body tissue. The therapeutic composition can be effectively administered into a damaged body tissue via injection or catheterization, thereby treating the damaged body tissue.

10. 发明申请

US20100247652A1 Alginate Biomaterials for the Treatment of Hepatic Disorders 有权
标题翻译：藻酸盐生物材料治疗肝病
公开(公告)号：US20100247652A1
公开(公告)日：2010-09-30
申请号：US12744512
申请日：2008-11-27
申请人： Yaron Ilan , Gadi Lalazar , Eyal Shteyer , Ami Ben-Yaakov , Smadar Cohen , Tsiona Elkayam
发明人： Yaron Ilan , Gadi Lalazar , Eyal Shteyer , Ami Ben-Yaakov , Smadar Cohen , Tsiona Elkayam
IPC分类号： A61K31/734 , A61K9/10 , A61K9/00 , A61K38/02 , A61P1/16
CPC分类号： A61K31/738 , A61K31/734 , A61L27/20 , A61L31/042 , A61P1/16 , C08L5/04
摘要： The present invention relates to methods for the treatment of hepatic disorders in a subject in need thereof. More specifically, the methods of the invention are based on the administration, preferably, systemic administration, of a therapeutically effective amount of at least one biocompatible alginate biomaterial, any modification thereof and any combination thereof. The invention further provides methods for sustaining serum albumin levels, and/or reducing serum AST and ALT, in subjects suffering from hepatic disorder. Still further, the invention provides methods for reducing apoptosis and inducing cell proliferation in a damaged liver tissue of a subject suffering of hepatic disorder, using the alginate biomaterial described by the invention.
摘要翻译：本发明涉及在有需要的受试者中治疗肝脏疾病的方法。更具体地，本发明的方法基于治疗有效量的至少一种生物相容性藻酸盐生物材料，其任何修饰以及它们的任何组合，优选全身施用。本发明还提供了在患有肝脏障碍的受试者中维持血清白蛋白水平和/或降低血清AST和ALT的方法。此外，本发明提供了使用本发明描述的藻酸盐生物材料减少患有肝脏疾病的受试者的损伤的肝组织中细胞凋亡和诱导细胞增殖的方法。

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