JP2021526137A - 軟骨損傷関連の疾患を処置するための、ヒアルロン酸及び幹細胞を含む医薬組成物 - Google Patents
軟骨損傷関連の疾患を処置するための、ヒアルロン酸及び幹細胞を含む医薬組成物 Download PDFInfo
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- JP2021526137A JP2021526137A JP2020564727A JP2020564727A JP2021526137A JP 2021526137 A JP2021526137 A JP 2021526137A JP 2020564727 A JP2020564727 A JP 2020564727A JP 2020564727 A JP2020564727 A JP 2020564727A JP 2021526137 A JP2021526137 A JP 2021526137A
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- hyaluronic acid
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Abstract
Description
変形性関節症誘発ラットを生成するため、スプラーグドーリーラットに、5mg/kgの用量でZoletil 50(VIRBAC、France)及び2.5mg/kgの用量でキシラジン(ロンプン(Rompun)(登録商標))、Bayer AG、Germany)の腹腔内投与によって麻酔をかけた。次いで、クリッパーを使用して、両膝の周りの部域を剃毛した。切開されるべき部域をポビドン及び70%アルコールで消毒し、次いで、膝皮膚を切開した。周辺の皮膚組織を鈍的切開にかけることで、右大腿骨の遠位端部で関節表面を露出した。次いで、前十字靱帯を剪刀でカットし、4〜0ナイロンを使用して創傷を縫合した。7日後、軟骨の破壊及び疼痛を引き起こすヨード酢酸一ナトリウム(MIA)を1mlのシリンジに充填し、50μlの量にて60mg/mlの濃度で関節内投与した。左膝については、前十字靱帯をカットすることなくMIAの投与のみを行った。
実施例2:組織病理学的検査
各群におけるラットを16週目に屠殺し、関節組織を回収した。次いで、組織を脱ミネラル化、トリミング、脱水、パラフィン包埋及びミクロトームカッティングにかけることで、組織病理学的検査のための標本を調製した。次いで、ヘマトキシリン及びエオシン(H&E)、サフラニン−O、並びに抗II型コラーゲン抗体を使用して染色を行い、光学顕微鏡(オリンパスBX53、日本)を使用して観察を行った(図1及び図2)。
実施例3:重量負荷試験
Panlabインキャパシタンス試験器を使用し、薬物投与後0週目及び16週目にプラスチック固定具をラットに60度の傾斜で直立させるようにすること、及び次いで、各群におけるラットの後肢に10秒間適用された力の平均を算出することによって、重量負荷試験を行った。薬物が注射された後肢に分布された体重の百分率を、以下の算出式を介して測定した(図3)。
結果として、薬物投与後16週目で、全ての関節炎誘発群(G2〜G5)は、重量負荷の点で、G1群(p<0.001)よりも統計的に有意に低いことが示された。加えて、G4群は、G3群(p<0.05)と比較して、有意に改善された重量負荷を有していた。さらに、G5群は、G3群及びG4群(p<0.05及びp<0.001)と比較して、有意に改善された重量負荷を有していた。これらの結果から、ヒアルロン酸が最初に投与され、その後に間葉系幹細胞の投与が続いた場合において、こうした順序で行われた投与は、重量負荷によって引き起こされる疼痛を緩和し得ることが同定された(図4)。
実施例4:マイクロコンピューター断層撮影(マイクロCT)
薬物投与の前に及び16週目で屠殺の後にマイクロCTによって、膝関節における損傷部域の写真を撮った。プログラム(HP DECwindows Motif for OpenVMS、バージョン1.7)を用いて、脛骨及び大腿骨の横断面画像における構造要素及び骨密度を分析することによって、膝関節の評価を行った。
Claims (9)
- ヒアルロン酸;及び
間葉系幹細胞
を含む、軟骨損傷関連の疾患を処置するための医薬組成物であって、
医薬組成物がそれを必要とする患者に投与される場合、ヒアルロン酸が最初に投与され、その後に間葉系幹の投与が続く、
医薬組成物。 - ヒアルロン酸が、0.5%(w/v)〜2.0%(w/v)の濃度を有する、請求項1に記載の医薬組成物。
- 間葉系幹細胞が、1.0×105細胞/ml〜1.0×108細胞/mlの量で含有される、請求項1に記載の医薬組成物。
- ヒアルロン酸が、0.5%(w/v)〜2.0%(w/v)の濃度を有し、間葉系幹細胞が、1.0×105細胞/ml〜1.0×108細胞/mlの量で含有される、請求項1に記載の医薬組成物。
- 間葉系幹細胞が、臍帯血から誘導される、請求項1に記載の医薬組成物。
- 軟骨損傷関連の疾患が、変形性関節症、半月板断裂、変形関節炎又は軟骨軟化症である、請求項1に記載の医薬組成物。
- 変形性関節症が起こる部位が、顎関節、肩関節、肘関節、手首関節、手指関節、脊椎関節、股関節、膝関節、足首関節又はつま先関節である、請求項6に記載の医薬組成物。
- 関節内投与される、請求項1に記載の医薬組成物。
- (i)ヒアルロン酸を個体に投与するステップ;及び
(ii)ステップ(i)の後で間葉系幹細胞を個体に投与するステップ
を含む、軟骨損傷関連の疾患を処置するための方法。
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CA3100471A1 (en) | 2019-12-12 |
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