JP6875988B2 - 損傷末梢神経治療用組成物 - Google Patents
損傷末梢神経治療用組成物 Download PDFInfo
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- JP6875988B2 JP6875988B2 JP2017527465A JP2017527465A JP6875988B2 JP 6875988 B2 JP6875988 B2 JP 6875988B2 JP 2017527465 A JP2017527465 A JP 2017527465A JP 2017527465 A JP2017527465 A JP 2017527465A JP 6875988 B2 JP6875988 B2 JP 6875988B2
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7008—Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7012—Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid
Description
粘度平均分子量 = ((極限粘度(dL/g))×105/36)1/0.78
・レオメーター:回転式(例えばアントン・パール社製MCR300)
・測定治具:コーンプレート型治具(例えばアントン・パール社製CP50−1)
・測定温度:25℃
・剪断速度:0.1(1/s)
粘度平均分子量190万のヒアルロン酸ナトリウム(電気化学工業社製)を乾燥重量として10.0g採取し、滅菌済の2Lの円筒形プラスチックボトル(コーニング社製)に無菌的に入れた。ここに、無菌的に調製した1Lのリン酸緩衝生理食塩液(pH7.2)を加えて振り混ぜた。これを室温で1日間、攪拌溶解し、「1.0w/v%−Mη190万試料」とした。なおヒアルロン酸ナトリウムの乾燥重量は、湿重量と、第十六改正日本薬局方 医薬品各条 精製ヒアルロン酸ナトリウムの乾燥減量の項で求めた乾燥減量値から求めた。
粘度平均分子量190万のヒアルロン酸ナトリウム(電気化学工業社製)を乾燥重量として20.0g採取した以外は、試料調製例1と同様に行い、「2.0w/v%−Mη190万試料」とした。
粘度平均分子量190万のヒアルロン酸ナトリウム(電気化学工業社製)を乾燥重量として30.0g採取した以外は、試料調製例1と同様に行い、「3.0w/v%−Mη190万試料」とした。
粘度測定装置であるレオメーターとして、MCR300(商品名、アントン・パール製)を使用した。コーンプレートはCP50−1(コーン角1.009°,D=49.938mm)を用い、測定温度25℃、剪断速度:0.01〜1000(1/s)(せんだん速度の対数が一定間隔となるよう増加)、測定点数:51点、試料量:0.6mL、測定時間:10秒/点にて測定した。得られたデータのうち、剪断速度0.1(1/s)に最も近く、0.1(1/s)を挟む2点のデータを基に、補間法により剪断速度0.1(1/s)における粘度の値を算出した。表1に粘度の測定結果を示す。
第十六改正日本薬局方 医薬品各条 精製ヒアルロン酸ナトリウム の項に準じて、ウベローデ型粘度計で測定した時の流下時間が0.2mol/L塩化ナトリウム試液の2.0〜2.4倍となるよう、0.2mol/L塩化ナトリウム試液にて希釈し、この液をさらに4段階に希釈し、第十六改正日本薬局方 一般試験法 粘度測定法 第1法に従いウベローデ型粘度計にて各試料の流下時間を測定、極限粘度を算出した。極限粘度の値からは、下記の式にて粘度平均分子量を算出した。表2に粘度平均分子量の測定結果を示す。
粘度平均分子量 = ((極限粘度(dL/g))×105/36)1/0.78
ヒアルロン酸ナトリウムが神経損傷時における神経腫発生に及ぼす作用を、ラット実験的神経損傷モデルを用いて検討した。
動物としては、6週齢のSDラット(体重230−250g)、雄16匹を用いた。動物は、可動式ラックに装着したブラケット式金属製金網床ケージ(292W×400D×200H mm)にまとめて収容し、温度23±2℃、湿度50±10%、換気回数10〜15回/時間、照明時間8:00〜20:00(明12時間、暗12時間)の環境下で飼育した。動物を入荷後10日間馴化させた。
術後3週間で全てのラットを灌流固定した。セボフルラン麻酔後、8%抱水クロラール0.5ml/100g とヘパリン1cc投与を腹腔内投与した。開胸して右心房を切開して生理食塩水を左心室に投与した後に4%パラホルムアルデヒドを続けて注射して固定を行った。その後、一晩後固定を行い、PBSで洗浄した。手術部位を含む下顎を摘出し、50%ギ酸と20%クエン酸を等量混和した脱灰液に浸漬して、1週間脱灰を行った。脱水した後にパラフィンで包埋した。
形態学的観察のためにはアザン染色を用いた。包埋した切片を脱パラフィンした。その後60℃アゾカルミン液、0.1%アニリンアルコール、酢酸アルコールに順次浸漬し、さらに5%リンタングステン酸に浸漬してアニリンブルー・オレンジG液に漬けた。水洗した後、純アルコールで分別し、封入した後に顕微鏡下で切断神経の再生とその周囲の骨変化を観察した。
Claims (5)
- 損傷した末梢神経の損傷箇所の瘢痕化を防止又は抑制するための組成物であって、
脂質が結合していないGlcNAc及びGlcAを構成糖とする糖又はその塩を0.01w/v%以上3.5w/v%以下の濃度で含有し、
前記GlcNAc及びGlcAを構成糖とする糖又はその塩の粘度平均分子量が150万超であり、
前記組成物は、前記末梢神経を治療すると共に骨形成を促進することを特徴とする、組成物。 - 前記GlcNAc及びGlcAを構成糖とする糖又はその塩は、0.8w/v%以上3.5w/v%以下の濃度で含有することを特徴とする、請求項1に記載の組成物。
- 前記末梢神経は、三叉神経であることを特徴とする、請求項1又は2に記載の組成物。
- 前記GlcNAc及びGlcAを構成糖とする糖又はその塩の、25℃、せん断速度0.1s−1における粘度が1000mPa・s以上であることを特徴とする、請求項1から3のいずれかに記載の組成物。
- 前記GlcNAc及びGlcAを構成糖とする糖は、ヒアルロン酸である、請求項1から4のいずれかに記載の組成物。
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