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1. 发明授权

US09251937B2 Heat stable nanoparticle preparations and associated methods thereof 有权
标题翻译：热稳定纳米颗粒制剂及其相关方法
公开(公告)号：US09251937B2
公开(公告)日：2016-02-02
申请号：US13538493
申请日：2012-06-29
申请人： Brian Christopher Bales , Brian James Grimmond , Daniel Eugene Meyer , Bruce Allan Hay , Michael Todd Luttrell
发明人： Brian Christopher Bales , Brian James Grimmond , Daniel Eugene Meyer , Bruce Allan Hay , Michael Todd Luttrell
IPC分类号： A61K49/18 , H01F1/00 , B82Y5/00 , B82Y15/00 , B82Y30/00 , B82Y40/00
CPC分类号： H01F1/0054 , A61K49/1842 , A61K49/186 , B82Y5/00 , B82Y15/00 , B82Y30/00 , B82Y40/00
摘要： A method of sterilizing a nanoparticle preparation at a high temperature is provided. A plurality of nanoparticles are purified to form the preparation, wherein the nanoparticles comprise at least a core and a shell and the shell comprises one or more ligand species attached to the core. The nanoparticle preparation is made by a purified nanoparticle composition, a carrier fluid and an excess of the one or more ligand species not attached to the core. The ligand species attached to the core and the excess ligand species added after purification are structurally identical. The nanoparticle preparation provided by the present invention may be used as contrast agents in medical imaging techniques such as X-ray and magnetic resonance imaging.
摘要翻译：提供了一种在高温下对纳米颗粒制剂进行灭菌的方法。纯化多个纳米颗粒以形成制剂，其中所述纳米颗粒至少包含核和壳，并且所述壳包含连接到核的一种或多种配体物质。纳米颗粒制备由纯化的纳米颗粒组合物，载体流体和过量的未连接到核的一种或多种配体物质制备。在核心附着的配体物质和纯化后加入的过量配体物质在结构上是相同的。本发明提供的纳米颗粒制剂可用作医学成像技术如X射线和磁共振成像中的造影剂。

2. 发明申请

US20140003997A1 HEAT STABLE NANOPARTICLE PREPARATIONS AND ASSOCIATED METHODS THEREOF 有权
标题翻译：热稳定的纳米材料制备及其相关方法
公开(公告)号：US20140003997A1
公开(公告)日：2014-01-02
申请号：US13538493
申请日：2012-06-29
申请人： Brian Christopher Bales , Brian James Grimmond , Daniel Eugene Meyer , Bruce Allan Hay , Michael Todd Luttrell
发明人： Brian Christopher Bales , Brian James Grimmond , Daniel Eugene Meyer , Bruce Allan Hay , Michael Todd Luttrell
IPC分类号： A61L2/04 , B82Y5/00 , B82Y40/00
CPC分类号： H01F1/0054 , A61K49/1842 , A61K49/186 , B82Y5/00 , B82Y15/00 , B82Y30/00 , B82Y40/00
摘要： A method of sterilizing a nanoparticle preparation at a high temperature is provided. A plurality of nanoparticles are purified to form the preparation, wherein the nanoparticles comprise at least a core and a shell and the shell comprises one or more ligand species attached to the core. The nanoparticle preparation is made by a purified nanoparticle composition, a carrier fluid and an excess of the one or more ligand species not attached to the core. The ligand species attached to the core and the excess ligand species added after purification are structurally identical. The nanoparticle preparation provided by the present invention may be used as contrast agents in medical imaging techniques such as X-ray and magnetic resonance imaging.
摘要翻译：提供了一种在高温下对纳米颗粒制剂进行灭菌的方法。纯化多个纳米颗粒以形成制剂，其中所述纳米颗粒至少包含核和壳，并且所述壳包含连接到核的一种或多种配体物质。纳米颗粒制备由纯化的纳米颗粒组合物，载体流体和过量的未连接到核的一种或多种配体物质制备。在核心附着的配体物质和纯化后加入的过量配体物质在结构上是相同的。本发明提供的纳米颗粒制剂可用作医学成像技术如X射线和磁共振成像中的造影剂。

3. 发明授权

US09474810B2 Superparamagnetic nanoparticles with PEG substituted α-hydroxy phosphonate shells 有权
标题翻译：具有PEG取代的α-羟基膦酸酯壳的超顺磁性纳米颗粒
公开(公告)号：US09474810B2
公开(公告)日：2016-10-25
申请号：US13411004
申请日：2012-03-02
申请人： Bruce Allan Hay , Daniel Eugene Meyer , Brian Christopher Bales , Michael Todd Luttrell
发明人： Bruce Allan Hay , Daniel Eugene Meyer , Brian Christopher Bales , Michael Todd Luttrell
IPC分类号： A61K49/18 , A61K47/48 , A61K33/26 , A61K33/28 , A61K33/24 , A61K33/32 , A61K33/34
CPC分类号： A61K49/186 , A61K33/24 , A61K33/26 , A61K33/32 , A61K33/34 , A61K47/548 , A61K47/60 , A61K47/6923 , A61K47/6929 , A61K49/1842 , Y10T428/2982
摘要： The present application discloses nanoparticles, particularly nanoparticles of superparamagnetic iron oxide, which find utility in iron therapy and diagnostic imaging such as magnetic resonance (MR). The disclosed nanoparticles have been treated with an α-hydroxyphosphonic acid conjugate containing polyethylene glycol as a hydrophilic moiety to render the nanoparticles sufficiently hydrophilic to find utility in diagnostic imaging. Among the modified hydrophilic nanoparticles disclosed are those in which the hydrophilic moieties of the modifying conjugate are polyethylene oxide-based polymers and have a molecular weight greater than 5,000 dalton and less than or equal to about 30,000 daltons. Surprisingly, these nanoparticles have a more rapid and complete processing in liver of retained nanoparticles when compared to similar nanoparticles in which the PEG-based hydrophilic moiety has a molecular weight less than 5,000.
摘要翻译：本申请公开了纳米颗粒，特别是超顺磁性氧化铁的纳米颗粒，其可用于铁疗法和诸如磁共振（MR）的诊断成像。所公开的纳米颗粒已经用含有聚乙二醇作为亲水部分的α-羟基膦酸缀合物进行处理，以使纳米颗粒充分亲水以发现在诊断成像中的应用。所公开的改性亲水性纳米粒子是其中改性缀合物的亲水部分是聚环氧乙烷基聚合物并具有大于5,000道尔顿且小于或等于约30,000道尔顿的分子量的那些。令人惊讶的是，与其中基于PEG的亲水部分具有小于5,000的分子量的类似纳米颗粒相比，这些纳米颗粒在保留的纳米颗粒的肝中具有更快速和完整的加工。

4. 发明申请

US20120156141A1 NANOPARTICLE COMPOSITION AND ASSOCIATED METHODS THEREOF 有权
标题翻译：纳米材料组合物及其相关方法
公开(公告)号：US20120156141A1
公开(公告)日：2012-06-21
申请号：US12968577
申请日：2010-12-15
申请人： Bruce Allan Hay , Brian Christopher Bales , Michael Todd Luttrell , Binil Itty Ipe Kandapallil
发明人： Bruce Allan Hay , Brian Christopher Bales , Michael Todd Luttrell , Binil Itty Ipe Kandapallil
IPC分类号： A61K49/18 , A61P35/00 , B82Y30/00
CPC分类号： A61K49/1842 , A61K49/1845 , B82Y5/00 , B82Y15/00 , B82Y30/00 , B82Y40/00
摘要： A nanoparticle composition is provided, wherein the composition comprises a nanoparticulate metal oxide; and a phosphorylated polyol comprising at least two phosphate groups. The polyol comprises one or more hydrophilic groups selected from the group consisting of polyethylene ether moieties, polypropylene ether moieties, polybutylene ether moieties, and combinations of two or more of the foregoing hydrophilic moieties. A method of making the nanoparticle composition is also provided. The nanoparticle compositions provided by the present invention may be used as contrast agents in medical imaging techniques such as X-ray and magnetic resonance imaging.
摘要翻译：提供纳米颗粒组合物，其中所述组合物包含纳米颗粒金属氧化物; 和包含至少两个磷酸酯基团的磷酸化多元醇。多元醇包含一个或多个选自聚乙烯醚部分，聚丙烯醚部分，聚丁烯醚部分以及前述亲水部分中两个或更多个的组合的亲水基团。还提供了制备纳米颗粒组合物的方法。本发明提供的纳米颗粒组合物可用作医学成像技术如X射线和磁共振成像中的造影剂。

5. 发明授权

US08895068B2 Nanoparticle composition and associated methods thereof 有权
标题翻译：纳米粒子组成及其相关方法
公开(公告)号：US08895068B2
公开(公告)日：2014-11-25
申请号：US12968577
申请日：2010-12-15
申请人： Bruce Allan Hay , Brian Christopher Bales , Michael Todd Luttrell , Binil Itty Ipe Kandapallil
发明人： Bruce Allan Hay , Brian Christopher Bales , Michael Todd Luttrell , Binil Itty Ipe Kandapallil
IPC分类号： A61K9/14 , A61B5/055 , B82Y15/00 , A61K49/18 , B82Y30/00 , B82Y5/00 , B82Y40/00
CPC分类号： A61K49/1842 , A61K49/1845 , B82Y5/00 , B82Y15/00 , B82Y30/00 , B82Y40/00
摘要： A nanoparticle composition is provided, wherein the composition comprises a nanoparticulate metal oxide; and a phosphorylated polyol comprising at least two phosphate groups. The polyol comprises one or more hydrophilic groups selected from the group consisting of polyethylene ether moieties, polypropylene ether moieties, polybutylene ether moieties, and combinations of two or more of the foregoing hydrophilic moieties. A method of making the nanoparticle composition is also provided. The nanoparticle compositions provided by the present invention may be used as contrast agents in medical imaging techniques such as X-ray and magnetic resonance imaging.
摘要翻译：提供纳米颗粒组合物，其中所述组合物包含纳米颗粒金属氧化物; 和包含至少两个磷酸酯基团的磷酸化多元醇。多元醇包含一个或多个选自聚乙烯醚部分，聚丙烯醚部分，聚丁烯醚部分以及前述亲水部分中两个或更多个的组合的亲水基团。还提供了制备纳米颗粒组合物的方法。本发明提供的纳米颗粒组合物可用作医学成像技术如X射线和磁共振成像中的造影剂。

6. 发明授权

US08889103B2 Diagnostic agent composition and associated methods thereof 有权
标题翻译：诊断剂组合物及其相关方法
公开(公告)号：US08889103B2
公开(公告)日：2014-11-18
申请号：US12968645
申请日：2010-12-15
申请人： Bruce Allan Hay , Brian Christopher Bales , Michael Todd Luttrell , Binil Itty Ipe Kandapallil
发明人： Bruce Allan Hay , Brian Christopher Bales , Michael Todd Luttrell , Binil Itty Ipe Kandapallil
IPC分类号： A61B5/055 , A61K49/18 , B82Y5/00 , B82Y15/00
CPC分类号： B82Y15/00 , A61K49/1842 , A61K49/1845 , B82Y5/00
摘要： A diagnostic agent composition is provided which comprises a nanoparticle composition and a pharmaceutically acceptable carrier or excipient. The nanoparticle composition comprises a nanoparticulate metal oxide and a phosphorylated polyol, wherein the phosphorylated polyol comprises at least two phosphate groups and one or more hydrophilic groups selected from the group consisting of polyethylene ether moieties, polypropylene ether moieties, polybutylene ether moieties, and combinations of two or more of the foregoing hydrophilic moieties. The disclosure provides detailed guidance on methods of making and using such diagnostic agent compositions. The diagnostic agent compositions provided by the present invention are useful as contrast agents for medical diagnostic imaging techniques such as magnetic resonance (MR) imaging and X-ray imaging. The diagnostic agent composition may be administered to a subject via a variety of techniques, among them injection, inhalation, and ingestion.
摘要翻译：提供了一种诊断剂组合物，其包含纳米颗粒组合物和药学上可接受的载体或赋形剂。纳米颗粒组合物包含纳米颗粒金属氧化物和磷酸化多元醇，其中磷酸化多元醇包含至少两个磷酸基团和一个或多个亲水基团，所述亲水基团选自聚醚醚部分，聚丙烯醚部分，聚丁烯醚部分，以及两个或更多个上述亲水部分。本公开提供了制备和使用这种诊断剂组合物的方法的详细指导。本发明提供的诊断剂组合物可用作医学诊断成像技术如磁共振（MR）成像和X射线成像的造影剂。诊断剂组合物可以通过各种技术施用于受试者，其中包括注射，吸入和摄取。

7. 发明申请

US20120156142A1 DIAGNOSTIC AGENT COMPOSITION AND ASSOCIATED METHODS THEREOF 有权
标题翻译：诊断试剂组合物及其相关方法
公开(公告)号：US20120156142A1
公开(公告)日：2012-06-21
申请号：US12968645
申请日：2010-12-15
申请人： Bruce Allan Hay , Brian Christopher Bales , Michael Todd Luttrell , Binil Itty Ipe Kandapallil
发明人： Bruce Allan Hay , Brian Christopher Bales , Michael Todd Luttrell , Binil Itty Ipe Kandapallil
IPC分类号： A61K49/00 , A61K49/04 , A61K49/06 , B82Y5/00
CPC分类号： B82Y15/00 , A61K49/1842 , A61K49/1845 , B82Y5/00
摘要： A diagnostic agent composition is provided which comprises a nanoparticle composition and a pharmaceutically acceptable carrier or excipient. The nanoparticle composition comprises a nanoparticulate metal oxide and a phosphorylated polyol, wherein the phosphorylated polyol comprises at least two phosphate groups and one or more hydrophilic groups selected from the group consisting of polyethylene ether moieties, polypropylene ether moieties, polybutylene ether moieties, and combinations of two or more of the foregoing hydrophilic moieties. The disclosure provides detailed guidance on methods of making and using such diagnostic agent compositions. The diagnostic agent compositions provided by the present invention are useful as contrast agents for medical diagnostic imaging techniques such as magnetic resonance (MR) imaging and X-ray imaging. The diagnostic agent composition may be administered to a subject via a variety of techniques, among them injection, inhalation, and ingestion.
摘要翻译：提供了一种诊断剂组合物，其包含纳米颗粒组合物和药学上可接受的载体或赋形剂。纳米颗粒组合物包含纳米颗粒金属氧化物和磷酸化多元醇，其中磷酸化多元醇包含至少两个磷酸基团和一个或多个亲水基团，所述亲水基团选自聚醚醚部分，聚丙烯醚部分，聚丁烯醚部分，以及两个或更多个上述亲水部分。本公开提供了制备和使用这种诊断剂组合物的方法的详细指导。本发明提供的诊断剂组合物可用作医学诊断成像技术如磁共振（MR）成像和X射线成像的造影剂。诊断剂组合物可以通过各种技术施用于受试者，其中包括注射，吸入和摄取。

8. 发明授权

US08728529B2 Nanoparticle contrast agents for diagnostic imaging 有权
标题翻译：用于诊断成像的纳米颗粒造影剂
公开(公告)号：US08728529B2
公开(公告)日：2014-05-20
申请号：US12344606
申请日：2008-12-29
申请人： Matthew David Butts , Robert Edgar Colborn , Peter John Bonitatibus, Jr. , Amit Mohan Kulkarni , Bruce Allan Hay , Andrew Soliz Torres , Brian Christopher Bales , Michael Ernest Marino
发明人： Matthew David Butts , Robert Edgar Colborn , Peter John Bonitatibus, Jr. , Amit Mohan Kulkarni , Bruce Allan Hay , Andrew Soliz Torres , Brian Christopher Bales , Michael Ernest Marino
IPC分类号： A61K9/14 , A61K9/51 , A61K49/04 , A61K49/06
CPC分类号： A61K49/1848 , A61K49/0428 , B82Y5/00
摘要： Compositions of nanoparticles functionalized with at least one zwitterionic moiety, methods for making a plurality of nanoparticles, and methods of their use as diagnostic agents are provided. The nanoparticles have characteristics that result in minimal retention of the particles in the body compared to other nanoparticles. The nanoparticle comprises a core, having a core surface essentially free of silica, and a shell attached to the core surface. The shell comprises at least one silane-functionalized zwitterionic moiety.
摘要翻译：提供了用至少一个两性离子部分官能化的纳米颗粒的组合物，制备多个纳米颗粒的方法及其用作诊断剂的方法。与其他纳米颗粒相比，纳米颗粒具有导致颗粒在体内的最小保留的特征。纳米颗粒包括具有基本上不含二氧化硅的核心表面的核心，以及附着于核心表面的壳体。壳包含至少一个硅烷官能化的两性离子部分。

9. 发明授权

US08574549B2 Nanoparticle contrast agents for diagnostic imaging 有权
标题翻译：用于诊断成像的纳米颗粒造影剂
公开(公告)号：US08574549B2
公开(公告)日：2013-11-05
申请号：US12344608
申请日：2008-12-29
申请人： Matthew David Butts , Robert Edgar Colborn , Peter John Bonitatibus, Jr. , Amit Mohan Kulkarni , Bruce Allan Hay , Andrew Soliz Torres , Brian Christopher Bales , Michacl Ernest Marino
发明人： Matthew David Butts , Robert Edgar Colborn , Peter John Bonitatibus, Jr. , Amit Mohan Kulkarni , Bruce Allan Hay , Andrew Soliz Torres , Brian Christopher Bales , Michacl Ernest Marino
IPC分类号： A61K49/04
CPC分类号： A61K49/1848 , A61K49/0428 , B82Y5/00
摘要： Compositions of nanoparticles functionalized with at least one zwitterionic moiety, methods for making a plurality of nanoparticles, and methods of their use as diagnostic agents are provided. The nanoparticles have characteristics that result in minimal retention of the particles in the body compared to other nanoparticles. The nanoparticle comprises a core, having a core surface essentially free of silica, and a shell attached to the core surface. The shell comprises at least one silane-functionalized zwitterionic moiety.
摘要翻译：提供了用至少一个两性离子部分官能化的纳米颗粒的组合物，制备多种纳米颗粒的方法及其用作诊断剂的方法。与其他纳米颗粒相比，纳米颗粒具有导致颗粒在体内的最小保留的特征。纳米颗粒包括具有基本上不含二氧化硅的核心表面的核心，以及附着于核心表面的壳体。壳包含至少一个硅烷官能化的两性离子部分。

10. 发明申请

US20100166665A1 NANOPARTICLE CONTRAST AGENTS FOR DIAGNOSTIC IMAGING 有权
标题翻译：用于诊断成像的纳米对比剂
公开(公告)号：US20100166665A1
公开(公告)日：2010-07-01
申请号：US12344606
申请日：2008-12-29
申请人： Matthew David Butts , Robert Edgar Colborn , Peter John Bonitatibus, JR. , Amit Mohan Kulkarni , Bruce Allan Hay , Andrew Soliz Torres , Brian Christopher Bales , Michael Ernest Marino
发明人： Matthew David Butts , Robert Edgar Colborn , Peter John Bonitatibus, JR. , Amit Mohan Kulkarni , Bruce Allan Hay , Andrew Soliz Torres , Brian Christopher Bales , Michael Ernest Marino
IPC分类号： A61K49/18 , A61K49/04 , B82B1/00
CPC分类号： A61K49/1848 , A61K49/0428 , B82Y5/00
摘要： Compositions of nanoparticles functionalized with at least one zwitterionic moiety, methods for making a plurality of nanoparticles, and methods of their use as diagnostic agents are provided. The nanoparticles have characteristics that result in minimal retention of the particles in the body compared to other nanoparticles. The nanoparticle comprises a core, having a core surface essentially free of silica, and a shell attached to the core surface. The shell comprises at least one silane-functionalized zwitterionic moiety.
摘要翻译：提供了用至少一个两性离子部分官能化的纳米颗粒的组合物，制备多个纳米颗粒的方法及其用作诊断剂的方法。与其他纳米颗粒相比，纳米颗粒具有导致颗粒在体内的最小保留的特征。纳米颗粒包括具有基本上不含二氧化硅的核心表面的核心，以及附着于核心表面的壳体。壳包含至少一个硅烷官能化的两性离子部分。

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