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    Method for producing protein microspheres
    33.
    发明授权
    Method for producing protein microspheres 失效
    蛋白质微球的制备方法

    公开(公告)号：US5271961A

    公开(公告)日：1993-12-21

    申请号：US902505

    申请日：1992-06-23

    Applicant: Edith Mathiowitz ,  Howard Bernstein ,  Eric Morrel ,  Kirsten Schwaller

    Inventor： Edith Mathiowitz ,  Howard Bernstein ,  Eric Morrel ,  Kirsten Schwaller

    IPC: A61K9/16 ,  A61K9/50 ,  B01J13/12 ,  A61K9/52 ,  A61K9/54

    CPC classification number: A61K9/1658 ,  A61K9/1647 ,  A61K9/5052

    Abstract: Protein microspheres are formed by phase separation in a non-solvent followed by solvent removal. The preferred proteins are prolamines, such as zein, that are hydrophobic, biodegradable, and can be modified proteolytically or chemically to endow them with desirable properties, such as a selected degradation rate. Composite microspheres can be prepared from a mixture of proteins or a mixture of proteins with one or more bioerodible polymeric materials, such as polylactides. Protein coatings can also be made. Compounds are readily incorporated into the microspheres for subsequent release. The process does not involve agents which degrade most labile proteins. The microspheres have a range of sizes and multiple applications, including drug delivery and delayed release of pesticides, fertilizers, and agents for environmental cleanup. Selection of microsphere size in the range of less than five microns and mode of administration can be used to target the microparticles to the cells of the reticuloendothelial system, or to the mucosal membranes of the mouth or gastrointestinal tract. Larger implants formed from the microspheres can also be utilized, especially for agricultural applications.

    Abstract translation: 通过在非溶剂中相分离形成蛋白质微球，随后除去溶剂。 优选的蛋白质是疏水性的，可生物降解的，可以被蛋白水解或化学修饰以赋予它们所需性质（例如选择的降解速率）的醇溶蛋白，例如玉米醇溶蛋白。 复合微球可以由蛋白质或蛋白质与一种或多种生物可腐蚀的聚合物材料如聚交酯的混合物的混合物制备。 蛋白质涂层也可以制成。 化合物容易地并入微球体中用于随后的释放。 该过程不涉及降解大多数不稳定蛋白质的试剂。 微球具有一定范围的尺寸和多种应用，包括药物输送和农药，肥料和环境清洁剂的延迟释放。 可以使用在小于5微米范围内的微球大小的选择和给药方式将微粒靶向网状内皮系统的细胞，或将其靶向口腔或胃肠道的粘膜。 也可以利用由微球形成的更大的植入物，特别是在农业应用中。

    Method of making hydroxamic acid polymers from primary amide polymers
    34.
    发明授权
    Method of making hydroxamic acid polymers from primary amide polymers 失效
    由一级酰胺聚合物制备异羟肟酸聚合物的方法

    公开(公告)号：US5128420A

    公开(公告)日：1992-07-07

    申请号：US283594

    申请日：1988-12-13

    Applicant: Abraham J. Domb ,  Robert S. Langer ,  Ernest G. Cravalho ,  Gershon Golomb ,  Edith Mathiowitz ,  Cato T. Laurencin

    Inventor： Abraham J. Domb ,  Robert S. Langer ,  Ernest G. Cravalho ,  Gershon Golomb ,  Edith Mathiowitz ,  Cato T. Laurencin

    IPC: C08F8/32

    CPC classification number: C08F8/32 ,  C08F2800/10 ,  C08F2810/20

    Abstract: A method for preparing hydroxamic acid polymers from primary amide polymers wherein polyvinyl monomers such as polyacrylamide are reacted with hydroxyl amine in aqueous solution at room temperature. The low reaction temperature is crucial to producing a high yield (70%) of polymer with hydroxamic acid groups and having a low carboxylic acid content (less than 15%, preferably less than 3%). The polymers display high metal affinity over a broad pH range.The polymers are particularly useful for biomedical applications due to the low carboxylic acid content and for the removal and purification of metals due to the high binding constants and rapid reaction rates.

    Abstract translation: 由聚酰胺聚合物制备异羟肟酸聚合物的方法，其中聚乙烯基单体例如聚丙烯酰胺在室温下与羟胺在水溶液中反应。 低反应温度对于用异羟肟酸基团产生高产率（70％）的聚合物和低羧酸含量（小于15％，优选小于3％）是至关重要的。 聚合物在宽pH范围内显示出高的金属亲和力。 由于高的结合常数和快速的反应速率，由于羧酸含量低以及金属的去除和纯化，聚合物特别适用于生物医学应用。

    One step preparation of poly(amide-anhydride)
    35.
    发明授权
    One step preparation of poly(amide-anhydride) 失效
    聚（酰胺 - 酐）一步法制备

    公开(公告)号：US4933431A

    公开(公告)日：1990-06-12

    申请号：US269448

    申请日：1988-11-09

    Applicant: Abraham J. Domb ,  Robert S. Langer ,  Eyal Ron ,  Steven Giannos ,  Rohit Kothari ,  Edith Mathiowitz

    Inventor： Abraham J. Domb ,  Robert S. Langer ,  Eyal Ron ,  Steven Giannos ,  Rohit Kothari ,  Edith Mathiowitz

    IPC: C08G67/04 ,  C08G69/08 ,  C08G69/10

    CPC classification number: C08G69/08 ,  C08G67/04 ,  C08G69/10

    Abstract: A method for synthetizing polyanhydrides in solution using coupling agents and a removable acid acceptor to effect a one-step polymerization of dicarboxylic acids. As used in the method, these coupling agents include phosgene, diphosgene, and acid chlorides. Insoluble acid acceptors include insoluble polyamines and crosslinked polyamines such as polyethyleneimine and polyvinylpyridine and inorganic bases such as K.sub.2 CO.sub.3, Na.sub.2 CO.sub.3, NaHCO.sub.3, and CaCO.sub.3. The only byproduct formed is a removable hydrochloric acid-acid acceptor.Examples are provided of the polymerization of highly pure polyanhydrides using phosgene, diphosgene or an acid chloride as the coupling agent, in combination with either an insoluble acid acceptor or a soluble acid acceptor in a solvent wherein the polymerizaiton byproduct or polymer is insoluble.A particularly important application of these polyanhydrides is in the formation of drug delivery devices containing bioactive compounds. The method is also useful in the polymerization of dicarboxylic acids including heat liable dipeptides of glutamic or aspartic acid.

    Abstract translation: 使用偶联剂和可除去的酸受体在溶液中合成聚酐以实现二羧​​酸的一步聚合的方法。 如该方法所用，这些偶联剂包括光气，双光气和酰氯。 不溶性酸受体包括不溶性多胺和交联聚胺如聚乙烯亚胺和聚乙烯吡啶以及无机碱如K 2 CO 3，Na 2 CO 3，NaHCO 3和CaCO 3。 形成的唯一副产物是可除去的盐酸酸受体。 提供了使用光气，双光气或酰氯作为偶联剂的高纯度聚酐与在溶剂中的不溶性酸受体或可溶性酸受体组合的聚合反应，其中聚合物副产物或聚合物是不溶的。 这些多酸酐的特别重要的应用是形成含有生物活性化合物的药物递送装置。 该方法也可用于二羧酸的聚合，包括谷氨酸或天冬氨酸的热应答二肽。

    COMPOSITIONS AND METHODS FOR LOOP DIURETICS WITH CONSISTENT BIOAVAILABILITY
    36.
    发明申请
    COMPOSITIONS AND METHODS FOR LOOP DIURETICS WITH CONSISTENT BIOAVAILABILITY 有权
    具有一致性生物利用度的环路滤膜的组合物和方法

    公开(公告)号：US20120053156A1

    公开(公告)日：2012-03-01

    申请号：US13217764

    申请日：2011-08-25

    Applicant: Edith Mathiowitz ,  Bryan Laulicht

    Inventor： Edith Mathiowitz ,  Bryan Laulicht

    IPC: A61K31/635 ,  A61K47/32 ,  A61P3/00 ,  A61P5/00 ,  A61P13/12 ,  A61P9/00 ,  C07D307/54 ,  A61P1/16

    CPC classification number: A61K31/635 ,  A61K9/146 ,  A61K9/19 ,  C07D213/74 ,  C07D277/42 ,  C07D295/155 ,  C07D307/14 ,  C07D409/12

    Abstract: Diuretic bioactivity profiles of phase inversion micronized furosemide and furosemide co-precipitated with Eudragit L100, and mixtures of those formulations with stock furosemide, reduced or eliminated the rapid spike in diuresis associated with immediate release formulations and maintained cumulative urine output. Of the formulations tested, each of a mixture of micronized furosemide with stock furosemide, and Eudragit L100 polymer with stock furosemide demonstrated optimal diuretic bioactivity profiles in subjects.

    Abstract translation: 与Eudragit L100共沉淀的相转化微粉碎呋塞米和呋塞米的利尿生物活性曲线，以及那些制剂与储备呋塞米的混合物，减少或消除了与立即释放制剂相关的利尿的快速穗状态，并维持累积的尿量。 在所测试的制剂中，微粉化呋塞米与储备呋塞米的混合物以及具有储备呋塞米的Eudragit L100聚合物在受试者中表现出最佳的利尿生物活性曲线。

    NANOPARTICLE COMPOSITIONS AND METHODS FOR IMPROVED ORAL DELIVERY OF ACTIVE AGENTS
    37.
    发明申请
    NANOPARTICLE COMPOSITIONS AND METHODS FOR IMPROVED ORAL DELIVERY OF ACTIVE AGENTS 有权
    纳米材料组合物和改进的活性剂的口服递送方法

    公开(公告)号：US20120009267A1

    公开(公告)日：2012-01-12

    申请号：US13179205

    申请日：2011-07-08

    Applicant: Daniel Cho ,  Joshua Reineke ,  Edith Mathiowitz ,  Bryan Laulicht

    Inventor： Daniel Cho ,  Joshua Reineke ,  Edith Mathiowitz ,  Bryan Laulicht

    IPC: A61K9/50 ,  A61K38/02 ,  A61K48/00 ,  B29B9/12 ,  A61K47/34 ,  A61K47/32 ,  A61K47/36 ,  A61K38/22 ,  A61K31/713

    CPC classification number: A61K31/713 ,  A61K9/5026 ,  A61K9/5031 ,  A61K9/5073 ,  A61K9/5089 ,  A61K9/5138 ,  A61K9/5146 ,  A61K9/5192 ,  A61K38/00

    Abstract: Nanoparticles, compositions, and methods for the improved uptake of active agents are disclosed herein. The compositions contain a monodisperse population of nanoparticles, preferably including an active agent, where the nanoparticles are formed from a polymeric material possessing specified bioadhesion characteristics. Following enteral administration, preferably oral administration, the nanoparticles exhibit total intestinal uptakes of greater than 20%, preferably greater than 45%, more preferably greater than 65%. When compared to uptake of the same composition in the absence of the bioadhesive polymeric material, the nanoparticles have significantly increased uptake with intestinal uptake of the increased by more than 100%, preferably even greater than 500%. Further disclosed herein is a method of producing multi-walled nanoparticles, as well as methods of using thereof. Multi-walled particles prepared using the method disclosed herein are useful for controlling the release of active agents.

    Abstract translation: 本文公开了用于改善摄取活性剂的纳米颗粒，组合物和方法。 组合物含有单分散的纳米颗粒群体，优选包括活性剂，其中纳米颗粒由具有特定生物粘附特性的聚合物形成。 在肠内施用之后，优选口服给药，纳米颗粒显示出大于20％，优选大于45％，更优选大于65％的总肠吸收。 当与没有生物粘附性聚合物材料的相同组合物的吸收相比时，纳米颗粒具有显着增加的摄取，肠吸收增加超过100％，优选甚至大于500％。 本文进一步公开的是制备多壁纳米颗粒的方法及其使用方法。 使用本文公开的方法制备的多壁颗粒可用于控制活性剂的释放。

    PARTICLES WITH HIGH UNIFORM LOADING OF NANOPARTICLES AND METHODS OF PREPARATION THEREOF
    39.
    发明申请
    PARTICLES WITH HIGH UNIFORM LOADING OF NANOPARTICLES AND METHODS OF PREPARATION THEREOF 审中-公开
    具有高均匀加载纳米颗粒的颗粒及其制备方法

    公开(公告)号：US20090311295A1

    公开(公告)日：2009-12-17

    申请号：US12300304

    申请日：2007-05-14

    Applicant: Edith Mathiowitz ,  Ljiljana Kundakovic ,  A. Peter Morello ,  Michael W. Harrison ,  Joshua James Reineke

    Inventor： Edith Mathiowitz ,  Ljiljana Kundakovic ,  A. Peter Morello ,  Michael W. Harrison ,  Joshua James Reineke

    IPC: A61K8/11 ,  C08L33/12 ,  A61K9/14 ,  A61K47/32 ,  A61P43/00 ,  A61Q90/00 ,  B01J13/04 ,  B01J13/00

    CPC classification number: A61K9/1694 ,  A61K8/11 ,  A61K49/0021 ,  A61K49/0034 ,  A61K49/0036 ,  A61K49/0091 ,  A61K49/0093 ,  A61K2800/412 ,  A61Q1/02 ,  A61Q19/00 ,  C09C1/00

    Abstract: Methods to produce polymeric microparticles containing nanoparticles such, as pigments, dyes and other chromophores for cosmetic use, plastic surgery therapeutic use, and tattoos have been developed. The microparticles contain within the polymer a very uniform dispersion of dye particles. The methods by which the particles are made ensure a homogeneous mixture and high loading. The microparticles are made using air, one of a number of known methods such as phase inversion, solvent evaporation, and melt processing. The improvement is in the use of a method that makes, a stable dispersion of the nanoparticles in the liquid polymer before formation of the microparticles. This is achieved through selection of appropriate solvent, optionally including surfactant, and then subjecting the dispersion to mechanical processing that stabilizes the dispersion within the polymer solvent, so that the nanoparticles remain suspended for at least thirty minutes, in some cases two hours to 48 hours, sometimes up to three months. The mechanical processing can be sonication and/or production of shear forces, for examples, resulting from use of an open blade or rotor stator mixer or milling with a concentric shaft, at a speed such as between 5000 and 25,000 RPM.

    Abstract translation: 已经开发了制备含有纳米颗粒的聚合物微粒，例如颜料，染料和用于化妆品用途的其它发色团，整容手术治疗用途和纹身的方法。 微粒在聚合物内含有非常均匀的染料颗粒分散体。 制备颗粒的方法可确保均匀的混合物和高负载量。 微粒使用空气制成，已知的方法之一是相转化，溶剂蒸发和熔融加工。 改进之处在于使用在形成微粒之前使纳米颗粒稳定地分散在液体聚合物中的方法。 这通过选择合适的溶剂，任选地包括表面活性剂，然后使分散体经受使聚合物溶剂中的分散体稳定的机械加工来实现，使得纳米颗粒保持悬浮至少30分钟，在一些情况下为2小时至48小时 有时长达三个月。 例如，通过使用开式叶片或转子定子混合器或以同心轴铣削，以5000至25,000RPM之间的速度，机械加工可以是超声处理和/或产生剪切力。

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