JP2021518352A - チモロールを含む医薬組成物 - Google Patents
チモロールを含む医薬組成物 Download PDFInfo
- Publication number
- JP2021518352A JP2021518352A JP2020549581A JP2020549581A JP2021518352A JP 2021518352 A JP2021518352 A JP 2021518352A JP 2020549581 A JP2020549581 A JP 2020549581A JP 2020549581 A JP2020549581 A JP 2020549581A JP 2021518352 A JP2021518352 A JP 2021518352A
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- Prior art keywords
- pharmaceutical composition
- timolol
- alkane
- hemifluoride
- eye
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
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Abstract
Description
(a)チモロール及び/又はその薬学的に許容され得る塩と、
(b)半フッ化アルカンを含む液体ビヒクルと
を含む医薬組成物を提供する。
(a)チモロール及び/又はその薬学的に許容され得る塩と、
(b)半フッ化アルカンを含む液体ビヒクルと
を含む医薬組成物を提供する。
CF3(CF2)n(CH2)mCH3 (II)
の半フッ化アルカンを含み、
式中、添字nは、2〜10から選択される整数であり、mは2〜10から選択される整数である。好ましくは、本発明の医薬組成物の液体ビヒクルは、一般式(II)の半フッ化アルカンを含み、式中、添字nは、3〜7から選択される整数であり、mは4〜7から選択される整数であり、より好ましくは、式中、添字nは、3〜5から選択される整数であり、mは4〜7から選択される整数である。
(a)チモロール及び/又はその薬学的に許容され得る塩と、
(b)半フッ化アルカンを含む液体ビヒクルと
を含む医薬組成物を提供する。
(a)チモロール及び/又はその薬学的に許容され得る塩と、
(b)半フッ化アルカンを含む液体ビヒクルと
を含む医薬組成物を、処置を必要とする対象の眼に投与することを含む。
−
(a)チモロール及び/又はその薬学的に許容され得る塩と、
(b)半フッ化アルカンを含む液体ビヒクルと
を含む組成物を提供することと、
−前記組成物を対象又は患者の眼の表面に局所投与することと、を含む。
(a)チモロール及び/又はその薬学的に許容され得る塩と、
(b)半フッ化アルカンを含む液体ビヒクルと
を含む医薬組成物の、
緑内障、眼圧の上昇、高眼圧症及び/又はそれに関連する症状の処置のための医薬の製造のための使用を提供する。本発明のこの態様による医薬の製造については、本発明の他の態様に関連して上述した全実施形態及び好ましい実施形態が各々適用されることを理解するべきである。
(a)チモロール及び/又はその薬学的に許容され得る塩と、
(b)半フッ化アルカンを含む液体ビヒクルと
を含む医薬組成物と、
医薬組成物を保持するように適合された容器とを含む、医薬キットを提供する。好ましくは、本発明の医薬組成物を含む容器は、医薬組成物の投与に適合された液滴ディスペンサー又は装置を更に含む。
(a)チモロール及び/又はその薬学的に許容され得る塩と;
(b)半フッ化アルカンを含む液体ビヒクルと
を含む医薬組成物。
CF3(CF2)n(CH2)mCH3 (II)
(式中、
nは3〜7の整数であり、
mは4〜7の整数であり;
又は
nは2〜10の整数であり、
mは2〜10の整数である)
の半フッ化アルカンを含む、項目1に記載の医薬組成物。
図1は、水溶液中の濃度0.5%(w/v)のチモロールの製剤に対する、1−ペルフルオロヘキシル−オクタン(F6H8)中の濃度0.5%(w/v)のチモロールの懸濁液の1日1回投与後の、インビボでの眼圧の測定の結果のグラフ表示である。グラフは、mmHgで測定された平均眼圧(IOP)の時間的進行を示す。
109.34mgのチモロールマレイン酸塩、CAS番号26921−17−5(LKT Labs;純度99.5%)を直径2mmのステンレス鋼球で満たした25mL容器に導入した。その後、8mLの1−ペルフルオロヘキシル−オクタン(F6H8)を加え、容器を閉鎖し、遊星ボールミル(PM 100、Retsch GmbH Germany)を用いてミリングを150rpmで10分間の間隔で3時間行った(向きを変えながら)。ミリング後、それによって形成された縣濁液をガラスバイアルに移動し、Vortexシェーカー上で最小30秒間振盪し、密封した。1.3668mgのチモロールマレイン酸塩が1.0mgのチモロール遊離塩基に対応すると考えると、F6H8中の1.0%(w/v)チモロール縣濁液(10mg/mL)が得られた。
水溶液の形態で投与された市販のチモロール溶液と比較して、IOP(眼圧)を低下させる能力に関してチモロール及び半フッ化アルカンを含む組成物の薬力学を評価するために、8匹の正常血圧の犬を使用して動物試験を行った。試験設定及び設計は、以下の通りであった。
−健康、正常な眼球表面;
−試験前の少なくとも1か月間に侵襲性眼科手術;特に一般に角膜又は前眼部セグメントに関与する手術なし;
−少なくとも1か月間、局所又は全身コルチコステロイド処置なし;
−臨床試験に使用される典型的なウォッシュアウト期間と等しい、以前の局所眼球試験薬物からのウォッシュアウト(少なくとも1週間)。
Claims (15)
- (a)チモロール及び/又はその薬学的に許容され得る塩と、
(b)半フッ化アルカンを含む液体ビヒクルと:
を含む医薬組成物。 - 前記半フッ化アルカンが、式(II)
CF3(CF2)n(CH2)mCH3 (II)、
(式中、
nは3〜7の整数であり、
mは4〜7の整数である)
を有する、請求項1に記載の医薬組成物。 - 前記半フッ化アルカンが、1−ペルフルオロブチル−ペンタン(CF3(CF2)3(CH2)4CH3;F4H5)及び1−ペルフルオロヘキシル−オクタン(CF3(CF2)5(CH2)7CH3;F6H8)からなる群から選択される、請求項1又は2に記載の医薬組成物。
- チモロール及び/又はその薬学的に許容され得る塩が、半フッ化アルカンを含む前記液体ビヒクル中に懸濁される、請求項1〜3のいずれか一項に記載の医薬組成物。
- 遊離塩基としてのチモロールの濃度が、約0.3〜約2.5%(w/v)である、請求項1〜4のいずれか一項に記載の医薬組成物。
- 遊離塩基としてのチモロールの濃度が、約0.5〜約2.0%(w/v)、好ましくは約0.5〜約1.5%(w/v)である、請求項5に記載の医薬組成物。
- 好ましくは約0.4〜約3.4%(w/v)、より好ましくは約0.68〜約2.7%(w/v)の濃度、最も好ましくは約0.68%〜約2.1%(w/v)の濃度の、チモロールマレイン酸塩の形態のチモロールを含む、請求項1〜6のいずれか一項に記載の医薬組成物。
- チモロール及び/又はその薬学的に許容され得る塩の懸濁粒子の少なくとも約90%が、約15μm以下のサイズを有する、請求項4〜7のいずれか一項に記載の医薬組成物。
- 医薬として使用するための、請求項1〜8のいずれか一項に記載の医薬組成物。
- 緑内障、眼圧の上昇、高眼圧症及び/又はそれに関連する症状の処置における使用のための、請求項1〜9のいずれか一項に記載の医薬組成物。
- 前記組成物が、1日4回まで、好ましくは1日2回まで、より好ましくは1日1回、対象の眼に投与される、請求項10に記載の使用のための医薬組成物。
- 前記医薬組成物が、1眼当たり約8〜約15μl、好ましくは約10〜約12μlの投与量で投与される、請求項10又は11に記載の使用のための医薬組成物。
- 前記半フッ化アルカンが、1−ペルフルオロヘキシル−オクタン(CF3(CF2)5(CH2)7CH3、F6H8)である、請求項10〜12のいずれか一項に記載の使用のための医薬組成物。
- 共溶媒を更に含む、請求項1〜13のいずれか一項に記載の医薬組成物。
- 請求項1〜14のいずれか一項に記載の医薬組成物と、前記医薬組成物を保持するための容器とを含むキット。
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EP18164563.1 | 2018-03-28 | ||
EP18164563 | 2018-03-28 | ||
EP18185436.5 | 2018-07-25 | ||
EP18185436 | 2018-07-25 | ||
PCT/EP2019/057429 WO2019185543A1 (en) | 2018-03-28 | 2019-03-25 | Pharmaceutical composition comprising timolol |
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JP2021518352A true JP2021518352A (ja) | 2021-08-02 |
JPWO2019185543A5 JPWO2019185543A5 (ja) | 2022-03-31 |
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ES2969758T3 (es) | 2016-09-22 | 2024-05-22 | Novaliq Gmbh | Composiciones farmacéuticas para usar en la terapia de la blefaritis |
CN109906085B (zh) | 2016-09-23 | 2024-03-08 | 诺瓦利克有限责任公司 | 含有环孢素的眼用组合物 |
US11723861B2 (en) | 2017-09-27 | 2023-08-15 | Novaliq Gmbh | Ophthalmic compositions comprising latanoprost for use in the treatment of ocular diseases |
SG11202007858VA (en) | 2018-03-02 | 2020-09-29 | Novaliq Gmbh | Pharmaceutical compositions comprising nebivolol |
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IL276888A (en) | 2020-10-29 |
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US20210121471A1 (en) | 2021-04-29 |
CN111867560A (zh) | 2020-10-30 |
EP3773469A1 (en) | 2021-02-17 |
MX2020010078A (es) | 2021-02-26 |
KR20200136403A (ko) | 2020-12-07 |
AU2019246035A1 (en) | 2020-09-10 |
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