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TARGETING AGENT FOR NEOVASCULARIZATION

外国特許コード F200010108
整理番号 2570
掲載日 2020年5月18日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2010JP059917
国際公開番号 WO 2010143708
国際出願日 平成22年6月11日(2010.6.11)
国際公開日 平成22年12月16日(2010.12.16)
優先権データ
  • 特願2009-140757 (2009.6.12) JP
発明の名称 (英語) TARGETING AGENT FOR NEOVASCULARIZATION
発明の概要(英語) Disclosed is a targeting agent which enables the drug delivery to a part where neovascularization occurs or the imaging of the part utilizing the effect of accumulation of the targeting agent in the part. Specifically disclosed is a targeting agent for a part where neovascularization occurs, which comprises a gelatin-like protein.
従来技術、競合技術の概要(英語) BACKGROUND ART
Angiogenesis is, mainly, to form new blood vessels from existing blood vessels represents a phenomenon. As the normal physiological angiogenesis, and angiogenesis in embryonic stage, the endometrium and corpus luteum formation, wound healing such as angiogenesis is involved in present. On the other hand, the pathogenic angiogenesis is, the growth of solid tumors and metastasis, diabetic retinopathy, chronic inflammation such as rheumatoid arthritis and the like are deeply involved is known. Research on tumor angiogenesis in particular, the treatment, diagnosis are actively researched and from both sides. 1-2 mm tumor tumor diameter existing oxygen and nutrients diffusion from blood vessels is considered to be obtained, more proliferation of angiogenesis is required. In adult healthy subjects, an event that an angiogenesis a limited location, since there are only in limited cases, that target tumor angiogenesis therapeutic drugs or imaging agents, tumor-specific and universal drug, diagnostic agents which can be expected.
Current, in the diagnosis of tumor, tumor site FDG (fluorodeoxyglucose) using PET(positron emission tomography) but the diagnosis is performed, and the cells metabolic activity glucose FDG, targeted tissue site only, is not sufficient for tumor specificity. By integrated physiological FDG, brain, heart, that indicate the high integration also such as the liver, it may be difficult to diagnosis of tumors in question. Also, kidney, ureter, the urinary system is bladder, urine discharged into the background by a large amount of FDG is increased, it is difficult to diagnosis. Therefore, by targeting mechanism separate from the glucose metabolism by targeting, mainly targeting agent targeting angiogenesis (targeting agent) which has been developed.
On the other hand, in the treatment of angiogenesis event can be used, are implemented as angiogenesis therapy. Wound healing, as therapy for ischemic diseases, in addition, the organ regeneration or cell transplantation, such as enhancement of the effect of the natural healing, widely referred to as regenerative medicine in the treatment, the importance of angiogenesis been demonstrated. Angiogenesis itself exhibits a therapeutic effect, or to enhance the therapeutic effects of angiogenesis. Therefore, targeted angiogenesis targeting agent or therapeutic agent, imaging agents, a variety of therapeutic, agent in the regenerative medicine, diagnostic agent, therapeutic effect evaluation means are anticipated.
Particularly of a reproduction in the medical field, an operator of a detailed study its therapeutic effect is poor, the authenticity for its therapeutic effect, the presence of a combination of conventional diagnostic methods, in order to evaluate the direct non-stationary. In particular as described above, angiogenesis is an important role in regenerative medicine has a, distinct from the existing blood vessel and a technique for evaluating blood vessels is poor. Especially vascularized imaging means allows visualization of only the blood vessel and thus, the lack of specificity of neovascularization of the imaging agent, such as lack of sustained or, by various problems and does not lead to provide a result sufficiently yet.
As a means for targeting angiogenesis, endothelial cells during angiogenesis in (and in some tumor cells) have been reported highly expressed αV β3 targeted integrin targeting agent, the development of imaging agents are implemented. Α v β3 integrins are, arginine - glycine - aspartic acid (RGD) peptide having the sequence from recognize. Therefore, RGD sequence as a base and, in particular the various cyclic RGD and cyclic RGD-containing peptides is similar compounds have been developed and are, for example Munich Institute Kessler et al. developed by a cyclic pentapeptide c-RGDfV cyclo-RGDfK and lead compounds, cyclo-RGDyV, cyclo-RGDfY, a number of compounds such as cyclo-RGDyK (non-patent document 1) present.
However, the above-described compound is a cyclic RGD, mainly by renal excretion and so the emitted to the outside quickly after administration, short dwell time in vivo. Therefore, drug delivery agent or imaging agent is used as the targeting agent such as, its targeting ability can be utilized as a shorter period of time, before reaching to the target site, most being emitted to the outside is a problem. On the other hand, imaging of blood vessels, in the diagnosis or imaging, a fluorescent dye to the targeting agent or a radioactive isotope for labeling the probe, from the viewpoint of safety, the detection of the site, as soon as possible after the diagnosis is not signal, that is after the diagnosis is, from the corresponding parts required may be lost at an early stage. However, cyclic RGD peptide, even if the head reaches to a target site, neovascularity Integrin expressed from the strong bonding to, the loss of signal from a site of angiogenic blood vessels in case there is prolonged, in question. From these, 'long in vivo residence time of the loss of signal from the site of new blood vessels' and' rapid ' imaging material is demanded.
On the other hand, biological macromolecules including gelatin is widely known heretofore have been used as medical materials, can be utilized to image blood vessels has not been known until now. In addition, in recent years due to advances in genetic engineering techniques, to introduce the gene of E. coli or yeast is performed by protein synthesis. By the procedure, a variety of genes into the recombinant collagen-like protein (for example Patent Document 1 and 2) combined and compared to natural gelatin, noninfectious is excellent, uniform and, since the sequence is determined intensity, can be biodegradable to accurately design the advantages and can be used. However, these applications have been proposed alternative beyond the natural gelatin is not, of course also find application as imaging agents for neovascularization has not been known.
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • FUJIFILM CORPORATION
  • KYOTO UNIVERSITY
  • 発明者(英語)
  • NAKAMURA Kentaro
  • TABATA Yasuhiko
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IS JP KE KG KM KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PE PG PH PL PT RO RS RU SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ MD RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG
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