TW201000149A - Ophthalmic solutions displaying improved efficacy - Google Patents
Ophthalmic solutions displaying improved efficacy Download PDFInfo
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- TW201000149A TW201000149A TW098108695A TW98108695A TW201000149A TW 201000149 A TW201000149 A TW 201000149A TW 098108695 A TW098108695 A TW 098108695A TW 98108695 A TW98108695 A TW 98108695A TW 201000149 A TW201000149 A TW 201000149A
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- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
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- 239000002699 waste material Substances 0.000 description 1
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- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
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- A61L12/00—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor
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Description
201000149 六、發明說明： 【相關申請案】 之優 本申請案主張享有美國臨時性中請案號61/〇37894 先權，該案全部併入參考。 【發明所屬之技術領域】 本發明係、關於一種眼用組成物；更詳而言之，本發明係 e 關於一種表現改善之抗真菌功效的眼用溶液。 【先前技術】 有許多商業可得的眼用溶液。溶液對於可與眼睛接觸之 主種二田，及真菌與駐於眼睛上之裝置如隱形眼鏡應提供消 毋。在溶液使用壽命期間，溶液必須保持不受汙染。為了達 ^此^求，溶液含有防腐劑成分或以單一使用劑量滅菌包 、二ί=隱形眼鏡潔淨與護理溶液及櫃台銷售眼藥水而言， ❹=诏里^器係文歡迎的。此等溶液需要包含防腐劑（針對眼 樂水)及消毒組成物(針對隱形眼鏡潔淨與護理溶液）。 過氧化氳於眼甩溶液中已被使用作為消毒劑或防腐 然而，過氧化氫不穩定，必須以刺痛眼睛之濃度含入， 含有額外成分以穩定過氧化氫。揭示有用作為過 氧萨虱穩定劑之化合物包含膦酸鹽、磷酸鹽、與錫酸鹽、及 膦西欠(如一伸乙二胺五亞曱基膦酸)之特定實例生理可接受鹽 類亦已揭示胺基多繞酸螯合劑 ，如伸乙二胺四醋酸。 一伸乙二胺五亞曱基膦酸(DTPPA)及伸乙二胺四醋酸 3 201000149 (EDTA)於相對低水平為細胞毒性並具有低pH。因此，此等 穩定劑可僅以少1：被含人’及需要添加中和劑以提供與人類 眼睛能共容之溶液。 於是，針對直接滴人眼㈣料Μ，或針對於鏡片放 置在眼睛上料需要被職__眼鏡料與護理溶液 而言’必須有額外過氧化氫穩定劑。 【發明内容】 本發明有關-種眼用組成物，其係包括ΡΗ介於約6至 =且約50至約1500 ppm之過氧化氯、、約議 約 ί 種亞氯酸鹽化合物、及約至刚㈣ 至>一種飽和聚合四級錢鹽。 本發明進一步有關一種眼用 分，呈表！所列之用量。 设包括表1所列之成 j明有關-種包括低濃度過 液。本發明進-步有關一種貯存 ：之新穎眼用命 之眼用溶液。 濃度過氧化氫 本文所用之貯存穩定意指在貯 贼’溶液於3G日姻損失小於3叫^如溫度小於約 化氫，在若干㈣實财於30日内顿H减中之過氧 眼用組成物為可直接滴入眼睛中 ：… 潤洗、貯存n射觀職 於浸>»、潔淨、 用裝置之任何組成物。眼 中或眼睛上的任何眼 溶液、潔淨溶液、胃實例包含眼用裝置包裝 調即/谷液、貯存溶液、眼藥水、洗眼水、 201000149 以及眼用懸浮液、凝膠與軟膏等。在本發明具體實例中，該 眼用組成物為眼用溶液。 Λ 眼用裝置包含可放置在眼睛上或眼睛任何部分(例如但 不限於在眼瞼下或於淚點中）之任何裝置。眼用裝置實例^ ^ ^ . ^<fi^(punctualplug) 本發明眼用組成物包括介於約5〇至約1〇〇〇ppm之過氧 ❹域。在若干具體實例中，過氧化氫係以濃度介於約1〇〇至 約500 ppm且在其他具體實例中介於約1〇〇至約3〇〇卯瓜存 在。 或者，組成物可包含過氧化氫來源。適合的過氧化氫來 源為已知且包含於水中水解之過氧化合物。過氧化氫來源實 例包含鹼金屬過硼酸鹽或過碳酸鹽，如過硼酸鈉及過碳酸 鈉。 已發現包括呈上述用量之過氧化氳之眼用組成物可藉 ❹ 由包含介於約〇.005重量°/〇(50 ppm)至約0.15重量％(15〇〇 PPm)且在若干具體實例中約100至約1000 ppm之至少一種 眼用能共容穩定劑予以穩定，例如至少一種二伸乙三胺五醋 I之鹽，其包括二伸乙三胺五醋酸之至少一種齊鹽、鋅鹽或 混合鈣/辞鹽。如本文所用，術語鈣鹽、鋅鹽或混合鈣/鋅鹽 意指DTPA包括至少一種特定陽離子。所以例如，DTpA2 鈣鹽包含包括至少一種鈣離子之1)71>八鹽。實例包含dtpa 之二鈣鹽、DTPA之二鈣—三鈉鹽、DTPA之單鋅鹽、及其 混合物。本發明的鹽可進一步包括額外眼用能共容陽離子如 201000149 鈉、鎂、其組合等。在-具體實例中，DTPA鹽包括二約 DTPA。二伸乙三胺五醋酸鹽之濃度係介於約5〇至約1〇〇() ppm。 一 DTPA鹽可分別形成且添加於溶液或五醋三胺（二伸乙 三胺五醋酸），所欲陽離子之過氧化物鹽可以化學計量添如 於溶液而就地(in situ)形成所欲DTPA鹽。 已發現二伸乙三胺五醋酸二鈣為至少有效，且在若干濃 ，較了伸乙二胺五亞曱基膦酸(DTppA)更有效於穩定含過❹ 氧化氫之眼用溶液。二伸乙三胺五亞曱基膦酸亦較 為更少細胞毒性及具有更中性pH。 本發明眼用組成物亦具有pH介於約6至8，在若干具-體實例中介於約6.5至約7.5。此允許本發明組成物直接滴 入眼目月中及用於被放置眼環境中之眼用裝置上。 眼用組成物可進-步包括至少一種額外過氧化物穩定 劑。可使祕何已知的過氧化物穩定劑，只要其於所用濃度 為非細胞毒性且與其他眼用組成物成分能共容即可。例如， 額外過氧化物穩定劑應不干涉組成物中所含任何其他成分ϋ =作用且應不與任何其他成分反應。適合的額外過氧化物穩 定劑實例包含膦酸鹽、魏鹽、伸乙二胺四醋酸、氮基三醋 酸、任何前述之眼用能共容水溶性鹽、其等混合物等。在一 具體實例中，額外過氧化物穩定劑包括DTPPA或DTPPA之 至少一種醫藥可接受鹽。 至少一種額外過氧化物穩定劑可以濃度高至約1000 ’且在若干具體實例中介於約酬至約500 ppm存在。當 201000149 額外過氡化物穩定劑包括DTPPA或DTPPA之至少—種醫藥 可接受鹽時’其係以濃度高至約1000卯瓜且在若干具體實 例中介於約100至約500 ppm存在。
本發明眼用組成物可進一步包括額外成分，例如但不限 於pH調整劑、滲性調整劑、緩衝劑、活性劑、潤滑劑、消 毒劑、黏度調整劑、界面活性劑及其等混合物。當眼用組成 物為眼用溶液時，本發明眼用溶液中之所有成分應為水溶 性、。如本文所用，水溶性意指在常見於製造、滅菌及貯存眼 用溶液之所選濃度及橫越溫度與pH轄域，單獨或與其他成 分組合之成分無法形成人類眼睛可見之沉澱物或凝膠顆粒。 眼用組成物之pH可使用酸及鹼調整，如礦酸例如但不 限於鼠氣酸及驗例如氫氧化鈉。 眼用組成物之滲性(tonicity)可藉由包含滲性調整劑調 整。在若干具體實例中，對眼用组成物而言想要者為相對於 正常人類眼淚為轉壓、或接近等轉。適合特性調整劑 為技藝中已知且包含鹼金屬鹵化物、磷酸鹽、磷酸氫鹽及硼 ，鹽。滲性調整劑之特定實例包含氣化鈉、氯化卸、氯化到、 氣化鎂、氯化鋅、其等組合等。 目=，成物可進—步包括至少—種與二伸乙三胺五醋 夂i犯，、谷之緩衝劑。適合的緩衝劑實例包含硼酸鹽緩衝 液、磷酸鹽緩衝液、硫酸鹽緩讎、其等組合等。在一具體 ^例中’緩衝劑包括魏鹽緩衝液。在另-具體實例/，、緩 衝液。特定實例包含·緩衝的鹽水及 7 201000149 眼用組成物除了過氧化氫外亦可包括至少一種消毒 劑。消毒劑應於使用濃度無法造成眼睛刺痛或損害且應對其 他組成物成分為惰性。適合的消毒劑包含聚合縮二胍、聚合 四級錄化合物、亞氯酸鹽、雙縮二胍、四級銨化合物及其等 混合物。 在一具體實例中，消毒成分包括至少一種亞氣酸鹽化合 物。適合的亞氯酸鹽化合物包含水溶性鹼金屬亞氯酸鹽、水 溶性鹼土金屬亞氣酸鹽及其等混合物。亞氯酸鹽化合物之特 〇 定實例包含亞氣酸鉀、亞氣酸鈉、亞氣酸鈣、亞氯酸鎂及其 等混合物。在一具體實例中，亞氯酸鹽化合物包括亞氯酸鈉。 適合於亞氣酸鹽化合物之濃度包含濃度介於约100至 ， 約2000??111，在若干具體實例中介於約100至約100〇1)1)111， 在其他具體實例中介於約100至約500 ppm，及在其他具體 實例中介於約200至約500 ppm。 適合的過氧化物/亞氯酸鹽消毒劑之組合係揭示於US 6,488,965、US 6,592,907、US 20060127497、US 2004/0037891、US 2007/0104798。此等專利以及本文揭示之❹ 所有其他專利以其等全部於此併入參考。 本發明眼用組成物可進一步包括至少一種選自完全飽 和聚合四級錢鹽所組成組群之額外消毒化合物，如揭示於 US 5,300,296及US 5,380,303之聚[氧伸乙基(-二曱基亞胺基） 伸乙基-(二甲基亞胺基）伸乙基二氯化物](CAS稱號為 31512-74-0 ’ 本文稱為聚四級敍-42 “P〇lyquaternium-42”）。 聚合四級錢鹽期望地為完全飽和，以確保其等於有過氧化氫 201000149 參與情況下為穩定的。完全飽和聚合四級銨鹽可於溶液以用 量介於約10至約100 ppm且在若干具體實例中約25至約 lOOppm存在。已發現當至少一種完全飽和聚合四級銨鹽如 聚四級銨-42與過氧化氫及亞氯酸鹽一起含入眼用溶液中 時，所得溶液表現令人驚訝改善的抗真菌性質，特別是對於 腐皮鐮孢菌。 一或多種潤滑劑亦可含入眼用組成物中。潤滑劑包含水 ❹ 溶性纖維質化合物、玻尿酸、及玻尿酸衍生物、聚葡萄胺糠、 包含水溶性聚胺曱酸酯之水溶性有機聚合物、聚乙二醇、其 等組合等。適合潤滑劑之特定實例包含聚乙烯吡咯烷酮 (「PVP」）、羥丙基甲基纖維素、羧甲基纖維素、甘油、丙 二醇、1，3-丙烷二醇、聚乙二醇、其等混合物等。一般潤滑 劑具有分子量超過100,000。當使用甘油、丙二醇及13-丙 烧二醇作為潤滑劑時’其等可具有分子量低於戰麵。 當使用潤滑劑時，其可以用量高至約5重量％且在若干 ❿ 具體實例中介於約100 ppm至約2重量％含入。 • 一或多種活性劑亦可被併入眼用溶液中。可使用廣泛^ 種治療劑，只要所選雜於有聽化物參與情況下為惰士 適合的治療劑包含治療或標餘何部份包含眼睛前廷 3面^之眼環境者，且包含醫藥劑、維他命、營養食品 it 的活性劑種類包含抗組織胺、抗生素、， 士 =、=軒酶抑制劑、抗病毒劑、抗炎劑、非細 樂抗原蟲樂品、其等組合等。當包含六 4 201000149 性劑時’其等以足夠產品所欲治療結果之用量（「治療有效 量」）含入。 本發明眼用組成物亦可包含一或多種界面活性劑、清潔 劑或其等混合物。適合的實例包含商業可得自BASF之泰洛 沙泊（tyloxapol)、泊洛沙姆(p〇i〇xonier)(聚（環氧乙烷)-b-聚（環 氧丙烷）_b-聚（環氧乙烷））類型界面活性劑及泊洛沙胺 (poloxamine)類型界面活性劑（非離子性、以環氧乙烷/環氧丙 炫為主之終止於一級羥基之四官能嵌段共聚物，以商品名 . 〇
Tetronic商業可得自BASF)。特定實例為Pluronic F-147及
Tetronic 1304。泰洛沙泊為非離子性低分子量界面活性劑且 完全溶於磷酸鹽緩衝液。泰洛沙泊為商業可得自Pressure
Chemical Company公司之清潔劑。在包含泰洛沙泊之具體實 例中，其係以用量介於約500至約2000 ppm含入。 界面活性劑可以用量高至約5重量％且在若干具體實例 中高至約2重量％使用。 若干界面活性劑亦可作為消毒增進劑。本發明溶液用之 消毒增進劑包含Cwo多元醇，如ι，2-辛烷二醇（辛醯二醇）、❹ 甘油單辛酸酯、山梨醇酐單月桂酸酯(TWEEN 80)、其等組 合等。消毒增進劑可以用量約5〇至約2000 ppm存在。 此外，眼用組成物可包括一或多種黏度調整劑或增稠 劑。適合的黏度調整劑為技藝中已知且包含聚乙烯醇、聚乙 二醇、古亞膠(guar gum)、其等組合等。黏度調整劑可以必 須達到所欲黏度之用量使用。 將領會所有成分以其等於本文使用之濃度將溶於緩衝 201000149 溶液甲，與其它溶液成分能共容，且將無法造成眼疼痛或損 害。 根據本發明眼用溶液之實例係揭示於表1及2。 表1 成分 化學式 濃度 過氧化氫 H2〇2 50-1000 ppm 100-500 ppm 100 至 300 ppm 亞氣酸鈉 NaC102 100-2000 ppm 100-1000 ppm 100-500 ppm 200 至 500 ppm 聚四級銨-42 〔WSCP，聚塞銨 (polixetonium)〕 (CH10H24N2O.2Cl)„ 10-100 ppm 25 至 l〇0 ppm 聚乙烯吡咯烷酮K90 〔PVP，聚維酮 (povidone)] (C6H9NO)n 0.1 至 1.0% 二伸乙三胺五醋酸 (DTPA) C14H23N3O10 50-500 ppm 100 至 500 ppm 硼酸 b(oh)3 0.15 至 1.00% 硼酸鈉 Na2B4O710H2O 辛醯二醇（1，2-辛烷二 醇） CsHi8〇2 50 至 1000 ppm 甘油單月桂酸酯 C15H30O4 50 至 1000 ppm 泊洛沙姆 (poloxamer)407 OH(C2H4O)101(C3H6)56- (C2H40)i〇iH 0.1 至 1.5% 氯化納 NaCl 調整至滲性 水 H20 Q.S. 11 201000149 表2 成分 化學式 濃度 過氧化氫 H2〇2 50-500 ppm 亞氣酸鈉 NaC102 100-1000 ppm 聚四級錢-42 〔WSCP，聚塞銨 (polixetonium)〕 (CH10H24N2O.2Cl)n 10-100 ppm 25 至 l〇0 ppm 聚乙烯吡咯烷酮K90 〔PVP，聚維酮 (povidone)〕 (C6H9NO)n 500 至 2500 ppm DTPA，單辦鹽 CaCi4H23N3〇i〇 0 至 1,000 ppm 構酸二氫卸 KH2P〇4 0.15 至 0.5% 鱗酸氫二鉀 Na2HP04*2H20 泊洛沙姆 (poloxamer)407 ΟΗ(〇2Η4Ο)ι01(〇3Η6)56' _ (〇2Η4〇)|〇]Η 500-10,000 ppm 泰洛沙泊（tyloxapol) (c14h22oc2h4o.ch2o) 250-5,000 ppm 檸檬酸納__ 氣化鈉 ~ -Na3C6H,07»2H2Q NaCl 0.065-0.65% 調整至滲性 純水 ------------ lHHSZZZ： Q.S. …本發明眼用溶液可藉由將所選成分與水混合而形成。其❹ 匕眼用組成物可藉由將所選成分與適合的載體混合而形成。 為了闡述本發明，包含下列實施例。此等實施例並不限 制本發明。其專僅意欲建議一種實行本發明之方法。熟知隱 形眼鏡以及其他專業者可發現實行本發明之其他方法。然 而彼等方法被視為本發明範嘴内。 12 201000149 【實施方式】 [實施例1至3及比較例1與2] 下列表3所示之基礎溶液係如下製作。將HpMC稱重 入約100 ml去離子水並和緩加熱使所有材料溶解。使 溶液冷卻並添加額外約5〇〇 ml去離子水。
將NaCl、硼酸、及泊洛沙姆(p〇1〇xamer)以表3所列之 用量添加於溶液。以表4所列之用量添加Dequest2〇6〇(CAS 15827_6〇_8，來自 Fluka sigma Aldrich)、DTPA 之二辦鹽（ISP Columbus)或兩者之混合物。徹底混合溶液直到所有成分完 全溶解。以Na〇H溶液(0.1N)滴定溶液直到pH為7.2至7 4。 添加去離子水以補償總計約950 m卜若需要，檢查及校 正fH為7.2至7.4。以表3所列之用量添加亞氯酸鹽及過氧 化氫並徹底混合。視需要’再檢查pH並以Na〇H溶液中和。 添加去離子水以補償至l〇〇〇g總數。將溶液貯存於不透明聚 丙烯或高密度聚乙烯容器中。 "
將含有如下列表4所示DTPPA、DTPA或兩者用量之 l〇〇g等分溶液放置於不透明塑膠容器並用標籤標明。 13 201000149 移除來自各容器之5 m丨樣品並使用偏釩酸鹽比色 據Talanta，第66卷’第1期，第86至91頁，2〇〇5年艮 31日所揭示之方法）分析過氧化氫。此為記述於下列表 4攔中之基線(t=0)過氧化氫濃度。將各容器稱重，記錄美線 重量。使容器貯存於4(tc。在表4所示之各間隔°，將ς容 器稱重’鑛5 ml樣品以如上述過氧化氮測定。結果顯示 於，4。自該樣品的原始過氧化纽度減去在表 4所示時間 測量的各絲巾魏域濃度，計算ΔΡΡΓΠ數值。將在表4 所不時間測量的各溶液中過氧化氫濃度除以該樣品的原始 過氧化氫濃度，計算％厶。 [實施例4至9及比較例3與4] ，複實施例1至3及比較例】，只有在添加穩^劍後但 ，亞氣酸鹽前添加5ppm硫酸鐵或祕銅。如實施例i矣3 評估過氧化物穩定性，結果顯示於下列表Μ銅)及6(鐵）。 201000149
第36日 [H202] <1 cs CN VO CN B α 身 ν〇 1 r—( 1 S 1 VO 1 第29曰 [H2021 <1 CN CN m (N Β 1 S 1 in 1 σ> in 1 m r—i ^2 0 < m CN 寸 a α 〇〇 cn σ\ ro 1 1 m 1 ra π <1 00 CTs r- Β α 口 1 CN (N 1 r- 1 ra q 寸9) 城：s < Β α r < 1 »〇 1 1 1 起始 [H2o2] ppm <N in <N (N OO <N DTPA (mmol/100 ml) ο 〇 S 〇 τ·Η o o DTPPA (mmol/100 ml) ο s o 〇 τ··Η o o 實例編號 比較例1 比較例2 <N CO (uldd ς)0-ρ?^塚：ς< 第36日 [H2〇2] o o CN 1 s 1 v〇 1 第29日 ΓΗ2021 s o CN m <N 1 S Ό VO 1 1 1 m 城：® s o o r- τ-Η CO τ··Η 1 s (N 可 OO CM 1 沄 1 tn π 9, 城r £ s o o o 1 1 1 寸 1 cn ^ o C\ IT) v〇 1 〇\ 1 CN CN 1 CS r-H 1 1 起始 [H202] ppm as T·^ CN o in (S On m CN DTPA (mmol/100 ml) o 〇 p o r-H o o DTPPA (mmol/100 ml) o s o o H o 實例編號 比較例3 寸 ^T) ?iid«n)Df 廢鲧： 第36日 [Η202] < VO m (N oo CN CN a o <^s 1 m vo 1 1 m νο I m 姝a < (N CO m CS »r> <Ν <Ν CN s § 1 in 1 <Ν νο I νο *Τ) I tn <1 CN <N 2 <Ν a 1 in cn 1 νο m 1 r~H m 1 tn ^ ^ 9, 城® < 寸 卜 Ο VO 1 m 1 oo 1 I 寸 1 m 9. 妹a < 寸 卜 ν〇 1 1 1 1 v〇 τ-Η 1 起始 [H2o2] ppm 〇 CN 寸 *rl CN 寸 m (N 〇 T—H < o 自羞官 o Ο S Ο o DTPPA (mmol/100 ml) o s ο Ο r-H o o 實例編號 比較例4 卜 οο 201000149 鳞 上述表4中數據顯示以DTPA之二鈣鹽穩定的過氧化物 溶液較未穩定的溶液或以DTPPA穩定的溶液損失更少過氧 化氫。本發明經穩定的溶液於4〇。(：約30日期間損失小於25% 且在若干個案中小於約20%過氧化物。表5及6中數據顯示° 以DTPA之二鈣鹽穩定的過氧化物溶液較未穩定的溶液大體 上損失更少過氧化氫。沒有溶液由於評估過程期間之蒸發作 用而損失大於約0.4g。 [實施例10至11] 重複實施例2，只有DTPA之二鈣鹽濃度如下列表7所 示改變’且在添加DTPA後並未調整pH。在下列表7所列 之各間隔，將樣品移開並如實施例2所述測試。 表7 實例 編號 DTPA ㈣ 起始 [H2o2] ppm 第7曰 [Η2ο2ι 第18曰 [η2ο2] 一 第29曰 [H2〇2l 第48曰 [Η2021 △ppm %Δ △ppm %Δ △ppm %Δ Δρρηι %Δ 比較 例1 0 257 -25 10 -69 27 -103 40 -132 51 4 0.01 259 -13 5 -31 12 -48 19 -79 30 5 0.025 263 -15 6 -36 AJ -53 j 20 -84 32 [實施例12至17] 下列表8所示之基礎溶液係如下製作。將PVP及泊洛 沙姆(poloxamer)稱重入約1〇〇 ml去離子水並和緩加熱使所 有材料溶解。使PVP溶液冷卻並添加額外約500 ml去離子 水。 16 201000149 將NaCl及硼酸以表8所列之用量添加於溶液。以表9 所列之用量添加DTPA之二鈣鹽(ISP Columbus)。徹底混合 溶液直到所有成分完全溶解。以NaOH溶液(〇 in)滴定溶液 直到pH為7.2至7.4。 添加去離子水以補償總計約950 m卜若需要，檢查及校 正pH為7.2至7.4。以表8所列之用量添加亞氯酸鹽及過氧 化氫並徹底混合。視需要，再檢查pH並以NaOH溶液中和。 添加去離子水以補償至1000g總數。將溶液貯存於不透明聚 丙烯或高密度聚乙烯容器中。 表8 成分 來源 重量(gm) NaCl Fisher Science ED 7.5 H3BO3 Fisher Science ED 4.5 Na】B4〇7· 1OH2O Fisher Science ED 0.25 泊洛沙姆(Poloxamer)F-127 BASF 1 聚乙烯吡咯烷酮K90(PVP) ISP 1.5 亞氣酸納 Acros 0.5 過氧化氫(30%) Fisher Scientific 0.7 純水 Q.S. 1000 將來自實施例12至17及比較例5與6之隱形眼鏡消毒 溶液使用ISO 14729中所述之單獨程序測試抗微生物功效。 各溶液以五種不同生物挑戰。所用細菌為綠濃桿菌 、金黃色葡萄球菌 awrewW、及黏質賽氏桿菌（Serrai/fl marcescewW。所用真菌為 17 201000149 白色念珠菌（Candida albicans)反腐复鐮孢菌（fusarium 。測試生物係自ISO 14729中所述代表性ATCC菌株 培養。 將10 ml等分測試隱形眼鏡消毒溶液放置入滅菌硼矽酸 鹽玻璃或聚丙烯螺旋蓋試管中。對此溶液添加〇 〇1至〇丨ml 等分於有機質土中代表性測試生物之懸浮液。此測試生物之 起始接種體以測試溶液稀釋時係介於1χ1〇5至1χ1〇6 CFU/ml·。在測试隱形眼鏡消毒溶液之25%、5〇%、75°/。及100% 最小推薦消毒時間（MRDT)取得等分溶液。中和各等分之殘 留消毒活性，並將溶液置於平板用以微生物計數。測試額外 時間點400%最小推薦消毒時間之各真菌。自起始接種體減 去剩餘活菌生物，對各測試的時間點計算各生物之對數約化 (Log reduction)。微生物約化之主要準則為在最小推薦消毒 時間内對細菌之3.0對數（99·9%)及對真菌之1〇對數 (90.0%)。 結果顯示於下列表9中。
表9 實例 [PQ-42] ppm [DTPA] ppm --數約化(¾ MRDT PA SA SM CA FS 12 25 300 — >4.8 4.6 ----— 4.6 4.7 ~4J~ 0.5 0.4 0.9 ΓΤ 13 50 14 75 300 >4.8 4.6 4 7 n 5 17 15 25 750 ~4X] 4.5 0.4 1 16 50 750 ---- 4.4 4.7 0 5 14 17 75 750 >4.8 ~4T] 4.7 0.5 1.7 18 201000149 PQ-42—聚四級錢_42 PA 綠 /農桿菌（pseudomonas aeruginosa) SA -金黃色葡萄球菌（staph aureus) SM —黏質赛氏桿菌（Serratia marcescens) CA ~白色念珠菌（Candida albicans) FS -腐皮鐮孢菌（fusarium s〇iani)
[比較例5至8J 重複實施例12與13，只有無添加過氧化氫與亞氯酸鹽 或無添加聚四級銨-42。表10顯示比較例及實施例π與13 中所用亞氯酸鋼、過氧化物及聚四級銨_42之濃度。對細菌 及真菌之活性係如實施例12至13所述測量’其結果與實施 例12及13的結果一起列於表1〇中。 表10 實例 亞氯酸鹽 ppm [PQ-42] ppm [H202] ppm 對數約化®MRDT PA SA SM CA FS 12 500 25 200 >4.8 4.6 4 7 0.5 0.9 比較例 5 500 0 200 >4.8 1.1 2 0.6 -0.07 13 500 50 200 >4.8 4.6 4.7 0 4 1.4 比較例 6 0 50 0 0.5 3.7 1.6 -0.3 0.7 PQ-42 -聚四級錢_42 PA —綠濃桿菌（pseudomonas aeruginosa) SA -金黃色葡萄球菌（staph aureus) 19 201000149 SM 點質赛氏桿菌（Serratia marcescens) CA 白色念珠菌（Candida albicans) FS 腐皮鐮孢菌（fusarium solani) 將含有過氧化氫/亞氣酸鹽及聚四級銨_42兩者之實施 ^ 12及13與比較例5(無聚四級銨-42)及6(無過氧化氫/亞氯 酉文鹽）相較’可見對於腐皮鐮孢菌之抗真菌活性有令人驚舒 ，增加。過氧化物/亞氣酸鹽消毒劑表現無約化於腐皮鐮孢 菌’且聚四級銨-42於50 ppm表現0.7對數約化。然而，過 氧化物/亞氯酸鹽消毒劑與聚四級銨-42之組合於50 ppm表 現1.4對數約化於腐皮鐮孢菌，其優於眼用溶液功效所需要 之1對數約化。 【圖式簡單說明】 無。 【主要元件符號說明】 無0 20
Claims (1)
- 201000149 七、申請專利範圍： h 一種眼用組成物，其係包括PH介於約6至約8且約50至 約1000ppm之過氧化氫、約1〇〇 PPm至約2000 ppm之至 少-種亞氯酸鹽化合物、及約1〇至議卯m之至少一種 飽和聚合四級錢鹽。 2.如申請專利範圍第！項之組成物，其中該過氧化氮係以濃 度介於約100至約500ppm存在。 3·如申請專利範圍第i項之組成物，其中該過氧化氮係以濃 度介於約100至約3〇〇ppm存在。 4. 如申睛專利範圍帛丄項之組成物，其中該pH係介於約6 5 至約7.5。 5. 如申請專利範圍第i項之組成物，進一步包括至少一種穩 定劑。 6. 如申δ月專利範圍第5項之組成物’其中該至少一種穩定劑 係選自一伸乙二胺五醋酸鹽所組成之組群，其係選自二伸 ^二胺五醋酸的約鹽、二伸乙三胺五醋酸的鋅鹽及二伸乙 三胺五醋酸的混合鈣/鋅鹽所組成之組群。 7. 如申凊專利範圍第5項之組成物，其中該二伸乙三胺五醋 酸係以濃度介於約50至約1500ppm存在。 8. 如申請專利範圍第丨項之組成物，進一步包括水。 9. 如申请專利範圍第5項之組成物，其中該整合劑包括二伸 乙三胺五亞曱基膦酸。 10. 如申請專利範圍第9項之組成物，其中該二伸乙三胺五亞 甲基膦酸係以濃度介於約1〇〇至約1〇〇〇ppm存在。 21 201000149 11.如申請專利範圍第9項之組成物，其中該二伸乙三胺五亞 甲基膦酸係以濃度介於約1〇〇至約500 ppm存在。 12·如申請專利範圍第5項之組成物，其係包括至少兩種螯合 劑。 13. 如申凊專利範圍第1項之組成物，進一步包括至少一種選 自滲性調整劑、緩衝劑、活性劑、潤滑劑、消毒劑、界面 活性劑及其等混合物所組成組群之額外成分。 14. 如申請專利範圍第13項之組成物，進一步包括選自硼酸 鹽緩衝液、磷酸鹽緩衝液、硫酸鹽緩衝液、及其等混合物 所組成組群之緩衝劑。 15. 如申請專利範圍第14項之組成物，其中該緩衝劑包括硼 酸鹽緩衝液或磷酸鹽緩衝液。 16. 如申請專利範圍第1項之組成物，其中該至少一種飽和聚 合四級銨鹽包括聚[氧伸乙基(_二曱基亞胺基）伸乙基_(二 曱基亞胺基)伸乙基二氯化物]。 17. 如申請專利範圍第1項之組成物，其中該至少一種亞氯酸 鹽化合物係以用量約lOOppm至約1000ppm存在。 18. 如申請專利範圍第17項之組成物，其中該亞氯酸鹽化合 物係選自水溶性鹼金屬亞氯酸鹽、水溶性鹼土金屬亞氯酸 鹽及其等混合物所組成之組群。 19. 如申請專利範圍第π項之組成物，其中該亞氯酸鹽化合 物係選自亞氯酸鉀、亞氣酸鈉、亞氯酸鈣、亞氯酸鎂及其 等混合物所組成之組群。 20. 如申請專利範圍第17項之組成物，其中該亞氣酸鹽化合 22 201000149 物包括亞氯酸鈉。 21. 如申請專利範圍第I? 物係以用量介㈣組成物，其中該亞氯酸鹽化合 22. 如申請專利範圍· 2〇 、、、、500 Ppm存在。 物係以用量介㈣物，其巾該亞該鹽化合 &如中請專利範圍第7項3，，存在。 酸係以用量介於約刚^成物’其中該二伸乙三胺五醋 Ο ο 24_如申請專利範圍第4==00 PPm存在。 ! , , %峭之級成物，進一步包括約0.1至約 1亶直/〇之至少一種潤滑劑。 25. 如申請專利範圍第1項 液。 〈組成物’其中該組成物係眼用溶 26. 如申請專利範圍第24 乙烯鱗_。 組錢，其巾制滑劑包括聚 27. 如申請專利範圍第1項 毒增進劑。 、、旦成物，進一步包括至少一種消 28·如申請專利範圍第27頊 C & _喟之組成物，其中該至少一種消毒 μ 疋醇所組成之組群。 。.如τ請專利範圍第27項之組成物，其中該至少—種消毒 增進劑係以用量介於約50ppm至約2〇〇〇ppm存在且係選 自1，2-辛烷二醇、甘油單辛酸酯、山梨醇酐單月桂酸酯 (TWEEN 80)及其等組合所組成之組群。 23 201000149 四、指定代表圖： (一) 本案指定代表圖為：無。 (二) 本代表圖之元件符號簡單說明：無。 五、本案若有化學式時，請揭示最能顯示發明特徵的化學式： 無。
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| US3789408P | 2008-03-19 | 2008-03-19 | |
| US12/399,662 US20090239775A1 (en) | 2008-03-19 | 2009-03-06 | Ophthalmic solutions displaying improved efficacy |
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| TW201000149A true TW201000149A (en) | 2010-01-01 |
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| TW098108695A TW201000149A (en) | 2008-03-19 | 2009-03-18 | Ophthalmic solutions displaying improved efficacy |
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| TW098108694A TW200950822A (en) | 2008-03-19 | 2009-03-18 | Phosphate buffered ophthalmic solutions displaying improved efficacy |
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| US (2) | US20090239775A1 (zh) |
| EP (2) | EP2271313A1 (zh) |
| JP (2) | JP2011515393A (zh) |
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| US11738043B2 (en) | 2018-04-27 | 2023-08-29 | Allergan, Inc. | Sodium chlorite compositions with enhanced antimicrobial efficacy and reduced toxicity |
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| TW201127423A (en) * | 2009-12-17 | 2011-08-16 | Alcon Res Ltd | Ophthalmic solutions with improved disinfection profiles |
| JP2011251932A (ja) * | 2010-06-01 | 2011-12-15 | Mandom Corp | 点眼剤及び洗眼剤 |
| JP5345745B1 (ja) * | 2012-02-27 | 2013-11-20 | ロート製薬株式会社 | 眼科用組成物 |
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| CN114318343A (zh) * | 2020-09-29 | 2022-04-12 | 上海飞凯材料科技股份有限公司 | 一种蚀刻液及其应用 |
| TW202430231A (zh) * | 2022-12-21 | 2024-08-01 | 美商壯生和壯生視覺關懷公司 | 眼用裝置之組成物 |
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| WO2024134382A1 (en) * | 2022-12-21 | 2024-06-27 | Johnson & Johnson Vision Care, Inc. | Compositions for ophthalmologic devices |
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-
2009
- 2009-03-06 US US12/399,662 patent/US20090239775A1/en not_active Abandoned
- 2009-03-06 US US12/399,681 patent/US20090239954A1/en not_active Abandoned
- 2009-03-09 BR BRPI0909763A patent/BRPI0909763A2/pt not_active IP Right Cessation
- 2009-03-09 BR BRPI0909000-2A patent/BRPI0909000A2/pt not_active IP Right Cessation
- 2009-03-09 AU AU2009226113A patent/AU2009226113A1/en not_active Abandoned
- 2009-03-09 EP EP09721932A patent/EP2271313A1/en not_active Withdrawn
- 2009-03-09 JP JP2011500771A patent/JP2011515393A/ja not_active Abandoned
- 2009-03-09 WO PCT/US2009/001495 patent/WO2009117056A1/en not_active Ceased
- 2009-03-09 CN CN2009801106195A patent/CN101977590A/zh active Pending
- 2009-03-09 RU RU2010142462/15A patent/RU2010142462A/ru unknown
- 2009-03-09 JP JP2011500772A patent/JP2011515394A/ja not_active Abandoned
- 2009-03-09 CA CA2718866A patent/CA2718866A1/en not_active Abandoned
- 2009-03-09 KR KR1020107023033A patent/KR20100135813A/ko not_active Withdrawn
- 2009-03-09 RU RU2010142488/15A patent/RU2010142488A/ru not_active Application Discontinuation
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- 2009-03-09 EP EP09722447A patent/EP2276462A1/en not_active Withdrawn
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- 2009-03-18 TW TW098108695A patent/TW201000149A/zh unknown
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11738043B2 (en) | 2018-04-27 | 2023-08-29 | Allergan, Inc. | Sodium chlorite compositions with enhanced antimicrobial efficacy and reduced toxicity |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2718864A1 (en) | 2009-09-24 |
| KR20100135813A (ko) | 2010-12-27 |
| RU2010142462A (ru) | 2012-04-27 |
| CN101977590A (zh) | 2011-02-16 |
| BRPI0909000A2 (pt) | 2015-08-04 |
| AU2009226112A1 (en) | 2009-09-24 |
| AR070999A1 (es) | 2010-05-19 |
| JP2011515394A (ja) | 2011-05-19 |
| JP2011515393A (ja) | 2011-05-19 |
| CA2718866A1 (en) | 2009-09-24 |
| AR071001A1 (es) | 2010-05-19 |
| WO2009117056A1 (en) | 2009-09-24 |
| US20090239775A1 (en) | 2009-09-24 |
| WO2009117057A1 (en) | 2009-09-24 |
| US20090239954A1 (en) | 2009-09-24 |
| RU2010142488A (ru) | 2012-04-27 |
| BRPI0909763A2 (pt) | 2015-10-06 |
| EP2276462A1 (en) | 2011-01-26 |
| CN101977591A (zh) | 2011-02-16 |
| TW200950822A (en) | 2009-12-16 |
| KR20100126512A (ko) | 2010-12-01 |
| AU2009226113A1 (en) | 2009-09-24 |
| EP2271313A1 (en) | 2011-01-12 |
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