JP2020515566A - がんを処置する組成物及び方法 - Google Patents
がんを処置する組成物及び方法 Download PDFInfo
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- JP2020515566A JP2020515566A JP2019552970A JP2019552970A JP2020515566A JP 2020515566 A JP2020515566 A JP 2020515566A JP 2019552970 A JP2019552970 A JP 2019552970A JP 2019552970 A JP2019552970 A JP 2019552970A JP 2020515566 A JP2020515566 A JP 2020515566A
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Landscapes
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Abstract
Description
本出願は、米国特許法第119条に基づいて、2017年3月27日に出願された米国特許仮出願第62/477,370号、及び2018年3月2日に出願された米国特許仮出願第62/638,058号の優先権を主張し、その開示内容は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(National Institutes of Health)により授与された認可番号AI083358の下で政府援助を用いて行われた。政府は、本発明における一定の権利を有する。
「Sequence_ST25.txt」というタイトルの、2018年3月26日に作成された、98,239バイトのデータを有する、IBM-PC、MS-ウインドウズオペレーティングシステムでマシンフォーマットされた配列番号を本ファイルに添付する。これによって、上記配列番号は、あらゆる目的のために、その全容が参照により本明細書に組み込まれる。
本発明の例示的微生物(表皮ブドウ球菌(Staphylococcus epidermidis)MO34及び表皮ブドウ球菌MO38)を、2018年3月22日に、ブダペスト条約の下で、American Type Culture Collection、10801 University Boulevard、Manassas、Va.20110-2209に、ATCC番号_______(菌株名称S.epi-MO38 UCSD 20180315)として及びATCC番号_______(菌株名称S.epi-MO34 UCSD 20180315)として、寄託した。本寄託物は、試料の最新の分譲要請が寄託機関により受理された後の少なくとも5年間、寄託の日付後の少なくとも30年間、又は関連特許の法的強制力のある期間のいずれか最長の期間、承認された寄託機関において維持され、突然変異、非生育又は破壊の場合には交換される。これらの細胞株の公共への利用可能性に対する全ての制限は、その出願から特許の発行時に撤回不能に取り除かれる。
ロアルケニル、場合によって置換されたアリール、及び場合によって置換された複素環から選択される]
を有する化合物又は薬学的に許容されるその塩若しくはプロドラッグを提供する。
を有する化合物又は薬学的に許容されるその塩若しくはプロドラッグを提供する。
-COOR[式中、Rは水素又はアルキル基若しくはアリール基であり、より詳細には、Rはメチル、エチル、プロピル、ブチル、又はフェニル基であり、これらの全ては場合によって置換される];
-COR[式中、Rは水素又はアルキル基若しくはアリール基であり、より詳細には、Rはメチル、エチル、プロピル、ブチル、又はフェニル基であり、これらの基の全ては場合によって置換される];
-CON(R)2[式中、各Rは、互いに独立して、Rは、水素又はアルキル基若しくはアリール基であり、より詳細には、Rはメチル、エチル、プロピル、ブチル、又はフェニル基であり、これらの基の全ては場合によって置換され;R及びRは、1つ以上の二重結合を含有し得る環を形成することができる];
-OCON(R)2[式中、各Rは、互いに独立してRは、水素又はアルキル基若しくはアリール基であり、より詳細には、Rはメチル、エチル、プロピル、ブチル、又はフェニル基であり、これらの基の全ては場合によって置換され;R及びRは、1つ以上の二重結合を含有し得る環を形成することができる];
-N(R)2[式中、各Rは、互いに独立して、Rは、水素、又はアルキル基、アシル基若しくはアリール基であり、より詳細には、Rはメチル、エチル、プロピル、ブチル、又はフェニル若しくはアセチル基であり、これらの全ては場合によって置換されるか;又はR及びRは、1つ以上の二重結合を含有し得る環を形成することができる];
-SR、-SO2R、又は-SOR[式中、Rはアルキル基又はアリール基であり、より詳細には、Rはメチル、エチル、プロピル、ブチル、フェニル基であり、これらの全ては場合によって置換され、例えば、-SR、Rは水素であり得る];
-OCOOR[式中、Rはアルキル基又はアリール基である];
-SO2N(R)2[式中、Rは水素、アルキル基、又はアリール基であり、R及びRは環を形成することができる];並びに
-OR[式中、R=H、アルキル、アリール、又はアシルであり;例えば、Rは、-OCOR*を生じるアシルであってもよく、式中、R*は、水素又はアルキル基若しくはアリール基であり、より詳細にはR*はメチル、エチル、プロピル、ブチル、又はフェニル基であり、これらの基の全ては場合によって置換される]
が含まれる。
N1〜N5は窒素原子であり;
X1〜X2は炭素原子であり;
破線で結合しているR基は、存在するか、又は該R基が、共有二重結合により別の原子と結合している原子に連結している場合には存在せず;
直線及び破線の両方で表されている結合は、該結合が共有単結合又は共有二重結合であり得ることを示し;
縮合複素環系は、X1と二重結合を形成するN2又はN3との、及びX2と二重結合を形成するN4又はN5との3個の二重結合を含み;
R1は、ヒドロキシル、エステル、カルボン酸、又は-O-R10であり;
R2、R4、R5、R7〜R9は、独立して、H、D、場合によって置換された(C1〜C6)-アルキル、場合によって置換された(C1〜C6)-アルケニル、場合によって置換された(C1〜C6)-アルキニル、場合によって置換された(C3〜C12)シクロアルキル、場合によって置換された(C4〜C12)シクロアルケニル、場合によって置換されたアリールであり;
R3及びR6は、H、D、場合によって置換された(C1〜C6)-アルキル、場合によって置換された(C1〜C6)-ヘテロアルキル、場合によって置換された(C1〜C6)-アルケニル、場合によって置換された(C1〜C6)-ヘテロアルケニル、場合によって置換された(C1〜C6)-アルキニル、場合によって置換された(C1〜C6)-ヘテロアルキニル、場合によって置換された(C3〜C12)シクロアルキル、場合によって置換された(C4〜C12)シクロアルケニル、場合によって置換されたアリール、場合によって置換された複素環、ハロゲン化物、ヒドロキシル、カルボニル、アルデヒド、カルボキシル、エステル、アルコキシ、カルボキシアミド、アミン、イミン、アジド、シアノ、ニトロ、ニトロソ、チオール、スルフィド、スルホキシド、スルホン、及びホスフェートから独立して選択され;
R10は、D、場合によって置換された(C1〜C6)-アルキル、場合によって置換された(C1〜C6)-ヘテロアルキル、場合によって置換された(C1〜C6)-アルケニル、場合によって置換された(C1〜C6)-ヘテロアルケニル、場合によって置換された(C1〜C6)-アルキニル、場合によって置換された(C1〜C6)-ヘテロアルキニル、場合によって置換された(C3〜C12)シクロアルキル、場合によって置換された(C4〜C12)シクロアルケニル、場合によって置換されたアリール、及び場合によって置換された複素環から選択される]
を有する抗菌性/抗がん性分子又は薬学的に許容されるその塩若しくはプロドラッグも提供する。別の実施形態では、化合物は、式I(b)の一般式:
N1〜N5は窒素原子であり;
X1〜X2は炭素原子であり;
破線で結合しているR基は、存在するか、又は該R基が、共有二重結合により別の原子と結合している原子に連結している場合には存在せず;
直線及び破線の両方で表されている結合は、該結合が共有単結合又は共有二重結合であり得ることを示し;
縮合複素環系は、X1と二重結合を形成するN2又はN3との、及びX2と二重結合を形成するN4又はN5との3個の二重結合を含み;
R1は、ヒドロキシル、エステル、カルボン酸、又は-O-R10であり;
R2、R4、R5、及びR7は、独立して、H、D、場合によって置換された(C1〜C6)-アルキル、場合によって置換された(C1〜C6)-アルケニル、場合によって置換された(C1〜C6)-アルキニル、場合によって置換された(C3〜C12)シクロアルキル、場合によって置換された(C4〜C12)シクロアルケニル、場合によって置換されたアリールであり;
R10は、D、場合によって置換された(C1〜C6)-アルキル、場合によって置換された(C1〜C6)-ヘテロアルキル、場合によって置換された(C1〜C6)-アルケニル、場合によって置換された(C1〜C6)-ヘテロアルケニル、場合によって置換された(C1〜C6)-アルキニル、場合によって置換された(C1〜C6)-ヘテロアルキニル、場合によって置換された(C3〜C12)シクロアルキル、場合によって置換された(C4〜C12)シクロアルケニル、場合によって置換されたアリール、及び場合によって置換された複素環から選択される]
を有するか、又は薬学的に許容されるその塩若しくはプロドラッグである。
ト(phenamet);ピラルビシン;ロソキサンチオン(losoxantione);ポドフィリン酸(podophyllinic acid);2-エチルヒドラジド;プロカルバジン;PSK(登録商標)多糖複合体(JHS Natural Products、Eugene、Oreg.);ラゾキサン;リゾキシン;シゾフィラン;スピロゲルマニウム;テヌアゾン酸;トリアジコン;2,2 2''-トリクロロトリエチルアミン;トリコセシン(特にT-2トキシン、ベラクリンA(verracurin A)、ロリジンA及びアングイジン);ウレタン;ビンデシン;ダカルバジン;マンノムスチン;ミトブロニトール;ミトラクトール;ピポブロマン;ガシトシン(gacytosine);アラビノシド(「Ara-C」);シクロホスファミド;チオテパ;タキソイド、例えば、TAXOL(登録商標)パクリタキセル(Bristol-Myers Squibb Oncology、Princeton、N.J.)、ABRAXANE(登録商標)クレモホール無含有、パクリタキセルのアルブミン-操作されたナノ粒子製剤(American Pharmaceutical Partners、Schaumberg、Ill.)、及びTAXOTERE(登録商標)(ドセタキセル)(Rhone-Poulenc Rorer、Antony、France);クロラムブシル;GEMZAR(登録商標)(ゲムシタビン);6-チオグアニン;メルカプトプリン;トトレキサート;シスプラチン、オキサリプラチン及びカルボプラチン等の白金配位錯体;ビンブラスチン;白金;エトポシド(VP-16);イホスファミド;ミトキサントロン;ビンクリスチン; NAVELBINE(登録商標)ビノレルビン;ノバントロン;テニポシド;エダトレキサート;ダウノマイシン;アミノプテリン;ゼローダ;イバンドロネート;イリノテカン(例えば、CPT-11);トポイソメラーゼ阻害剤RFS 2000;ジフルオロメチルオルニチン(DFMO);レチノイン酸等のレチノイド;カペシタビン;ロイコボリン(LV);イリノテカン;副腎皮質抑制剤;副腎皮質ステロイド;プロゲスチン;エストロゲン;アンドロゲン;ゴナドトロピン放出ホルモン類似体;並びに任意の上述の薬学的に許容される塩、酸又は誘導体が含まれる。また本定義には、例えば、タモキシフェン(NOLVADEX(登録商標)タモキシフェンを含む)、ラロキシフェン、ドロロキシフェン、4-ヒドロキシタモキシフェン、トリオキシフェン(trioxifene)、ケオキシフェン(keoxifene)、LY117018、オナプリストン(onapristone)、及びFARESTON-トレミフェンを含む、抗エストロゲン及び選択的エストロゲン受容体調節薬(SERM)等の、腫瘍に対するホルモン作用を調節するか又は阻害するために作用する抗ホルモン剤;例えば、4(5)-イミダゾール、アミノグルテチミド、MEGASE(登録商標)酢酸メゲストロール、AROMASL(登録商標)エキセメスタン、ホルメスタン、ファドロゾール、RIVISOR(登録商標)ボロゾール、FEMARA(登録商標)レトロゾール、及びARTMIDEX(登録商標)アナストロゾール等の副腎におけるエストロゲン産生を調節する、酵素アロマターゼを阻害するアロマターゼ阻害剤;並びにフルタミド、ニルタミド、ビカルタミド、リュープロリド、及びゴセレリン等の抗アンドロゲン;同様にトロキサシタビン(1,3-ジオキソランヌクレオシドシトシン類似体);詳細には、例えばPKC-アルファ、Ralf及びH-Ras等の、異常細胞増殖に関係づけられるシグナル伝達経路における遺伝子の発現を阻害する、アンチセンスオリゴヌクレオチド;VEGF-A発現阻害剤(例えば、ANGIOZYME(登録商標)リボザイム)及びHER2発現阻害剤等のリボザイム;例えば、ALLOVECTIN(登録商標)ワクチン、LEUVECTIN(登録商標)ワクチン、及びVAXID(登録商標)ワクチンのような遺伝子療法用ワクチン;PROLEUKIN(登録商標)rJL-2;LURTOTECAN(登録商標)トポイソメラーゼ1阻害剤;ABARELLX(登録商標)rmRH等のワクチン;トラスツズマブ等の抗体、並びに任意の上述の薬学的に許容される塩、酸又は誘導体も含まれる。
剤;アルファ-アドレナリン系薬剤;クロロチアジド、ヒドロキオロチアジド、フルメチアジド、ヒドロフルメチアジド、ベンドロフルメチアジド、メチルクロロチアジド、トリキオロメチアジド、ポリチアジド、ベンゾチアジド、エタクリン酸、チクリナフェン、クロルタリドン、フロセニルド(furosenilde)、ムゾリミン、ブメタニド、トリアムテレン、アミロリド、及びスピロノラクトン等の利尿薬;組織プラスミノーゲン活性化因子(tPA)、組換え型tPA、ストレプトキナーゼ、ウロキナーゼ、プロウロキナーゼ、及びアニソイル化プラスミノーゲンストレプトキナーゼ活性因子複合体(APSAC)等の血小板溶解剤;ビグアニド(例えば、メトホルミン)、グルコシダーゼ阻害剤(例えば、アカルボース)、インスリン、メグリチニド(例えば、レパグリニド)、スルホニル尿素(例えば、グリメピリド、グリブライド、及びグリピジド)、チオゾリジンジオン(例えば、トログリタゾン、ロシグリタゾン及びピオグリタゾン)、並びにPPAR-ガンマアゴニスト等の抗糖尿病剤;スピロノラクトン及びエプレレノン等のミネラルコルチコイド受容体アンタゴニスト;成長ホルモン分泌促進物質;aP2阻害剤;PDE III阻害剤(例えば、シロスタゾール)及びPDE V阻害剤(例えば、シルデナフィル、タダラフィル、バルデナフィル)等のホスホジエステラーゼ阻害剤;プロテインチロシンキナーゼ阻害剤;抗炎症薬;メトトレキサート、FK506(タクロリムス、プログラフ)、ミコフェノール酸モフェチル等の抗増殖薬;化学療法剤;免疫抑制薬;抗がん剤及び細胞傷害性薬物(例えば、ナイトロジェンマスタード、スルホン酸アルキル、ニトロソ尿素、エチレンイミン、及びトリアゼン等のアルキル化剤);ホレートアンタゴニスト、プリン類似体、及びピリジン類似体等の代謝拮抗薬;アントラサイクリン、ブレオマイシン、マイトマイシン、ダクチノマイシン、及びプリカマイシン等の抗生物質;L-アスパラギナーゼ等の酵素;ファルネシル-タンパク質転移酵素阻害剤;グルココルチコイド(例えば、コルチゾン)、エストロゲン/抗エストロゲン薬、アンドロゲン/抗アンドロゲン薬、プロゲスチン、及び黄体ホルモン-放出ホルモンアンタゴニスト、並びに酢酸オクトレオチド等のホルモン剤;エクチナサイジン等の微小管-攪乱剤;パクリタキセル、ドセタキセル、及びエポチロンA〜F等の微小管-安定化剤;ビンカアルカロイド、エピポドフィロトキシン、及びタキサン等の植物由来の生成物;並びにトポイソメラーゼ阻害剤;プレニル-タンパク質転移酵素阻害剤;並びにシクロスポリン;アザチオプリン及びシクロホスファミド等の細胞毒性薬;テニダップ等のTNF-アルファ阻害剤;エタネルセプト、ラパマイシン、及びレフルノミド等の抗TNF抗体又は可溶性TNF受容体;並びにセレコキシブ及びロフェコキシブ等のシクロオキシゲナーゼ-2(COX-2)阻害剤;並びに種々の薬剤、例えば、ヒドロキシ尿素、プロカルバジン、ミトタン、ヘキサメチルメラミン、金化合物、シスプラチン、サトラプラチン、及びカルボプラチン等の白金配位錯体を含むが、これらに限定されない、他の種類の化合物と組み合わせて、好ましくは経時的に投与することもできる。
Claims (24)
- 前がん、がん又は腫瘍性細胞の成長、遊走、増殖及び/又は転移を阻害するための、又は病原体を阻害するための方法であって、細胞又は病原体を、化合物式I(a):
N1〜N5は窒素原子であり;
X1〜X2は炭素原子であり;
破線で結合しているR基は、存在するか、又は該R基が、共有二重結合により別の原子と結合している原子に連結している場合には存在せず;
直線及び破線の両方で表されている結合は、該結合が共有単結合又は共有二重結合であり得ることを示し;
縮合複素環系は、X1と二重結合を形成するN2又はN3との、及びX2と二重結合を形成するN4又はN5との3個の二重結合を含み;
R1は、ヒドロキシル、エステル、カルボン酸、又は-O-R10であり;
R2、R4、R5、R7〜R9は、独立して、H、D、場合によって置換された(C1〜C6)-アルキル、場合によって置換された(C1〜C6)-アルケニル、場合によって置換された(C1〜C6)-アルキニル、場合によって置換された(C3〜C12)シクロアルキル、場合によって置換された(C4〜C12)シクロアルケニル、場合によって置換されたアリールであり;
R3及びR6は、H、D、場合によって置換された(C1〜C6)-アルキル、場合によって置換された(C1〜C6)-ヘテロアルキル、場合によって置換された(C1〜C6)-アルケニル、場合によって置換された(C1〜C6)-ヘテロアルケニル、場合によって置換された(C1〜C6)-アルキニル、場合によって置換された(C1〜C6)-ヘテロアルキニル、場合によって置換された(C3〜C12)シクロアルキル、場合によって置換された(C4〜C12)シクロアルケニル、場合によって置換されたアリール、場合によって置換された複素環、ハロゲン化物、ヒドロキシル、カルボニル、アルデヒド、カルボキシル、エステル、アルコキシ、カルボキシアミド、アミン、イミン、アジド、シアノ、ニトロ、ニトロソ、チオール、スルフィド、スルホキシド、スルホン、及びホスフェートから独立して選択され;
R10は、D、場合によって置換された(C1〜C6)-アルキル、場合によって置換された(C1〜C6)-ヘテロアルキル、場合によって置換された(C1〜C6)-アルケニル、場合によって置換された(C1〜C6)-ヘテロアルケニル、場合によって置換された(C1〜C6)-アルキニル、場合によって置換された(C1〜C6)-ヘテロアルキニル、場合によって置換された(C3〜C12)シクロアルキル、場合によって置換された(C4〜C12)シクロアルケニル、場合によって置換されたアリール、及び場合によって置換された複素環から選択される]
又は薬学的に許容されるその塩若しくはプロドラッグを含む阻害有効量の組成物と接触させることを含む、方法。 - 前記化合物が、式I(b)の一般式:
N1〜N5は窒素原子であり;
X1〜X2は炭素原子であり;
破線で結合しているR基は、存在するか、又は該R基が、共有二重結合により別の原子と結合している原子に連結している場合には存在せず;
直線及び破線の両方で表されている結合は、該結合が共有単結合又は共有二重結合であり得ることを示し;
縮合複素環系は、X1と二重結合を形成するN2又はN3との、及びX2と二重結合を形成するN4又はN5との3個の二重結合を含み;
R1は、ヒドロキシル、エステル、カルボン酸、又は-O-R10であり;
R2、R4、R5、及びR7は、独立して、H、D、場合によって置換された(C1〜C6)-アルキル、場合によって置換された(C1〜C6)-アルケニル、場合によって置換された(C1〜C6)-アルキニル、場合によって置換された(C3〜C12)シクロアルキル、場合によって置換された(C4〜C12)シクロアルケニル、場合によって置換されたアリールであり;
R10は、D、場合によって置換された(C1〜C6)-アルキル、場合によって置換された(C1〜C6)-ヘテロアルキル、場合によって置換された(C1〜C6)-アルケニル、場合によって置換された(C1〜C6)-ヘテロアルケニル、場合によって置換された(C1〜C6)-アルキニル、場合によって置換された(C1〜C6)-ヘテロアルキニル、場合によって置換された(C3〜C12)シクロアルキル、場合によって置換された(C4〜C12)シクロアルケニル、場合によって置換されたアリール、及び場合によって置換された複素環から選択される]
又は薬学的に許容されるその塩若しくはプロドラッグを含む、請求項1に記載の方法。 - 前記化合物が、一般式II:
- 前記前がん、がん又は腫瘍性細胞が、黒色腫、扁平上皮癌、日光角化症、角化棘細胞腫、及び基底細胞癌からなる群から選択される、請求項1、2又は3に記載の方法。
- がん細胞を、in vivoで接触させる、請求項1、2又は3に記載の方法。
- 前記接触が、局所投与を介する、請求項1、2又は3に記載の方法。
- 前記組成物が、化学療法剤を更に含む、請求項1、2又は3に記載の方法。
- 前記組成物が、局所投与用に製剤化される、請求項1、2又は3に記載の方法。
- 前記組成物が、全身投与用に製剤化される、請求項1、2又は3に記載の方法。
- 前記組成物が、式I(a)、I(b)又はIIの化合物を産生する共生プロバイオティック細菌を含む、請求項1、2又は3に記載の方法。
- 前記共生プロバイオティック細菌が、配列番号1、3、5、7、9、11、13、15、17、19、21、23、25、27、29、31、33、35、37、39、41、43、45、47、49、51、53、及び/又は55に記載の1つ以上の配列を発現する、請求項10に記載の方法。
- 前記共生プロバイオティック細菌が、表皮ブドウ球菌株MO34及び/又はMO38を含む、請求項10に記載の方法。
- 皮膚ミクロビオームのバランスを産生又は維持する、及び/又は感染又は新生物を処置するための局所的プロバイオティック組成物であって、式I(a):
N1〜N5は窒素原子であり;
X1〜X2は炭素原子であり;
破線で結合しているR基は、存在するか、又は該R基が、共有二重結合により別の原子と結合している原子に連結している場合には存在せず;
直線及び破線の両方で表されている結合は、該結合が共有単結合又は共有二重結合であり得ることを示し;
縮合複素環系は、X1と二重結合を形成するN2又はN3との、及びX2と二重結合を形成するN4又はN5との3個の二重結合を含み;
R1は、ヒドロキシル、エステル、カルボン酸、又は-O-R10であり;
R2、R4、R5、R7〜R9は、独立して、H、D、場合によって置換された(C1〜C6)-アルキル、場合によって置換された(C1〜C6)-アルケニル、場合によって置換された(C1〜C6)-アルキニル、場合によって置換された(C3〜C12)シクロアルキル、場合によって置換された(C4〜C12)シクロアルケニル、場合によって置換されたアリールであり;
R3及びR6は、H、D、場合によって置換された(C1〜C6)-アルキル、場合によって置換された(C1〜C6)-ヘテロアルキル、場合によって置換された(C1〜C6)-アルケニル、場合によって置換された(C1〜C6)-ヘテロアルケニル、場合によって置換された(C1〜C6)-アルキニル、場合によって置換された(C1〜C6)-ヘテロアルキニル、場合によって置換された(C3〜C12)シクロアルキル、場合によって置換された(C4〜C12)シクロアルケニル、場合によって置換されたアリール、場合によって置換された複素環、ハロゲン化物、ヒドロキシル、カルボニル、アルデヒド、カルボキシル、エステル、アルコキシ、カルボキシアミド、アミン、イミン、アジド、シアノ、ニトロ、ニトロソ、チオール、スルフィド、スルホキシド、スルホン、及びホスフェートから独立して選択され;
R10は、D、場合によって置換された(C1〜C6)-アルキル、場合によって置換された(C1〜C6)-ヘテロアルキル、場合によって置換された(C1〜C6)-アルケニル、場合によって置換された(C1〜C6)-ヘテロアルケニル、場合によって置換された(C1〜C6)-アルキニル、場合によって置換された(C1〜C6)-ヘテロアルキニル、場合によって置換された(C3〜C12)シクロアルキル、場合によって置換された(C4〜C12)シクロアルケニル、場合によって置換されたアリール、及び場合によって置換された複素環から選択される]
の構造を有する1つ以上の化合物、又は薬学的に許容されるその塩若しくはプロドラッグの治療有効量又は阻害有効量を含む、局所的プロバイオティック組成物。 - 前記化合物が、式I(b)の一般式:
N1〜N5は窒素原子であり;
X1〜X2は炭素原子であり;
破線で結合しているR基は、存在するか、又は該R基が、共有二重結合により別の原子と結合している原子に連結している場合には存在せず;
直線及び破線の両方で表されている結合は、該結合が共有単結合又は共有二重結合であり得ることを示し;
縮合複素環系は、X1と二重結合を形成するN2又はN3との、及びX2と二重結合を形成するN4又はN5との3個の二重結合を含み;
R1は、ヒドロキシル、エステル、カルボン酸、又は-O-R10であり;
R2、R4、R5、及びR7は、独立して、H、D、場合によって置換された(C1〜C6)-アルキル、場合によって置換された(C1〜C6)-アルケニル、場合によって置換された(C1〜C6)-アルキニル、場合によって置換された(C3〜C12)シクロアルキル、場合によって置換された(C4〜C12)シクロアルケニル、場合によって置換されたアリールであり;
R10は、D、場合によって置換された(C1〜C6)-アルキル、場合によって置換された(C1〜C6)-ヘテロアルキル、場合によって置換された(C1〜C6)-アルケニル、場合によって置換された(C1〜C6)-ヘテロアルケニル、場合によって置換された(C1〜C6)-アルキニル、場合によって置換された(C1〜C6)-ヘテロアルキニル、場合によって置換された(C3〜C12)シクロアルキル、場合によって置換された(C4〜C12)シクロアルケニル、場合によって置換されたアリール、及び場合によって置換された複素環から選択される]
又は薬学的に許容されるその塩若しくはプロドラッグを含む、請求項13に記載の局所的プロバイオティック組成物。 - 前記化合物が、一般式II:
- 少なくとも1つのプロバイオティック共生皮膚細菌を含む、請求項13に記載の局所的プロバイオティック組成物。
- 前記プロバイオティック共生皮膚細菌が、表皮ブドウ球菌株MO34及び/又はMO38である、請求項16に記載の局所的プロバイオティック組成物。
- ローション剤、シェイクローション剤、クリーム剤、軟膏剤、ゲル剤、フォーム剤、散剤、固形剤、ペースト剤又はチンキ剤として製剤化される、請求項13から16のいずれか一項に記載の局所的プロバイオティック組成物。
- 請求項13から16のいずれか一項に記載の局所的プロバイオティック組成物を含む、絆創膏又は包帯。
- UV照射に起因する皮膚の損傷を処置する方法であって、皮膚を、請求項13から16のいずれか一項に記載の局所的プロバイオティック組成物と接触させることを含む、方法。
- 式I(a)、I(b)及び/又はIIの化合物並びに1つ以上の薬学的に許容される担体を含む、医薬組成物。
- 1つ以上の化学療法剤を更に含む、請求項21に記載の医薬組成物。
- 経口、非経口、又は局所の投与に好適である、請求項21又は22に記載の医薬組成物。
- 局所剤形が、クリーム剤、軟膏剤、ゲル剤、スプレー剤又はローション剤の形態のいずれかである、請求項23に記載の医薬組成物。
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