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公开(公告)号：US5853698A
公开(公告)日：1998-12-29
申请号：US745676
申请日：1996-11-08
CPC分类号： A61B8/481 , A61K49/223
摘要： It has been discovered that the incorporation of fluorinated gases, especially a perfluorocarbon such as octafluoropropane, into synthetic polymeric microparticles, significantly enhances echogenicity as compared with microparticles having air incorporated therein. The microencapsulated perfluorocarbon is manufactured with a diameter suitable for the targeted tissue to be imaged, for example, for intravenous or oral administration. In one embodiment, bioadhesive microparticles are formed for enhanced imaging of mucosal surfaces.
摘要翻译： 已经发现，与合并有空气的微粒相比，将氟化气体，特别是全氟化碳如八氟丙烷掺入到合成的聚合物微粒中显着增强回波反应性。 制造微胶囊化全氟化碳，其直径适用于待成像的目标组织，例如用于静脉内或口服给药。 在一个实施方案中，形成生物粘附微粒用于增强粘膜表面的成像。
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公开(公告)号：US6132699A
公开(公告)日：2000-10-17
申请号：US158295
申请日：1998-09-22
CPC分类号： A61B8/481 , A61K49/223
摘要： It has been discovered that the incorporation of fluorinated gases, especially a perfluorocarbon such as octafluoropropane, into synthetic polymeric microparticles, significantly enhances echogenicity as compared with microparticles having air incorporated therein. The microencapsulated perfluorocarbon is manufactured with a diameter suitable for the targeted tissue to be imaged, for example, for intravenous or oral administration. In one embodiment, bioadhesive microparticles are formed for enhanced imaging of mucosal surfaces.
摘要翻译： 已经发现，与合并有空气的微粒相比，将氟化气体，特别是全氟化碳如八氟丙烷掺入到合成的聚合物微粒中显着增强回波反应性。 制造微胶囊化全氟化碳，其直径适用于待成像的目标组织，例如用于静脉内或口服给药。 在一个实施方案中，形成生物粘附微粒用于增强粘膜表面的成像。
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3.发明授权
公开(公告)号：US6045777A
公开(公告)日：2000-04-04
申请号：US885933
申请日：1997-06-30
CPC分类号： A61B8/481 , A61K49/223
摘要： It has been discovered microparticles formed from natural or synthetic polymer with thicker walls have significantly enhanced echogenicity as compared with microparticles having thinner walls. The effect of wall thickness has been determined experimentally as well as inserted into a formula for use in predicting the optimum conditions. In the preferred embodiment, the polymers are synthetic biodegradable polymers and the wall thickness is between about 100 and 660 nm, although wall thicknesses from about 20 nm to in excess of 500 nm can be used. The microparticles are manufactured with a diameter suitable for the targeted tissue to be imaged, for example, with a diameter of between 0.5 and 8 microns for intravascular administration, and a diameter of between 0.5 and 5 mm for oral administration for imaging of the gastrointestinal tract or other lumens. Preferred polymers are polyhydroxy acids such as polylactic acid-co-glycolic acid, polylactide or polyglycolide, most preferably conjugated to polyethylene glycol or other materials inhibiting uptake by the reticuloendothelial system (RES). The microspheres may be used in a variety of ultrasound imaging applications including cardiology applications, blood perfusion applications as well as for organ and peripheral vein imaging.
摘要翻译： 与具有较薄壁的微粒相比，发现由具有较厚壁的天然或合成聚合物形成的微粒具有显着增强的回声性。 实验确定了壁厚的影响，并将其插入到用于预测最佳条件的公式中。 在优选的实施方案中，聚合物是合成的可生物降解聚合物，并且壁厚度在约100至660nm之间，尽管可以使用约20nm至超过500nm的壁厚。 制造具有适于待成像的目标组织的直径的微粒，例如，用于血管内施用的直径为0.5至8微米，并且用于口服给药以用于胃肠道成像的直径为0.5至5毫米 或其他流明。 优选的聚合物是聚羟酸，例如聚乳酸 - 共 - 乙醇酸，聚丙交酯或聚乙交酯，最优选与聚乙二醇缀合或抑制网状内皮系统（RES）吸收的其它物质。 微球可以用于各种超声成像应用，包括心脏应用，血液灌注应用以及器官和外周静脉成像。
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公开(公告)号：US5837221A
公开(公告)日：1998-11-17
申请号：US681710
申请日：1996-07-29
CPC分类号： A61K49/0002 , A61K49/0004 , A61K49/223
摘要： It has been discovered that the incorporation of gases, especially fluorinated gases such as perfluorocarbons, into microparticles formed from the combination of a natural or synthetic polymer and lipid have significantly enhanced echogenicity as compared with microparticles not including the lipid. Compounds other than lipids which are hydrophobic and limit the penetration and/or uptake of water into the microparticles can also be incorporated into the microparticles to enhance echogenicity. In the preferred embodiment, the polymers are synthetic biodegradable polymers. The microparticles are manufactured with a diameter suitable for the targeted tissue to be imaged, for example, with a diameter of between 0.5 and 8 microns for intravascular administration, and a diameter of between 0.5 and 5 mm for oral administration for imaging of the gastrointestinal tract or other lumens. Preferred polymers are polyhydroxy acids such as polylactic acid-co-glycolic acid, most preferably conjugated to polyethylene glycol or other materials inhibiting uptake by the reticuloendothelial system (RES). The most preferred lipids are phospholipids, preferably dipalmitoylphosphatidylcholine (DPPC), distearoylphosphatidylcholine (DSPC), diarachidoylphosphatidylcholine (DAPC), dibehenoylphosphatidylcholine (DBPC), ditricosanoylphosphatidylcholine, dilignoceroylphatidylcholine (DLPC), incorporated at a ratio of between 0.01-30 (w lipid/w polymer), most preferably between 0.1-10 (w lipid/w polymer). Microparticles for imaging using other detectable agents can be similarly manufactured.
摘要翻译： 已经发现，与不包括脂质的微粒相比，将天然或合成聚合物和脂质的组合形成的气体，特别是氟化气体（例如全氟化碳）并入微型颗粒中显着增强了回声反应性。 疏水性的脂质以外的化合物也限制在微粒中的渗透和/或吸收也可以并入微粒中以增强回声性。 在优选的实施方案中，聚合物是合成的可生物降解的聚合物。 制造具有适于待成像的目标组织的直径的微粒，例如直径为0.5至8微米，用于血管内施用，并且用于口服给药的直径在0.5至5mm之间以用于胃肠道成像 或其他流明。 优选的聚合物是聚羟基酸，例如聚乳酸 - 共 - 乙醇酸，最优选与聚乙二醇缀合或抑制网状内皮系统（RES）摄取的其它物质。 最优选的脂质是磷脂，优选二棕榈酰磷脂酰胆碱（DPPC），二硬脂酰磷脂酰胆碱（DSPC），二酰氨基磷脂酰胆碱（DAPC），二苯甲酰磷脂酰胆碱（DBPC），二硫代酰基磷脂酰胆碱，二烯酰基脂肪酰胆碱（DLPC），其比例为0.01-30（w脂质/ ），最优选0.1-10（w脂/ w聚合物）。 可以类似地制造用于使用其它可检测试剂成像的微粒。
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公开(公告)号：US5611344A
公开(公告)日：1997-03-18
申请号：US611248
申请日：1996-03-05
CPC分类号： A61B8/481 , A61K49/223
摘要： It has been discovered that the incorporation of fluorinated gases, especially a perfluorocarbon such as octafluoropropane, into synthetic polymeric microparticles, significantly enhances echogenicity as compared with microparticles having air incorporated therein. The microencapsulated perfluorocarbon is manufactured with a diameter suitable for the targeted tissue to be imaged, for example, for intravenous or oral administration. In one embodiment, bioadhesive microparticles are formed for enhanced imaging of mucosal surfaces.
摘要翻译： 已经发现，与合并有空气的微粒相比，将氟化气体，特别是全氟化碳如八氟丙烷掺入到合成的聚合物微粒中显着增强回波反应性。 制造微胶囊化全氟化碳，其直径适用于待成像的目标组织，例如用于静脉内或口服给药。 在一个实施方案中，形成生物粘附微粒用于增强粘膜表面的成像。
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6.发明申请Formulations of Tetrahydropyridine Antiplatelet Agents for Parenteral or Oral Administration 审中-公开用于肠胃外或口服给药的四氢吡啶抗血小板药物的制剂公开(公告)号：US20100062066A1
公开(公告)日：2010-03-11
申请号：US12514763
申请日：2007-11-08
申请人： Howard Bernstein , Olinda Carneiro , Rajeev A. Jain , Namrata Pandit , Shveta Rane , Julie Ann Straub
发明人： Howard Bernstein , Olinda Carneiro , Rajeev A. Jain , Namrata Pandit , Shveta Rane , Julie Ann Straub
IPC分类号： A61K9/113 , A61K31/4365
CPC分类号： A61K31/4365 , A61K9/0019 , A61K9/1075 , A61K9/1617 , A61K9/19
摘要： A pharmaceutical composition for the oral or parenteral administration of a compound of Formula (I) comprising an oil in water emulsion, wherein the oil phase comprises the free base of or a pharmaceutically acceptable salt thereof of a compound of Formula (I), and one or more surfactants which are soluble in the oil phase and/or the aqueous phase. The emulsion optionally contains one or more excipients that are soluble in the oil phase and/or the aqueous phase, such as pH modifying agents such as buffers, osmolality/tonicity modifying agents, emulsifying agents, water-soluble polymers, and preservatives. The compound of Formula (I) can be formulated as a solid material and stored until needed. Kits for forming the emulsion are provided. Prior to administration, the solid material can be reconstituted in an aqueous medium to form the emulsion.
摘要翻译： 一种用于口服或肠胃外给药包含水包油乳液的式（I）化合物的药物组合物，其中所述油相包含式（I）化合物的游离碱或其药学上可接受的盐，和一种 或更多的可溶于油相和/或水相的表面活性剂。 乳液任选地含有一种或多种可溶于油相和/或水相的赋形剂，如pH调节剂如缓冲液，重量摩尔渗透压浓度/张力调节剂，乳化剂，水溶性聚合物和防腐剂。 式（I）的化合物可以配制成固体物质并储存直至需要。 提供了用于形成乳液的试剂盒。 在施用前，固体材料可以在水性介质中重构以形成乳液。
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公开(公告)号：US5679377A
公开(公告)日：1997-10-21
申请号：US261690
申请日：1994-06-17
CPC分类号： B01J13/12 , A01N25/28 , A61K9/1658 , B01J13/125 , Y10S514/866 , Y10S514/963 , Y10S514/965 , Y10T428/2984 , Y10T428/2985 , Y10T428/2989
摘要： Biodegradable, protein microspheres for in vivo release of a biologically active agent, as well as agricultural and environmental applications. The microspheres can be administered orally, intravenously, or subcutaneously for subsequent release. By selecting particular size ranges and the specific protein used to form the microsphere, it is possible to target the microspheres to a cell types such as macrophages, or to effect localized absorption of the microspheres to regions such as the mucosal membranes of the mouth, gastrointestinal tract, or urogenital areas. Larger forms of the microspheres can also be made using standard techniques of the desirable degradation properties.
摘要翻译： 可生物降解的蛋白质微球，用于体内释放生物活性剂，以及农业和环境应用。 微球可以口服，静脉内或皮下给药以便随后释放。 通过选择特定尺寸范围和用于形成微球的特定蛋白质，可以将微球靶向诸如巨噬细胞的细胞类型，或者将微球局部吸收到诸如口腔粘膜的区域，胃肠道 道或泌尿生殖系。 也可以使用所需降解性能的标准技术制备较大形式的微球。
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公开(公告)号：US5271961A
公开(公告)日：1993-12-21
申请号：US902505
申请日：1992-06-23
CPC分类号： A61K9/1658 , A61K9/1647 , A61K9/5052
摘要： 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.
摘要翻译： 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。
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公开(公告)号：US20110251562A1
公开(公告)日：2011-10-13
申请号：US13166611
申请日：2011-06-22
申请人： Donald E. Chickering, III , Shawn Davis , Ramin Haghgooie , Howard Bernstein , Douglas A. Levinson , Mark Michelman
发明人： Donald E. Chickering, III , Shawn Davis , Ramin Haghgooie , Howard Bernstein , Douglas A. Levinson , Mark Michelman
IPC分类号： A61M5/00
CPC分类号： A61B5/6849 , A61B5/14532 , A61B5/150022 , A61B5/150099 , A61B5/150221 , A61B5/150229 , A61B5/150297 , A61B5/150389 , A61B5/150412 , A61B5/150503 , A61B5/150755 , A61B5/150969 , A61B5/150977 , A61B5/150984 , A61B5/15105 , A61B5/15113 , A61B5/15117 , A61B5/15125 , A61B5/15144 , A61B5/15186 , A61B5/157 , A61B5/685
摘要： The present invention generally relates to systems and methods for delivering and/or withdrawing a substance or substances such as blood or interstitial fluid, from subjects, e.g., from the skin and/or from beneath the skin. In one aspect, the present invention is generally directed to devices and methods for withdrawing or extracting blood from a subject, e.g., from the skin and/or from beneath the skin, using devices containing a fluid transporter (for example, one or more microneedles), and a storage chamber having an internal pressure less than atmospheric pressure prior to receiving blood. In some cases, the device may be self-contained, and in certain instances, the device can be applied to the skin, and activated to withdraw blood from the subject. The device, or a portion thereof, may then be processed to determine the blood and/or an analyte within the blood, alone or with an external apparatus. For example, blood may be withdrawn from the device, and/or the device may contain sensors or agents able to determine the blood and/or an analyte suspected of being contained in the blood. Other aspects of the present invention are directed at other devices for withdrawing blood (or other bodily fluids, e.g., interstitial fluid), kits involving such devices, methods of making such devices, methods of using such devices, and the like.
摘要翻译： 本发明一般涉及用于递送和/或从皮肤和/或皮肤下方的受试者递送和/或从物质或诸如血液或间质液体中取出物质的方法。 一方面，本发明一般涉及使用包含流体转运器（例如，一个或多个微针）的装置从例如皮肤和/或从皮肤下面抽取或提取血液的装置和方法 ）和在接收血液之前具有小于大气压的内部压力的储存室。 在一些情况下，该装置可以是独立的，并且在某些情况下，可以将该装置应用于皮肤并被激活以从受试者中抽出血液。 然后可以处理装置或其一部分，以单独或与外部装置一起确定血液和/或血液内的分析物。 例如，血液可以从装置中取出，和/或该装置可以包含能够确定血液和/或怀疑含在血液中的分析物的传感器或试剂。 本发明的其它方面涉及用于抽出血液（或其他体液，例如间质液）的其他装置，涉及这种装置的试剂盒，制造这种装置的方法，使用这种装置的方法等。
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公开(公告)号：US20110129533A1
公开(公告)日：2011-06-02
申请号：US13022776
申请日：2011-02-08
申请人： Julie Straub , David Altreuter , Howard Bernstein , Donald E. Chickering, III , Sarwat Khattak , Greg Randall
发明人： Julie Straub , David Altreuter , Howard Bernstein , Donald E. Chickering, III , Sarwat Khattak , Greg Randall
IPC分类号： A61K31/337 , A61K9/10 , A61P35/00
CPC分类号： A61K9/1635 , A61K9/1611 , A61K9/1623 , A61K9/1688 , A61K9/1694
摘要： Drugs, especially low aqueous solubility drugs, are provided in a porous matrix form, preferably microparticles, which enhances dissolution of the drug in aqueous media. The drug matrices preferably are made using a process that includes (i) dissolving a drug, preferably a drug having low aqueous solubility, in a volatile solvent to form a drug solution, (ii) combining at least one pore forming agent with the drug solution to form an emulsion, suspension, or second solution and hydrophilic or hydrophobic excipients that stabilize the drug and inhibit crystallization, and (iii) removing the volatile solvent and pore forming agent from the emulsion, suspension, or second solution to yield the porous matrix of drug. Hydrophobic or hydrophilic excipients may be selected to stabilize the drug in crystalline form by inhibiting crystal growth or to stabilize the drug in amorphous form by preventing crystallization. The pore forming agent can be either a volatile liquid that is immiscible with the drug solvent or a volatile solid compound, preferably a volatile salt. In a preferred embodiment, spray drying is used to remove the solvents and the pore forming agent. The resulting porous matrix has a faster rate of dissolution following administration to a patient, as compared to non-porous matrix forms of the drug. In a preferred embodiment, microparticles of the porous drug matrix are reconstituted with an aqueous medium and administered parenterally, or processed using standard techniques into tablets or capsules for oral administration.
摘要翻译： 药物，特别是低含水溶性药物以多孔基质形式提供，优选微粒，其增强药物在水性介质中的溶解。 药物基质优选使用以下方法制备，所述方法包括（i）将挥发性溶剂中的药物（优选为低溶解度的药物）溶解以形成药物溶液，（ii）将至少一种成孔剂与药物溶液 以形成稳定药物并抑制结晶的乳液，悬浮液或第二溶液和亲水或疏水赋形剂，和（iii）从乳液，悬浮液或第二溶液中除去挥发性溶剂和成孔剂以产生多孔基质 药物。 可以选择疏水性或亲水性赋形剂，以通过抑制晶体生长来稳定药物的结晶形式，或者通过防止结晶来稳定药物的无定形形式。 成孔剂可以是与药物溶剂或挥发性固体化合物，优选挥发性盐不混溶的挥发性液体。 在优选的实施方案中，使用喷雾干燥来除去溶剂和成孔剂。 与药物的无孔基质形式相比，得到的多孔基质在给予患者后具有更快的溶解速率。 在优选的实施方案中，多孔药物基质的微粒用水性介质重新配制，并肠胃外给药，或使用标准技术加工成用于口服给药的片剂或胶囊。
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