JP5690732B2 - 群発頭痛障害を治療するための方法及びキット - Google Patents
群発頭痛障害を治療するための方法及びキット Download PDFInfo
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- JP5690732B2 JP5690732B2 JP2011526923A JP2011526923A JP5690732B2 JP 5690732 B2 JP5690732 B2 JP 5690732B2 JP 2011526923 A JP2011526923 A JP 2011526923A JP 2011526923 A JP2011526923 A JP 2011526923A JP 5690732 B2 JP5690732 B2 JP 5690732B2
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Description
ブロモ-LSD、BOL、BOL 148、(8β)-2-ブロモ-9,10-ジデヒドロ-N,N-ジエチル-6-メチルエルゴリン-8-カルボキサミド、2-ブロモ-N,N-ジエチル-D-リセルガミド、及びブロモリセルギドとしても知られる化合物2-ブロモリセルグ酸ジエチルアミドは以下の構造を有する:
ブロモリセルギドの製剤としては、限定するものではないが、溶液剤、懸濁液剤、錠剤、又はカプセル剤が挙げられる。製剤の製造のために当技術分野で周知の方法は、例えば、「Remington: The Science and Practice of Pharmacy」 (第21版) A.R. Gennaro編, 2005, Lippincott, Philadelphia, PAに見られる。製剤中の化合物の濃度は、投与容量及び投与経路を含む多数の因子により変化するであろう。投与対象の薬物の投与量は、障害の重症度、該当する被験者の全体的な健康状態、化合物の製剤及び投与経路などの可変要素に依存する場合が多い。
頻発性群発頭痛障害を有する被験者を治療するために、ブロモリセルギドを投与することができる。頻発性群発頭痛障害は、反復性又は慢性であり得る。本発明のこの実施形態では、ブロモリセルギド投与の治療効果としては、発作中に被験者が見舞われる痛みの減少又は除去、群発期中の発作の頻度の減少、又は群発頭痛障害に伴う他の症状の緩和が挙げられる。本出願人らは、投与の治療効果が投与後の数週間又は数ヵ月間持続し得るので、ブロモリセルギドを継続的に投与する必要はないことを見出した(例えば、実施例1及び3を参照されたい)。
ブロモリセルギドを、本発明の方法を実施するためのキットにパッケージ化することができる。キットは、1名の患者用の単回使用単位用量、1名の特定の患者用の複数回使用分として製造することができ、又はキットが複数患者への投与のために好適な複数用量を含んでもよい(「バルクパッケージ」)。キットの構成要素は、カートン、ブリスターパック、瓶、チューブなどに集めることができる。キットはまた、何らかの指示及び/又は本明細書中に記載された投与レジメンを用いて医薬組成物を投与するための使用説明書を含むこともできる。
所望の量のブロモリセルギド(塩酸塩)をデキストロースと混合し、慢性群発頭痛障害に罹患している被験者への投与のためにゼラチンカプセルに詰めた。
緩和期を延長するために、群発頭痛障害と診断された被験者にブロモリセルギドを投与することもできる。
Hannover Medical Schoolの疼痛外来(Pain Clinic)に紹介された患者は、頭痛障害の国際分類の各診断基準を満たした場合、群発頭痛と特定された(Headache Classification Committee of the International Headache Society (2004) The International Classification of Headache Disorders, 第2版, Cephalalgia 24 Suppl 1:1-160)。さらに、全ての患者はベラパミル及び他の予防的薬物治療に応答しなかった(すなわち、各患者に関して表1に挙げられた予防的薬物治療に不応性であった)。ドイツの国及び地方の倫理委員会規則に従い、全ての患者はインフォームドコンセントに署名し、その中で患者は、群発頭痛に対するブロモリセルギドの例外的使用(compassionate use)に関する、このプロジェクトに参加することへの同意を宣言した。患者は、ブロモリセルギド投与の少なくとも2週間前から、群発頭痛症状の標準化された日誌をつけた。ブロモリセルギド(塩酸塩)は、THCpharm GmbH(Frankfurt am Main, Germany)により製造されたものであった。HPLC及び他の分析試験により、>99.2%の純度が明らかになった。30μg/kg体重の塩酸ブロモリセルギドを蒸留水に溶解し、5日に1回、合計3用量を経口投与した。投与後の3〜4時間の観察時間の間、意識状態、思考障害、及びバイタルサイン(血圧、心拍数)の変化を測定した。患者は、次の月の間、又は新たな連続する群発発作に3日間見舞われるまで、毎日の頭痛日誌を埋めることを続けるよう依頼された。
本明細書中で言及した全ての刊行物、特許及び特許出願は、個々の刊行物又は特許出願が具体的かつ個別に参照により組み入れられるように示されているのと同程度に、参照により本明細書中に組み入れられる。
Claims (19)
- 頻発性群発頭痛障害の治療を必要とする被験者において、頻発性群発頭痛障害を治療するための医薬組成物あって、2-ブロモリセルグ酸ジエチルアミド又は製薬上許容されるその塩を含む、上記医薬組成物。
- 慢性群発頭痛障害の治療を必要とする被験者において、慢性群発頭痛障害を治療するための医薬組成物であって、2-ブロモリセルグ酸ジエチルアミド又は製薬上許容されるその塩を含む、上記医薬組成物。
- 反復性群発頭痛障害の治療を必要とする被験者において、反復性群発頭痛障害を治療するための医薬組成物であって、2-ブロモリセルグ酸ジエチルアミド又は製薬上許容されるその塩を含む、上記医薬組成物。
- 群発頭痛障害を有する被験者の緩和期を延長するための医薬組成物であって、2-ブロモリセルグ酸ジエチルアミド又は製薬上許容されるその塩を含む、上記医薬組成物。
- 前記群発頭痛障害が反復性群発頭痛障害である、請求項4に記載の医薬組成物。
- 前記群発頭痛障害が慢性群発頭痛障害である、請求項4に記載の医薬組成物。
- 前記被験者が、切迫群発頭痛発作に特徴的な自律神経症状に見舞われている、請求項4に記載の医薬組成物。
- 20〜50μg/kgの2-ブロモリセルグ酸ジエチルアミド又は製薬上許容されるその塩の1用量を前記被験者に投与する、請求項1〜7のいずれか1項に記載の医薬組成物。
- 20〜50μg/kgの2-ブロモリセルグ酸ジエチルアミド又は製薬上許容されるその塩の2用量を、2〜7日間にわたって前記被験者に投与する、請求項8に記載の医薬組成物。
- 20〜50μg/kgの2-ブロモリセルグ酸ジエチルアミド又は製薬上許容されるその塩の3用量を、4〜20日間にわたって前記被験者に投与する、請求項9に記載の医薬組成物。
- 1.5〜5mgの2-ブロモリセルグ酸ジエチルアミド又は製薬上許容されるその塩を含む単位投与剤形を前記被験者に投与する、請求項1〜4のいずれか1項に記載の医薬組成物。
- 1.5〜5mgの2-ブロモリセルグ酸ジエチルアミド又は製薬上許容されるその塩を含む単位投与剤形の2用量を、2〜7日間にわたって前記被験者に投与する、請求項11に記載の医薬組成物。
- 1.5〜5mgの2-ブロモリセルグ酸ジエチルアミド又は製薬上許容されるその塩を含む単位投与剤形の3用量を、4〜20日間にわたって前記被験者に投与する、請求項12に記載の医薬組成物。
- 1.5〜3mgの2-ブロモリセルグ酸ジエチルアミド又は製薬上許容されるその塩を含む単位投与剤形の3用量を、7〜12日間にわたって前記被験者に投与する、請求項13に記載の医薬組成物。
- 1.5〜3mgの2-ブロモリセルグ酸ジエチルアミド又は製薬上許容されるその塩を含む単位投与剤形の3用量を、11日間にわたって5日に1回、前記被験者に投与する、請求項14に記載の医薬組成物。
- 前記2-ブロモリセルグ酸ジエチルアミド又は製薬上許容されるその塩を、経口的、皮下的、静脈内、又は筋肉内に投与する、請求項1〜10のいずれか1項に記載の医薬組成物。
- 前記被験者が1種以上の予防的療法に対して不応性である群発頭痛障害を有する、請求項1〜16のいずれか1項に記載の医薬組成物。
- 前記群発頭痛障害が、コルチコステロイド、三環系抗うつ剤、カルシウムチャネルブロッカー、β-ブロッカー、抗けいれん剤、メチセルギド、又はリチウムを用いた治療に対して不応性である、請求項17に記載の医薬組成物。
- (i) 1.5〜5mgの2-ブロモリセルグ酸ジエチルアミド又は製薬上許容されるその塩を含む単位投与剤形の医薬組成物;及び
(ii)頻発性群発頭痛障害、反復性群発頭痛障害、又は慢性群発頭痛障害の治療のために被験者に該組成物を投与することに関する使用説明書
を含むキットであって、
2〜4用量の前記医薬組成物を含み、かつ4〜20日間にわたって前記被験者に該用量を投与することに関する使用説明書を含む、上記キット。
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GB2475660A (en) | 2011-05-25 |
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US20130252996A1 (en) | 2013-09-26 |
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