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1. 发明授权

US08071132B2 Unagglomerated core/shell nanocomposite particles 有权
标题翻译：未凝聚的核/壳纳米复合材料颗粒
公开(公告)号：US08071132B2
公开(公告)日：2011-12-06
申请号：US11142913
申请日：2005-06-01
申请人： James H. Adair , Sarah M. Rouse , Jun Wang , Mark Kester , Christopher Siedlecki , William B. White , Erwin Vogler , Alan Snyder , Carlo G. Pantano , Victor Ruiz-Velasco , Lawrence Sinoway
发明人： James H. Adair , Sarah M. Rouse , Jun Wang , Mark Kester , Christopher Siedlecki , William B. White , Erwin Vogler , Alan Snyder , Carlo G. Pantano , Victor Ruiz-Velasco , Lawrence Sinoway
IPC分类号： A61K9/14
CPC分类号： A61K49/0041 , A61K47/6923 , A61K47/6929 , A61K49/0093 , B01J13/02 , B82Y5/00 , B82Y30/00 , Y10T428/2982 , Y10T428/2984 , Y10T428/2989 , Y10T428/2991 , Y10T428/2995
摘要： The present invention provides a method for the synthesis of unagglomerated, highly dispersed, stable core/shell nanocomposite particles comprised of preparing a reverse micelle microemulsion that contains nanocomposite particles, treating the microemulsion with a silane coupling agent, breaking the microemulsion to form a suspension of the nanocomposite particles by adding an acid/alcohol solution to the microemulsion that maintains the suspension of nanocomposite particles at a pH of between about 6 and 7, and simultaneously washing and dispersing the suspension of nanocomposite particles, preferably with a size exclusion HPLC system modified to ensure unagglomeration of the nanocomposite particles. The primary particle size of the nanocomposite particles can range in diameter from between about 1 to 100 nm, preferably from between about 10 to 50 nm, more preferably about 10 to 20 nm, and most preferably about 20 nm.
摘要翻译：本发明提供了一种用于合成非聚集的，高度分散的，稳定的核/壳纳米复合材料颗粒的方法，其包括制备含有纳米复合颗粒的反胶束微乳液，用硅烷偶联剂处理微乳液，破碎微乳液以形成悬浮液该纳米复合颗粒通过向微乳液中加入酸/醇溶液，将纳米复合材料颗粒的悬浮液保持在约6和7之间的pH，同时洗涤和分散纳米复合颗粒的悬浮液，优选用尺寸排阻HPLC系统修饰为确保纳米复合材料颗粒的团聚。纳米复合材料颗粒的一次粒径可以在约1至100nm之间，优选约10至50nm，更优选约10至20nm，最优选约20nm的范围内。

2. 发明授权

US08771741B2 In vivo photodynamic therapy of cancer via a near infrared agent encapsulated in calcium phosphate nanoparticles 有权
标题翻译：通过封装在磷酸钙纳米粒子中的近红外线的体内光动力治疗癌症
公开(公告)号：US08771741B2
公开(公告)日：2014-07-08
申请号：US12657556
申请日：2010-01-22
申请人： James H. Adair , Mark Kester , Erhan I. Altinoglu , Brian M. Barth , Timothy J. Russin , James M. D. Kaiser , Thomas T. Morgan , Karen L. Eklund
发明人： James H. Adair , Mark Kester , Peter C. Eklund , Erhan I. Altinoglu , Brian M. Barth , Timothy J. Russin , James M. D. Kaiser , Thomas T. Morgan
IPC分类号： A61K9/14
CPC分类号： A61K41/0057 , A61K9/51 , A61K47/6921 , A61K47/6923
摘要： Nano-encapsulated photosensitizers and their use in the treatment of tumors and/or imaging is described. Preferably, the photosensitizers are encapsulated in a calcium phosphate nanoparticle (CPNP). Encapsulating the PS in a CPNP increases the half-life of the PS, increases absorption of the PS into the target cell tissue, increases the photostability of the PS, increases the photoefficiency of the PS, increases in vivo retention of the PS, or combinations thereof, ultimately making it a highly efficacious agent for use in photodynamic therapy, imaging target tissues, vessels, or tumors, and/or detecting or locating tumors.
摘要翻译：描述了纳米包封的光敏剂及其在治疗肿瘤和/或成像中的用途。优选地，将光敏剂包封在磷酸钙纳米颗粒（CPNP）中。将PS封装在CPNP中增加PS的半衰期，增加PS进入靶细胞组织的吸收，增加PS的光稳定性，增加PS的光效，增加PS的体内保留或组合最终使其成为用于光动力疗法，成像靶组织，血管或肿瘤，和/或检测或定位肿瘤的高效药物。

3. 发明申请

US20100247436A1 In vivo photodynamic therapy of cancer via a near infrared agent encapsulated in calcium phosphate nanoparticles 有权
标题翻译：通过封装在磷酸钙纳米粒子中的近红外线的体内光动力治疗癌症
公开(公告)号：US20100247436A1
公开(公告)日：2010-09-30
申请号：US12657556
申请日：2010-01-22
申请人： James H. Adair , Mark Kester , Peter C. Eklund , Karen L. Eklund , Erhan Altinoglu , Brian M. Barth , Timothy J. Russin , James M.D. Kaiser , Thomas T. Morgan
发明人： James H. Adair , Mark Kester , Peter C. Eklund , Karen L. Eklund , Erhan Altinoglu , Brian M. Barth , Timothy J. Russin , James M.D. Kaiser , Thomas T. Morgan
IPC分类号： A61K49/00 , A61K9/14 , A61K39/395 , A61P35/04 , A61P35/00 , A61M37/00
CPC分类号： A61K41/0057 , A61K9/51 , A61K47/6921 , A61K47/6923
摘要： Nano-encapsulated photosensitizers and their use in the treatment of tumors and/or imaging is described. Preferably, the photosensitizers are encapsulated in a calcium phosphate nanoparticle (CPNP). Encapsulating the PS in a CPNP increases the half-life of the PS, increases absorption of the PS into the target cell tissue, increases the photostability of the PS, increases the photoefficiency of the PS, increases in vivo retention of the PS, or combinations thereof, ultimately making it a highly efficacious agent for use in photodynamic therapy, imaging target tissues, vessels, or tumors, and/or detecting or locating tumors.
摘要翻译：描述了纳米包封的光敏剂及其在治疗肿瘤和/或成像中的用途。优选地，将光敏剂包封在磷酸钙纳米颗粒（CPNP）中。将PS封装在CPNP中增加PS的半衰期，增加PS进入靶细胞组织的吸收，增加PS的光稳定性，增加PS的光效，增加PS的体内保留或组合最终使其成为用于光动力疗法，成像靶组织，血管或肿瘤，和/或检测或定位肿瘤的高效药物。

4. 发明申请

US20110129413A1 Bioconjugation of Calcium Phosphosilicate Nanoparticles For Selective Targeting of Cells In Vivo 有权
标题翻译：磷酸钙纳米粒子用于体内细胞选择性靶向的生物缀合
公开(公告)号：US20110129413A1
公开(公告)日：2011-06-02
申请号：US12941719
申请日：2010-11-08
申请人： Thomas T. Morgan , Brian M. Barth , James H. Adair , Rahul Sharma , Mark Kester , Sriram S. Shanmugavelandy , Jill P. Smith , Erhan I. Altinoglu , Gail L. Matters , James M. Kaiser , Christopher McGovern
发明人： Thomas T. Morgan , Brian M. Barth , James H. Adair , Rahul Sharma , Mark Kester , Sriram S. Shanmugavelandy , Jill P. Smith , Erhan I. Altinoglu , Gail L. Matters , James M. Kaiser , Christopher McGovern
IPC分类号： A61K51/12 , C07K14/77 , C07K16/00 , C07K2/00 , C07K7/06 , A61K49/00 , A61K47/42 , A61K47/22 , A61K49/18 , A61K9/14 , B82Y5/00 , B82Y40/00
CPC分类号： A61K49/0093 , A61K41/0057 , A61K47/48861 , A61K47/6923 , A61K49/0034 , A61K49/0043
摘要： Non-aggregating resorbable calcium phosphosilicate nanoparticles (CPNPs) are bioconjugated to targeting molecules that are specific for particular cells. The CPNPs are stable particles at normal physiological pH. Chemotherapy and imaging agents may be integrally formed with the CPNPs so that they are compartmentalized within the CPNPs. In this manner, the agents are protected from interaction with the environment at normal physiological pH. However, once the CPNPs have been taken up, at intracellular pH, the CPNPs dissolve releasing the agent. Thus, chemotherapeutic or imaging agents are delivered to specific cells and permit the treatment and/or imaging of those cells. Use of the bioconjugated CPNPs both limits the amount of systemic exposure to the agent and delivers a higher concentration of the agent to the cell. The methods and principals of bioconjugating CPNPs are taught by examples of bioconjugation of targeting molecules for breast cancer, pancreatic cancer, and leukemia.
摘要翻译：非聚集的可再吸收的磷酸钙纳米粒子（CPNP）被生物缀合成靶向特定细胞特异性的分子。 CPNPs在正常生理pH下是稳定的颗粒。化疗和成像剂可以与CPNP整体形成，使得它们在CPNP内被分隔。以这种方式，保护试剂免于在正常生理pH下与环境的相互作用。然而，一旦CPNP被摄取，在细胞内的pH值下，CPNP溶解释放药剂。因此，化学治疗或显像剂被递送到特定的细胞并允许这些细胞的治疗和/或成像。使用生物共轭CPNP都限制了全身暴露于药剂的量，并将更高浓度的药剂递送至细胞。生物缀合CPNP的方法和原理通过乳腺癌，胰腺癌和白血病靶向分子的生物缀合的实例来教导。

5. 发明授权

US09028863B2 Method and system for systemic delivery of growth arresting, lipid-derived bioactive compounds 有权
标题翻译：用于系统递送生长停滞，脂质衍生生物活性化合物的方法和系统
公开(公告)号：US09028863B2
公开(公告)日：2015-05-12
申请号：US10835520
申请日：2004-04-26
申请人： Mark Kester , Thomas Stover , Tao Lowe , James H. Adair , Young Shin Kim
发明人： Mark Kester , Thomas Stover , Tao Lowe , James H. Adair , Young Shin Kim
IPC分类号： A61K31/164 , A61K47/48 , A61K9/51 , B82Y5/00 , A61K48/00 , A61K9/50 , A61K47/02 , A61K9/127
CPC分类号： A61K31/164 , A61K9/1271 , A61K9/1272 , A61K9/501 , A61K9/51 , A61K9/5115 , A61K47/02 , A61K47/593 , A61K47/60 , A61K47/645 , A61K48/00 , B82Y5/00 , Y10S977/783 , Y10S977/907
摘要： A system and method for optimizing the systemic delivery of growth-arresting lipid-derived bioactive drugs or gene therapy agents to an animal or human in need of such agents utilizing nanoscale assembly systems, such as liposomes, resorbable and non-aggregating nanoparticle dispersions, metal or semiconductor nanoparticles, or polymeric materials such as dendrimers or hydrogels, each of which exhibit improved lipid solubility, cell permeability, an increased circulation half life and pharmacokinetic profile with improved tumor or vascular targeting.
摘要翻译：用于优化生长阻滞的脂质衍生的生物活性药物或基因治疗剂向需要这种药剂的动物或人的系统和方法，其使用纳米尺度装配系统，例如脂质体，可再吸收和非聚集的纳米颗粒分散体，金属或半导体纳米颗粒，或聚合物材料，例如树枝状聚合物或水凝胶，其各自表现出改善的脂溶性，细胞渗透性，增加的循环半衰期和具有改善的肿瘤或血管靶向的药代动力学特征。

6. 发明授权

US09149544B2 Bioconjugation of calcium phosphosilicate nanoparticles for selective targeting of cells in vivo 有权
标题翻译：钙磷硅酸盐纳米颗粒的生物缀合用于体内细胞的选择性靶向
公开(公告)号：US09149544B2
公开(公告)日：2015-10-06
申请号：US12941719
申请日：2010-11-08
申请人： Thomas T. Morgan , Brian M. Barth , James H. Adair , Rahul Sharma , Mark Kester , Sriram S. Shanmugavelandy , Jill P. Smith , Erhan I. Altinoglu , Gail L. Matters , James M. Kaiser , Christopher McGovern
发明人： Thomas T. Morgan , Brian M. Barth , James H. Adair , Rahul Sharma , Mark Kester , Sriram S. Shanmugavelandy , Jill P. Smith , Erhan I. Altinoglu , Gail L. Matters , James M. Kaiser , Christopher McGovern
IPC分类号： A61K49/00 , A61K41/00 , A61K47/48
CPC分类号： A61K49/0093 , A61K41/0057 , A61K47/48861 , A61K47/6923 , A61K49/0034 , A61K49/0043
摘要： Non-aggregating resorbable calcium phosphosilicate nanoparticles (CPNPs) are bioconjugated to targeting molecules that are specific for particular cells. The CPNPs are stable particles at normal physiological pH. Chemotherapy and imaging agents may be integrally formed with the CPNPs so that they are compartmentalized within the CPNPs. In this manner, the agents are protected from interaction with the environment at normal physiological pH. However, once the CPNPs have been taken up, at intracellular pH, the CPNPs dissolve releasing the agent. Thus, chemotherapeutic or imaging agents are delivered to specific cells and permit the treatment and/or imaging of those cells. Use of the bioconjugated CPNPs both limits the amount of systemic exposure to the agent and delivers a higher concentration of the agent to the cell. The methods and principals of bioconjugating CPNPs are taught by examples of bioconjugation of targeting molecules for breast cancer, pancreatic cancer, and leukemia.
摘要翻译：非聚集的可再吸收的磷酸钙纳米粒子（CPNP）被生物缀合成靶向特定细胞特异性的分子。 CPNPs在正常生理pH下是稳定的颗粒。化疗和成像剂可以与CPNP整体形成，使得它们在CPNP内被分隔。以这种方式，保护试剂免于在正常生理pH下与环境的相互作用。然而，一旦CPNP被摄取，在细胞内的pH值下，CPNP溶解释放药剂。因此，化学治疗或显像剂被递送到特定的细胞并允许这些细胞的治疗和/或成像。使用生物共轭CPNP都限制了全身暴露于药剂的量，并将更高浓度的药剂递送至细胞。生物缀合CPNP的方法和原理通过乳腺癌，胰腺癌和白血病靶向分子的生物缀合的实例来教导。

7. 发明申请

US20110046241A1 CALCIUM BASED CARRIER PARTICLES 审中-公开
公开(公告)号：US20110046241A1
公开(公告)日：2011-02-24
申请号：US12546369
申请日：2009-08-24
申请人： Timothy S. Keizer , Brett M. Showalter , Bruce A. Keiser , James H. Adair
发明人： Timothy S. Keizer , Brett M. Showalter , Bruce A. Keiser , James H. Adair
IPC分类号： C09K3/00 , C02F5/00 , A01N25/00 , C09K11/00 , C07F9/08
CPC分类号： D21H19/38 , C02F1/50 , C02F2303/08
摘要： The present invention relates to a method for forming a calcium-based carrier particle consisting of the calcium-based material, an active, with or without a surface modification, a stabilizing agent, and the related composition. The calcium-based particle is illustrated by the general formula Cax(PO4)y(OH)zR and may also include a silica or silica oxide substituent. R is an active or actives such as an organic or inorganic molecule that includes markers, amines, thiols, epoxies, organosilicones, organosilanes, sulfates, and water soluble agents and, as needed, a surface modification, S, which may be either organic or inorganic. A stabilizing agent may be necessary to maintain dispersion of the particles in aqueous media. Examples of a surface modifying material and stabilizing agents are inorganic salts of aluminum and boron or organic materials such as organosilanes or low molecular weight polymers. As such, the particle can be used in a variety of applications including any of a variety of high temperature, at acidic, neutral, or basic pH, or pressure environments. The carrier particles have applications as diverse as papermaking, water treatment, chemical tracing, personal care, microbiological control, oil recovery, delivery of polymers, for example.

8. 发明申请

US20110046240A1 CALCIUM-BASED CARRIER PARTICLES 审中-公开
标题翻译：基于钙的载体颗粒
公开(公告)号：US20110046240A1
公开(公告)日：2011-02-24
申请号：US12546336
申请日：2009-08-24
申请人： Timothy S. Keizer , Brett M. Showalter , Bruce A. Keiser , James H. Adair
发明人： Timothy S. Keizer , Brett M. Showalter , Bruce A. Keiser , James H. Adair
IPC分类号： C09K3/00 , C02F5/00 , A01N25/00 , C08K3/32 , C09K11/00
CPC分类号： A01N25/08 , C02F1/50 , C02F2303/08
摘要： The present invention relates to a method for forming a calcium-based carrier particle consisting of the calcium-based material, an active, with or without a surface modification, a stabilizing agent, and the related composition. The calcium-based particle is illustrated by the general formula Cax(PO4)y(OH)zR and may also include a silica or silica oxide substituent. R is an active or actives such as an organic or inorganic molecule that includes markers, amines, thiols, epoxies, organosilicones, organosilanes, sulfates, and water soluble agents and, as needed, a surface modification, S, which may be either organic or inorganic. A stabilizing agent may be necessary to maintain dispersion of the particles in aqueous media. Examples of a surface modifying material and stabilizing agents are inorganic salts of aluminum and boron or organic materials such as organosilanes or low molecular weight polymers. As such, the particle can be used in a variety of applications including any of a variety of high temperature, at acidic, neutral, or basic pH, or pressure environments. The carrier particles have applications as diverse as papermaking, water treatment, chemical tracing, personal care, microbiological control, oil recovery, delivery of polymers, for example.
摘要翻译：本发明涉及一种钙基载体颗粒的形成方法，该钙基载体颗粒由钙基材料，活性物质，表面改性活性物质，稳定剂和相关组合物组成。钙基颗粒由通式Cax（PO4）y（OH）zR表示，也可以包括二氧化硅或二氧化硅氧化物取代基。 R是活性物质或活性物质，例如有机或无机分子，其包括标记物，胺，硫醇，环氧化物，有机硅氧烷，有机硅烷，硫酸盐和水溶性试剂，并且根据需要可以是表面改性S，其可以是有机的或有机的无机的。可能需要稳定剂以保持颗粒在水性介质中的分散。表面改性材料和稳定剂的实例是铝和硼的无机盐或有机材料如有机硅烷或低分子量聚合物。因此，颗粒可以用于各种应用，包括各种高温，酸性，中性或碱性pH或压力环境中的任何一种。载体颗粒具有例如造纸，水处理，化学追踪，个人护理，微生物控制，油回收，聚合物递送等应用。

9. 发明申请

US20110046239A1 CALCIUM BASED CARRIER PARTICLES 审中-公开
标题翻译：基于钙的载体颗粒
公开(公告)号：US20110046239A1
公开(公告)日：2011-02-24
申请号：US12546319
申请日：2009-08-24
申请人： Bruce A. Keiser , Timothy S. Keizer , Brett M. Showalter , Tiffany Bohnsack , James H. Adair , Mylisa Parette , Amy Knupp , Andrei S. Zelenev , Jason R. Burney
发明人： Bruce A. Keiser , Timothy S. Keizer , Brett M. Showalter , Tiffany Bohnsack , James H. Adair , Mylisa Parette , Amy Knupp , Andrei S. Zelenev , Jason R. Burney
IPC分类号： C07F9/08 , C07F9/572 , C07F9/655 , C02F5/00 , C09K3/00 , C09K11/00 , A01N25/00
CPC分类号： A01N25/08 , C02F1/50 , C02F2303/08
摘要： The present invention relates to a method for forming a calcium-based carrier particle consisting of the calcium-based material, an active, with or without a surface modification, a stabilizing agent, and the related composition. The calcium-based particle is illustrated by the general formula Cax(PO4)y(OH)zR and may also include a silica or silica oxide substituent. R is an active or actives such as an organic or inorganic molecule that includes markers, amines, thiols, epoxies, organosilicones, organosilanes, sulfates, and water soluble agents and, as needed, a surface modification, S, which may be either organic or inorganic. A stabilizing agent may be necessary to maintain dispersion of the particles in aqueous media. Examples of a surface modifying material and stabilizing agents are inorganic salts of aluminum and boron or organic materials such as organosilanes or low molecular weight polymers. As such, the particle can be used in a variety of applications including any of a variety of high temperature, at acidic, neutral, or basic pH, or pressure environments. The carrier particles have applications as diverse as papermaking, water treatment, chemical tracing, personal care, microbiological control, oil recovery, delivery of polymers, for example.
摘要翻译：本发明涉及一种钙基载体颗粒的形成方法，该钙基载体颗粒由钙基材料，活性物质，表面改性活性物质，稳定剂和相关组合物组成。钙基颗粒由通式Cax（PO4）y（OH）zR表示，也可以包括二氧化硅或二氧化硅氧化物取代基。 R是活性物质或活性物质，例如有机或无机分子，其包括标记物，胺，硫醇，环氧化物，有机硅氧烷，有机硅烷，硫酸盐和水溶性试剂，并且根据需要可以是表面改性S，其可以是有机的或有机的无机的。可能需要稳定剂以保持颗粒在水性介质中的分散。表面改性材料和稳定剂的实例是铝和硼的无机盐或有机材料如有机硅烷或低分子量聚合物。因此，颗粒可以用于各种应用，包括各种高温，酸性，中性或碱性pH或压力环境中的任何一种。载体颗粒具有例如造纸，水处理，化学追踪，个人护理，微生物控制，油回收，聚合物递送等应用。

10. 发明授权

US06514894B1 Ceramic slip composition and method for making the same 失效
标题翻译：陶瓷滑移组合物及其制备方法
公开(公告)号：US06514894B1
公开(公告)日：2003-02-04
申请号：US09693407
申请日：2000-10-20
申请人： James H. Adair , Stephen A. Costantino
发明人： James H. Adair , Stephen A. Costantino
IPC分类号： C04B3546
CPC分类号： C04B35/63488 , C04B35/581 , C04B35/584 , C04B35/632 , C04B35/634 , C04B35/63444
摘要： A uniform suspension of ceramic powder and method for making the same. The suspension is prepared by mixing finely divided ceramic powder in an aqueous carrier fluid, combining with a dispersing agent, and alternatively, an organic binder when forming a slip. The ceramic powder has an average particle size of about 0.5 micron or less and is present in the suspension in a loading of up to 30% by volume of the total solids in suspension. A passivating agent is present in the carrier fluid in an amount of 0.5 to 5% by weight of the ceramic powder present for suspension and slip respectively. After the addition of a dispersant, the suspension has a Bingham yield point of less than 230 dynes/cm2 and an apparent viscosity of less than 3000 cps. A green layer produced from the slip exhibits a pore size of less than 0.5 micron.
摘要翻译：陶瓷粉末的均匀悬浮液及其制造方法。通过将细分散的陶瓷粉末混合在水性载体流体中，与分散剂组合，或者在形成滑移时与有机粘合剂混合来制备悬浮液。陶瓷粉末具有约0.5微米或更小的平均粒度，并且以悬浮液中总固体的至多30体积％的负载量存在于悬浮液中。载体流体中的钝化剂分别以用于悬浮和滑动的陶瓷粉末的0.5至5重量％的量存在。添加分散剂后，悬浮液的Bingham屈服点小于230达因/ cm2，表观粘度小于3000cps。由滑动层产生的绿色层表现出小于0.5微米的孔径。

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