JP2010037302A - 医薬組成物及び関節障害の予防治療剤 - Google Patents
医薬組成物及び関節障害の予防治療剤 Download PDFInfo
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- JP2010037302A JP2010037302A JP2008204339A JP2008204339A JP2010037302A JP 2010037302 A JP2010037302 A JP 2010037302A JP 2008204339 A JP2008204339 A JP 2008204339A JP 2008204339 A JP2008204339 A JP 2008204339A JP 2010037302 A JP2010037302 A JP 2010037302A
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Abstract
【解決手段】医薬組成物及び予防治療剤は、ビタミンB1類(フルスルチアミン又はその塩など)、グリコサミノグリカン類(コンドロイチン硫酸又はその塩など)およびグルクロン酸類(グルクロン酸又はその塩、アミド、鎖状エステル又はラクトン)を含有し、関節炎又は関節症、変形性関節症、関節機能障害の予防又は治療に有用である。
【選択図】図1
Description
フルスルチアミン塩酸塩、コンドロイチン硫酸ナトリウム及びグルクロノラクトンの併用経口投与による軟骨変性抑制作用について、ウサギの膝関節半月板部分切除による実験的変形性関節症モデルを用いて検討した。試験には14〜15週齢の雄性ウサギ(Kbl:JW、北山ラベス株式会社)32羽を使用した。動物を1群8羽の4群に分け、下記の群構成で被験薬を4週間経口投与した。なお、被験薬は純水を用いて懸濁し、直近に測定した各個体の体重を基準に8mL/kgの投与液量で強制経口投与した。
グルクロノラクトン(被験物質A)、コンドロイチン硫酸ナトリウム(被験物質B)、フルスルチアミン塩酸塩(被験物質C)を用い、被験薬群として、被験薬1(被験物質A単独)投与群、被験薬2(被験物質B+C)投与群及び被験薬3(被験物質A+B+C)投与群の3群、および媒体(純水)投与の対照群を加え、計4群を用いた。詳細は以下の通りである。
コンドロイチン硫酸ナトリウム及びフルスルチアミン塩酸塩の投与量は、下記文献1(小林らの同種試験の報告)を参考に設定した。グルクロノラクトンの投与量は、本試験に先行して実施の予備的検討(ウサギ膝関節半月板部分切除による実験的変形性関節症に対するグルクロノラクトン等経口投与の作用)で、グルクロノラクトン2用量(200mg/kg/日及び1000mg/kg/日)とコンドロイチン硫酸ナトリウム(800mg/kg/日)及びフルスルチアミン塩酸塩(109.16mg/kg/日)の組み合わせの試験結果から、軟骨変性抑制作用を認めた1000mg/kg/日の投与量を選択した。
下記文献2(舘田らの方法)及び文献3(野地らの方法)を参考に、ウサギの半月板部分切除変形性関節症モデルを作製した。塩酸ケタミン及びキシラジンによる併用麻酔下で、ウサギの外側側副靭帯及び膝窩筋起始部の腱を切断し、外側半月板のほぼ中央部を1.5−2.0 mm切除した。
関節液の採取後、左側膝関節部位の大腿骨顆部及び脛骨顆部を摘出し、摘出組織を0.5%セチルピリジニウムクロライド含有10%中性緩衝ホルマリン液にて固定した。
大腿骨と脛骨の関節軟骨組織病変の発現範囲(傷害面積)をトレースし、画像処理ソフトを用いて傷害面積を算出した。なお、計測時に主観が入ることを避けるため、盲検化を行って実施した。
下記文献3(野地らの方法)に従い大腿骨及び脛骨関節軟骨の病理組織標本を作製した。
傷害面積及び病理組織学的検査における評価項目の合計評点について、各群で平均値及び標準誤差を算出した。有意差検定は、対照群と各被験薬投与群との間で実施した。
文献2:舘田智昭,永峯春代,岩館克治,中村亨 表題「ウサギの実験的変形性関節症(OA)モデルおよび固定関節拘縮(PS)モデルにおけるヒアルロン酸ナトリウム製剤(ME3710)の薬効薬理試験」「薬理と治療」1995;23:833−41
文献3:野地裕美,八木直美,小田康弘,岩館克治,田元浩一,関川彬 表題「室温保存可能な新規高分子ヒアルロン酸ナトリウム製剤の生物学的同等性試験」「薬理と治療」2005;33:303−12
文献4:Colombo C, Butler M, O’Byrne E, Hickman L, Swartzendruber D, Selwyn M, Steinetz B. A new model of osteoarthritis in rabbits. I. Development of knee joint pathology following lateral meniscectomy and section of the fibular collateral and sesamoid ligaments. Arthritis Rheum 1983; 26: 875-86
文献5:Kikuchi T, Yamada H, Shinmei M. Effect of high molecular weight hyaluronanon articular cartilage degeneration in a rabbit model of osteoarthritis. Osteoarthritis and Cartilage 1995; 4: 99-110。
流動層造粒機(FD−3S型、パウレック(株))にフルスルチアミン塩酸塩218.32g、コンドロイチン硫酸ナトリウム1600g、粉末還元麦芽糖水アメ419.56gを加え、0.04重量%シアノコバラミン溶液を300g噴霧した後、8重量%ヒドロキシプロピルセルロースの水溶液600gを噴霧して造粒後、粉砕(パワーミル、昭和化学機械(株))してT群整粒末を得た。次に流動層造粒機(FD−3S型、パウレック(株))にピリドキシン塩酸塩40gとグルクロノラクトン(市販品を平均粒子径約35μm、粒度範囲23.8〜52.6μmに粉砕した粉砕物、以下同じ)2000gと粉末還元麦芽糖水アメ142gとを加え、8重量%ヒドロキシプロピルセルロースの水溶液850gを噴霧して造粒後、粉砕(パワーミル、昭和化学機械(株))してB群整粒末を得た。T群整粒末2057.4g及びB群整粒末2025gにクロスポビドン162g、ステアリン酸マグネシウム21.6gを加えて混合し、得られた混合末をロータリー式打錠機で直径9.5mmの臼、局率半径8mmのR面杵にて製錠し、素錠(1錠当たりの重量395mg、厚み5.5mm)を得た。
製剤例1と同様にしてT群整粒末を得た。次に流動層造粒機(FD−3S型、パウレック(株))にピリドキシン塩酸塩40gとグルクロノラクトン2000gに粉末還元麦芽糖水アメ316gを加え、8重量%ヒドロキシプロピルセルロースの水溶液925gを噴霧して造粒後、粉砕(パワーミル、昭和化学機械(株))してB群整粒末を得た。T群整粒末2057.4g、B群整粒末2187gにステアリン酸マグネシウム21.6gを加えて混合して混合し、製剤例1と同様にして素錠及びフィルムコーティング錠を得た。
製剤例1と同様にして得られたT群整粒末2057.4g及びB群整粒末2025gにクロスカルメロースナトリウム162g、ステアリン酸マグネシウム21.6gを加えて混合し、得られた混合末をロータリー式打錠機で打錠する以外、製剤例1と同様にして、素錠およびフィルムコーティング錠を得た。
Claims (11)
- ビタミンB1類、グリコサミノグリカン類およびグルクロン酸類を含有する医薬組成物。
- フルスルチアミン又はその塩と、コンドロイチン硫酸又はその塩と、グルクロン酸又はその塩、そのアミド、その鎖状エステル及びそのラクトンから選択された少なくとも一種とを含む請求項1記載の医薬組成物。
- ビタミンB1類、グリコサミノグリカン類およびグルクロン酸類を含有する、変形性又は炎症性関節障害の予防治療剤。
- フルスルチアミン又はその塩と、コンドロイチン硫酸又はその塩と、グルクロン酸又はその塩、アミド、鎖状エステル及びラクトンから選択された少なくとも一種とを含む請求項3記載の予防治療剤。
- 関節炎又は関節症の予防治療剤である請求項3又は4記載の予防治療剤。
- 変形性関節症の予防治療剤である請求項3〜5のいずれかに記載の予防治療剤。
- 関節機能障害の予防治療剤である請求項3〜6のいずれかに記載の予防治療剤。
- 関節痛の予防治療剤である請求項3〜7のいずれかに記載の予防治療剤。
- 関節炎又は関節症における疼痛を緩和する請求項3〜8のいずれかに記載の予防治療剤。
- グリコサミノグリカン類を含む製剤群と、グルクロン酸類を含む製剤群とに分離され、ビタミンB1類が、グリコサミノグリカン類を含む製剤群及びグルクロン酸類を含む製剤群の少なくとも一方の製剤群又は他の製剤群に含有されている請求項3〜9のいずれかに記載の予防治療剤。
- ビタミンB1類、グリコサミノグリカン類、及びグルクロン酸類のうち、(1)2つの成分を含む製剤および1つの成分を含む製剤、又は(2)各成分をそれぞれ含む3つの製剤で構成された医薬キット。
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JP2002145779A (ja) * | 2000-11-10 | 2002-05-22 | Rohto Pharmaceut Co Ltd | 関節痛治療または予防用組成物 |
JP2004010533A (ja) * | 2002-06-06 | 2004-01-15 | Koyo Chemical Kk | 軟骨生成促進剤及び軟骨損傷由来疾病予防治療剤 |
JP2007161688A (ja) * | 2005-12-16 | 2007-06-28 | Hiroshima Univ | 軟骨生成促進剤 |
JP2010024181A (ja) * | 2008-07-18 | 2010-02-04 | Takeda Chem Ind Ltd | 固形製剤及びその製造方法 |
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JP2002145779A (ja) * | 2000-11-10 | 2002-05-22 | Rohto Pharmaceut Co Ltd | 関節痛治療または予防用組成物 |
JP2004010533A (ja) * | 2002-06-06 | 2004-01-15 | Koyo Chemical Kk | 軟骨生成促進剤及び軟骨損傷由来疾病予防治療剤 |
JP2007161688A (ja) * | 2005-12-16 | 2007-06-28 | Hiroshima Univ | 軟骨生成促進剤 |
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