JP6279465B2 - 治療計画 - Google Patents
治療計画 Download PDFInfo
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- JP6279465B2 JP6279465B2 JP2014503910A JP2014503910A JP6279465B2 JP 6279465 B2 JP6279465 B2 JP 6279465B2 JP 2014503910 A JP2014503910 A JP 2014503910A JP 2014503910 A JP2014503910 A JP 2014503910A JP 6279465 B2 JP6279465 B2 JP 6279465B2
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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Description
本発明のさらなる記載の前に、本発明がより簡易に理解されるために、まず特定の用語を本明細書で定義および収集する。
SIDまたはQD=1日1回、BID=1日2回、TID=1日3回、QID=1日4回、q.h.s=毎晩
一態様において、本発明は、対象の性的欲求低下障害を調節することのできる化合物を提供する。このような化合物は、5−HT2Aアンタゴニスト、5−HT1A受容体アゴニスト、ノルエピネフリン−ドーパミン再取り込み阻害剤、および内分泌活性剤を含む。本発明の化合物は、薬学的に許容可能なキャリアーをさらに含む。
一実施形態において、本発明は、本明細書に記載する組成物を対象に投与することを含む、対象の性的欲求低下障害(HSDD)を治療する方法を提供する。特定の実施形態において、この対象は、例えば、ヒトなどの霊長類などの哺乳類である。態様において、治療の化合物、組成物、および方法に関連するその疾患、障害、または症状は、精神障害の診断と統計の手引き(DSM−I−TRV),アメリカ精神医学会に記載される。
本発明は同様に、本明細書に記載した効果的な有効量の化合物および薬学的に許容可能なキャリアーを含む薬学的組成物を提供する。さらなる実施形態において、有効量は、上述のように、性的欲求低下障害を治療するために効果的である。
所望の徐放プロフィール、他のポリマーマトリクス、リポソームおよび/または微粒子を提供するための調製を変動して活性成分の徐放の遅延または制御を提供するために処方されてもよい。これらは、例えば、バクテリア保持フィルターを介しての濾過、または使用前の無菌水または他のいくつかの即座に注入可能な無菌媒体内に溶解することのできる無菌性の固体組成物の形態にて無菌剤を組み込むことにより無菌化してもよい。同様に、これらの組成物は、任意に不透明剤をも含んでよく、活性成分のみ、または好ましくは、消化管の一部内で任意に遅延した方法において除法する組成物であってもよい。使用することのできる包埋剤の例は、ポリマー物質およびワックスを含むことができる。この活性成分は、同様に、マイクロカプセル化されてもよく、必要であれば、1つ以上の上述の賦形剤を有してもよい。
小分子化合物−ブプロピオン、トラゾドンおよびテストステロン(ならびにそれらの塩、溶媒和化合物、水和物、アイソマー、エナンチオマー、ジアステレオマー、ラセミ体であり、それらすべては本明細書に含まれる)は、商業的に入手可能であり、当業者に公知の方法および試薬を使用して容易に合成される。ブプロピオンは、β−ケト−3−クロロ−N−tert−ブチルアンフェタミン、すなわち(±)−2−(tert−ブチルアミノ)−1−(3−クロロフェニル)プロパン−1−オンとして知られ、トラゾドンも、2−{3−[4−(3−クロロフェニル)ピペリジン−1−イル]プロピル}[1,2,4]トリアゾロ[4,3−a]ピリジン−3(2H)−オンとして知られている。
臨床プトロコル−単盲検の連続試験において、それぞれ3〜4週間おきに、用量を増加してブプロピオンおよびトラゾドンを対象に投与する。すなわち、3(または4)週間のプラセボベースラインから、(次の3〜4週間に)中間用量に増やし、(最後の3〜4週間に)最大用量を、それぞれ投与する。この対象の主観的(例えば、感情、感覚、一般的な反応)および客観的(例えば、反応時間、性質の特性、パートナーの反応)なフィードバック/記録を、用量に対して収集および分析する。同様に、この試験では、第2および第3の対象が活性成分(例えば、ブプロピオンおよびトラゾドン)の規定した比率を有する異なる固定用量の組み合わせをそれぞれ投与され、対照(2つの活性の間の相乗効果を示す)として、ブプロピオンのみを投与される1人以上の患者を含む。
現在、性的障害がなく、2年間安定した婚姻関係のある36歳の健康な男性の志願者に、それぞれ4週間、(1)治療B:即時徐放(IR)Bupを朝に150mgおよび夕方に100mg(2)治療T:1日3回Trzを50mg(3)治療Llow、1日2回IRでTrzを25mg+IRで朝にBupを150mg、夕方に100mg、ならびに(4)治療Lhigh、IRでTrzを1日3回50mg、+IRでBupを1日3回75mgの、4つの治療を連続して行った。各治療の間に約1〜4週間のウォッシュアウトが行われた。性的欲求のレベルおよび頻度が、非改善(0)、いくらか改善(1)、または顕著に改善(2)により、毎日点数化された。性的事象の3つの分野(性的興奮、オルガズム、およびこの事象に対する総合的満足度)が集計され点数化された。このさまざまな性的事象のそれぞれが、患者の印象の改善度(PGI:治療前のベースラインと比較した当日の改善の有無を表す)に変換された。この性的事象の3つの分野の改善が、分析のために合計された。Bupは、すでにHSDDの治療として推奨されているが、Trzはまだ推奨されていない。したがって、治療B対治療Llowおよび治療B対治療Lhighについて、PGIにフィッシャー直接検定が事後適用された。
性的欲求においては、LlowおよびLhighの平均スコアは、治療Bの約2倍であり(両側t検定、p<0.0001)、治療Bは、治療Tよりも優れていた。興奮、オルガズムおよび性的事象の満足度において、Llowは、使用第3および第4週で治療Bより大きな改善に関連していた。Lhighは、使用第3および第4週ならびに4週の合計について治療Bよりも大きな改善に関連していた。両側フィッシャー直接検定は、ブプロピオン+トラゾドンの組み合わせが、性的事象の改善の3つの分野の合計において優れていたことを示した(p<0.05)。ブプロピオン+トラゾドンの組み合わせで行ったこの試験は、ブプロピオン単独またはトラゾドン単独のいずれかと比較して、4週間曝露した後、性的興奮、オルガズムおよび事象の満足度において高い効果を示した。この効果は、それらの現在の(抗鬱剤と)分類されるブプロピオンまたはトラゾドンの標的となる用量以下で発生した。
1.P値対対応する治療Bup、両側t検定
2.P値対対応する治療Bup、両側フィッシャー直接検定
3.興奮、オルガズム、および総合的満足度で改善がみられたnの合計
注.0.1を超えるP値は、表から除外している。
BまたはBupはブプロピオン単独、Tまたはtrzはトラゾドン単独、Llowは、Bup/Trzの組み合わせの低用量、LhighはBup/Trzの組み合わせの高用量をそれぞれ示す。
第1週:治療#1
第1群
ブプロピオン+トラゾドンの低用量の組み合わせ:250mg BUP+75mg TRZ/日(朝に150mgのSR BUPおよび夕方に100mgのSR BUP、および1日1回75mgのSRとして与える)、ならびに検査バッテリー。この検査バッテリーには、単一用量PK、定常状態のPK、および薬力学検査が含まれる。薬力学検査は、一連の認知検査および感情状態の数値化スケール(NRS)を含み、投与の初日および最終日の朝、投与前、投与後、1、2、4、および8時間に行われる。この認知検査バッテリーは、選択反応時間、言葉の想起、写真の認識、数字および空間ワーキングメモリを含む。この鎮静/活発の感情状態の自己評価NRSには、眠気、めまい、神経質、動揺、および高揚が含まれる。認知検査は上記時間の20分前以内に行われ、血液サンプリングは上記時間に行われ、VASは上記時間の後15分以内に行われる。
または
第2群
朝に150mgのSRBUPおよび夕方に100mgのSRBUP。
第2週:1回目のウォッシュアウト♯1
第3週:治療#2
第1群
ブプロピオン+トラゾドンの高用量の組み合わせ(250mg BUP+150mg TRZ/日、朝に150mgのSR BUPおよび夕方に100mgのSR BUP、および1日一回150mgのSRトラゾドンとして与える)、ならびに検査バッテリー
または
第2群
1日1回150mgのSRトラゾドン
第4週:2回目のウォッシュアウト♯2
本発明の組成物は、活性剤(すなわち、ブプロピオンおよびトラゾドン)を、カルナウバワックス、システイン塩酸塩、ヒプロメロース、ステアリン酸マグネシウム、セルロース、微結晶、ポリエチレン、グリコール、ポリソルベート 80、二酸化チタン、FD&C BLUE NO.1、ヒドロキシプロピル リン酸架橋デンプン(Contramid(登録商標))、ヒプロメロース、フマル酸ステアリルナトリウム、コロイド状2酸化ケイ素、黄色酸化鉄、赤色酸化鉄、タルク、ポリエチレングリコール3350、二酸化チタン、ポリビニルアルコール、黒色インキ(食品グレード)などの賦形剤の1種以上と組み合わせることにより作製することができる。
Claims (22)
- トラゾドンまたはその薬学的に許容可能な塩、ブプロピオンまたはその薬学的に許容可能な塩、および薬学的に許容可能なキャリアーを含む、女性性機能不全(FSD)の治療用医薬組成物であって、
25〜450mgの範囲の用量のトラゾドンまたはその薬学的に許容可能な塩、および25〜450mgの範囲の用量のブプロピオンまたはその薬学的に許容可能な塩を含む、医薬組成物。 - 前記女性性機能不全(FSD)が、性的欲求低下障害(HSDD)である、請求項1に記載の組成物。
- 前記女性性機能不全(FSD)が、女性オルガズム障害(FOD)である、請求項1に記載の組成物。
- 前記女性性機能不全(FSD)が、女性性的興奮障害(FSAD)である、請求項1に記載の組成物。
- 前記女性性機能不全(FSD)が、性的疼痛機能不全である、請求項1に記載の組成物。
- 75〜150mgの範囲の用量のトラゾドンまたはその薬学的に許容可能な塩、および100〜300mgの範囲の用量のブプロピオンまたはその薬学的に許容可能な塩を含む、請求項1〜5のいずれか1項に記載の組成物。
- 75〜150mgの範囲の用量のトラゾドンまたはその薬学的に許容可能な塩、および225〜300mgの範囲の用量のブプロピオンまたはその薬学的に許容可能な塩を含む、請求項1〜5のいずれか1項に記載の組成物。
- 50〜100mgの範囲の用量のトラゾドンまたはその薬学的に許容可能な塩、および100〜275mgの範囲の用量のブプロピオンまたはその薬学的に許容可能な塩を含む、請求項1〜5のいずれか1項に記載の組成物。
- 50〜100mgの範囲の用量のトラゾドンまたはその薬学的に許容可能な塩、および200〜275mgの範囲の用量のブプロピオンまたはその薬学的に許容可能な塩を含む、請求項1〜5のいずれか1項に記載の組成物。
- 50〜100mgの範囲の用量のトラゾドンまたはその薬学的に許容可能な塩、および225〜300mgの範囲の用量のブプロピオンまたはその薬学的に許容可能な塩を含む、請求項1〜5のいずれか1項に記載の組成物。
- 50〜150mgの範囲の用量のトラゾドンまたはその薬学的に許容可能な塩、および100〜300mgの範囲の用量のブプロピオンまたはその薬学的に許容可能な塩を含む、請求項1〜5のいずれか1項に記載の組成物。
- 50〜150mgの範囲の用量のトラゾドンまたはその薬学的に許容可能な塩、および225〜250mgの範囲の用量のブプロピオンまたはその薬学的に許容可能な塩を含む、請求項1〜5のいずれか1項に記載の組成物。
- 前記組成物が、経口投与に適している、請求項1〜5のいずれか1項に記載の組成物。
- 前記組成物が、局所投与に適している、請求項1〜5のいずれか1項に記載の組成物。
- 前記組成物が、経口的に投与される、請求項1〜5のいずれか1項に記載の組成物。
- 前記組成物が、局所的に投与される、請求項1〜5のいずれか1項に記載の組成物。
- うつ病と診断されており治療中である対象に投与される、請求項1〜5のいずれか1項に記載の組成物。
- うつ病の治療を受けていない対象に投与される、請求項1〜5のいずれか1項に記載の組成物。
- 追加的な治療薬を同時に処方されている対象に投与される、請求項1〜14のいずれか1項に記載の組成物。
- 追加的な治療薬を同時に処方されていない対象に投与される、請求項1〜14のいずれか1項に記載の組成物。
- トラゾドンまたはその薬学的に許容可能な塩、ブプロピオンまたはその薬学的に許容可能な塩、および薬学的に許容可能なキャリアーを含む、女性性機能不全(FSD)の治療用の長期徐放医薬組成物であって、
25〜450mgの範囲の用量のトラゾドンまたはその薬学的に許容可能な塩、および25〜450mgの範囲の用量のブプロピオンまたはその薬学的に許容可能な塩を含む、長期徐放医薬組成物。 - トラゾドンまたはその薬学的に許容可能な塩、ブプロピオンまたはその薬学的に許容可能な塩、および薬学的に許容可能なキャリアーを含む、女性性機能不全(FSD)の治療用の単回用量医薬組成物であって、
25〜450mgの範囲の用量のトラゾドンまたはその薬学的に許容可能な塩、および25〜450mgの範囲の用量のブプロピオンまたはその薬学的に許容可能な塩を含む、単回用量医薬組成物。
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Application Number | Priority Date | Filing Date | Title |
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US201161471505P | 2011-04-04 | 2011-04-04 | |
US61/471,505 | 2011-04-04 | ||
PCT/US2012/031991 WO2012138653A2 (en) | 2011-04-04 | 2012-04-03 | Treatment regimens |
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JP2018030870A (ja) * | 2011-04-04 | 2018-03-01 | エスワン バイオファーマ,インコーポレイテッド | 治療計画 |
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SG10201908587PA (en) * | 2012-08-06 | 2019-10-30 | S1 Pharmaceuticals Inc | Treatment regimens |
US11977085B1 (en) | 2023-09-05 | 2024-05-07 | Elan Ehrlich | Date rape drug detection device and method of using same |
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MXPA06012059A (es) * | 2004-04-22 | 2007-01-25 | Boehringer Ingelheim Int | Nuevas composiciones farmaceuticas para el tratamiento de los trastornos sexuales ii. |
US20060004076A1 (en) * | 2004-06-30 | 2006-01-05 | Inflabloc Pharmaceuticals, Inc. | Co-administration of dehydroepiandrosterone (DHEA) congener with pharmaceutically active agents for treating inflammation |
US7769770B2 (en) * | 2004-07-14 | 2010-08-03 | Microsoft Corporation | Secondary index and indexed view maintenance for updates to complex types |
JP4201747B2 (ja) * | 2004-07-29 | 2008-12-24 | 三洋電機株式会社 | 自走式掃除機 |
CA2599721A1 (en) * | 2005-03-04 | 2006-09-14 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for the treatment and/or prevention of depression |
WO2008075162A2 (en) * | 2006-12-15 | 2008-06-26 | Pfizer Limited | Selective mu opioid receptor antagonists for the treatment of female sexual dysfunction |
MX354989B (es) * | 2011-04-04 | 2018-03-28 | S1 Biopharma Inc | Regimenes de tratamiento. |
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