JP2016166231A - 神経因性疾病の治療のための医薬 - Google Patents
神経因性疾病の治療のための医薬 Download PDFInfo
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Abstract
Description
例1
75 mgのプレガバリンを蒸留水3 mlに溶解した。この水溶液を頸椎症に起因すると診断される右腕(特に上腕部)の神経因性疼痛の患部である右腕上腕部を中心に塗布して乾燥させた。3 mlの水溶液で片腕全体(約500 cm2)に適用することができた。痛みの程度はグレード7(10点スケール)(睡眠の大きな障害)であった。痛みは30分程度で大きく軽快し(グレード3〜4)、鎮痛作用は6時間以上継続し、十分な睡眠が可能になった。
両肢ふくらはぎとした下肢に圧痛を感じ歩行に大きな支障のある痛みを訴える患者(73歳男性)の、より痛みの強い片足に例1の水溶液を1 mlを塗布した。およそ30分後に軽快感があり、12時間後には明らかに痛みは抑えられていた。3日間継続すると痛みは大幅に減衰し、投与していない下肢に比べて著しい効果が明確であった。4日目には未投与の肢に同じように投与を開始した。3日目で先に投与した肢と同じように痛みは軽快した。投与後のリバウンドはなかった。
第5腰椎の椎間板ヘルニアと診断された腰痛患者(64歳女性)での試験例:
腰の激痛で歩けなくなり、同時に肢の指先から付け根辺りまでしびれる患者にプレガバリンを投与した。
1月8日:神経ブロックしたが痛みはかわらない。
1月15日:プレガバリン(リリカ)、セレコックス、ガスターを処方される。リリカ(経口)は激しい眩暈と吐き気のため、自己判断で2日間で服用を停止。激痛としびれは2月上旬までつづく。
2月28日:プレガバリンの外用(例1の水溶液にヒアルロン酸0.1%を加えたものを一日2回痛みの部位〈腰、太もも、及び足のうしろ〉に2 mlずつ塗布した。3日目を過ぎて塗布後30分〜1時間ぐらいから全く痛みがなくなった。ただ、朝に塗布すると昼過ぎには痛みを感じる状態が約1ヶ月続いた。
4月22日:痛みが気にならなくなる時間が長くなり、通常の生活を送っている場合には、夕方頃から痛み出すが、激痛にはならなかった。痺れは続いた。
5月27日:外用を終了した。この間、ふらふらすることや皮膚が赤くなることはなかった。
例1において用いた蒸留水の代わりに食塩の等張液を用いて水溶液を調製した。
例5
例1において用いた蒸留水の代わりに蒸留水とエタノールの混合物(容量比9:1)を用いて水溶液を調製した。
例6
例1において用いたプレガバリンに代えてガバペンチン75 mgを用いて同様に水溶液を調製した。
プレガバリン75 mgを蒸留水(温水)2 mlに溶解し、この水溶液に0.25%のヒアルロン酸ナトリウム水溶液(1 ml)を加えて約3 mlの水溶液を調製した。
例8
例1で調製した水溶液に酢酸緩衝液を加えてpHを約5.5に調節した水溶液を調製した。
例9
例1で調整した水溶液に酢酸ナトリウム溶液を加えて、pH 8.7に調節した水溶液を調整した。
例10
例1で調製した水溶液に0.1%のエチルパラベンを添加して溶解させた水溶液を調製した。
ポリアクリル酸ナトリウム(日本触媒製、ポリアクリル酸ナトリウム HAS、(1.0%、10 ml)に例1と同様にして製したプレガバリン水溶液10 mlを加えた。本剤はこのまま患部に適用することができる。また、ポリアクリル酸ナトリウムの濃度を10%とした溶液に例1で製造した水溶液20 mlを加えてよく攪拌した後、コンディショニングミキサー(株式会社シンキー製、商品名:あわとり錬太郎)を用いて脱泡した。本剤をポリエステル製の不織布(日本バイリーン株式会社製、商品名:貼付薬用基布)の片面に2 mm厚で延伸塗布し、適度に水分を蒸発の後、塗布面をナイロンフィルムで覆い100 mm×50 mmに裁断した。
成人〈男性73歳〉の背中にプレガバリン150mgを含む水溶液を塗布した。塗布の後、血液を採取し、血漿を除蛋白の後ジニトロベンゼンスルフォニルクロリドと反応させ誘導体となし、LC/MSによりプレガバリンを定量した。投与後30分で9 ng/mlに達し、その後3時間以上その濃度を保っていた。
マウス(n=6)の神経L5、L6を絹糸で結索して疼痛モデルを作成した。対象にSham群を用意した(n=6)。4週間の後、測定の5分前にプレガバリン2.5 mg/mlあるいは7.5 mg/mlの水溶液(プレガバリン75 mgを蒸留水10 ml又は30 mlに溶解したもの)に右後脚全体の毛が湿るまで浸漬し、塗布30分後に自然乾燥した状態でvon Fryの標準針をもちいて疼痛閾値を測定し、その後、60分、90分、及び180分に同様に疼痛閾値を測定した。プレガバリンの低用量及び高用量ともに神経結索群の疼痛閾値に媒体溶媒群との間に統計的に有意な改善が認められ(図1及び2)、3時間後にもなお有効であった。
ラットの疼痛試験はSeltzer の方法に準じてモデルで実施した(Seltzer, Pain 1990,43, pp.205-218)。すなわち、イソフルランの2%吸入麻酔下でラットの左大腿部の皮膚を切開して坐骨神経を露出させ、その神経の1/2〜1/3を絹糸(8−0)結紮し、筋層を1〜2箇所縫合した。モデル作成後14日に左右足蹠の疼痛閾値を測定した。測定にはvon Freyのフィラメントを使用しアップダウン法により疼痛閾値を求めた。0.1%Tween80を含む水にプレガバリン10.0 mg/mLを溶解し、上記モデル作成後17日目に溶液0.10 mLを両肢の足蹠に塗布した。1、3、及び5時間後に左右の疼痛閾値(g)を測定した。疼痛モデル肢に1時間後に十分な閾値の上昇が見られた。表1にはモデル肢(左)、表2には正常肢(右)の結果を示す。正常肢にも閾値上昇が認められた。
Claims (5)
- 神経因性疾患の局所症状を治療するために外用剤として適用する医薬であって、ガバペンチン又はプレガバリン及び増粘剤を水溶液の形態で含み、ガバペンチン又はプレガバリンの経皮吸収を促進するための成分を含有しない医薬。
- 局所症状が疼痛又は掻痒感である請求項1に記載の医薬。
- 神経因性疾患が神経因性疼痛である請求項1又は2に記載の医薬。
- 局所症状がむずむず病である請求項1に記載の医薬。
- 虫刺されによる急性局所アレルギー症状又はアトピー性皮膚炎のの掻痒感を治療するために外用剤として適用する医薬であって、ガバペンチン又はプレガバリン及び増粘剤を水溶液の形態で含み、ガバペンチン又はプレガバリンの経皮吸収を促進するための成分を含有しない医薬。
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006511604A (ja) * | 2002-12-13 | 2006-04-06 | ワーナー−ランバート カンパニー リミティド ライアビリティー カンパニー | 線維筋痛症及び関連する他の障害の治療のためのプレガバリン及びその誘導体 |
WO2010036937A1 (en) * | 2008-09-27 | 2010-04-01 | Taraxos Inc. | Topical formulations for treatment of neuropathy |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1338779C (en) | 1989-03-17 | 1996-12-10 | Harry Hind | Method for treating pain associated with herpes-zoster and post-herpetic neuralgia by topical application of local anesthetics |
US6197819B1 (en) * | 1990-11-27 | 2001-03-06 | Northwestern University | Gamma amino butyric acid analogs and optical isomers |
NZ332762A (en) | 1996-07-24 | 2000-09-29 | Warner Lambert Co | Isobutylgaba and its derivatives for the treatment of pain |
US6572880B2 (en) | 1996-10-24 | 2003-06-03 | Pharmaceutical Applications Associates Llc | Methods and transdermal compositions for pain relief |
US6211171B1 (en) | 1998-05-19 | 2001-04-03 | Dalhousie University | Use of antidepressants for local analgesia |
DE60022333T2 (de) * | 1999-04-09 | 2006-07-06 | Euro-Celtique S.A. | Natrium kanalblocker zusammensetzungen und deren verwendung |
US7687080B2 (en) * | 2002-11-25 | 2010-03-30 | Taraxos Inc. | Treatment of neuropathy |
US20040265364A1 (en) | 2003-06-25 | 2004-12-30 | Binnur Ozturk | Neuropathy cream |
CA2537402C (en) | 2003-09-12 | 2009-05-05 | Pfizer Inc. | Combinations comprising alpha-2-delta ligands and serotonin / noradrenaline re-uptake inhibitors |
US20050209319A1 (en) * | 2004-03-18 | 2005-09-22 | Xenoport, Inc. | Treatment of local pain |
CN100395230C (zh) * | 2005-07-04 | 2008-06-18 | 上海华理生物医药有限公司 | 一种制备高纯度加巴喷丁的方法 |
GB2423711B (en) | 2005-10-24 | 2007-02-14 | Fortune Apex Dev Ltd | Method for preparing a pharmaceutical composition with enhanced mucoadhesion |
WO2008067991A2 (en) | 2006-12-08 | 2008-06-12 | Antares Pharma Ipl Ag | Skin-friendly drug complexes for transdermal administration |
AU2009269129B2 (en) | 2008-06-30 | 2015-08-20 | Afgin Pharma, Llc | Topical regional neuro-affective therapy |
US8394759B2 (en) | 2008-11-21 | 2013-03-12 | Cymbiotics, Inc. | Transdermal delivery of medicaments with combinations of cetylated fatty ester penetrant complexes |
EP2316420B1 (en) * | 2009-10-22 | 2014-02-26 | Consorzio Universitario Unifarm | Topical ophthalmic composition to reduce pain |
WO2014112152A1 (ja) * | 2013-01-18 | 2014-07-24 | 有限会社ケムフィズ | 神経因性疾病の治療のための医薬 |
WO2014168228A1 (ja) | 2013-04-12 | 2014-10-16 | マルホ株式会社 | 局所用組成物 |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006511604A (ja) * | 2002-12-13 | 2006-04-06 | ワーナー−ランバート カンパニー リミティド ライアビリティー カンパニー | 線維筋痛症及び関連する他の障害の治療のためのプレガバリン及びその誘導体 |
WO2010036937A1 (en) * | 2008-09-27 | 2010-04-01 | Taraxos Inc. | Topical formulations for treatment of neuropathy |
Non-Patent Citations (2)
Title |
---|
SOMMER, M ET AL.: "Pregabalin in restress legs syndrome with and without neuropathic pain", ACTA NEUROL. SCAND., vol. 115, no. 5, JPN6017017435, May 2007 (2007-05-01), pages 347 - 350 * |
中原保裕: "新薬の光と影 第42回 1)レグナイト錠300mg[レストレッグス症候群治療薬] 2)コルベット錠25mg[関節リウマチ", NURS. TODAY, vol. 27, no. 6, JPN6017017434, 15 November 2012 (2012-11-15), JP, pages 59 - 63 * |
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Free format text: JAPANESE INTERMEDIATE CODE: R250 |