JP6324751B2 - 変形性関節症改善剤及びその製造方法 - Google Patents
変形性関節症改善剤及びその製造方法 Download PDFInfo
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- JP6324751B2 JP6324751B2 JP2014026063A JP2014026063A JP6324751B2 JP 6324751 B2 JP6324751 B2 JP 6324751B2 JP 2014026063 A JP2014026063 A JP 2014026063A JP 2014026063 A JP2014026063 A JP 2014026063A JP 6324751 B2 JP6324751 B2 JP 6324751B2
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- ethanol
- osteoarthritis
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- licorice
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- 201000008482 osteoarthritis Diseases 0.000 title claims description 25
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 48
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 claims description 16
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 claims description 15
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 claims description 15
- 229940010454 licorice Drugs 0.000 claims description 15
- 239000003795 chemical substances by application Substances 0.000 claims description 13
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000007787 solid Substances 0.000 claims description 8
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- 229960004949 glycyrrhizic acid Drugs 0.000 description 6
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 6
- 235000019410 glycyrrhizin Nutrition 0.000 description 6
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 6
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Description
下記方法で甘草抽出物を得た。
甘草(グリチルリイザ グラブラ:Glycyrrhiza glabra)の根茎を粉砕し、チップ状にした。この甘草チップ1.0kgを10Lの3%アンモニア水(pH10)で一晩抽出した後、固液分離した。得られた抽出液に対し、1%硫酸溶液により酸性析出処理を行い、グリチルリチン酸等を沈殿させ、濾過により沈殿物及び抽出濾液に分けた。この内、沈殿物にエタノール1Lを加え、常温で1時間攪拌し、濾過を行った。ろ物を回収し乾燥させることで、20gの褐色抽出物粉末であるエタノール不溶部(甘草抽出物)を得た。このエタノール不溶部(甘草抽出物)のタンパク質含量は35%であった。得られたエタノール不溶部(甘草抽出物)について、変形性関節症動物モデルであるSTR/ortマウスを用いて、変形性関節症の評価に用いられるMankin法及びOARSI法、関節軟骨分解マーカーであるCOMPを用いて、下記試験を行った。
<マウス群>
(1)(−)control群:変形性関節症非発症群(n=9)
ノーマルマウス(雌マウス)
(2)(+)control群:変形性関節症発症群(n=9)
変形性関節症動物モデルであるSTR/ortマウス(雄マウス)
(3)エタノール不溶部(甘草抽出物):変形性関節症発症群(n=7)
変形性関節症動物モデルであるSTR/ortマウス(雄マウス)
<サンプル投与量>
(1)(−)control群:サンプル無投与
(2)(+)control群:サンプル無投与
(3)エタノール不溶部(甘草抽出物)群:23mg/kg(体重),
サンプル投与は胃ゾンデにより、毎日1ヵ月間行なう。投与開始週齢(31〜34週齢)に達した個体から投与を順次開始した。投与開始から1ヵ月後、解剖を行う。解剖時の週齢が揃うように解剖を行なった。
[病理切片]
投与開始から一カ月後に解剖を行い、マウスの血液、尿、両後肢を採取した。病理用左脚は大腿骨骨端から脛骨骨端を採取し、マイルドホルムにて固定する。その後、パラフィン固定切片を作製する。切片はヘマトキシリン・エオシン染色、サフラニン−O染色で染色し、病理切片における関節軟骨の組織学的変性度について、Mankin法及びOARSI法で評価し、スコア化した。
[血清]
血清中の関節軟骨分解マーカーであるCOMPの測定を行った。血清は解剖時に採血した物を、−4℃で24時間静置した後、回収した。回収した血清は−80℃で保存し、分析に用いた。COMPの分析はELISA Kit(96well)Animal COMP ELISA(AMM社)のものを用いた。結果を図1〜3に示す。
[配合例1]
常法により、以下の組成を有する錠剤を製造した。
エタノール不溶部(甘草抽出物) 50.0mg
ヒアルロン酸 50.0mg
マルチトール 185.0mg
ショ糖脂肪酸エステル 15.0mg
合計 300.0mg
常法により、以下の組成を有する錠剤を製造した。
エタノール不溶部(甘草抽出物) 10.0mg
グルコサミン 200.0mg
デキストリン 125.0mg
ショ糖脂肪酸エステル 15.0mg
合計 350.0mg
常法により、以下の組成を有するカプセル剤を製造した。なお、カプセルとしては、1
号ハードゼラチンカプセルを使用した。
<1カプセル(1錠200mg)中の組成>
エタノール不溶部(甘草抽出物) 30.0mg
コーンスターチ 70.0mg
乳糖 80.0mg
乳酸カルシウム 10.0mg
ヒドロキシプロピルセルロース(HPC−L) 10.0mg
合計 200.0mg
常法により、以下の組成を有する経口液状製剤を製造した。
<1アンプル(1本100mL)中の組成>
エタノール不溶部(甘草抽出物) 0.1質量%
果糖ぶどう糖液糖 12.0質量%
トレハロース 3.0質量%
香料 0.5質量%
ステビア抽出物 0.1質量%
ビタミンC 0.1質量%
安息香酸ナトリウム 0.1質量%
精製水 残部
合計 100.0質量%
Claims (4)
- 甘草の中性乃至アルカリ性水抽出液を酸処理することにより生成した沈殿物を、エタノール処理した後のエタノール不溶部を有効成分として含有する変形性関節症改善剤。
- 変形性膝関節症改善剤である請求項1記載の変形性関節症改善剤。
- エタノール不溶部中のタンパク質含有量が、5〜50質量%(固形分)である請求項1又は2記載の変形性関節症改善剤。
- 甘草の中性乃至アルカリ性水抽出液を、酸処理することにより沈殿物を生成させ、得られた沈殿物をエタノール処理し、エタノール処理後のエタノール不溶部を得る工程を含む、前記エタノール不溶部を有効成分として含有する変形性関節症改善剤を製造する製造方法。
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