JP5399898B2 - 神経因性疼痛の治療用カンナビノイド - Google Patents
神経因性疼痛の治療用カンナビノイド Download PDFInfo
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- JP5399898B2 JP5399898B2 JP2009517376A JP2009517376A JP5399898B2 JP 5399898 B2 JP5399898 B2 JP 5399898B2 JP 2009517376 A JP2009517376 A JP 2009517376A JP 2009517376 A JP2009517376 A JP 2009517376A JP 5399898 B2 JP5399898 B2 JP 5399898B2
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Description
疼痛は、患者が医療を模索する最も一般的な理由の一つであり、結果として、疼痛は働けなかった多大な日数/年をもたらす。
・ THCを抽出物中の総カンナビノイド含有量の90%より多く含む大麻ベース医学的抽出物と
・ CBDを抽出物中の総カンナビノイド含有量の90%より多く含む大麻ベース医学的抽出物
とから製剤化される。
多くの薬物に対して難治性の慢性疼痛を弱体化させる、神経因性疼痛を有効に治療することができる薬物が有意に必要である。
神経因性疼痛のラットモデルにおける侵害行動への大麻(Cannabis sativa)抽出物の影響
有痛性神経障害を200〜220 g重量のオスウィスター系ラットにて誘発させた(Harlan, Italy)。動物をペントバルビタールナトリウム(60 mg kg-1 i.p.)で麻酔し、外科手術を施してBennet&Xie(1988)により神経因性疼痛を誘発させた。
偽動物(結紮糸なしの坐骨神経曝露)を対照として用いた。
試験化合物をエタノール、クレモフォール(cremophor)および食塩水の1:1:18混合物に溶解した。
繰り返し投与研究にて、外科手術後7日目から開始して、ラットに試験化合物またはビヒクルを1日1回7日間経口投与した。
温熱性痛覚過敏はHargreaves手順(Hargreaves et al., 1988)により足底試験(Ugo Basile, Varese, Italy)を用いて試験した。
機械的異痛はダイナミック・プランター・アステシオメーター(Dynamic Plantar Aesthesiometer;Ugo Basile, Varese, Italy)を用いて評価した。特に、動物をワイヤーメッシュ床の試験ケージに置き、von Frey型フィラメントの先端を後ろ足の足底表面の中央部に適用した。フィラメントは検出の閾値以下の力にて開始して徐々に増大させ、動物がその足を取り出すまで増大させた。離脱閾値はgの許容レベルとして表現した。
1. 温熱性痛覚過敏における被験物質の急性投与の効果
以下の第2表は、傷害発症後14日における偽動物へのビヒクルの急性投与またはCCIの動物へのビヒクルもしくは被験物質の投与により得られたデータを記載する。Figure 2は温熱性痛覚過敏における被験物質またはビヒクルの急性投与の効果を示す。
ビヒクルで処置されたCCI動物にて、離脱待ち時間は完全な試験期間にわたり約5.5秒であった。
第2表およびFigure 2から分かるとおり、純粋THCはビヒクル処置動物よりも離脱待ち時間を増大した。純粋THCの疼痛緩和効果は、最初の行動評価点にて早くも投与後30分に開始された。離脱待ち時間はビヒクル処置動物よりも高かったが、離脱待ち時間は偽動物と同じレベルに達しなかった。疼痛緩和効果は研究期間にわたって減少し、投与後120分にてビヒクルおよび純粋THCの離脱待ち時間と差がなくなった。
CBD:THC(24:1)を含むカンナビノイド含有植物抽出物で処置した動物の離脱待ち時間は、偽動物および純粋THCで処置した動物の両方により産生されたものを超えた離脱待ち時間をもたらした試験期間の最初の90分を超えた離脱待ち時間の安定した増大を示した。カンナビノイド含有植物抽出物が純粋THCより疼痛の緩和に有効であり、他のいずれの被験物質よりも長い疼痛緩和プロフィールを産生することができることを示す。
以下の第3表は、傷害発症後14日における偽動物へのビヒクルの急性投与またはCCIの動物へのビヒクルもしくは被験物質の投与により得られたデータを記載する。Figure 3はこれらのデータを図的に記載する。
ビヒクルで処置されたCCI動物にて、離脱閾値は完全な試験期間にわたり10〜12 g程度であった。
第3表およびFigure 3から分かるとおり、純粋THCは投与後90分でビヒクル処置動物よりも離脱閾値を増大した。純粋THCの疼痛緩和効果は、離脱閾値がビヒクル処置動物のものまで減少した後、120分後に20 gのピークに達した。
CBD:THC(24:1)を含むカンナビノイド含有植物抽出物で処置した動物の離脱閾値は、被験物質が投与された後60分の離脱閾値における増大を示した。離脱閾値は26 gのこれらの動物にて120分後にピークに達し、次いで180分後にビヒクル処置動物により示されるように、同様の離脱待ち時間に減少した。
以下の第4表は、偽動物へのビヒクルの繰り返し投与またはCCIの動物へのビヒクルもしくは被験物質の投与により得られたデータを記載する。被験物質またはビヒクルは絞扼性神経損傷が適用された後7日で投与され、1日1回さらに7日間投与した。Figure 4はこれらのデータを図的に記載する。
薬物処置段階の開始前7日目にとった偽動物のデータを他の試験動物(すべてCCIである)と比較した場合、CCIが動物がより疼痛を感じる原因となったことが分かる。CCI前の離脱待ち時間はすべての動物について10〜11秒の間であったが、CCI後はすべてのCCI動物について離脱待ち時間が5.5秒程度劇的に減少した。
三つの被験物質、純粋THC、純粋CBD、およびCBD:THC(24:1)を含むカンナビノイド含有植物抽出物は非常に異なる結果を得たことが示された。
CBD:THC(24:1)を含むカンナビノイド含有植物抽出物で処置した動物の離脱待ち時間はまた、繰り返し投与の7日後の増大を示した。離脱待ち時間は被験物質の繰り返し投与後5秒〜10秒増大した。離脱待ち時間のレベルは、CCI前の動物により経験されたものと同様のレベルに達した。
以下の第5表は、偽動物へのビヒクルの繰り返し投与またはCCIの動物へのビヒクルもしくは被験物質の投与により得られたデータを記載する。被験物質またはビヒクルは絞扼性神経損傷が適用された後7日で投与され、1日1回さらに7日間投与した。Figure 5はこれらのデータを図的に記載する。
薬物処置段階の開始前7日目に取られた偽動物についてのデータを他の試験動物(すべてCCIである)と比較した場合に、CCIが動物がより疼痛を感じる原因となったことが分かった。CCI前の離脱閾値はすべての動物について30〜33 gであるが、CCI後のすべてのCCI動物についての離脱閾値は13 g程度まで劇的に減少した。
三つの被験物質、純粋THC、純粋CBD、およびCBD:THC(24:1)を含むカンナビノイド含有植物抽出物はまた、非常に異なる結果を得たことを示した。
CBD:THC(24:1)を含むカンナビノイド含有植物抽出物で処置した動物の離脱閾値はまた、繰り返し投与の7日後の増大も示した。離脱閾値は被験物質の繰り返し投与後に13 g〜22 gに増大した。
第6表は、百分率としてビヒクルと比較した場合の被験物質の平均疼痛緩和効果を示す。
急性投与試験にて、カンナビノイドCBDおよびTHCを含むカンナビノイド含有植物抽出物は、純粋化合物THCおよびCBDのいずれかよりも神経因性疼痛の緩和に明らかに有効であることが分かった。純粋THCは疼痛緩和効果を有することを示したが、この効果は長続きせず、ビヒクル処置動物と比較した場合の緩和量がカンナビノイド含有植物抽出物のものよりも低かった。
繰り返し投与試験にて、カンナビノイドCBDおよびTHCを含むカンナビノイド含有植物抽出物もまた、純粋化合物THCおよびCBDのいずれかよりも神経因性疼痛の緩和に有効であることが分かった。興味深いことに、急性投与実験における疼痛緩和を産生することが示された純粋THCよりも、純粋CBDは薬物の繰り返し投与後に疼痛緩和効果を産生した。上記略表は、この効果がカンナビノイドCBDおよびTHCを含むカンナビノイド含有植物抽出物ほど有効ではないことを示す。
これらのデータは、カンナビノイドCBDおよびTHCを含む一般的なカンナビノイド含有植物抽出物が神経因性疼痛の治療における使用に、より適切であることを示す。
神経因性疼痛の治療におけるカンナビノイド含有植物抽出物と鎮痛性医薬との同時投与の効果
異なる大麻ベース医学的抽出物(CBME)の6週間二重盲検、無作為、並列群、プラセボ対照研究を開始した。研究された被験物質はCBME THC:CBD(1:1)およびマッチング・プラセボであった。
研究医薬は、研究期間を通して患者の既存薬との併用を維持されるものである。患者により臨床で摂取されるすべての医薬の概要は以下の第8表に示す。
Claims (15)
- 末梢神経因性疼痛の治療のための医薬の製造におけるカンナビジオール(CBD)およびテトラヒドロカンナビノール(THC)を含む大麻ベース医学的抽出物(CBME)の使用であって、CBDのTHCに対する重量比が18:1〜30:1である、使用。
- 末梢神経因性疼痛に関連する睡眠障害の治療のための医薬の製造における、請求項1記載のCBMEの使用。
- 純粋THCよりも長い疼痛緩和プロフィールを有する医薬の製造における請求項1または2のいずれか記載のCBMEの使用。
- 急性投与のための医薬の製造における請求項1〜3のいずれか記載のCBMEの使用。
- 毎日繰り返し投与後の疼痛緩和を生じる医薬の製造における請求項1〜3のいずれか記載のCBMEの使用。
- 急性投与後および毎日繰り返し投与後の両方の疼痛緩和を提供する医薬の製造における請求項4または5のいずれか記載のCBMEの使用。
- CBD:THCの重量比が22:1〜26:1である、請求項1〜6のいずれか記載のCBMEの使用。
- CBD:THCの重量比が24:1である、請求項1〜7のいずれか記載のCBMEの使用。
- 送達が舌下;口腔;非経口;経口;直腸、鼻腔および肺系統からなる群から選択される領域に標的化されるように医薬が梱包される、請求項1〜8のいずれか記載のCBMEの使用。
- 医薬がゲル;ゲルスプレー;錠剤;液剤;カプセルおよび蒸気用からなる群から選択される形態である、請求項9記載のCBMEの使用。
- 医薬が:
a)THCを抽出物中の総カンナビノイド含有量の90%より多く含む大麻ベース医学的抽出物と
b)CBDを抽出物中の総カンナビノイド含有量の90%より多く含む大麻ベース医学的抽出物
との比率化された生成物として製剤化される、請求項1〜10のいずれか記載のCBMEの使用。 - 1以上の他の薬剤との併用である、請求項1〜11のいずれか記載のCBMEの使用。
- 1以上の他の薬剤が1以上の鎮痛剤である、請求項12記載のCBMEの使用。
- 1以上の他の薬剤が1以上のアヘン剤またはアヘン関連薬剤、1以上の抗痙攣剤、および1以上の抗うつ薬からなる群から選択される、請求項12記載のCBMEの使用。
- 1以上の他の薬物と別々に、同時にまたは連続して投与される、請求項12〜14のいずれか記載のCBMEの使用。
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GB2439393B (en) * | 2006-06-23 | 2011-05-11 | Gw Pharma Ltd | Cannabinoids for use in the treatment of neuropathic pain |
GB2450753B (en) * | 2007-07-06 | 2012-07-18 | Gw Pharma Ltd | New Pharmaceutical formulation |
ES2534900T3 (es) | 2007-07-30 | 2015-04-30 | Zynerba Pharmaceuticals, Inc. | Profármacos de cannabidiol, composiciones que comprenden los profármacos de cannabidiol y métodos de uso de los mismos |
GB2456183A (en) * | 2008-01-04 | 2009-07-08 | Gw Pharma Ltd | Anti-psychotic composition comprising cannabinoids and anti-psychotic medicament |
GB2471523A (en) * | 2009-07-03 | 2011-01-05 | Gw Pharma Ltd | Use of tetrahydrocannibivarin (THCV) and optionally cannabidiol (CBD) in the treatment of epilepsy |
GB2478595B (en) * | 2010-03-12 | 2018-04-04 | Gw Pharma Ltd | Phytocannabinoids in the treatment of glioma |
US8445034B1 (en) | 2010-11-02 | 2013-05-21 | Albert L Coles, Jr. | Systems and methods for producing organic cannabis tincture |
GB2524689B (en) * | 2011-05-20 | 2016-01-27 | Gw Pharma Ltd | Cannabinoids for use in the treatment of neuropathic pain |
US20150313868A1 (en) | 2012-12-18 | 2015-11-05 | Kotzker Consulting Llc | Use of cannabinoids and terpenes for treatment of organophosphate and carbamate toxicity |
GB2516814B (en) | 2013-06-19 | 2016-08-31 | Otsuka Pharma Co Ltd | Use of phytocannabinoids for increasing radiosensitivity in the treatment of cancer |
GB2524469A (en) | 2014-02-14 | 2015-09-30 | Kind Consumer Ltd | A cannabinoid inhaler and composition therefor |
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GB2391865B (en) * | 2002-08-14 | 2005-06-01 | Gw Pharma Ltd | Improvements in the extraction of pharmaceutically active components from plant materials |
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GB2414933B (en) * | 2004-06-08 | 2009-07-15 | Gw Pharma Ltd | Cannabinoid compositions for the treatment of disease and/or symptoms in arthritis |
GB2439393B (en) * | 2006-06-23 | 2011-05-11 | Gw Pharma Ltd | Cannabinoids for use in the treatment of neuropathic pain |
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2007
- 2007-06-21 JP JP2009517376A patent/JP5399898B2/ja active Active
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JP2009541479A (ja) | 2009-11-26 |
US20100016418A1 (en) | 2010-01-21 |
CA2656698C (en) | 2015-10-13 |
US20190224140A1 (en) | 2019-07-25 |
GB0612512D0 (en) | 2006-08-02 |
GB2439393B (en) | 2011-05-11 |
WO2007148094A1 (en) | 2007-12-27 |
EP2037902B1 (en) | 2013-07-03 |
GB2439393A (en) | 2007-12-27 |
ES2429406T3 (es) | 2013-11-14 |
US20120245224A1 (en) | 2012-09-27 |
EP2037902A1 (en) | 2009-03-25 |
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