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1. 发明授权

US06423547B1 Non-covalent bioconjugates useful for diagnosis and therapy 有权
标题翻译：用于诊断和治疗的非共价生物缀合物
公开(公告)号：US06423547B1
公开(公告)日：2002-07-23
申请号：US09646765
申请日：2000-09-21
申请人： Raghavan Rajagopalan , Joseph E. Bugaj , Richard Bradley Dorshow , Samuel I. Achilefu
发明人： Raghavan Rajagopalan , Joseph E. Bugaj , Richard Bradley Dorshow , Samuel I. Achilefu
IPC分类号： G01N33531
CPC分类号： A61K49/0034 , A61K41/0057 , A61K49/0021 , A61K49/0032 , A61K49/0052 , A61K49/0054 , A61K49/0056
摘要： A composition comprising non-covalent carrier-hapten bioconjugates having the formula: HM-CM wherein HM is a hapten molecule whose molecular weight is generally, but not always, less than 1000 Daltons and is capable of performing specific functions; CM is a carrier molecule, whose molecular weight is generally, but not always, more than 1000 Daltons and is capable of transporting the hapten to a specific site; and the dashed line is a non-covalent bond between the carrier molecule and the hapten molecule. Preferably, the bioconjugates are formed from fluorescent dye haptens such as cyanine, indocyanine, squaraine, porphyrrins, Rose Bengal, and methylene blue dye and carrier molecules such as methylated serum albumin, polyarginine, polyaspartic acid, polyglutamic acid, cyclodextrin, and inulin. The bioconjugates are useful in diagnostic and therapeutic medical procedures because they are stable in vitro before being used and stable in vivo during and after use.
摘要翻译：包含具有下式的非共价载体 - 半抗原生物缀合物的组合物：其中HM是其分子量通常但不总是小于1000道尔顿并且能够执行特定功能的半抗原分子; CM是一种载体分子，其分子量通常但不总是大于1000道尔顿，并且能够将半抗原转运到特定位点; 并且虚线是载体分子和半抗原分子之间的非共价键。优选地，生物缀合物由荧光染料半抗原如花青，吲哚菁，方酸，卟啉，玫瑰红和亚甲基蓝染料以及载体分子形成作为甲基化血清白蛋白，聚精氨酸，聚天冬氨酸，聚谷氨酸，环糊精和菊粉。生物缀合物在诊断和治疗医疗过程中是有用的，因为它们在使用前和使用后和使用后在体内稳定，在体内稳定。

2. 发明授权

US07303926B2 Methods and compositions for dual phototherapy 失效
标题翻译：双光疗法和组合物
公开(公告)号：US07303926B2
公开(公告)日：2007-12-04
申请号：US10776840
申请日：2004-02-11
申请人： Raghavan Rajagopalan , Samuel I. Achilefu , Joseph E. Bugaj , Richard B. Dorshow
发明人： Raghavan Rajagopalan , Samuel I. Achilefu , Joseph E. Bugaj , Richard B. Dorshow
IPC分类号： G01N33/533 , G01N21/76 , A61K39/00
CPC分类号： B82Y5/00 , A61K41/0057 , A61K41/0071 , A61K47/62 , A61K47/64 , A61K47/66 , A61K49/0021 , A61K49/0056 , C09B47/045 , Y10S435/968 , Y10S436/80
摘要： The present invention discloses dye-azide derivatives and their bioconjugates for dual phototherapy of tumors and other lesions. The compounds of the present invention may contain either a mixture of Type 1 and Type 2 agents or a single entity that integrates both units in the same molecules. The compounds are designed to produce both Type 1 and Type 2 phototherapeutic effect at once using dual wavelength light source that will produce singlet oxygen and nitrene at the lesion of interest.
摘要翻译：本发明公开了染料叠氮化物衍生物及其生物缀合物用于肿瘤和其他病变的双重光疗。本发明的化合物可以含有1型和2型试剂的混合物，或者可以将相同分子中的两个单元整合的单个实体。该化合物被设计成同时使用将在感兴趣的病变处产生单线态氧和氮烯的双波长光源产生1型和2型光疗效应。

3. 发明授权

US07011817B2 Hydrophilic cyanine dyes 失效
公开(公告)号：US07011817B2
公开(公告)日：2006-03-14
申请号：US09757332
申请日：2001-01-09
申请人： Samuel I. Achilefu , Raghavan Rajagopalan , Richard B. Dorshow , Joseph E. Bugaj
发明人： Samuel I. Achilefu , Raghavan Rajagopalan , Richard B. Dorshow , Joseph E. Bugaj
IPC分类号： A61B10/00 , A61B5/00 , A61B8/00
CPC分类号： A61K49/0056 , A61K41/0033 , A61K41/0057 , A61K49/0032 , C09B23/0016 , C09B23/0025 , C09B23/0066 , C09B23/0075 , C09B23/086
摘要： Cyanine dye bioconjugates useful for diagnostic imaging and therapy are disclosed. The conjugates include several cyanine dyes with a variety of bis- and tetrakis (carboxylic acid) homologues. The compounds may be conjugated to bioactive peptides, carbohydrates, hormones, drugs, or other bioactive agents. The small size of the compounds allows more favorable delivery to tumor cells as compared to larger molecular weight imaging agents. The various dyes are useful over the range of 350-1300 nm, the exact range being dependent upon the particular dye. Use of dimethylsulfoxide helps to maintain the fluorescence of the compounds. The inventive compounds are useful for diagnostic imaging and therapy, in endoscopic applications for the detection of tumors and other abnormalities, for localized therapy, for photoacoustic tumor imaging, detection and therapy, and for sonofluorescence tumor imaging, detection and therapy.

4. 发明授权

US06641798B2 Tumor-targeted optical contrast agents 有权
公开(公告)号：US06641798B2
公开(公告)日：2003-11-04
申请号：US09863971
申请日：2001-05-23
申请人： Samuel I. Achilefu , Raghavan Rajagopalan , Richard B. Dorshow , Joseph E. Bugaj
发明人： Samuel I. Achilefu , Raghavan Rajagopalan , Richard B. Dorshow , Joseph E. Bugaj
IPC分类号： A61B1000
CPC分类号： A61K41/0033
摘要： Cyanine dye bioconjugates useful for diagnostic imaging and therapy are disclosed. The conjugates include several cyanine dyes with a variety of bis- and tetrakis (carboxylic acid) homologes. The compounds may be conjugated to bioactive peptides, carbohydrates, hormones, drugs, or other bioactive agents. The small size of the compounds allows more favorable delivery to tumor cells as compared to larger molecular weight imaging agents. The various dyes are useful over the range of 350 to 1,300 nm, the exact range being dependent upon the particular dye. The use of dimethylsulfoxide helps to maintain the fluorescence of the compounds. The inventive compounds are useful for diagnostic imaging and therapy, in endoscopic applications for the detection of tumors and other abnormalities, for localized therapy, for photoacoustic tumor imaging, detection and therapy, and for sonofluorescence tumor imaging, detection and therapy.

5. 发明授权

US08658433B2 Dye compounds as photoactive agents 有权
标题翻译：染料化合物作为光敏剂
公开(公告)号：US08658433B2
公开(公告)日：2014-02-25
申请号：US11931683
申请日：2007-10-31
申请人： Raghavan Rajagopalan , Gary L. Cantrell , Samuel I. Achilefu , Joseph E. Bugaj , Richard B. Dorshow
发明人： Raghavan Rajagopalan , Gary L. Cantrell , Samuel I. Achilefu , Joseph E. Bugaj , Richard B. Dorshow
IPC分类号： G01N33/532 , G01N33/533 , C07K1/13 , A61K39/395
CPC分类号： B82Y5/00 , A61K41/0057 , A61K41/0071 , A61K47/62 , A61K47/64 , A61K47/66 , A61K49/0021 , A61K49/0056 , C09B47/045 , Y10S435/968 , Y10S436/80
摘要： Novel azo, azide, and sulfenate photoactive compounds and methods using the compounds for photodiagnostic and/or phototherapeutic procedures. The compounds have the formula E-L-DYE-X—Y, wherein DYE is a photoactive component comprising a photoactive diagnostic agent, a photoactive type 1 agent, a photoactive type 2 agent, or a combination thereof; Y is a photoactive component comprising a photoactive type 1 agent, a photoactive type 2 agent, or a combination thereof; E is a targeting component for targeting the compound to an anatomical and/or physiological site of a patient; L is a linking component for linking E to DYE; and X is a linking component for linking DYE to Y.
摘要翻译：新型偶氮，叠氮化物和次氯酸盐光敏化合物和使用该化合物进行光诊断和/或光疗法的方法。所述化合物具有式E-L-DYE-X-Y，其中DYE是包含光敏性诊断剂，光活性型1剂，光活性型2剂或其组合的光活性组分; Y是包含光活性型1剂，光活性型2剂或其组合的光活性组分; E是将化合物靶向患者的解剖和/或生理部位的靶向成分; L是连接E与DYE的连接成分; X为连接DYE与Y的连接成分。

6. 发明申请

US20080233050A1 Diagnostic and therapeutic optical agents 审中-公开
标题翻译：诊断和治疗光学剂
公开(公告)号：US20080233050A1
公开(公告)日：2008-09-25
申请号：US11371572
申请日：2006-03-09
申请人： Samuel I. Achilefu , Raghavan Rajagopalan , Richard B. Dorshow , Joseph E. Bugaj
发明人： Samuel I. Achilefu , Raghavan Rajagopalan , Richard B. Dorshow , Joseph E. Bugaj
IPC分类号： A61K38/08 , C07K7/00 , C07K7/50 , A61K38/12 , A61K38/02 , A61K38/10 , A61K49/00
CPC分类号： C07D209/12 , A61K41/0033 , A61K41/0057 , A61K49/0021 , A61K49/0032 , A61K49/0056 , C07D403/06 , C07D403/08 , C07D405/14 , C09B23/0016 , C09B23/0025 , C09B23/0066 , C09B23/0075 , C09B23/08 , C09B23/086
摘要： Disclosed herein are compounds that may be characterized by some as cyanine and indocyanine dye bioconjugates. Compounds disclosed herein may be utilized (e.g., in the form of a pharmaceutically acceptable composition) in a number of medical procedures, such as in the visualization and detection of tumors.
摘要翻译：本文公开的化合物可以被某些特征化为花青和吲哚菁染料生物缀合物。本文公开的化合物可以在许多医学过程中使用（例如，以药学上可接受的组合物的形式），例如在肿瘤的可视化和检测中。

7. 发明授权

US07351807B2 Cyanine-sulfenates for dual phototherapy 失效
公开(公告)号：US07351807B2
公开(公告)日：2008-04-01
申请号：US09898809
申请日：2001-07-03
申请人： Raghavan Rajagopalan , Samuel I. Achilefu , Joseph E. Bugaj , Richard B. Dorshow
发明人： Raghavan Rajagopalan , Samuel I. Achilefu , Joseph E. Bugaj , Richard B. Dorshow
IPC分类号： C07K1/00 , C07K16/00 , C12P21/08 , C07D401/00 , C07D403/00
CPC分类号： A61K41/0033 , A61K41/0057 , A61K41/0071 , A61K49/0032 , A61K49/0056 , C09B23/083 , C09B47/065 , C09B47/0678 , C09B47/26
摘要： Dye-sulfenate derivatives and their bioconjugates for dual phototherapy of tumors and other lesions. The compounds comprise sulfenates having the formula, t,0080where E is selected from the group consisting of somatostatin receptor binding molecules, heat sensitive bacterioendotoxin receptor binding molecules, neurotensin receptor binding molecules, bombesin receptor binding molecules, cholecystekinin receptor binding molecules, steroid receptor binding molecules, and carbohydrate receptor binding molecules, and dihydoxyindolecarboxylic acid; L and X are independently selected from the group consisting of —(R5)NOC—, —(R5)NOCCH2O—, —(R5)NOCCH2CH2O—, —OCN(R5)—, —HNC(═S)NH—, and HNC(═O)NH—; DYE is an aromatic or a heteroaromatic radical derived from the group consisting of cyanines, indocyanines, phthalocyanines, rhodamines, phenoxazines, phenothiazines, phenoselenazines, fluoresceins, porphyrins, benzoporphyrins, squaraines, corrins, croconiums, azo dyes, methine dyes, indolenium dyes, crellins, and hypocrellins; R1 to R5 are independently selected from the group comprising hydrogen, C1-C10 alkyl, C5-C10 aryl, C1-C10 polyhydroxyalkyl, and C1-C10 polyalkoxyalkyl; and Ar is an aromatic or heteroaromatic radical derived from the group consisting of benzenes, naphthalenes, naphthoquinones, diphenylmethanes, fluorenes, anthracenes, anthraquinones, phenanthrenes, tetracenes, naphthacenediones, pyridines, quinolines, isoquinolines, indoles, isoindoles, pyrroles, imidiazoles, oxazoles, thiazoles, pyrazoles, pyrazines, purines, benzimidazoles, furans, benzofurans, dibenzofurans, carbazoles, acridines, acridones, phenanthridines, thiophenes, benzothiophenes, dibenzothiophenes, xanthenes, xanthones, flavones, coumarins, and anthacylines. The compounds are designed to produce both Type 1 and Type 2 phototherapeutic effects at once using a dual wavelength light source that will produce singlet oxygen and free radicals at the lesion of interest.

8. 发明授权

US06706254B2 Receptor-avid exogenous optical contrast and therapeutic agents 失效
标题翻译：受体 - 狂热的外源性光学对比和治疗剂
公开(公告)号：US06706254B2
公开(公告)日：2004-03-16
申请号：US09864011
申请日：2001-05-23
申请人： Samuel I. Achilefu , Raghavan Rajagopalan , Richard B. Dorshow , Joseph E. Bugaj
发明人： Samuel I. Achilefu , Raghavan Rajagopalan , Richard B. Dorshow , Joseph E. Bugaj
IPC分类号： A61B1000
CPC分类号： A61K49/0032 , A61K41/0033 , A61K41/0057 , A61K49/0056 , C09B23/0066 , C09B23/08
摘要： Cyanine dye bioconjugates useful for diagnostic imaging and therapy are disclosed. The conjugates include several cyanine dyes with a variety of bis- and tetrakis (carboxylic acid) homologes. The compounds may be conjugated to bioactive peptides, carbohydrates, hormones, drugs, or other bioactive agents. The small size of the compounds allows more favorable delivery to tumor cells as compared to larger molecular weight imaging agents. The various dyes are useful over the range of 350 to 1,300 nm, the exact range being dependent upon the particular dye. The use of dimethylsulfoxide helps to maintain the fluorescence of the compounds. The inventive compounds are useful for diagnostic imaging and therapy, in endoscopic applications for the detection of tumors and other abnormalities, for localized therapy, for photoacoustic tumor imaging, detection and therapy, and for sonofluorescence tumor imaging, detection and therapy.
摘要翻译：公开了可用于诊断成像和治疗的花青染料生物缀合物。缀合物包括几种具有多种双和四（羧酸）同系物的花青染料。化合物可以与生物活性肽，碳水化合物，激素，药物或其他生物活性剂缀合。与较大的分子量成像剂相比，化合物的小尺寸允许更有利于肿瘤细胞的递送。各种染料在350至1,300nm的范围内是有用的，精确的范围取决于特定的染料。使用二甲基亚砜有助于维持化合物的荧光。本发明化合物可用于诊断成像和治疗，用于检测肿瘤和其他异常的内窥镜应用，局部治疗，光声肿瘤成像，检测和治疗以及用于声发射肿瘤成像，检测和治疗。

9. 发明申请

US20080275017A1 AROMATIC SULFENATES FOR TYPE I PHOTOTHERAPY 审中-公开
标题翻译： I型照相机的AROMATIC SULFENATES
公开(公告)号：US20080275017A1
公开(公告)日：2008-11-06
申请号：US12173235
申请日：2008-07-15
申请人： Raghavan Rajagopalan , Gary L. Cantrell , Samuel I. Achilefu , Joseph E. Bugaj , Richard B. Dorshow
发明人： Raghavan Rajagopalan , Gary L. Cantrell , Samuel I. Achilefu , Joseph E. Bugaj , Richard B. Dorshow
IPC分类号： A61K31/565 , A61K31/165 , A61K31/473 , A61K31/352
CPC分类号： A61K41/0057
摘要： Novel sulfenate derivatives and their bioconjugates for phototherapy of tumors and other lesions. The sulfenates of the present invention are designed to absorb low-energy ultraviolet, visible, or near-infrared (NIR) region of the electromagnetic spectrum. The phototherapeutic effect is caused by direct interaction of free radicals, the reactive intermediate produced upon photofragmentation of the sulfenate moiety, with the tissue of interest.
摘要翻译：新型次氯酸盐衍生物及其生物缀合物用于肿瘤和其他病变的光疗。本发明的次氯酸盐被设计成吸收电磁光谱的低能量紫外线，可见光或近红外（NIR）区域。光疗效应是由自由基（在次硫酸盐部分的光分解产生的反应性中间体）与感兴趣的组织的直接相互作用引起的。

10. 发明授权

US07235685B2 Aromatic sulfenates for type I phototherapy 失效
标题翻译：用于I型光疗法的芳族亚磺酸盐
公开(公告)号：US07235685B2
公开(公告)日：2007-06-26
申请号：US09898887
申请日：2001-07-03
申请人： Raghavan Rajagopalan , Gary L. Cantrell , Samuel I. Achilefu , Joseph E. Bugaj , Richard B. Dorshow
发明人： Raghavan Rajagopalan , Gary L. Cantrell , Samuel I. Achilefu , Joseph E. Bugaj , Richard B. Dorshow
IPC分类号： C07K313/08
CPC分类号： A61K41/0057
摘要： The present invention discloses novel sulfenate derivatives and their bioconjugates for phototherapy of tumors and other lesions. The sulfenates of the present invention are designed to absorb low-energy ultraviolet, visible, or near-infrared (NIR) region of the electromagnetic spectrum. The phototherapeutic effect is caused by direct interaction of free radicals, the reactive intermediate produced upon photofragmentation of the sulfenate moiety, with the tissue of interest.
摘要翻译：本发明公开了用于肿瘤和其他病变光疗的新型次氯酸盐衍生物及其生物缀合物。本发明的次氯酸盐被设计成吸收电磁光谱的低能量紫外线，可见光或近红外（NIR）区域。光疗效应是由自由基（在次硫酸盐部分的光分解产生的反应性中间体）与感兴趣的组织的直接相互作用引起的。

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