JP2022504834A - 外陰膣障害の治療 - Google Patents
外陰膣障害の治療 Download PDFInfo
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- JP2022504834A JP2022504834A JP2021520301A JP2021520301A JP2022504834A JP 2022504834 A JP2022504834 A JP 2022504834A JP 2021520301 A JP2021520301 A JP 2021520301A JP 2021520301 A JP2021520301 A JP 2021520301A JP 2022504834 A JP2022504834 A JP 2022504834A
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Abstract
【選択図】なし
Description
本出願は、2018年10月9日に出願された米国仮出願第62/743,237号および2018年10月22日に提出された米国仮出願第62/748,875号に対する優先権を主張する。それらの出願の内容は、その全体が参照により本明細書に組み込まれる。
本発明は、国立衛生研究所により授与されたHD069313の下で政府の支援を受けなされた。政府は本発明において一定の権利を有する。
本明細書で使用される場合、「炎症収束性メディエーター」は、炎症の消散を促進する脂質由来の化合物または物質を指し、例えば、細胞または生物における炎症の1つの徴候または症状を軽減することができる。炎症収束性メディエーターには、「特異的炎症収束性メディエーター」(SPM)と呼ばれる脂質のクラス、それらの前駆体、異なるSPMの混合物、異なるSPM前駆体の混合物、およびSPMとSPM前駆体の混合物が含まれる。
上記の炎症収束性メディエーター化合物および関連する組成物は、炎症に関連する過敏などの様々な炎症性障害または状態を治療する方法において有用である。そのために、外陰部痛の発症リスクの増加について見出された最も初期の指標は、性交後の長期にわたる疼痛/過敏の女性の認識である(Reed BD,et al.,Journal of Women’s Health 2012;21:1139-43)。したがって、上記の炎症収束性メディエーター化合物および本発明の関連組成物は、女性がこれを問題として認識したときに適用される場合、外陰部痛発症の一次予防モダリティとして使用することができる。
本実施例では、線維芽細胞ベースのインビトロLPVモデルが確立された。簡単に言えば、線維芽細胞株は、Falsetta et al.Am J Obstet Gynecol 2015,vol.213,pp.38 e1-12 and Foster et al.,Pain 2015,vol.156,pp.386-96に記載されている方法で、限局性誘発性外陰痛(LPV)患者の下部生殖管と無痛の対照の2つの領域(図1)から得られた。
この実施例では、アッセイを実施して、実施例1に記載のインビトロLPVモデルにおいて、初代ヒト細胞からの炎症誘発性および疼痛促進性メディエーター産生を減少させるSPMの能力を調査した。
この実施例では、LPVのマウスモデルで疼痛と炎症のエンドポイントを減少させる能力について、いくつかのSPMを試験する。ごく最近、LPVの最初の動物モデルが開発された。24この元のモデルは、治療薬の前臨床試験には使用されていない。前臨床試験は、LPVに切実に必要とされている新しい効果的なFDA承認の治療法の開発に不可欠なステップである。28、29したがって、ヒトの臨床試験の前に使用できるヒトのLPVを正確に反映する前臨床動物モデルに対する緊急の満たされていないニーズがある。この必要性と一致して、LPVのこの最適化されたマウスモデルは、強力な裏付けデータによって証明されるように、治療薬の前臨床試験のタスクに理想的である。
この実施例では、実施例3に記載されているように、LPVのマウスモデルを使用して、SPM前駆体であるDHAが疼痛および炎症性エンドポイントを減少させる能力を調査するためにアッセイを実施した。
この実施例では、上記のLPVのマウスモデルを使用して、ドコサヘキサエン酸(DHA)と追加の特異的炎症収束性メディエーター(SPM)前駆体分子(14-HDHA、17-HDHA、および18-HEPE)を含む混合物が、疼痛および炎症性エンドポイントを減少させる能力を調査するためにアッセイを実施した。
この実施例では、上記の実施例5で試験したマウスを、上記の方法で17週間、疼痛と炎症のエンドポイントを減少させるリピノバの効果についてさらに調べた。
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Claims (16)
- 対象において、外陰膣障害を治療するか、または下部生殖管の過敏(irritation)を減少もしくは予防する方法であって、有効量の炎症収束性(pro-resolving)メディエーターを前記対象の下部生殖管の治療部位に局所的に投与することを含む、方法。
- 前記過敏が、生殖管の炎症状態に関連する疼痛または掻痒である、請求項1に記載の方法。
- 前記生殖管の炎症状態が、限局性誘発性外陰部痛(LPV)、扁平苔癬、硬化性苔癬、剥離性炎症性膣炎、乳癌に関連する萎縮性外陰膣炎、および慢性掻痒からなる群から選択される、請求項2に記載の方法。
- 前記生殖管の炎症状態が、LPVである、請求項2に記載の方法。
- 前記炎症収束性メディエーターが、0.0001mg/kg~100mg/kgで投与される、請求項1~4のいずれか一項に記載の方法。
- 前記炎症収束性メディエーターが、週に1回、週に2~3回、1日1回、1日2回、または1日3回投与される、請求項1~5のいずれか一項に記載の方法。
- 前記対象が二次過敏を引き起こす刺激を受ける前に、前記炎症収束性メディエーターが投与される、請求項2~6のいずれか一項に記載の方法。
- 前記治療部位が、膣前庭を含む、請求項4~7のいずれか一項に記載の方法。
- 前記治療部位が、外部外陰(external vulva)、前庭、または膣を含む、請求項1から7のいずれか一項に記載の方法。
- 前記治療部位が、外部外陰を含む、請求項9に記載の方法。
- 前記炎症収束性メディエーターが、レゾルビンD2、レゾルビンD3、レゾルビンD4、レゾルビンD5、レゾルビンE1、マレシン-1、エピ-マレシン-1、リポキシンA4、プロテクチンD1、プロテクチンDX、14(S)-ヒドロキシドコサヘキサエン酸(14(S)HDHA)、17(S)-ヒドロキシドコサヘキサエン酸、(17(S)HDHA)、18-ヒドロキシエイコサペンタエン酸酸(18-HEPE)、ドコサヘキサエン酸(DHA)、エイコサペンタエン酸(EPA)、アラキドン酸(AA)、オメガ-3脂肪酸、オメガ-6脂肪酸、魚油、魚油抽出物、およびそれらの混合物からなる群から選択される、請求項1~10のいずれか一項に記載の方法。
- 前記炎症収束性メディエーターが、レゾルビンD2、レゾルビンD3、レゾルビンD4、レゾルビンD5、レゾルビンE1、マレシン-1、エピ-マレシン-1、リポキシンA4、プロテクチンD1、およびプロテクチンDXからなる群から選択される、請求項11に記載の方法。
- 前記混合物が、DHA、14-HDHA、17-HDHA、および18-HEPEを含む、請求項11に記載の方法。
- 前記対象に第2の治療薬を投与することをさらに含む、請求項1~13のいずれか一項に記載の方法。
- 前記第2の治療薬が、第2の炎症収束性メディエーターである、請求項14に記載の方法。
- 前記第2の治療薬が、抗菌剤または抗ウイルス剤である、請求項14に記載の方法。
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US62/748,875 | 2018-10-22 | ||
PCT/US2019/054234 WO2020076578A1 (en) | 2018-10-09 | 2019-10-02 | Treatment of vulvovaginal disorders |
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