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71.发明授权Method for extended storage of viable and pathogen-safe blood and blood components using carbon monoxide 有权使用一氧化碳延长存活和病原体安全的血液和血液成分的方法公开(公告)号：US07323295B2
公开(公告)日：2008-01-29
申请号：US10716625
申请日：2003-11-20
申请人： Nurith Shaklai , Matityahu Shaklai
发明人： Nurith Shaklai , Matityahu Shaklai
IPC分类号： A01N1/02
CPC分类号： A61K41/0009 , A01N1/0215 , A61K35/14
摘要： A method for inhibiting bacterial growth in whole blood and/or blood components, which may therefore also be used to extend the storage time for the whole blood and/or blood components, through treatment with carbon monoxide. This method is preferably used for the preservation of platelets, which are both particularly vulnerable to bacterial and other microbial infection, and which are also particularly suitable for use with the method of the present invention. Carbon monoxide may be present in an amount of from about 40% to about 100%. Platelets may be stored in a solution buffered by any suitable buffer, such as sodium bicarbonate. Platelet viability may be determined by measuring the ability to aggregate, for example in response to an agonist such as collagen.
摘要翻译： 一种抑制全血和/或血液成分中的细菌生长的方法，因此也可用于通过用一氧化碳处理来延长全血和/或血液成分的储存时间。 该方法优选用于保存特别易受细菌和其他微生物感染的血小板，并且还特别适用于本发明的方法。 一氧化碳可以以约40％至约100％的量存在。 血小板可以储存在由任何合适的缓冲液（例如碳酸氢钠）缓冲的溶液中。 血小板活力可以通过测量聚集的能力来确定，例如响应于诸如胶原的激动剂。
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72.发明授权公开(公告)号：US06251127B1
公开(公告)日：2001-06-26
申请号：US09139866
申请日：1998-08-25
申请人： Merrill A. Biel
发明人： Merrill A. Biel
IPC分类号： A61B1818
CPC分类号： A61K41/0057 , A61B2017/00057 , A61K41/0009 , A61N2005/0606 , A61N2005/0645
摘要： The invention relates to a method of treating an infection or sterilization including applying a dye such as methylene blue, toluidene blue, polymyxin B, or combinations thereof to the area of infection or area to be sterilized and exposing the area of infection or area of sterilization with a light having a light wavelength and light dosage and a light dosage rate. The dye may have a concentration ranging from about 10 &mgr;g/ml to about 500 &mgr;g/ml. The wavelength may range from about 610 nm to about 670 nm. The light dosage may range from about 0 J/cm2 to about 200 J/cm2. The light dosage rate may range from about 0 mw/cm2 to about 150 mw/cm2. The treatable infections include staphylococcus, Candida albicans, Escherichia coli, enterococcus, streptococcus, Pseudomanus aeruginosa, Hemophilus influenzae, or E-coli. The invention also relates to an infection treatment kit.
摘要翻译： 本发明涉及一种治疗感染或灭菌的方法，包括将染料如亚甲基蓝，甲苯蓝，多粘菌素B或其组合施用于感染或待灭菌区域，并暴露感染区域或灭菌区域 具有光波长和光量和轻剂量率的光。 该染料的浓度范围为约10ug / ml至约500mug / ml。 波长可以在约610nm至约670nm的范围内。 光剂量可以在约0J / cm 2至约200J / cm 2的范围内。 光剂量率可以在约0mw / cm 2至约150mw / cm 2的范围内。 可治疗感染包括葡萄球菌，白色念珠菌，大肠杆菌，肠球菌，链球菌，铜绿假单胞菌，流感嗜血杆菌或大肠杆菌。 本发明还涉及感染治疗试剂盒。
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公开(公告)号：US06235508B1
公开(公告)日：2001-05-22
申请号：US09153657
申请日：1998-09-15
IPC分类号： C12N1300
CPC分类号： A61L2/0011 , A61K41/0009
摘要： Viral and bacterial contaminants present in biological solutions are inactivated by mixing one of a novel class of photosensitizer with said solution and irradiating the mixture. Quinoline and quinolone compounds are useful as photosensitizers in this method. With certain photosensitizers a blocking agent may also be employed.
摘要翻译： 生物溶液中存在的病毒和细菌污染物通过将新型光敏剂之一与所述溶液混合并照射混合物来灭活。 喹啉和喹诺酮化合物在该方法中可用作光敏剂。 对于某些光敏剂，也可以使用封闭剂。
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公开(公告)号：US5994535A
公开(公告)日：1999-11-30
申请号：US31239
申请日：1998-02-26
IPC分类号： A61K31/40 , A61K41/00 , A61K49/00 , A61K49/06 , A61K49/08 , A61K51/04 , A61L2/00 , A61P35/00 , A61P43/00 , C07D487/22 , C07H17/02 , C07H21/00 , C07F9/6524
CPC分类号： A61K51/0485 , A61K41/0009 , A61K41/0038 , A61K41/0076 , A61K47/48069 , A61K49/0021 , A61K49/0036 , A61K49/0058 , A61K49/04 , A61K49/106 , A61K51/1093 , A61L2/0011 , C07D487/22 , C07H17/02 , C07H21/00
摘要： The present invention is directed to methods for synthesizing water soluble hydroxy-substituted texaphyrins retaining lipophilicity. The synthesis comprises condensing a diformyltripyrrole with an ortho-phenylenediamine to give a nonaromatic texaphyrin having at least one hydroxy substituent, and oxidizing the condensation product to form an aromatic texaphyrin metal complex having at least one hydroxy substituent. These expanded porphyrin-like macrocycles may be used for magnetic resonance imaging and for photodynamic therapy in the treatment of atheroma and tumors.
摘要翻译： 本发明涉及合成保持亲油性的水溶性羟基取代的泰克萨菲瑞的方法。 合成方法包括将二甲基三吡咯与邻苯二胺缩合，得到具有至少一个羟基取代基的非芳族泰克萨菲林，并氧化缩合产物以形成具有至少一个羟基取代基的芳族泰克萨菲瑞金属络合物。 这些扩大的卟啉大环可用于磁共振成像和光动力疗法治疗动脉粥样化和肿瘤。
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公开(公告)号：US5599923A
公开(公告)日：1997-02-04
申请号：US196964
申请日：1994-02-15
IPC分类号： A61K31/40 , A61K41/00 , A61K47/48 , A61K49/00 , A61K49/06 , A61K49/08 , A61K51/00 , A61K51/04 , A61L2/00 , A61P35/00 , C07D487/22 , C07H21/00
CPC分类号： C07D487/22 , A61K41/0009 , A61K41/0038 , A61K41/0076 , A61K49/0021 , A61K49/106 , A61K51/04 , A61K51/0485 , A61K51/1093 , A61L2/0011 , C07H21/00 , A61K2121/00
摘要： Texaphyrin metal complexes having improved functionalization including the addition of electron donating groups to positions 12, 15, 18 and/or 21 and/or the addition of electron withdrawing groups to positions 15 or 18 of the macrocycle. Electron donating groups at positions 12, 15, 18 and/or 21 contribute electrons to the aromatic .pi. system of the macrocycle which stabilizes the metal complex to demetallation and the imine bonds to hydrolysis, these texaphyrin metal complexes having enhanced stability are useful for localization, magnetic resonance imaging, radiosensitization, radiation therapy, fluorescence imaging, photodynamic tumor therapy and applications requiring singlet oxygen production for cytotoxicity. Electron withdrawing groups at positions 15 or 18 render the macrocycle more readily reduced, i.e. the redox potential is lower and the macrocycle more readily gains an electron to form a radical. Such texaphyrins having a low redox potential are useful for radiosensitization applications.
摘要翻译： 特拉法林金属配合物具有改进的官能化，包括向位置12,15,18和/或21添加给电子基团和/或向大环的位置15或18添加吸电子基团。 位置12,15,18和/或21处的供体基团向大环化合物的芳族π系统贡献电子，这使得金属络合物稳定化以脱金属，并且亚胺键合到水解，这些具有增强的稳定性的泰克萨菲瑞金属络合物可用于定位， 磁共振成像，放射增敏，放射治疗，荧光成像，光动力学肿瘤治疗和需要单线态氧产生细胞毒性的应用。 位置15或18处的吸电子基团使得大环化合物更容易降低，即氧化还原电位较低，大环化合物更容易获得电子以形成基团。 具有低氧化还原电位的这种泰克萨菲瑞可用于放射增敏应用。
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公开(公告)号：US5475104A
公开(公告)日：1995-12-12
申请号：US112786
申请日：1993-08-25
IPC分类号： A61K31/40 , A61K41/00 , A61K49/00 , A61K49/06 , A61K49/08 , A61K51/04 , A61L2/00 , A61P35/00 , A61P43/00 , C07D487/22 , C07H17/02 , C07H21/00 , C07F15/00
CPC分类号： A61K51/0485 , A61K41/0009 , A61K41/0038 , A61K41/0076 , A61K47/48069 , A61K49/0021 , A61K49/0036 , A61K49/0058 , A61K49/04 , A61K49/106 , A61K51/1093 , A61L2/0011 , C07D487/22 , C07H17/02 , C07H21/00
摘要： The present invention involves water soluble hydroxy-substituted texaphyrins retaining lipophilicity, the synthesis of such compounds and their uses. These expanded porphyrin-like macrocycles are efficient chelators of divalent and trivalent metal ions. Various metal (e.g., transition, main group, and lanthanide) complexes of the hydroxy-substituted texaphyrin derivatives of the present invention have unusual water solubility and stability. They absorb light strongly in a physiologically important region (i.e. 690-880 nm). They have enhanced relaxivity and therefore are useful in magnetic resonance imaging. They form long-lived triplet states in high yield and act as photosensitizers for the generation of singlet oxygen. Thus, they are useful for inactivation or destruction of human immunodeficiency virus (HIV-1), mononuclear or other cells infected with such virus as well as tumor cells. They are water soluble, yet they retain sufficient lipophilicity so as to have greater affinity for lipid rich areas such as atheroma and tumors. They may be used for magnetic resonance imaging followed by photodynamic tumor therapy in the treatment of atheroma and tumors. These properties, coupled with their high chemical stability and appreciable solubility in water, add to their usefulness.
摘要翻译： 本发明涉及保持亲油性的水溶性羟基取代的泰克萨菲瑞，合成这些化合物及其用途。 这些膨胀的卟啉大环是二价和三价金属离子的有效螯合剂。 本发明的羟基取代的泰克萨菲瑞衍生物的各种金属（例如，转变，主要和镧系元素）络合物具有不寻常的水溶性和稳定性。 它们在生理上重要的区域（即690-880nm）中强烈吸收光。 它们具有增强的放松性，因此在磁共振成像中是有用的。 它们以高产率形成长寿命的三重态，并且作为产生单线态氧的光敏剂。 因此，它们可用于灭活或破坏感染了这种病毒以及肿瘤细胞的人类免疫缺陷病毒（HIV-1），单核细胞或其他细胞。 它们是水溶性的，但它们保持足够的亲脂性，以便对富含脂质的区域如动脉粥样化和肿瘤具有更大的亲和力。 它们可用于磁共振成像，随后光动力学肿瘤治疗治疗动脉粥样化和肿瘤。 这些性质加上其高的化学稳定性和在水中的明显的溶解度，增加了它们的用途。
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77.发明授权
公开(公告)号：US5439570A
公开(公告)日：1995-08-08
申请号：US112871
申请日：1993-08-25
IPC分类号： A61K31/40 , A61K41/00 , A61K49/00 , A61K49/06 , A61K49/08 , A61K51/04 , A61L2/00 , A61P35/00 , A61P43/00 , C07D487/22 , C07H17/02 , C07H21/00 , C07C27/00
CPC分类号： A61K51/0485 , A61K41/0009 , A61K41/0038 , A61K41/0076 , A61K47/48069 , A61K49/0021 , A61K49/0036 , A61K49/0058 , A61K49/04 , A61K49/106 , A61K51/1093 , A61L2/0011 , C07D487/22 , C07H17/02 , C07H21/00
摘要： The present invention involves water soluble hydroxy-substituted texaphyrins retaining lipophilicity, the synthesis of such compounds and their uses. These expanded porphyrin-like macrocycles are efficient chelators of divalent and trivalent metal ions. Various metal (e.g., transition, main group, and lanthanide) complexes of the hydroxy-substituted texaphyrin derivatives of the present invention have unusual water solubility and stability. They absorb light strongly in a physiologically important region (i.e. 690-880 nm). They have enhanced relaxivity and therefore are useful in magnetic resonance imaging. They form long-lived triplet states in high yield and act as photosensitizers for the generation of singlet oxygen. Thus, they are useful for inactivation or destruction of human immunodeficiency virus (HIV-1), mononuclear or other cells infected with such virus as well as tumor cells. They are water soluble, yet they retain sufficient lipophilicity so as to have greater affinity for lipid rich areas such as atheroma and tumors. They may be used for magnetic resonance imaging followed by photodynamic tumor therapy in the treatment of atheroma and tumors. These properties, coupled with their high chemical stability and appreciable solubility in water, add to their usefulness.
摘要翻译： 本发明涉及保持亲油性的水溶性羟基取代的泰克萨菲瑞，合成这些化合物及其用途。 这些膨胀的卟啉大环是二价和三价金属离子的有效螯合剂。 本发明的羟基取代的泰克萨菲瑞衍生物的各种金属（例如，转变，主要和镧系元素）络合物具有不寻常的水溶性和稳定性。 它们在生理上重要的区域（即690-880nm）中强烈吸收光。 它们具有增强的放松性，因此在磁共振成像中是有用的。 它们以高产率形成长寿命的三重态，并且作为产生单线态氧的光敏剂。 因此，它们可用于灭活或破坏感染了这种病毒以及肿瘤细胞的人类免疫缺陷病毒（HIV-1），单核细胞或其他细胞。 它们是水溶性的，但它们保持足够的亲脂性，以便对富含脂质的区域如动脉粥样化和肿瘤具有更大的亲和力。 它们可用于磁共振成像，随后光动力学肿瘤治疗治疗动脉粥样化和肿瘤。 这些性质加上其高的化学稳定性和在水中的明显的溶解度，增加了它们的用途。
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公开(公告)号：US4428744A
公开(公告)日：1984-01-31
申请号：US274319
申请日：1981-06-16
申请人： Richard L. Edelson
发明人： Richard L. Edelson
CPC分类号： A61M1/3681 , A61K41/0009 , A61M1/3686 , Y10S128/03
摘要： A method and system are disclosed for externally treating human blood, with the objective of reducing the functioning lymphocyte population in the blood system of a human subject. According to the method, blood is withdrawn from the subject and passed through an ultraviolet radiation field in the presence of from about 1 nanogram to 100 micrograms per ml of blood, of a dissolved photoactive agent capable of forming photo-adducts with lymphocytic-DNA, mobile cortisone receptors or antigen sites to thereby effect covalent bonding between the photoactive agent and the same, thereby inhibiting the metabolic processes of the lymphocytes or complexing them; and thereupon returning the irradiated blood to the subject. The withdrawn blood may be formed into an extracorporeal stream and flowed through a treatment station whereat the irradiation is effected, as for example by exposure to UV radiation; and such flow process may be conducted on a continuous basis. If desired, at least portions of the treated blood may then be separated, as for example by a continuous centrifuge, before returning the remaining diverted blood to the subject.
摘要翻译： 公开了用于外部治疗人血液的方法和系统，目的是减少人类受试者的血液系统中的功能性淋巴细胞群体。 根据该方法，将血液从受试者中取出并通过紫外线辐射场，其存在约1毫微克至100微克/ ml血液，能够与淋巴细胞DNA形成光加合物的溶解光活性剂， 移动可的松受体或抗原位点，从而影响光活性剂与其之间的共价键，从而抑制淋巴细胞的代谢过程或使它们复合; 然后将照射的血液返回给受试者。 抽出的血液可以形成体外流，并流过其中进行照射的治疗站，例如通过暴露于紫外线辐射; 并且这种流动过程可以在连续的基础上进行。 如果需要，则可以将待处理的血液的至少一部分例如通过连续离心机分离，然后将剩余的转移的血液返回给受试者。
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