JP2019518730A - 眼の炎症性障害および疾患の組合せ処置 - Google Patents
眼の炎症性障害および疾患の組合せ処置 Download PDFInfo
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- JP2019518730A JP2019518730A JP2018558387A JP2018558387A JP2019518730A JP 2019518730 A JP2019518730 A JP 2019518730A JP 2018558387 A JP2018558387 A JP 2018558387A JP 2018558387 A JP2018558387 A JP 2018558387A JP 2019518730 A JP2019518730 A JP 2019518730A
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- Prior art keywords
- cyclodextrin
- inflammatory agent
- compound
- inflammatory
- uveitis
- Prior art date
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- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
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- 230000002459 sustained effect Effects 0.000 description 1
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- 235000002906 tartaric acid Nutrition 0.000 description 1
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- 150000003567 thiocyanates Chemical class 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 229960004906 thiomersal Drugs 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
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Abstract
Description
本出願は、米国特許法§119(e)の下、2016年5月9日に出願された米国仮出願第62/333,549号の利益を請求し、その内容は、その全体が参照によって本明細書に組み込まれる。
眼の炎症は、炎症の位置に応じて、様々な重症度の非常に多くの眼障害の形態で現れ得る。眼の炎症に起因する障害としては、とりわけ、ぶどう膜炎、アレルギー性結膜炎、強膜炎、視神経炎、角膜炎などが挙げられる。眼の炎症は、自己免疫障害から、環境の刺激および外科手術などの傷害に至るまで、非常に多くの原因を有する。一部の形態の眼の炎症は、細菌またはウイルス感染後に生じるが、一部の眼の炎症は、未知の病因を有する。症状としては、眼痛、眼の充血、羞明、飛蚊症(floater)、視力喪失、またはこのような症状の組合せを挙げることができる。
本開示は、アルデヒドと反応する能力がある化合物および抗炎症剤の組合せを、その必要がある被験体に投与することによって、眼炎症性障害および疾患を処置する方法を提供する。一部の実施形態において、化合物は、式(I):
[式中、
X、YおよびXは、それぞれ独立して、N、CH、またはNH2が結合したCであり、ここで、X、YおよびZの1つは、Nであり;
R1は、
Raは、それぞれ独立して、C1〜6アルキルであり、
Rbは、置換されたか、または無置換のC1〜6アルキルである)
からなる群から選択され;
R2は、それぞれ独立して、ハロゲン、ヒドロキシル、カルバモイル、アミノ、または無置換もしくは置換されたアリールであり;
pは、0、1、2または3である]
の構造を有する。
4.図面の簡単な説明
本開示は、眼炎症性障害および疾患を処置するための、縮合二環式アミン化合物および抗炎症剤の組合せを提供する。眼炎症性障害および疾患を処置するための医薬組成物をさらに提供する。
5.1.定義
5.2.眼炎症性障害および疾患の組合せ治療
[式中、
X、YおよびXは、それぞれ独立して、N、CH、またはNH2が結合したCであり、ここで、X、YおよびZの1つは、Nであり;
R1は、
Raは、それぞれ独立して、C1〜6アルキルであり、
Rbは、置換されたか、または無置換のC1〜6アルキルである)
からなる群から選択され;
R2は、それぞれ独立して、ハロゲン、ヒドロキシル、カルバモイル、アミノ、または無置換もしくは置換されたアリールであり;
pは、0、1、2または3である]、および
抗炎症剤
を、眼炎症性障害または疾患の被験体に投与することを含む、方法を提供する。
[式中、R1、R2およびpは、上記の通り定義される]である。
Raは、それぞれ独立して、C1〜6アルキルである)であり;
R2は、それぞれ独立して、ハロゲン、ヒドロキシル、カルバモイル、アミノ、または無置換もしくは置換されたアリールであり;
pは、0、1、2または3である。
5.3.医薬組成物
5.4.投与および有効用量
(実施例1)
前部ぶどう膜炎の患者においてNS2化合物の点眼薬を調べる、無作為化、評価者盲検の比較対照試験
ぶどう膜炎は、ぶどう膜の構造(例えば、虹彩、毛様体および脈絡膜)が関与する眼の炎症である。前部ぶどう膜炎は、詳細には、眼の前区におけるぶどう膜炎を指す。眼の後区または眼全体(全ぶどう膜炎)も関与し得る。前部ぶどう膜炎の臨床徴候および症状としては、痛み、霧視、結膜充血、前房細胞、前房のフレア、フィブリン沈着および角膜内皮の炎症性沈降を挙げることができる。ぶどう膜炎は、単一の疾患単位(disease entity)ではなく、むしろ、多様な感染性および非感染性状態の群と関連する眼の炎症の形態である。
群1 − NS2眼科用滴剤(0.5%);
群2 − NS2眼科用滴剤(0.5%)および1%Pred Forte(登録商標)(酢酸プレドニゾロンの眼科用懸濁剤);または
群3 − 1%Pred Forte(登録商標)(酢酸プレドニゾロンの眼科用懸濁剤)。
活動性の非感染性前部ぶどう膜炎の患者における局所眼(topical ocular)NS2についてのフェーズII臨床試験は、NS2が、眼の前房における炎症細胞数の減少において、標準治療コルチコステロイド投与と統計的に区別ができなかったことを示す。想定される炎症誘発性の役割において、アルデヒドは、炎症を早期にアップレギュレートし、ある特定のアミノ酸残基の結合に関与する新規のシグナル伝達機構を介してタンパク質の機能を改変するようである。十分なアルデヒドの結合は、タンパク質、特に、キナーゼ、およびその後に炎症誘発性転写因子の活性化をもたらす細胞受容体の機能を変化させ、次に、サイトカインによって媒介される炎症反応をもたらす。サイトカインは、炎症の古典的な標的であるが、アルデヒドは、これまで無視されており、したがって、炎症性疾患の処置のための新規な標的となる。
Claims (92)
- 眼炎症性障害または疾患を処置する方法であって、治療有効量の式(I)の化合物:
[式中、
X、YおよびXは、それぞれ独立して、N、CH、またはNH2が結合したCであり、ここで、X、YおよびZの1つは、Nであり;
R1は、
Raは、それぞれ独立して、C1〜6アルキルであり、
Rbは、置換されたか、または無置換のC1〜6アルキルである)
からなる群から選択され;
R2は、それぞれ独立して、ハロゲン、ヒドロキシル、カルバモイル、アミノ、または無置換もしくは置換されたアリールであり;
pは、0、1、2または3である]、および
抗炎症剤
を、眼炎症性障害または疾患の被験体に投与することを含む、方法。 - 前記式(I)の化合物が、構造式(1a)の化合物:
[式中、
R1は、
Raは、それぞれ独立して、C1〜6アルキルであり、
Rbは、置換されたか、または無置換のC1〜6アルキルである)
からなる群から選択され;
R2は、それぞれ独立して、ハロゲン、ヒドロキシル、カルバモイル、アミノ、または無置換もしくは置換されたアリールであり;
pは、0、1または2である]
である、請求項1に記載の方法。 - 前記式(I)の化合物が、化合物(2):
- 前記抗炎症剤が、ステロイド、非ステロイド性抗炎症化合物、代謝拮抗薬、免疫抑制抗生物質、アルキル化剤および抗炎症性サイトカイン抗体から選択される、請求項1から3のいずれか1項に記載の方法。
- 前記抗炎症剤が、ステロイドまたはそのプロドラッグである、請求項4に記載の方法。
- 前記ステロイドが、コルチコステロイドまたはそのプロドラッグである、請求項4に記載の方法。
- 前記コルチコステロイドが、コルチゾール、コルチゾン、プレドニゾン、プレドニゾロン、メチルプレドニゾン、トリアムシノロン、ベタメタゾン、デキサメタゾンおよびそれらのプロドラッグから選択される、請求項6に記載の方法。
- 前記コルチコステロイドが、プレドニゾロンである、請求項7に記載の方法。
- 前記コルチコステロイドが、酢酸プレドニゾロンである、請求項8に記載の方法。
- 前記抗炎症剤が、非ステロイド性抗炎症剤(NSAID)である、請求項4に記載の方法。
- 前記NSAIDが、ジクロフェナク、フルルビプロフェン、ケトプロフェン、ブロムフェナクおよびネパフェナクからなる群から選択される、請求項10に記載の方法。
- 前記抗炎症剤が、代謝拮抗薬である、請求項4に記載の方法。
- 前記代謝拮抗薬が、メトトレキサート、アザチオプリン、メルカプトプリン、ミコフェノール酸およびミコフェノール酸モフェチルから選択される、請求項12に記載の方法。
- 前記抗炎症剤が、免疫抑制抗生物質である、請求項4に記載の方法。
- 前記免疫抑制抗生物質が、シクロスポリン、タクロリムスおよびシロリムス(ラパマイシン)から選択される、請求項14に記載の方法。
- 前記抗炎症剤が、アルキル化剤である、請求項4に記載の方法。
- 前記アルキル化剤が、シクロホスファミドおよびクロラムブシルから選択される、請求項16に記載の方法。
- 前記眼炎症性障害または疾患が、アレルギー性結膜炎;春季カタル;アトピー性角結膜炎;ドライアイ症候群;マイボーム腺機能不全;白内障;円錐角膜;水疱性および他の角膜症;フックス角膜内皮変性症;眼部瘢痕性類天疱瘡;光反応性角膜切開(PRK)治癒および他の角膜治癒と関連する状態;涙液の脂質分解または涙腺機能不全と関連する状態;ぶどう膜炎;前部ぶどう膜炎;中間部ぶどう膜炎;後部ぶどう膜炎;全ぶどう膜炎;非感染性ぶどう膜炎;感染性ぶどう膜炎;角膜炎;強膜炎;虹彩炎;毛様体炎;眼移植片対宿主病(GVHD);視神経炎;眼スティーブンスジョンソン症候群;眼瞼炎;マイボーム腺機能不全を伴うか、または伴わない眼酒さ;白内障手術後;持続性角膜びらん;ならびに角膜の外傷、角膜移植および屈折手術と関連する炎症から選択される、請求項1から17のいずれか1項に記載の方法。
- 前記眼抗炎症性障害が、ぶどう膜炎である、請求項18に記載の方法。
- 前記ぶどう膜炎が、前部ぶどう膜炎である、請求項19に記載の方法。
- 前記ぶどう膜炎が、中間部ぶどう膜炎である、請求項19に記載の方法。
- 前記ぶどう膜炎が、後部ぶどう膜炎である、請求項19に記載の方法。
- 前記ぶどう膜炎が、全ぶどう膜炎である、請求項19に記載の方法。
- 前記ぶどう膜炎が、非感染性ぶどう膜炎である、請求項19に記載の方法。
- 前記ぶどう膜炎が、感染性ぶどう膜炎である、請求項19に記載の方法。
- 前記化合物が、シクロデキストリンを用いて製剤化される、請求項1から25のいずれか1項に記載の方法。
- 前記シクロデキストリンが、α−シクロデキストリン、β−シクロデキストリン、γ−シクロデキストリン、それらの誘導体およびそれらの組合せから選択される、請求項26に記載の方法。
- 前記化合物および前記抗炎症剤が、逐次的にまたは同時に、投与される、請求項1から27のいずれか1項に記載の方法。
- 前記化合物および前記抗炎症剤が、同じ経路によって、同時に、投与される、請求項28に記載の方法。
- 前記化合物および前記抗炎症剤が、異なる経路によって、同時に、投与される、請求項28に記載の方法。
- 前記化合物および前記抗炎症剤が、同じ経路によって、逐次的に、投与される、請求項28に記載の方法。
- 前記化合物および前記抗炎症剤が、異なる経路によって、逐次的に、投与される、請求項28に記載の方法。
- 前記化合物が投与され、続いて、前記抗炎症剤が投与される、請求項28に記載の方法。
- 前記抗炎症剤が投与され、続いて、前記化合物が投与される、請求項28に記載の方法。
- 前記化合物および前記抗炎症剤が、眼に局所的に投与され、該抗炎症剤が、該眼への局所投与に適切である、請求項1から27のいずれか1項に記載の方法。
- 前記抗炎症剤が、ステロイドを含む、請求項35に記載の方法。
- 前記化合物が、少なくとも、1日1回、1日2回、1日3回、1日4回、1日5回、1日6回、1日7回、1日8回、または治療効果を達成するために必要な場合、それよりも多くの回数、眼に局所的に投与される、請求項35から34のいずれか1項に記載の方法。
- 前記ステロイドが、少なくとも、1日1回、1日2回、1日3回、1日4回、または治療有用性を達成するためのそれよりも多くの回数、眼に局所的に投与される、請求項36から37のいずれか1項に記載の方法。
- 前記式(I)の化合物および抗炎症剤が、交互投与で投与される、請求項37から38のいずれか1項に記載の方法。
- 前記式(I)の化合物が、少なくとも、約0.1%w/v、約0.2%w/v、約0.3%w/v、約0.4%w/v、約0.5%w/v、約0.6%w/v、約0.7%w/v、約0.8%w/v、約0.9%w/v、約1%w/v、約1.5%w/v、約2%w/v、約3%w/v、約4%w/v、約5%w/v、または約10%w/vの濃度で存在する、請求項35から39のいずれか1項に記載の方法。
- 前記式(I)の化合物が、約0.05%w/v〜約10%w/v、約0.1%w/v〜約5%w/v、約0.2%w/v〜約4%w/v、約0.3%〜約3%w/v、約0.4%w/v〜約2%w/v、または約0.5%w/v〜約1.5%w/vの濃度で存在する、請求項35から39のいずれか1項に記載の方法。
- 前記ステロイドが、約0.1w/v〜約2%w/v、約0.2w/v〜約1.75%w/v、0.5%w/v〜約1.5%w/v、0.75%w/v〜約1.25%w/vの濃度で存在する、請求項36から41のいずれか1項に記載の方法。
- 前記ステロイドが、約0.1w/v、0.2%w/v、0.5%w/v、0.75%w/v、1%w/v、1.25%w/v、1.5%w/v、約1.75%w/v、または約2%w/vの濃度で存在する、請求項36から41のいずれか1項に記載の方法。
- 式(I)の化合物:
[式中、
X、YおよびXは、それぞれ独立して、N、CH、またはNH2が結合したCであり、ここで、X、YおよびZの1つは、Nであり;
R1は、
Raは、それぞれ独立して、C1〜6アルキルであり、
Rbは、置換されたか、または無置換のC1〜6アルキルである)
からなる群から選択され;
R2は、それぞれ独立して、ハロゲン、ヒドロキシル、カルバモイル、アミノ、または無置換もしくは置換されたアリールであり;
pは、0、1、2または3である]、および
抗炎症剤
の、医薬組成物。 - 前記式(I)の化合物が、構造式(1a)の化合物:
[式中、
R1は、
Raは、それぞれ独立して、C1〜6アルキルであり、
Rbは、置換されたか、または無置換のC1〜6アルキルである)
からなる群から選択され;
R2は、それぞれ独立して、ハロゲン、ヒドロキシル、カルバモイル、アミノ、または無置換もしくは置換されたアリールであり;
pは、0、1または2である]
である、請求項44に記載の医薬組成物。 - 前記式(I)の化合物が、化合物(2):
- 前記抗炎症剤が、ステロイド、非ステロイド性抗炎症化合物、代謝拮抗薬、免疫抑制抗生物質およびアルキル化剤から選択される、請求項44から46のいずれか1項に記載の医薬組成物。
- 前記抗炎症剤が、ステロイドまたはそのプロドラッグである、請求項47に記載の医薬組成物。
- 前記ステロイドが、コルチコステロイドまたはそのプロドラッグである、請求項48に記載の医薬組成物。
- 前記コルチコステロイドが、コルチゾール、コルチゾン、プレドニゾン、プレドニゾロン、メチルプレドニゾン、トリアムシノロン、ベタメタゾン、デキサメタゾンおよびそれらのプロドラッグから選択される、請求項48に記載の医薬組成物。
- 前記コルチコステロイドが、プレドニゾロンまたはそのプロドラッグである、請求項50に記載の医薬組成物。
- 前記コルチコステロイドが、酢酸プレドニゾロンである、請求項51に記載の医薬組成物。
- 前記抗炎症剤が、非ステロイド性抗炎症剤(NSAID)である、請求項47に記載の医薬組成物。
- 前記NSAIDが、ジクロフェナク、フルルビプロフェン、ケトプロフェン、ブロムフェナクおよびネパフェナクからなる群から選択される、請求項53に記載の医薬組成物。
- 前記抗炎症剤が、代謝拮抗薬である、請求項47に記載の医薬組成物。
- 前記代謝拮抗薬が、メトトレキサート、アザチオプリン、メルカプトプリン、ミコフェノール酸およびミコフェノール酸モフェチルから選択される、請求項55に記載の医薬組成物。
- 前記抗炎症剤が、免疫抑制抗生物質である、請求項47に記載の医薬組成物。
- 前記免疫抑制抗生物質が、シクロスポリン、タクロリムスおよびシロリムス(ラパマイシン)から選択される、請求項57に記載の医薬組成物。
- 前記抗炎症剤が、アルキル化剤である、請求項47に記載の医薬組成物。
- 前記アルキル化剤が、シクロホスファミドおよびクロラムブシルから選択される、請求項59に記載の医薬組成物。
- 1つもしくは複数の賦形剤またはキャリアをさらに含む、請求項44から60のいずれか1項に記載の医薬組成物。
- 式(I)の化合物:
[式中、
X、YおよびXは、それぞれ独立して、N、CH、またはNH2が結合したCであり、ここで、X、YおよびZの1つは、Nであり;
R1は、
Raは、それぞれ独立して、C1〜6アルキルであり、
Rbは、置換されたか、または無置換のC1〜6アルキルである)
からなる群から選択され;
R2は、それぞれ独立して、ハロゲン、ヒドロキシル、カルバモイル、アミノ、または無置換もしくは置換されたアリールであり;
pは、0、1、2または3である]、
抗炎症剤、および
1つまたは複数の眼科的に許容される賦形剤
を含む、眼科用水性製剤。 - 前記式(I)の化合物が、構造式(1a)の化合物:
[式中、
R1は、
Raは、それぞれ独立して、C1〜6アルキルであり、
Rbは、置換されたか、または無置換のC1〜6アルキルである)
からなる群から選択され;
R2は、それぞれ独立して、ハロゲン、ヒドロキシル、カルバモイル、アミノ、または置換されたか、もしくは無置換のアリールであり;
pは、0、1または2である]
である、請求項62に記載の眼科用水性製剤。 - 前記式(I)の化合物が、化合物(2):
- 前記化合物が、少なくとも、約0.1%w/v、約0.2%w/v、約0.3%w/v、約0.4%w/v、約0.5%w/v、約0.6%w/v、約0.7%w/v、約0.8%w/v、約0.9%w/v、約1%w/v、約1.5%w/v、約2%w/v、約3%w/v、約4%w/v、約5%w/v、または約10%w/vの濃度で存在する、請求項62から64のいずれか1項に記載の眼科用水性製剤。
- 前記化合物が、少なくとも、約0.05%w/v〜約10%w/v、約0.1%w/v〜約5%w/v、約0.2%w/v〜約4%w/v、約0.3%〜約3%w/v、約0.4%w/v〜約2%w/v、または約0.5%w/v〜約1.5%w/vの濃度で存在する、請求項62から64のいずれか1項に記載の眼科用水性製剤。
- 前記抗炎症剤が、ステロイド、非ステロイド性抗炎症化合物および、代謝拮抗薬、免疫抑制抗生物質から選択される、請求項62から66のいずれか1項に記載の眼科用水性製剤。
- 前記抗炎症剤が、ステロイドまたはそのプロドラッグである、請求項67に記載の眼科用水性製剤。
- 前記ステロイドが、コルチコステロイドまたはそのプロドラッグである、請求項68に記載の眼科用水性製剤。
- 前記コルチコステロイドが、コルチゾール、コルチゾン、プレドニゾン、プレドニゾロン、メチルプレドニゾン、トリアムシノロン、ベタメタゾン、デキサメタゾンおよびそれらのプロドラッグから選択される、請求項69に記載の眼科用水性製剤。
- 前記コルチコステロイドが、プレドニゾロンまたはそのプロドラッグである、請求項70に記載の眼科用水性製剤。
- 前記コルチコステロイドが、酢酸プレドニゾロンである、請求項71に記載の眼科用水性製剤。
- 前記ステロイドが、約0.1w/v〜約2%w/v、約0.2w/v〜約1.75%w/v、0.5%w/v〜約1.5%w/v、0.75%w/v〜約1.25%w/vの濃度で存在する、請求項68から72のいずれか1項に記載の眼科用水性製剤。
- 前記ステロイドが、約0.1w/v、0.2%w/v、0.5%w/v、0.75%w/v、1%w/v、1.25%w/v、1.5%w/v、約1.75%w/v、または約2%w/vの濃度で存在する、請求項68から72のいずれか1項に記載の眼科用水性製剤。
- 前記抗炎症剤が、非ステロイド性抗炎症剤(NSAID)である、請求項67に記載の眼科用水性製剤。
- 前記NSAIDが、ジクロフェナク、フルルビプロフェン、ケトプロフェン、ブロムフェナクおよびネパフェナクからなる群から選択される、請求項75に記載の眼科用水性製剤。
- 前記抗炎症剤が、代謝拮抗薬である、請求項67に記載の眼科用水性製剤。
- 前記代謝拮抗薬が、メトトレキサート、アザチオプリン、メルカプトプリン、ミコフェノール酸およびミコフェノール酸モフェチルから選択される、請求項77に記載の眼科用水性製剤。
- 前記抗炎症剤が、免疫抑制抗生物質である、請求項67に記載の眼科用水性製剤。
- 前記免疫抑制抗生物質が、シクロスポリン、タクロリムスおよびシロリムス(ラパマイシン)から選択される、請求項79に記載の眼科用水性製剤。
- 前記抗炎症剤が、アルキル化剤である、請求項67に記載の眼科用水性製剤。
- 前記アルキル化剤が、シクロホスファミドおよびクロラムブシルから選択される、請求項81に記載の眼科用水性製剤。
- 前記賦形剤が、シクロデキストリンを含む、請求項62から82のいずれか1項に記載の眼科用水性製剤。
- 前記シクロデキストリンが、α−シクロデキストリン、β−シクロデキストリン、γ−シクロデキストリン、それらの誘導体およびそれらの組合せから選択される、請求項83に記載の眼科用水性製剤。
- 前記シクロデキストリンまたはその誘導体が、カルボキシアルキルシクロデキストリン、ヒドロキシアルキルシクロデキストリン、スルホアルキルエーテルシクロデキストリン、アルキルシクロデキストリンおよびそれらの組合せから選択される、請求項83に記載の眼科用水性製剤。
- 前記シクロデキストリンが、α−シクロデキストリンまたはその誘導体を含む、請求項84に記載の眼科用水性製剤。
- 前記シクロデキストリンが、β−シクロデキストリンまたはその誘導体を含む、請求項85に記載の眼科用水性製剤。
- 前記β−シクロデキストリンまたはその誘導体が、カルボキシアルキル−β−シクロデキストリン、ヒドロキシアルキル−β−シクロデキストリン、スルホアルキルエーテル−β−シクロデキストリン、アルキル−β−シクロデキストリンおよびそれらの組合せから選択される、請求項87に記載の眼科用水性製剤。
- 前記β−シクロデキストリンが、スルホアルキルエーテル−β−シクロデキストリンまたはヒドロキシアルキル−β−シクロデキストリンである、請求項88に記載の眼科用水性製剤。
- 前記スルホアルキルエーテル−β−シクロデキストリンが、スルホブチルエーテル−β−シクロデキストリンである、請求項89に記載の眼科用水性製剤。
- 前記シクロデキストリンが、約0.1w/v〜約30%w/v、約0.1w/v〜約20%w/v、約0.5%w/v〜約10%w/v、または約1%w/v〜約5%w/vで存在する、請求項83から90のいずれか1項に記載の眼科用水性製剤。
- 前記シクロデキストリンが、約0.1%w/v、約0.2%w/v、約0.5%w/v、約1%w/v、約2%w/v、約3%w/v、約4%w/v、約5%w/v、約6%w/v、約7%w/v、約8%w/v、約9%w/v、約10%w/v、約12%w/v、約14%w/v、約16%w/v、約18%w/v、約20%w/v、約25%w/v、または約30%w/vまたはそれより多く存在する、請求項83から90のいずれか1項に記載の眼科用水性製剤。
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AU2017264697A1 (en) | 2018-11-22 |
CA3022665A1 (en) | 2017-11-16 |
US11129823B2 (en) | 2021-09-28 |
US20220184057A1 (en) | 2022-06-16 |
WO2017196881A1 (en) | 2017-11-16 |
EP3454858A4 (en) | 2020-01-15 |
US20190183878A1 (en) | 2019-06-20 |
IL262608A (en) | 2018-12-31 |
EP3454858A1 (en) | 2019-03-20 |
JP7116490B2 (ja) | 2022-08-10 |
CN109152774A (zh) | 2019-01-04 |
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