新規変形性関節症治療薬SI-613の膝関節における残存性評価

• 石井 聖弥

  生化学工業株式会社研究開発本部中央研究所

• 吉岡 敬二

  生化学工業株式会社研究開発本部中央研究所

• 森田 大輔

  生化学工業株式会社研究開発本部中央研究所

書誌事項

タイトル別名

• Residual Property of SI-613, a Novel Drug for Osteoarthritis, in Knee Joint
• シンキ ヘンケイセイ カンセツショウ チリョウヤク SI-613 ノ シツカンセツ ニ オケル ザンソンセイ ヒョウカ

抄録

Osteoarthritis is the most common joint disorder worldwide and one of the leading causes of disability in the elderly. We have reported that the novel sodium hyaluronate derivative chemically linked with diclofenac (DF), diclofenac etalhyaluronate (SI-613), exerted a potent and long-lasting analgesic effect in experimental arthritis models. In this study, we evaluated the properties of residual SI-613 in the knee joint after an intra-articular (IA) administration. After IA administration of fluorescent labeled SI-613 (FA-SI-613) or fluorescent labeled hyaluronic acid (FA-HA) to rabbits, fluorescence intensities in the synovial membrane and cartilage were higher in the FA-SI-613 group until 7 d after administration than in the FA-HA group. After IA administration of radiolabeled SI-613 (¹⁴C-SI-613) to rabbits, the radioactivity remained in the joint cavity and the joint tissues such as synovial membrane and cartilage until 84 d after administration. This residual radioactivity was identified mainly as HA linked with DF, since ¹⁴C-SI-613 was labeled at the benzene ring of DF and since more DF-linked HA oligomer was detected on metabolite analysis than free DF in the synovial membrane and synovial lavage fluid up to 28 d after administration. These results suggested that intra-articularly administered SI-613 remained for a longer time in the joint as HA linked with DF than when HA was administered. Therefore, SI-613 was considered to prolong the pharmacological effects of both HA and DF by remaining in the joint as HA linked with DF.

収録刊行物

• 薬学雑誌

  薬学雑誌 140 (9), 1141-1150, 2020-09-01

  公益社団法人 日本薬学会

キーワード

• osteoarthritis
• diclofenac etalhyaluronate
• residual property

詳細情報

• CRID: 1390003825209682944
• NII論文ID: 130007893761
• NII書誌ID: AN00284903
• DOI: 10.1248/yakushi.20-00008
• ISSN: 13475231
• ISSN: 00316903
• NDL書誌ID: 030646747
• PubMed: 32879246
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I030646747
• Web Site: https://www.jstage.jst.go.jp/article/yakushi/140/9/140_20-00008/_pdf
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可