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1. 发明申请

US20060057064A1 Compound binding to leukocytes and medicinal composition containing the compound in labeled state as the active ingredient 失效
标题翻译：化合物与白细胞结合，含有标记状态的化合物作为活性成分的药物组合物
公开(公告)号：US20060057064A1
公开(公告)日：2006-03-16
申请号：US10528771
申请日：2003-09-26
申请人： Ikuya Seki , Takayoshi Kawaguchi , Yoshifumi Shirakami
发明人： Ikuya Seki , Takayoshi Kawaguchi , Yoshifumi Shirakami
IPC分类号： A61K51/00 , A61K38/12
CPC分类号： C07K7/06 , A61K38/08 , A61K49/14 , A61K51/088 , C07K7/02 , Y02A50/409
摘要： A compound binding to leukocytes, which comprises Met-Leu-Phe or Nle-Leu-Phe serving as the leukocyte-binding site of a formyl peptide receptor (FPR), a binding part comprising Ser or Thr elevating the binding ratios to monocytes and lymphocytes in all leukocytes, a group which can be labeled with a radioactive metal or a paramagnetic metal, and a spacer binding them shows binding properties specific to all leukocytes, i.e., neutrophils, monocytes and lymphocytes both in vivo and in vitro and can be labeled with a radioactive metal or a paramagnetic metal. Owing to these characteristics, this compound is highly useful in SPECT image diagnosis, PET image diagnosis, MRI image diagnosis and so on wherein imaging is performed in a site with vigorous leukocyte infiltration accompanied by an immune reaction in an individual.
摘要翻译：与白细胞结合的化合物，其包含作为甲酰基肽受体（FPR）的白细胞结合位点的Met-Leu-Phe或Nle-Leu-Phe，包含Ser或Thr的结合部分提高与单核细胞和淋巴细胞的结合比在所有的白细胞中，可以用放射性金属或顺磁性金属标记的基团和结合它们的间隔基团显示出对体内和体外所有白细胞，即嗜中性粒细胞，单核细胞和淋巴细胞特异性的结合特性，并且可以用放射性金属或顺磁性金属。由于这些特征，该化合物在SPECT图像诊断，PET图像诊断，MRI图像诊断等中非常有用，其中在具有伴随着个体的免疫反应的剧烈白细胞浸润的部位进行成像。

2. 发明授权

US5785948A Metal chelate forming peptides and use thereof represented by three amino acid sequences 失效
标题翻译：金属螯合物形成肽及其用途由三个氨基酸序列表示
公开(公告)号：US5785948A
公开(公告)日：1998-07-28
申请号：US815530
申请日：1997-03-12
申请人： Yoshitoshi Itaya , Ikuya Seki , Koichi Hanaoka , Yoshifumi Shirakami
发明人： Yoshitoshi Itaya , Ikuya Seki , Koichi Hanaoka , Yoshifumi Shirakami
IPC分类号： A61K51/08 , C07K5/087 , C07K5/09 , C07K5/093 , C07K7/08 , A61K51/00 , A61M36/14
CPC分类号： C07K7/08 , A61K51/08 , A61K51/088 , C07K5/0812 , C07K5/0815 , C07K5/0819 , A61K2121/00 , A61K2123/00 , Y02P20/55
摘要： The invention provides, inter alia, metal radionuclide-labelled reagent comprising a metal radionuclide coordinated with a metal chelate forming peptide having an amino acid sequence of three amino acid residues represented by: X1-X2-Cys, wherein X1 represents an Asp residue, a Tyr residue or a Lys residue; X2 represents an amino acid residue other than a Cys residue and a Pro residue, provided that X2 does not represent a Gly residue when X1 represents an Asp residue; wherein functional groups at the N-terminus, C-terminus and side chain may be optionally substituted with protecting groups; and wherein each of the amino acid residues may be either D-form or L-form.
摘要翻译：本发明尤其提供了金属放射性核素标记的试剂，其包含与形成有金属螯合物的肽配位的金属放射性核素，所述金属螯合物具有由以下基团表示的三个氨基酸残基的氨基酸序列：X1-X2-Cys，其中X1表示Asp残基，酪氨酸残基或赖氨酸残基; X2表示除Cys残基和Pro残基以外的氨基酸残基，条件是当X1表示Asp残基时X 2不表示Gly残基; 其中N末端，C末端和侧链上的官能团可以任选被保护基取代; 并且其中每个氨基酸残基可以是D-型或L-型。

3. 发明授权

US4855353A High molecular compounds having amino groups, and their utilization 失效
标题翻译：具有氨基的高分子化合物及其利用
公开(公告)号：US4855353A
公开(公告)日：1989-08-08
申请号：US15633
申请日：1987-02-17
申请人： Miki Kurami , Yoshifumi Shirakami , Keietsu Takahashi , Nobuo Ueda
发明人： Miki Kurami , Yoshifumi Shirakami , Keietsu Takahashi , Nobuo Ueda
IPC分类号： A61K47/48 , A61K51/06 , A61K51/10
CPC分类号： A61K47/48692 , A61K47/48192 , A61K47/48315 , A61K51/065 , A61K51/1093 , A61K2121/00 , A61K2123/00 , Y10S530/811 , Y10S530/812 , Y10S530/816
摘要： A radioactive diagnostic or therapeutic agent, which comprises a metallic element-labeled high molecular compound which comprises one unit of (1) a polyamine compound having at least three amino groups in the side chains per molecule, at least two units of (2) a chelate-forming compound having a carboxyl group, at least one unit of (3) a physiologically active substance and (4) at least two radioactive metallic elements, each unit of the chelate-forming compound (2) and the physiologically active substance (3) being combined to any of the amino groups in the side chains of the polyamine compound (1) and each of the radioactive metallic element (4) being chelate-bonded to the chelate-forming compound (2).
摘要翻译：一种放射性诊断或治疗剂，其包含金属元素标记的高分子化合物，其包含一个单位的（1）每分子侧链具有至少三个氨基的多胺化合物，至少两个单位的（2）具有羧基的螯合形成化合物，（3）生理活性物质和（4）至少两个放射性金属元素，螯合形成化合物（2）和生理活性物质（3）的至少一个单元）与多胺化合物（1）的侧链中的任何氨基结合，并且每个放射性金属元素（4）与螯合形成化合物（2）螯合。

4. 发明授权

US5827498A Tumor affinity peptide, and radioactive diagnostic agent and radioactive therapeutic agent containing the peptide 失效
标题翻译：肿瘤亲和肽，放射性诊断剂和含有该肽的放射性治疗剂
公开(公告)号：US5827498A
公开(公告)日：1998-10-27
申请号：US463230
申请日：1995-06-05
申请人： Ikuya Seki , Yoshitoshi Itaya , Yoshifumi Shirakami , Komei Washino
发明人： Ikuya Seki , Yoshitoshi Itaya , Yoshifumi Shirakami , Komei Washino
IPC分类号： A61K38/00 , A61K51/10 , C07K16/18 , C07K16/30 , A61K51/00 , A61M36/14
CPC分类号： A61K51/1018 , A61K51/1045 , C07K16/18 , C07K16/30 , A61K38/00
摘要： A peptide having affinity with tumor or a salt thereof, which comprises an amino acid sequence containing 20 or less amino acid residues, said amino acid sequence being described as X.sub.1 -YCAREPPT-X.sub.2 wherein A, C, E, P, R, T and Y represent amino acid residues expressed by standard one-letter symbols, each of amino acid residues A, C, R and Y in the amino acid sequence YCAR may be in either L-form or D-form, X.sub.1 represents a basic organic compound having 1-3 amino groups, and X.sub.2 represents any given amino acid sequence, is provided together with a radioactive diagnostic agent and a radioactive therapeutic agent containing the above peptide or a salt thereof. The present tumor affinity peptide is high in radioactive metal labeling yield, useful for imaging and treating pathological tissues such as of breast cancer, ovarian cancer and colon cancer of mammals including human, and difficult to be readily metabolized in organisms and to accumulate in normal tissues especially at kidney and liver.
摘要翻译：一种与肿瘤或其盐具有亲和力的肽，其包含含有20个或更少氨基酸残基的氨基酸序列，所述氨基酸序列描述为X1-YCAREPPT-X2，其中A，C，E，P，R，T和 Y代表由标准单字母符号表示的氨基酸残基，氨基酸序列YCAR中的氨基酸残基A，C，R和Y中的每一个可以是L-型或D-型，X1表示具有 1-3个氨基，X2代表任何给定的氨基酸序列，与放射性诊断剂和含有上述肽或其盐的放射性治疗剂一起提供。本发明的肿瘤亲和肽具有放射性金属标记产率高，可用于成像和治疗诸如乳腺癌，卵巢癌和包括人在内的哺乳动物的结肠癌的病理组织，并且难以在生物体中代谢并积累在正常组织中特别是在肾脏和肝脏。

5. 发明授权

US5770178A Metal chelate forming peptides and use thereof 失效
标题翻译：金属螯合物形成肽及其用途
公开(公告)号：US5770178A
公开(公告)日：1998-06-23
申请号：US575863
申请日：1995-12-20
申请人： Yoshitoshi Itaya , Ikuya Seki , Koichi Hanaoka , Yoshifumi Shirakami
发明人： Yoshitoshi Itaya , Ikuya Seki , Koichi Hanaoka , Yoshifumi Shirakami
IPC分类号： A61K51/08 , C07K5/087 , C07K5/09 , C07K5/093 , C07K7/08 , A61K51/00 , A61M36/14
CPC分类号： C07K7/08 , A61K51/08 , A61K51/088 , C07K5/0812 , C07K5/0815 , C07K5/0819 , A61K2121/00 , A61K2123/00 , Y02P20/55
摘要： The invention provides a metal chelate forming peptide having an amino acid sequence of three amino acid residues represented by: X1-X2-Cys, wherein X1 represents an amino acid residue other than Cys residue; X2 represents an amino acid residue other than Cys residue and Pro residue; functional groups at the N-terminus, C-terminus and side chain may be substituted with protecting groups; and each of the amino acid residues may be any of D-form and L-form. Further, the invention provides a complex of the peptide with a physiologically active peptide, protein or other substance; a labeled reagent obtained by labeling the peptide or the complex with a metal radionuclide; and a radiodiagnostic and radiotherapeutic composition comprising the metal radionuclide-labeled reagent.
摘要翻译：本发明提供一种形成金属螯合物的肽，其具有由以下基团表示的三个氨基酸残基的氨基酸序列：X1-X2-Cys，其中X1表示除Cys残基以外的氨基酸残基; X2表示除Cys残基和Pro残基之外的氨基酸残基; N-末端，C-末端和侧链的官能团可以被保护基团取代; 并且每个氨基酸残基可以是D型和L-型中的任何一种。此外，本发明提供了肽与生理活性肽，蛋白质或其他物质的复合物; 通过用金属放射性核素标记肽或配合物获得的标记试剂; 以及包含金属放射性核素标记试剂的放射诊断和放射治疗组合物。

6. 发明授权

US07220827B2 Compound binding to leukocytes and medicinal composition containing the compound in labeled state as the active ingredient 失效
标题翻译：化合物与白细胞结合，含有标记状态的化合物作为活性成分的药物组合物
公开(公告)号：US07220827B2
公开(公告)日：2007-05-22
申请号：US10528771
申请日：2003-09-26
申请人： Ikuya Seki , Takayoshi Kawaguchi , Yoshifumi Shirakami
发明人： Ikuya Seki , Takayoshi Kawaguchi , Yoshifumi Shirakami
IPC分类号： A61K38/04
CPC分类号： C07K7/06 , A61K38/08 , A61K49/14 , A61K51/088 , C07K7/02 , Y02A50/409
摘要： A compound that comprises Met-Leu-Phe or Nle-Leu-Phe serving as the leukocyte-binding site of a formyl peptide receptor (FPR), a binding part comprising Ser or Thr that increases the binding ratio to monocytes and lymphocytes in all leukocytes, a group that can be labeled with a radioactive metal or a paramagnetic metal, and spacers binding the three moieties together shows binding properties specific to all leukocytes, i.e., neutrophils, monocytes and lymphocytes both in vivo and in vitro. Owing to this characteristic, this compound is highly useful in SPECT image diagnosis, PET image diagnosis, MRI image diagnosis and the like, for imaging sites of inflammation.
摘要翻译：包含作为甲酰肽受体（FPR）的白细胞结合位点的Met-Leu-Phe或Nle-Leu-Phe的化合物，包含Ser或Thr的结合部分，其增加与所有白细胞中的单核细胞和淋巴细胞的结合比，可以用放射性金属或顺磁金属标记的基团，以及将三个部分结合在一起的间隔物在体内和体外都显示出对所有白细胞，即嗜中性粒细胞，单核细胞和淋巴细胞特异性的结合特性。由于该特征，该化合物在SPECT图像诊断，PET图像诊断，MRI图像诊断等中对于炎症成像部位是非常有用的。

7. 发明申请

US20050063902A1 Stabiliser for radiopharmaceuticals 有权
标题翻译：放射性药物稳定剂
公开(公告)号：US20050063902A1
公开(公告)日：2005-03-24
申请号：US10296952
申请日：2001-06-18
申请人： Anthony Storey , Georg Brauers , Koichi Hanaoka , Yoshihito Minosako , Koichi Homma , Yoshifumi Shirakami
发明人： Anthony Storey , Georg Brauers , Koichi Hanaoka , Yoshihito Minosako , Koichi Homma , Yoshifumi Shirakami
IPC分类号： A61K47/02 , A61K47/16 , A61K47/18 , A61K47/22 , A61K47/24 , A61K51/00 , A61K51/04 , A61P43/00 , A61K31/66
CPC分类号： A61K51/0489
摘要： The present invention provides an improved stabiliser for radiopharmaceuticals which inhibits impurities from being produced by two kinds of decomposition mechanisms and exhibits such an effect that the shelf life of a radiopharmaceutical after its preparation is prolonged as compared with conventional ones. The improvement comprises a combination of an amino-substituted aromatic carboxylic acid or its salt, ester or amide in combination with a diphosphonic acid or its salt.
摘要翻译：本发明提供一种用于放射性药物的改进的稳定剂，其通过两种分解机制抑制杂质的产生，并且表现出与常规放射性药物相比，其制备后放射性药物的保质期延长的效果。改进包括氨基取代的芳族羧酸或其盐，酯或酰胺与二膦酸或其盐的组合。

8. 发明授权

US5821330A Peptide having inflammation affinity and radioactive diagnostic containing the same 失效
标题翻译：具有炎症亲和力的肽和包含其的放射性诊断
公开(公告)号：US5821330A
公开(公告)日：1998-10-13
申请号：US327459
申请日：1994-10-21
申请人： Yoshitoshi Itaya , Koichi Hanaoka , Yoshifumi Shirakami
发明人： Yoshitoshi Itaya , Koichi Hanaoka , Yoshifumi Shirakami
IPC分类号： A61K51/08 , A61K51/10 , C07K16/00 , C07K5/00 , A61K38/04
CPC分类号： A61K51/1093 , A61K51/088 , C07K16/00
摘要： A peptide having affinity with inflammation is disclosed, which contains at least one of the following amino acid sequences: LLGGPS (SEQ ID NO:1), LLGGPSV (SEQ ID NO:2), KEYKAKVSNKALPAPIEKTISK (SEQ ID NO:3), KEYKCKVSNKALPAPIEKTISK (SEQ ID NO:4), KTKPREQQYNSTYR (SEQ ID NO:5), and KTKPREQQYNSTYRVV (SEQ ID NO:6), wherein A, C, E, G, I, K, L, N, P, Q, R, S, T, V, and Y represent amino acid residues expressed by standard one-letter symbols. According to the present invention, a peptide and its chemically modified substances, radioactive metal labeled peptides derived therefrom, and radioactive diagnostics comprising such peptide are provided, which are useful for imaging inflammation region and easy in preparation handling, and accumulate at inflammation site immediately after administration while being excellent in clearance into urine. The imaging is possible in several ten minutes after administration.
摘要翻译：公开了具有炎症亲和力的肽，其含有以下氨基酸序列中的至少一个：LLGGPS（SEQ ID NO：1），LLGGPSV（SEQ ID NO：2），KEYKAKVSNKALPAPIEKTISK（SEQ ID NO：3），KEYKCKVSNKALPAPIEKTISK（ SEQ ID NO：4），KTKPREQQYNSTYR（SEQ ID NO：5）和KTKPREQQYNSTYRVV（SEQ ID NO：6），其中A，C，E，G，I，K，L，N，P，Q，R，S ，T，V和Y表示由标准单字母符号表示的氨基酸残基。根据本发明，提供肽及其化学修饰物质，由其衍生的放射性金属标记肽和包含该肽的放射性诊断物，其可用于成像炎症区域并且易于制备处理，并且在紧随其后的炎症部位积聚同时排尿良好。在施用后几十分钟内成像是可能的。

9. 发明授权

US07914768B2 Stabiliser for radiopharmaceuticals 有权
标题翻译：放射性药物稳定剂
公开(公告)号：US07914768B2
公开(公告)日：2011-03-29
申请号：US10296952
申请日：2001-06-18
申请人： Anthony E. Storey , Georg Brauers , Koichi Hanaoka , Yoshihito Minosako , Koichi Homma , Yoshifumi Shirakami
发明人： Anthony E. Storey , Georg Brauers , Koichi Hanaoka , Yoshihito Minosako , Koichi Homma , Yoshifumi Shirakami
IPC分类号： A61K51/00 , A61M36/14
CPC分类号： A61K51/0489
摘要： A stabilized radiopharmaceutical composition, a kit including same, and a method for making same, where the radiopharmaceutical is (i) susceptible to either reductive degradation or radiolysis and which includes a metal complex of a radionuclide with a ligand, (ii) a first stabilizer for the radiopharmaceutical which is an amino-substituted aromatic carboxylic acid or a salt, ester or amide thereof, and (iii) a second stabilizer for the radiopharmaceutical which is a diphosphonic acid or salt thereof. The first and second stabilizers are present in an amount effective to stabilize the radiopharmaceutical, and the radiopharmaceutical is not a metal complex of the diphosphonic acid.
摘要翻译：稳定的放射性药物组合物，包含其的试剂盒及其制备方法，其中放射性药物是（i）易于还原降解或放射分解，并且其包含放射性核素与配体的金属络合物，（ii）第一稳定剂对于作为氨基取代的芳族羧酸或其盐，酯或酰胺的放射性药物，和（iii）作为二膦酸的放射性药物的第二稳定剂或其盐。第一和第二稳定剂以有效稳定放射性药物的量存在，并且放射性药物不是二膦酸的金属络合物。

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