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COMPOSITION FOR INCREASING BONE MASS

外国特許コード F130007669
整理番号 S2012-0461-N0
掲載日 2013年10月17日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2013JP055555
国際公開番号 WO 2013129620
国際出願日 平成25年2月28日(2013.2.28)
国際公開日 平成25年9月6日(2013.9.6)
優先権データ
  • 特願2012-042160 (2012.2.28) JP
発明の名称 (英語) COMPOSITION FOR INCREASING BONE MASS
発明の概要(英語) It has been discovered that semaphorin 3A (Sema3A), which is expressed by osteoblastic cells, exhibits a strong bone-protecting action by simultaneously inhibiting bone resorption and promoting bone formation. It has also been found that systemic administration of Sema3A (by intravenous injection) or local administration thereof to a bone damage site makes it possible to increase bone mass of the administration target.
従来技術、競合技術の概要(英語) BACKGROUND ART
With the aging society, fracture, osteoporosis, rheumatoid arthritis, back pain such as pain increased bone disease patient. In bone tissue, osteoblasts responsible for bone formation, and osteoclasts responsible for bone resorption works in concert, a balanced bone resorption and bone formation by bone resorption, bone homeostasis, and thus the function of the bone tissue is maintained. Is in bone homeostasis, via Calcium is maintained primarily by the endocrine system and is considered over the years, the immune system and nervous system involved in the control factor is maintained by, being to recently been found (non-patent document 1-2). In addition, the bone homeostasis, as well as loss of ovarian function due to aging deforms due to such factors, such as a decrease in bone formation, and abnormal bone resorption or enhance, and a decrease in bone mass (bone density), various bone diseases occur (non-patent document 3-4). Such bone diseases, fractures, bone defects, osteoporosis, Osteomalacia, osteopenia, waist back pain, bone Paget's disease, ankylosing spondylitis, rheumatoid arthritis, osteoarthritis, metastatic bone tumor initial /, periodontal disease, periodontitis and the like implant known. And in particular elderly people suffering from bone disease, the required level of motion in the daily life become difficult even, in some cases, also the danger of the stay. Therefore, the aging proceeds in modern society, preventing bone diseases, is an important significance for the treatment.
The current, as a therapeutic agent for bone disease, active vitamin D3 agent, a bisphosphonate agent, calcitonin formulations, containing estradiol hormone preparations, vitamin K2 agent, such as parathyroid hormone (PTH) is generally used in the formulation. In addition, have fewer side effects, more effective as therapeutic agents, estradiol derivatives, active vitamin D3 derivatives, which have been developed bisphosphonate derivative (patent document 1).
However, the blood calcium concentration of vitamin D3 and has an effect on increasing, bisphosphonates for bone resorption inhibition of estradiol and has the effect that, both directly promote osteogenesis by osteoblasts effect may not. On the other hand, but PTH promotes bone formation, bone resorption do not significantly affect the for. In addition, bone resorption and bone formation and bone resorption (coupling factor) via a coupling factor for cooperating with the (non-patent document 5-6), a bisphosphonate anti-bone resorption agent such as estradiol and used for a long time, suppress the formation of an appropriate bone ulha and, low-quality bone as a result of the accumulation of the (non-patent document 6-9).
Therefore, truly effective bone disease, as well as the development of methods of therapeutic agent in order to enable, a mechanism to maintain homeostasis of the bone to elucidate in detail, while suppressing bone resorption, promoting bone formation to identify molecules that can has been urgently required. However, identification of such molecules has not been conducted, bone resorption and bone formation and bone resorption can be controlled is tuned to the prevention of bone diseases, such as the provision of the therapeutic agent yet developed.
On the other hand, axonal guidance molecule, and widely expressed outside the nervous system, where the cell migration, immune response, such as angiogenesis development and tissue revealed that the control (non-patent document 10-11) being. In addition, from recent research results, including the skeletal system, in various biological systems, axonal guidance molecule responsible for an important role has been suggested (non-patent document 12-14). Axonal guidance molecule 1 (Sema3A) is a type of the semaphorin 3A protein, and secreted proteins, membrane proteins (Neuropilin 1) and Nrp1 (Plexin A1) Plexin-A1 and form a complex, various signals that are known. Is in the nervous system, nerve axons of neuronal guidance factor determines a directivity function as has been made clear (non-patent document 15-16), in addition, in the immune system, such as factor inhibit the migration of dendritic cells, as a factor of suppressing the activation of T cells, also known function as a Sema3A (patent document 2). Further, with respect to the bone, in Sema3A knockout mice, an abnormality of the bone and cartilage formation and has been observed (non-patent document 17). In addition, the expression of Sema3A mRNA whereas osteoblasts, osteoclasts do not been confirmed (non-patent document 18). However, Sema3A protein, in osteoblasts and osteoclasts, which exert their effect whether has not been clarified.
  • 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
  • NATIONAL UNIVERSITY CORPORATION TOKYO MEDICAL AND DENTAL UNIVERSITY
  • 発明者(英語)
  • TAKAYANAGI Hiroshi
  • NAKASHIMA Tomoki
  • HAYASHI Mikihito
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN 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 PA PE PG PH PL PT QA RO RS RU RW 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 RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ 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 RS 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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