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1. 发明授权

US5240963A Branched polyanhydrides 失效
标题翻译：支链聚酐
公开(公告)号：US5240963A
公开(公告)日：1993-08-31
申请号：US948136
申请日：1992-09-18
申请人： Abraham J. Domb , Manoj Maniar
发明人： Abraham J. Domb , Manoj Maniar
IPC分类号： A61K6/00 , A61K9/16 , A61K9/20 , A61K47/48 , A61L31/06 , A61L31/16 , C08G67/04
CPC分类号： C08G67/04 , A61K47/48192 , A61K9/1641 , A61K9/2031 , A61L31/06 , A61L31/16 , A61L2300/602
摘要： Branched polyanhydrides that have superior properties for use in the controlled delivery of substances, prepared by the polymerization of a dicarboxylic acid monomer and a branching agent. The branching agent is a polycarboxylic acid monomer such as 1,3,5-benzenetricarboxylic acid ("BTC"), or an oligomerized fatty acid trimer. Alternatively, the branching agent is a polycarboxylic acid polymer such as poly(acrylic acid) ("PAA"). These branched polymers have significantly higher molecular weights and lower specific viscosity than linear polymers prepared under similar conditions. A major advantage of branched polyanhydrides is that the degradation and release kinetics can be substantially altered without significantly changing the physical properties of the polymer relative to the corresponding linear polymer. By manipulating both the diacid and the branching agent, a wide variety of biodegradable controlled delivery devices for diverse applications can be prepared.
摘要翻译：具有优异性能的支链聚酐，用于通过二羧酸单体和支化剂的聚合制备的物质的受控输送中。支化剂是诸如1,3,5-苯三甲酸（“BTC”）或低聚脂肪酸三聚体的多元羧酸单体。或者，支化剂是聚羧酸聚合物，例如聚（丙烯酸）（“PAA”）。这些支化聚合物具有比类似条件下制备的线性聚合物显着更高的分子量和更低的比粘度。支链聚酐的主要优点在于，相对于相应的线性聚合物，降解和释放动力学可以基本上改变而不显着改变聚合物的物理性质。通过操纵二酸和支化剂，可以制备用于各种应用的各种可生物降解的受控递送装置。

2. 发明授权

US5179189A Fatty acid terminated polyanhydrides 失效
标题翻译：脂肪酸封端的聚酐
公开(公告)号：US5179189A
公开(公告)日：1993-01-12
申请号：US756483
申请日：1991-09-09
申请人： Abraham J. Domb , Manoj Maniar
发明人： Abraham J. Domb , Manoj Maniar
IPC分类号： A61K9/22 , A61K6/00 , A61K9/20 , A61K47/30 , A61K47/48 , A61L31/06 , A61L31/16 , C08G63/00 , C08G67/00 , C08G67/04 , C08G69/10 , C08G69/48
CPC分类号： A61L27/16 , A61K47/48192 , A61K9/2031 , A61L27/18 , A61L31/06 , A61L31/16 , C08G67/04 , A61L2300/00
摘要： Fatty acid terminated polyanhydrides suitable for use as controlled release matrices in biodegradable sustained release drug delivery systems and methods for making thereof are described. The polymers are more soluble in organic solvents, and have a lower melting point than the corresponding non-fatty acid terminated polyanhydrides. The fatty acid terminated polyanhydrides are also more hydrophobic than the corresponding polyanhydrides that are not terminated with a fatty acid, and combine the properties of thermodynamic and hydrolytic stability, and easy storage. The polymers can be produced with a controlled and low molecular weight. The polyanhydrides are useful in a number of applications, including as a matrix in biodegradable drug delivery systems.
摘要翻译：描述适用于可生物降解的持续释放药物递送系统中的控制释放基质的脂肪酸封端的聚酐及其制备方法。聚合物更易溶于有机溶剂，并且具有比相应的非脂肪酸封端的聚酐更低的熔点。脂肪酸封端的聚酐也比不用脂肪酸终止的相应的多酸酐更疏水，并且结合了热力学和水解稳定性的特性，并且易于储存。聚合物可以以受控和低分子量生产。聚酐可用于许多应用，包括作为可生物降解药物递送系统中的基质。

3. 发明授权

US5482927A Controlled released microparticulate delivery system for proteins 失效
标题翻译：用于蛋白质的控制释放的微粒递送系统
公开(公告)号：US5482927A
公开(公告)日：1996-01-09
申请号：US200370
申请日：1994-02-23
申请人： Manoj Maniar , Abraham J. Domb
发明人： Manoj Maniar , Abraham J. Domb
IPC分类号： A61K9/00 , A61K9/16 , A61K38/27 , A61K47/02 , A61K47/26
CPC分类号： A61K47/02 , A61K38/27 , A61K47/26 , A61K9/0019 , A61K9/1617
摘要： An improved surface erodible controlled release composition and the manufacturing thereof, for the continuous administration of biologically active proteins or peptide fragments, is described. The biologically active protein is dissolved in water or a suitable solvent, alone or in combination with stabilizing agents. The solution is either lyophilized or spray dried to obtain a free flowing powder. The powder is then sieved to obtain the desired average particle size. The free flowing powder of the protein or the stabilized protein is then incorporated into a biodegradable matrix formed of fatty acid anhydride, fatty acid and/or a salt thereof. Examples using growth hormone and bovine serum albumin demonstrate enhanced release, stability and controlled release properties for the fatty acid anhydride microparticular system.
摘要翻译：描述了用于连续施用生物活性蛋白质或肽片段的改进的表面可侵蚀的控释组合物及其制备方法。生物活性蛋白质单独或与稳定剂组合溶于水或合适的溶剂中。将溶液冻干或喷雾干燥，得到自由流动的粉末。然后将粉末过筛以获得所需的平均粒度。然后将蛋白质或稳定化蛋白质的自由流动的粉末掺入由脂肪酸酐，脂肪酸和/或其盐形成的可生物降解的基质中。使用生长激素和牛血清白蛋白的实例证明脂肪酸酐微粒系统的增强的释放，稳定性和控制释放特性。

4. 发明授权

US5317079A Fatty acid terminated polyanhydride 失效
标题翻译：脂肪酸封端的聚酐
公开(公告)号：US5317079A
公开(公告)日：1994-05-31
申请号：US947048
申请日：1992-09-18
申请人： Abraham J. Domb , Manoj Maniar
发明人： Abraham J. Domb , Manoj Maniar
IPC分类号： A61K6/00 , A61K9/20 , A61K47/48 , A61L31/06 , A61L31/16 , C08G67/04
CPC分类号： A61L27/16 , A61K47/48192 , A61K9/2031 , A61L27/18 , A61L31/06 , A61L31/16 , C08G67/04 , A61L2300/00
摘要： Fatty acid terminated polyanhydrides suitable for use as controlled release matrices in biodegradable sustained release drug delivery systems and methods for making thereof are described. The polymers are more soluble in organic solvents, and have a lower melting point than the corresponding non-fatty acid terminated polyanhydrides. The fatty acid terminated polyanhydrides are also more hydrophobic than the corresponding polyanhydrides that are not terminated with a fatty acid, and combine the properties of thermodynamic and hydrolytic stability, and easy storage. The polymers can be produced with a controlled and low molecular weight. The polyanhydrides are useful in a number of applications, including as a matrix in biodegradable drug delivery systems.
摘要翻译：描述适用于可生物降解的持续释放药物递送系统中的控制释放基质的脂肪酸封端的聚酐及其制备方法。聚合物更易溶于有机溶剂，并且具有比相应的非脂肪酸封端的聚酐更低的熔点。脂肪酸封端的聚酐也比不用脂肪酸终止的相应的多酸酐更疏水，并且结合了热力学和水解稳定性的特性，并且易于储存。聚合物可以以受控和低分子量生产。聚酐可用于许多应用，包括作为可生物降解药物递送系统中的基质。

5. 发明授权

US5227165A Liposphere delivery systems for local anesthetics 失效
标题翻译：用于局部麻醉剂的脂质体输送系统
公开(公告)号：US5227165A
公开(公告)日：1993-07-13
申请号：US826218
申请日：1992-01-22
申请人： Abraham J. Domb , Manoj Maniar
发明人： Abraham J. Domb , Manoj Maniar
IPC分类号： A01N25/26 , A61K9/127 , A61K9/14 , A61K9/16 , A61K9/50
CPC分类号： A61K9/167 , A01N25/26 , A61K9/127 , A61K9/145 , A61K9/1617 , A61K9/5015 , Y10T428/2984 , Y10T428/2989
摘要： A local anesthetic microsuspension system is disclosed that includes lipospheres, that are solid, water-insoluble microparticles that have a layer of a phospholipid embedded on their surface. The core of the liposphere is a solid anesthetic such as lidocaine or marcaine, or an anesthetic dispersed in an inert solid vehicle, such as a wax. Anesthetic lipospheres provide a controlled delivery of local anesthetics to achieve extended, effective relief from pain by slowly releasing the anesthetic from the solid hydrophobic core. This is highly preferred over the situation in which an aqueous solution of local anesthetic must be frequently administered because it is quickly systemically absorbed.
摘要翻译：公开了一种局部麻醉微悬浮系统，其包括具有嵌入其表面上的磷脂层的固体，水不溶性微粒的脂质球。脂质圈的核心是固体麻醉剂如利多卡因或马可布，或分散在惰性固体载体如蜡中的麻醉剂。麻醉性脂质体提供局部麻醉剂的受控输送，以通过从固体疏水性核心缓慢释放麻醉剂来实现延长的，有效的缓解疼痛。这是局部麻醉剂的水溶液必须经常施用的情况，因为它被快速地系统地吸收，这是非常优选的。

6. 发明授权

US5175235A Branched polyanhydrides 失效
标题翻译：分支聚氨酯
公开(公告)号：US5175235A
公开(公告)日：1992-12-29
申请号：US532389
申请日：1990-06-04
申请人： Abraham J. Domb , Manoj Maniar
发明人： Abraham J. Domb , Manoj Maniar
IPC分类号： A61K47/30 , A61K9/16 , A61K9/20 , A61L27/00 , A61L29/00 , C08F20/02 , C08F220/04 , C08F220/06 , C08F222/06 , C08G67/00 , C08G67/04
CPC分类号： A61K9/2031 , A61K9/1641 , C08G67/04
摘要： Branched polyanhydrides that have superior properties for use in the controlled delivery of substances, prepared by the polymerization of a dicarboxylic acid monomer and a branching agent. The branching agent is a polycarboxylic acid monomer such as 1,3,5-benzenetricarboxylic acid ("BTC"), or an oligomerized fatty acid trimer. Alternatively, the branching agent is a polycarboxylic acid polymer such as poly(acrylic acid) ("PAA"). These branched polymers have significantly higher molecular weights and lower specific viscosity than linear polymers prepared under similar conditions. A major advantage of branched polyanhydrides is that the degradation and release kinetics can be substantially altered without significantly changing the physical properties of the polymer relative to the corresponding linear polymer. By manipulating both the diacid and the branching agent, a wide variety of biodegradable controlled delivery devices for diverse applications can be prepared.
摘要翻译：具有优异性能的支链聚酐，用于通过二羧酸单体和支化剂的聚合制备的物质的受控输送中。支化剂是诸如1,3,5-苯三甲酸（“BTC”）或低聚脂肪酸三聚体的多元羧酸单体。或者，支化剂是聚羧酸聚合物，例如聚（丙烯酸）（“PAA”）。这些支化聚合物具有比类似条件下制备的线性聚合物显着更高的分子量和更低的比粘度。支链聚酐的主要优点在于，相对于相应的线性聚合物，降解和释放动力学可以基本上改变而不显着改变聚合物的物理性质。通过操纵二酸和支化剂，可以制备用于各种应用的各种可生物降解的受控递送装置。

7. 发明授权

US5919835A Biodegradable polymer blends for drug delivery 失效
标题翻译：用于药物递送的可生物降解聚合物共混物
公开(公告)号：US5919835A
公开(公告)日：1999-07-06
申请号：US995952
申请日：1992-12-23
申请人： Abraham J. Domb , Manoj Maniar , Andrew S. T. Haffer
发明人： Abraham J. Domb , Manoj Maniar , Andrew S. T. Haffer
IPC分类号： A61K47/34 , A61K9/20 , C08L67/00 , C08L67/02 , C08L67/04 , C08L73/00 , C08L73/02 , C08L101/16 , A61F2/02
CPC分类号： C08L67/04 , A61K9/2031 , A61K9/204 , C08L67/02 , C08L73/02
摘要： Blends of polymers having properties distinct from the individual polymer components and that are suitable for use as carriers of pharmaceutically active agents, are prepared from two or more polyanhydrides, polyesters or mixtures of polyanhydrides and polyesters. The blends have different properties than the polymers used to prepare the blends, providing a means for altering the characteristics of a polymeric matrix without altering the chemical structure of the component polymers. Blends of various polyanhydrides, polyesters, and polyanhydrides and polyesters, containing pharmaceutically active agents, are prepared using solvent mixing or melt mixing procedures. It has been discovered that the rate of release of the agent from the blends is different than the rate of release from the individual polyanhydride and polyester polymer components, being a function of the blend composition
摘要翻译：由两种或更多种聚酐，聚酯或聚酐和聚酯的混合物制备具有不同于各个聚合物组分并且适合用作药物活性剂载体的性质的聚合物的共混物。共混物具有与用于制备共混物的聚合物不同的性质，提供了改变聚合物基质的特性而不改变组分聚合物的化学结构的方法。使用溶剂混合或熔融混合程序制备含有药物活性剂的各种聚酐，聚酯和聚酐和聚酯的共混物。已经发现，试剂从共混物中的释放速率不同于单独的聚酐和聚酯聚合物组分的释放速率，作为共混组合物的函数

8. 发明授权

US5512055A Anti-infective and anti-inflammatory releasing systems for medical devices 失效
标题翻译：用于医疗器械的抗感染和抗炎释放系统
公开(公告)号：US5512055A
公开(公告)日：1996-04-30
申请号：US316067
申请日：1994-09-30
申请人： Abraham J. Domb , Alain Shikani , Andrew S. T. Haffer , Manoj Maniar
发明人： Abraham J. Domb , Alain Shikani , Andrew S. T. Haffer , Manoj Maniar
IPC分类号： A61K9/00 , A61L27/54 , A61L29/16 , A61M16/04 , A61M25/16 , A61M5/32
CPC分类号： A61K9/0024 , A61L27/54 , A61L29/16 , A61L2300/106 , A61L2300/402 , A61L2300/404 , A61L2300/406 , A61L2300/408 , A61L2300/41 , A61L2300/42 , A61L2300/602 , A61L2300/606 , A61M16/04 , A61M16/0465
摘要： Devices are provided having a polymer coating incorporating compounds inhibiting inflammation and infection, along with subsequent tissue growth onto and around the device. Preferred embodiments include catheters, tubes, and implants that abut tissue following implantation into the body, especially for use in the naso-oto-pharyngeal areas of the body, where localized chronic infection/inflammation of the tissues surrounding the implant may be decreased by sustained release of antibiotics, antifungals, antivirals, anti-inflammatories, and other compounds, such as anticoagulants and anesthetics. Preferred polymeric coatings are thin, well adhered to the underlying device, and formed of a biocompatible, non-bioerodible polymer such as polyurethane or ethylene vinyl acetate. The drug is incorporated either by solvent casting or by absorption into the solidified polymer. The drug incorporated polymer can also be used to form devices, or portions of devices, for implantation.
摘要翻译：提供了具有聚合物涂层的装置，其包含抑制炎症和感染的化合物，以及随后的组织生长到装置上和周围。优选的实施方案包括导管，管和植入物，其在植入体内邻接组织，特别是用于身体的鼻 - 咽部区域，其中局部的慢性感染/植入物周围的组织的炎症可以通过持续的释放抗生素，抗真菌剂，抗病毒药，抗炎剂等化合物，如抗凝剂和麻醉剂。优选的聚合物涂层是薄的，良好地粘附到下面的装置上，并且由生物相容的非生物可侵蚀的聚合物如聚氨酯或乙烯 - 乙酸乙烯酯形成。药物通过溶剂浇铸或通过吸收掺入固化的聚合物中。药物掺入的聚合物也可用于形成用于植入的装置或装置的部分。

9. 发明授权

US08476320B2 Formulations for parenteral administration of amino-substituted (E)-2, 6-dialkoxystyryl 4-substituted benzylsulfones 有权
标题翻译：用于肠胃外给药氨基取代的（E）-2,6-二烷氧基苯甲酰基4-取代的苄基砜的制剂
公开(公告)号：US08476320B2
公开(公告)日：2013-07-02
申请号：US12523305
申请日：2008-01-16
申请人： Manoj Maniar , Janice W Bell
发明人： Stanley C. Bell , Manoj Maniar
IPC分类号： A61K31/10
CPC分类号： A61K31/496 , A61K9/0019 , A61K47/02 , A61K47/10
摘要： Formulations are provided for parenteral administration of (amino substituted (e)-2,6-dialkoxystyryl 4-substituted benzylsulfones and the sodium and potassium salts thereof for the prevention and/or treatment of conditions mediated by abnormal cell proliferation.Composition for parenteral administration are provided which comprise an effective amount of a compound of formula I or a compound of formula IIa and at least about 50% by weight of at least one water soluble polymer selected from the group consisting essentially of polyethylene glycol (PEG), poly-oxyethylene, poly-oxyethylene-poly-oxypropylene copolymers, polyglycerol, polyvinylalcohol, polyvinylpyrrolidone (PVP), polyvinylpyridine N-oxide, copolymer of vinylpyridine N-oxide and vinylpyridine.
摘要翻译：（氨基取代的（e）-2,6-二烷氧基苯乙烯基4-取代苄基砜及其钠和钾盐的肠胃外给药的制剂用于预防和/或治疗异常细胞增殖介导的病症。肠胃外给药的组合物为其包含有效量的式I化合物或式IIa化合物和至少约50重量％的至少一种选自基本上由聚乙二醇（PEG），聚氧乙烯，聚氧乙烯 - 聚氧化丙烯共聚物，聚甘油，聚乙烯醇，聚乙烯吡咯烷酮（PVP），聚乙烯基吡啶N-氧化物，乙烯基吡啶N-氧化物和乙烯基吡啶的共聚物。

10. 发明申请

US20060018951A1 pH-responsive film for intravaginal delivery of a beneficial agent 审中-公开
标题翻译：用于阴道内递送有益剂的pH响应膜
公开(公告)号：US20060018951A1
公开(公告)日：2006-01-26
申请号：US10912814
申请日：2004-08-06
申请人： Manoj Maniar , Shoreh Parandoosh
发明人： Manoj Maniar , Shoreh Parandoosh
IPC分类号： A61K9/14 , A61K9/70
CPC分类号： A61K9/0036 , A61K9/7007
摘要： The present invention provides a delivery system for the intravaginal administration of prophylactic and therapeutic agents. In one embodiment, the invention provides a pH-responsive, biocompatible film for intravaginal administration of a beneficial agent, comprising a biocompatible, hydrophilic polymer that is positively charged at a first pH and in electronically neutral form at a higher pH; an effective amount of a beneficial agent; and, optionally, at least one film-forming binder. The pH responsive film may also include other additives such as plasticizers, sustained release polymers, antioxidants, and antimicrobial agents. In another embodiment, the pH-responsive film of the present invention comprises a laminated composite of (a) a bioadhesive layer that serves to affix the film to a mucosal surface within the vagina and, laminated thereto, (b) at least one reservoir layer comprising at least one beneficial agent and a biocompatible hydrophilic polymer. The pH responsive films of the present invention can be used for contraception, treatment and/or prevention of viral infections, treatment of vaginal infections, relief of vaginal itch, vaginal cleansing, and enhancement of vaginal lubrication.
摘要翻译：本发明提供了阴道内施用预防和治疗剂的递送系统。在一个实施方案中，本发明提供用于阴道内施用有益剂的pH响应性生物相容性膜，其包含在较高pH下以第一pH和电子中性形式带正电的生物相容性亲水性聚合物; 有效量的有益剂; 和任选的至少一种成膜粘合剂。 pH响应膜还可以包括其它添加剂，例如增塑剂，缓释聚合物，抗氧化剂和抗微生物剂。在另一个实施方案中，本发明的pH响应薄膜包括层压复合物，其包含（a）用于将膜粘贴到阴道内的粘膜表面并且层压在其上的生物粘附层，（b）至少一个储层包含至少一种有益剂和生物相容的亲水性聚合物。本发明的pH响应薄膜可用于避孕，治疗和/或预防病毒感染，治疗阴道感染，缓解阴道瘙痒，阴道清洁和增强阴道润滑。

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