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131. 发明授权

US4948587A Ultrasound enhancement of transbuccal drug delivery 失效
标题翻译：超声提高了跨颊药物的输送
公开(公告)号：US4948587A
公开(公告)日：1990-08-14
申请号：US233590
申请日：1988-08-18
申请人： Joseph Kost , Robert S. Langer
发明人： Joseph Kost , Robert S. Langer
IPC分类号： A61K9/00 , A61K41/00 , A61M35/00 , A61M37/00
CPC分类号： A61K41/0047 , A61K9/0009 , A61M37/00 , A61M37/0092 , A61M35/00
摘要： A method using ultrasound for enhancing and controlling transbuccal permeation of a molecule, including drugs, antigens, vitamins, inorganic and organic compounds, and various combinations of these substances, through the buccal membranes and into the circulatory system. The frequency and intensity of ultrasonic energy which is applied, and the length of time of exposure are determined according to the location and nature of the buccal membrane and the substance to be infused. Levels of the infused molecules in the blood and urine measured over a period of time are initially used to determine under what conditions optimum transfer occurs. In a variation of the method, whereby ultrasound is applied directly to the compound and site where the compound is to be infused through the buccal membranes, the compound can be placed within a delivery device. In one variation, the ultrasound can control release both by direct interaction with the compound and membrane but also with the delivery device. In another variation, the delivery device helps to modulate release and infusion rate. The compound can also be administered in combination with a chemical agent which alters permeability of the buccal membrane, thereby aiding infusion of the compound into the circulatory system.
摘要翻译：一种使用超声波增强和控制分子（包括药物，抗原，维生素，无机和有机化合物）以及这些物质的各种组合的跨颊渗透通过颊膜进入循环系统的方法。应用超声能量的频率和强度以及暴露时间长短根据颊膜和待注射物质的位置和性质来确定。在一段时间内测量的血液和尿液中输注的分子的水平最初用于确定什么条件下最佳转移发生。在该方法的变型中，由此将超声波直接施加到化合物和通过颊膜输注化合物的部位，化合物可以放置在输送装置内。在一个变化中，超声波可以通过与化合物和膜的直接相互作用来控制释放，而且还可以通过递送装置控制释放。在另一个实施例中，递送装置有助于调节释放和输注速率。化合物还可以与改变颊膜渗透性的化学试剂组合施用，由此帮助化合物输注到循环系统中。

132. 发明授权

US4921757A System for delayed and pulsed release of biologically active substances 失效
标题翻译：延迟和脉冲释放生物活性物质的系统
公开(公告)号：US4921757A
公开(公告)日：1990-05-01
申请号：US92554
申请日：1987-09-03
申请人： Margaret A. Wheatley , Robert S. Langer , Herman N. Eisen
发明人： Margaret A. Wheatley , Robert S. Langer , Herman N. Eisen
IPC分类号： A61K9/127 , A61K9/50 , A61K9/70
CPC分类号： A61K9/703 , A61K9/127 , A61K9/5026 , A61K9/5031 , A61K9/7084 , Y10S436/829 , Y10S514/963 , Y10S514/965 , Y10T428/2984
摘要： A system for controlled release both in vivo and in vitro of entrapped substances, either at a constant rate over a period of time or in discrete pulses, is disclosed. Biologically active substances, such as drugs, hormones, enzymes, genetic material, antigens including viruses, vaccines, or inorganic material such as dyes and nutrients, are entrapped in liposomes which are protected from the biological environment by encapsulation within semi-permeable microcapsules or a permeable polymeric matrix. Release of the entrapped substance into the surrounding environment is governed by the permeability of both the liposome and surrounding matrix to the substance. Permeability of the liposome is engineered by modifying the composition and method for making the liposomes, thereby producing liposomes which are sensitive to a specific stimuli such as temperature, pH, or light; or by including a phospholipase within some or all of the liposomes or the surrounding matrix; or by destabilizing the liposome to break down over a period of time; or by any combination of these features.
摘要翻译：公开了一种在一段时间内或以离散脉冲以恒定速率在体内和体外捕获的物质的系统。诸如药物，激素，酶，遗传物质，包括病毒的抗原，疫苗或诸如染料和营养素的无机材料的生物活性物质被包埋在通过包封在半渗透性微胶囊内的生物环境中保护的脂质体中可渗透聚合物基体。被截留的物质释放到周围环境中由脂质体和周围基质对物质的渗透性决定。通过改变制备脂质体的组合物和方法来改进脂质体的渗透性，从而产生对特定刺激如温度，pH或光敏感的脂质体; 或通过在一些或全部脂质体或周围基质中包含磷脂酶; 或通过不稳定脂质体在一段时间内分解; 或通过这些特征的任意组合。

133. 发明授权

US4863735A Biodegradable polymeric drug delivery system with adjuvant activity 失效
标题翻译：具有佐剂活性的可生物降解聚合物药物递送系统
公开(公告)号：US4863735A
公开(公告)日：1989-09-05
申请号：US914380
申请日：1986-10-02
申请人： Joachim B. Kohn , Robert S. Langer , Steven M. Niemi , James G. Fox
发明人： Joachim B. Kohn , Robert S. Langer , Steven M. Niemi , James G. Fox
IPC分类号： A61K9/22 , A61K39/39 , A61K47/48 , C08G69/10
CPC分类号： C08G69/10 , A61K39/39 , A61K47/48192 , A61K2039/55516 , A61K2039/55555 , A61K2039/55566 , Y10S514/885 , Y10S514/953 , Y10S514/963 , Y10S514/964 , Y10S514/965
摘要： An antigen delivery system utilizing a biodegradable polymer with good mechanical properties in combination with a material stimulating the immune system. The material having adjuvant activity may be polymer degradation products or an adjuvant which is contained within or bound to the polymer. In one embodiment, the polymer is formed from tyrosine dipeptides. Poly(CTTH-iminocarbonate) is a preferred tyrosine dipeptide polymer for constructing implantable delivery systems for antigenic material. The polymer is not an adjuvant in itself but degrades into products which stimulate the immune system. The tyrosine dipeptide can also be used as a conventional adjuvant. The advantages of the system are that a polymer can be used to form a biodegradable integral structure which is useful as both an implantable source of an antigen or other biologically active compound and as a control means for the rate of release of the biologically active compound, wherein the result is sustained, relatively constant delivery of antigen with simultaneous stimulation of the immune response.
摘要翻译：使用具有良好机械性能的生物可降解聚合物与刺激免疫系统的材料组合的抗原递送系统。具有佐剂活性的材料可以是聚合物降解产物或包含在聚合物内或与聚合物结合的佐剂。在一个实施方案中，聚合物由酪氨酸二肽形成。聚（CTTH-亚氨基碳酸酯）是用于构建用于抗原材料的可植入递送系统的优选的酪氨酸二肽聚合物。聚合物本身不是佐剂，但会降解成刺激免疫系统的产物。酪氨酸二肽也可以用作常规佐剂。该系统的优点是可以使用聚合物形成可生物降解的整体结构，其可用作抗原的可植入源或其它生物活性化合物，并且作为生物活性化合物的释放速率的对照手段，其中所述结果是持续的，相对恒定的抗原递送，同时刺激免疫应答。

134. 发明授权

US4863611A Extracorporeal reactors containing immobilized species 失效
标题翻译：含有固定化物种的体外反应堆
公开(公告)号：US4863611A
公开(公告)日：1989-09-05
申请号：US44245
申请日：1987-04-30
申请人： Howard Bernstein , Margaret A. Wheatley , Robert S. Langer
发明人： Howard Bernstein , Margaret A. Wheatley , Robert S. Langer
IPC分类号： A61M1/36 , B01D15/02 , B01J20/32
CPC分类号： B01D15/02 , A61M1/3675 , B01J20/321 , B01J20/3212 , B01J20/3274
摘要： An apparatus for removing material from a biological solution consisting of a reactor chamber having an inlet and an outlet, a bioactive compound immobilized on particular supports within the reactor, means for retaining the particular supports within the reactor, means for recirculating the solution and the supports at a high flow rate within the reactor, and means for agitating or dispersing the recirculating solution-support mixture throughout the reactor chamber so as to prevent packing of the supports while not subjecting the solution to excessive or damaging forces.In the given example, an apparatus for the extracorporeal removal of heparin from blood is provided. Heparinase is immobilized on cross-linked agarose beads recirculated at a high flow rate through the reactor. Agitation of the blood-bead mixture sufficient to prevent packing of the beads within the reactor chamber is provided by means of a series of openings in the recirculation tube dispersing the mixture throughout the chamber.
摘要翻译：用于从由具有入口和出口的反应器室组成的生物溶液中去除材料的装置，固定在反应器内的特定载体上的生物活性化合物，用于将特定载体保持在反应器内的装置，用于将溶液和载体反应器内的高流速，以及用于搅拌或分散循环溶液 - 载体混合物到整个反应器室的装置，以防止支撑物的包装，同时不使溶液经受过度或破坏的力。在给出的实施例中，提供了用于从血液中体外去除肝素的装置。肝素酶固定在通过反应器以高流速再循环的交联琼脂糖珠上。借助于将混合物分散在整个室中的循环管中的一系列开口提供足以防止珠在反应器室内堆积的血珠混合物的搅动。

135. 发明授权

US4795703A Heparin assay 失效
标题翻译：肝素测定
公开(公告)号：US4795703A
公开(公告)日：1989-01-03
申请号：US837517
申请日：1986-03-07
申请人： Moses J. Folkman , Robert L. Hannan , Robert W. Thompson , Robert S. Langer
发明人： Moses J. Folkman , Robert L. Hannan , Robert W. Thompson , Robert S. Langer
IPC分类号： G01N33/66 , C12M1/40 , C12Q1/48 , C12Q1/56 , G01N33/86 , C12Q1/00
CPC分类号： G01N33/86 , C12Q1/56 , G01N2400/40 , Y10S435/81
摘要： The level of heparin in a blood sample is measured by measuring the clotting time of two aliquots of the blood sample, using standard clotting assays, with one of the aliquots being firstly treated with a heparin-degrading compound, such as heparinase. The difference in clotting times is a direct measure of the heparin concentration in the sample.
摘要翻译：通过使用标准凝血测定法测量血液样品的两个等分试样的凝血时间来测量血液样品中的肝素水平，其中一个等分试样首先用肝素降解化合物如肝素酶处理。凝血时间的差异是对样品中肝素浓度的直接测量。

136. 发明授权

US4779806A Ultrasonically modulated polymeric devices for delivering compositions 失效
标题翻译：用于输送组合物的超声波调制聚合物装置
公开(公告)号：US4779806A
公开(公告)日：1988-10-25
申请号：US936000
申请日：1986-11-28
申请人： Robert S. Langer , Joseph Kost
发明人： Robert S. Langer , Joseph Kost
IPC分类号： A61K9/00 , A61K9/20 , A61K41/00 , C08G67/04 , B02C19/18
CPC分类号： A61K9/0009 , A61K41/0047 , A61K9/2027 , A61K9/2031 , C08G67/04
摘要： A composition such as a biologically active substance is delivered upon demand from a polymeric matrix by exposing the polymeric matrix containing the composition to ultrasonic energy.
摘要翻译：通过将含有该组合物的聚合物基体暴露于超声波能量，可以根据需要从聚合物基质递送诸如生物活性物质的组合物。

137. 发明授权

US4666855A Rapid method for determining the isoelectric point for amphoteric molecules 失效
标题翻译：用于确定两性分子等电点的快速方法
公开(公告)号：US4666855A
公开(公告)日：1987-05-19
申请号：US761114
申请日：1985-07-31
申请人： Victor C. Yang , Robert S. Langer
发明人： Victor C. Yang , Robert S. Langer
IPC分类号： G01N33/68 , G01N33/84 , C12Q1/00
CPC分类号： G01N33/68 , G01N33/84
摘要： A rapid method for determining the isoelectric point for an amphoteric molecule of interest is provided which utilizes the pH-dependent binding affinity of the molecule for an ion-exchange material. The empirically derived pI values are within a range of 0.2 pH units or less of the reported values in the literature and may be more precisely determined by employing a narrower pH gradient as part of the procedure. The unique methodology allows isoelectric point determinations to be accomplished within one hour's time, avoids carrier ampholyte interaction or artifact formation, and allows the determination to be performed at any desired temperature with decreased risk of denaturation.
摘要翻译：提供了用于确定感兴趣的两性分子的等电点的快速方法，其利用分子对于离子交换材料的pH依赖性结合亲和力。经验派生的pI值在文献中所报告值的0.2pH单位或更小的范围内，并且可以通过使用较窄的pH梯度作为程序的一部分来更准确地确定。独特的方法允许在1小时内完成等电点测定，避免载体两性电泳相互作用或伪影形成，并允许在任何所需温度下进行测定，降低变性风险。

138. 发明授权

US4638045A Non-peptide polyamino acid bioerodible polymers 失效
标题翻译：非肽多氨基酸生物可腐蚀聚合物
公开(公告)号：US4638045A
公开(公告)日：1987-01-20
申请号：US703153
申请日：1985-02-19
申请人： Joachim Kohn , Robert S. Langer
发明人： Joachim Kohn , Robert S. Langer
IPC分类号： C08G69/10 , C07K1/06
CPC分类号： C08G69/10 , Y10S930/29
摘要： A novel bioerodible polymeric composition is provided comprising a plurality of monomer units of two or three amino acids which are polymerized via hydrolytically labile bonds at their respective side chains rather than at the amino or carboxylic acid terminals by amide bonds. Such polymers are useful for controlled release applications in vivo and in vitro for delivery of a wide variety of biologically and pharmacologically active ligands.
摘要翻译：提供了一种新的生物可腐蚀聚合物组合物，其包含多个通过水解不稳定键在其各自侧链聚合的两个或三个氨基酸的单体单元，而不是在氨基或羧酸末端通过酰胺键聚合。这样的聚合物可用于体内和体外用于递送各种生物和药理学活性配体的控制释放应用。

139. 发明授权

US10035871B2 Urethane-crosslinked biodegradable elastomers 有权
公开(公告)号：US10035871B2
公开(公告)日：2018-07-31
申请号：US13594834
申请日：2012-08-26
申请人： Robert S. Langer , Jeffrey M. Karp , Maria Jose Maio Nunes-Pereira , Ben Ouyang , Lino Da Silva Ferreira , Debanjan Sarkar
发明人： Robert S. Langer , Jeffrey M. Karp , Maria Jose Maio Nunes-Pereira , Ben Ouyang , Lino Da Silva Ferreira , Debanjan Sarkar
IPC分类号： C08G18/42 , C08G18/08
CPC分类号： C08G18/4236 , C08G18/14 , C08G18/4238 , C08G18/4283
摘要： Among other things, the present disclosure provides compositions and methods for an elastomeric cross-linked polyester material. Such an elastomeric cross-linked polyester material, in some embodiments, comprises a plurality of polymeric units of the general formula (-A-B—)p, wherein p is an integer greater than 1; and a plurality of urethane cross-links each of which covalently links two polymeric units to one another, which two linked polymeric unit each had at least one free hydroxyl or amino group prior to formation of the crosslink.

140. 发明授权

US09532956B2 PH sensitive biodegradable polymeric particles for drug delivery 有权
标题翻译： PH敏感的生物可降解聚合物颗粒用于药物递送
公开(公告)号：US09532956B2
公开(公告)日：2017-01-03
申请号：US12762348
申请日：2010-04-18
申请人： Aleksandar Filip Radovic-Moreno , Weiwei Gao , Archana Swami , Gershon Golomb , Robert S. Langer , Omid C. Farokhzad
发明人： Aleksandar Filip Radovic-Moreno , Weiwei Gao , Archana Swami , Gershon Golomb , Robert S. Langer , Omid C. Farokhzad
IPC分类号： A61K47/30 , G01N21/76 , A61K9/51 , A61K48/00 , C12N15/11 , C12N15/115
CPC分类号： A61K9/51 , A61K48/0008 , C12N15/111 , C12N15/115 , C12N2310/11 , C12N2310/14 , C12N2310/16 , C12N2320/32
摘要： The present invention generally relates to polymers and particles, such as nanoparticles. The particles and polymers generally include one or more buffering components. Additionally, the particles and polymers may include two or more components that impart useful properties (functionalities). The particles and polymers, for example, may include a buffering component and a degradable component. As described herein, the particles and polymers may also include a hydrophilic component and/or a cleavable bond component. The particles and polymers described herein have been found to be particularly effective when used for delivery of one or more agents, such as one or more pharmaceutical agents. Other aspects of the invention are directed to methods of using or administering such particles or polymers, kits involving such particles or polymers, and the like. The present invention also relates to particles containing a cleavable bond component and one or more fluorescence resonance energy transfer (FRET) pairs as well as methods of detecting the cleavage of the cleavable bond component of such particles.
摘要翻译：本发明一般涉及聚合物和颗粒，例如纳米颗粒。颗粒和聚合物通常包括一种或多种缓冲组分。此外，颗粒和聚合物可以包括赋予有用性质（功能）的两种或更多种组分。颗粒和聚合物例如可以包括缓冲组分和可降解组分。如本文所述，颗粒和聚合物还可以包括亲水组分和/或可裂解键组分。已经发现本文所述的颗粒和聚合物在用于递送一种或多种试剂如一种或多种药剂时是特别有效的。本发明的其它方面涉及使用或施用此类颗粒或聚合物的方法，涉及这种颗粒或聚合物的试剂等。本发明还涉及含有可切割键组分和一种或多种荧光共振能量转移（FRET）对的颗粒以及检测这些颗粒的可裂解键组分的切割的方法。

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