JP5722803B2 - プロスタグランジンを含有するカチオン性水中油型エマルジョンおよびその使用 - Google Patents
プロスタグランジンを含有するカチオン性水中油型エマルジョンおよびその使用 Download PDFInfo
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- JP5722803B2 JP5722803B2 JP2011552444A JP2011552444A JP5722803B2 JP 5722803 B2 JP5722803 B2 JP 5722803B2 JP 2011552444 A JP2011552444 A JP 2011552444A JP 2011552444 A JP2011552444 A JP 2011552444A JP 5722803 B2 JP5722803 B2 JP 5722803B2
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- water emulsion
- prostaglandin
- cationic oil
- colloidal cationic
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Images
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Description
本発明に係るカチオン性水中油型エマルジョンを、界面活性剤の総質量に対するプロスタグランジンの質量比が1、界面活性剤の総質量に対する飽和油の質量比が200にして、プロスタグランジン(ラタノプロスト)と飽和油(MCT)と塩化セタルコニウムを50℃で混合して油相を調製する工程、グリセリンと精製水を50℃で混合して水相を調製する工程、油相を水相に組み込む工程、当業者に知られている任意の好適な手段、例えば、16000rpmで5分間の高剪断混合(ポリトロン(Polytron)PT6100、Kinematica社、スイス)によってエマルジョンの液滴の大きさを減少させる工程、冷却したエマルジョンを15000psiで20分間均質化(Emulsiflex C3、Avestin社、カナダ)する工程、pHをNaOHで調整する工程、およびエマルジョンを高圧蒸気滅菌によって滅菌する工程によって調製する。
実施例1のエマルジョンの安定性は、加速条件「苛酷試験」(80℃で14日間)で評価し、カチオン性エマルジョン(発明)とキサラタン(登録商標)との比較分析を同じ「苛酷試験」条件で行なった。両方の試験において、HPLC−紫外部測定法によってプロスタグランジン含有量を分析した。その結果を表2(安定性試験)および表3(比較試験)に示す。
雄および雌のニュージランドホワイト種ウサギに表1のエマルジョンまたはキサラタン(登録商標)を投与し、投与後の異なる時点(0.25、0.5、1、4、6および24時間後)で、標的組織(結膜、角膜、眼房水および毛様体)におけるラタノプロスト遊離酸の濃度を測定した。TmaxおよびAUC0.5〜24時間を計算し、以下の表5に示す。
Claims (27)
- プロスタグランジンと、
2以下のヨウ素価を有する油と、
少なくとも1種の第四級アンモニウム化合物を含む1種または複数の界面活性剤と、
水と、
を含み、
正のゼータ電位を有し、かつ前記界面活性剤の総質量に対する前記プロスタグランジンの質量比は0.5〜5の範囲である水中油型エマルジョン。 - 前記界面活性剤の総質量に対する前記プロスタグランジンの質量比が0.5〜4であることを特徴とする、請求項1に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記界面活性剤の総質量に対する前記プロスタグランジンの質量比が0.5〜3であることを特徴とする、請求項1に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記界面活性剤の総質量に対する前記プロスタグランジンの質量比が0.5〜2であることを特徴とする、請求項1に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記界面活性剤の総質量に対する前記プロスタグランジンの質量比が0.6〜1.5であることを特徴とする、請求項1に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記界面活性剤の総質量に対する前記プロスタグランジンの質量比が0.7〜1.3であることを特徴とする、請求項1に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記界面活性剤の総質量に対する前記プロスタグランジンの質量比が1であることを特徴とする、請求項1に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記プロスタグランジンは、活性なプロスタグランジンのエステルプロドラッグもしくはアミドプロドラッグまたはそれらの混合物の中から選択され、
前記エステルプロドラッグはC 1 〜C 4 アルキルエステルプロドラッグであり、
前記アミドプロドラッグはC 1 〜C 4 アルキルアミドプロドラッグであることを特徴とする、請求項1〜7のいずれか1項に記載のコロイド状カチオン性水中油型エマルジョン。 - 前記プロスタグランジンは、ラタノプロスト、イソプロピルウノプロストン、トラボプロスト、ビマトプロスト、タフルプロストまたはそれらの混合物の中から選択されることを特徴とする、請求項1〜8のいずれか1項に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記第四級アンモニウム化合物は、セタルコニウムハロゲン化物、ベンザルコニウムハロゲン化物、ラウラルコニウムハロゲン化物、セトリミド、ヘキサデシルトリメチルアンモニウムハロゲン化物、テトラデシルトリメチルアンモニウムハロゲン化物、ドデシルトリメチルアンモニウムハロゲン化物、セトリモニウムハロゲン化物、ベンゼトニウムハロゲン化物、ベヘナルコニウムハロゲン化物、セテチルジモニウムハロゲン化物、セチルピリジニウムハロゲン化物、ベンゾドデシニウムハロゲン化物、クロラリルメテナミンハロゲン化物、ミリスチルアルコニウム(myristylalkonium)ハロゲン化物、ステアラルコニウムハロゲン化物またはそれらの混合物の中から選択される、請求項1〜9のいずれか1項に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記第四級アンモニウム化合物は、塩化セタルコニウム、塩化ベンザルコニウムまたはそれらの混合物の中から選択される、請求項10に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記油は、油性脂肪酸、油性脂肪族アルコール、脂肪酸エステル、植物油、動物油、鉱油、流動パラフィン、半合成油またはそれらの混合物の中から選択されることを特徴とする、請求項1〜11のいずれか1項に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記脂肪酸エステルはミリスチン酸イソプロピルまたはパルミチン酸イソプロピルを含み、前記鉱油はワセリンを含み、前記半合成油は植物油から得られる分別油を含むことを特徴とする、請求項12に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記分別油は中鎖脂肪酸トリグリセリド(MCT)であることを特徴とする、請求項13に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記界面活性剤は、ポロクサマー、チロキサポール、ポリソルベート、ソルビタンエステル、ステアリン酸ポリオキシルまたはそれらの混合物の中から選択される、請求項1〜14のいずれか1項に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記エマルジョンの総重量に対するプロスタグランジンの量は、0.001〜1%w/wの範囲である、請求項1〜15のいずれか1項に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記エマルジョンの総重量に対するプロスタグランジンの量は、0.002〜0.3%w/wの範囲である、請求項1〜15のいずれか1項に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記エマルジョンの総重量に対するプロスタグランジンの量は、0.004〜0.15%w/wの範囲である、請求項1〜15のいずれか1項に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記組成物全体に対する前記第四級アンモニウム化合物の量は、0.001〜0.1%w/wの範囲である、請求項1〜18のいずれか1項に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記組成物全体に対する前記第四級アンモニウム化合物の量は、0.002〜0.05%w/wの範囲である、請求項1〜18のいずれか1項に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記組成物全体に対する前記第四級アンモニウム化合物の量は、0.002〜0.03%w/wの範囲である、請求項1〜18のいずれか1項に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記エマルジョンの総重量に対する前記油の量は、7%w/w以下である、請求項1〜21のいずれか1項に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記エマルジョンの総重量に対する前記油の量は、0.5〜5%w/w以下である、請求項1〜21のいずれか1項に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記エマルジョンの総重量に対する前記油の量は、1〜3%w/w以下である、請求項1〜21のいずれか1項に記載のコロイド状カチオン性水中油型エマルジョン。
- 前記界面活性剤の総質量に対する前記プロスタグランジンの質量比は0.5〜4の範囲であり、前記界面活性剤の総質量に対する前記油の質量比は50〜500の範囲である、請求項1〜24のいずれか1項に記載のコロイド状カチオン性水中油型エマルジョン。
- 高眼圧症および/または緑内障の治療に使用される請求項1〜25のいずれか1項に記載のコロイド状カチオン性水中油型エマルジョン。
- 請求項1〜26のいずれか1項に記載のコロイド状カチオン性水中油型エマルジョンを含む送達装置。
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R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |