本發明關於一種兩性離子性軟式隱形眼鏡用眼科用組成物，其係呈現澄清透明的外觀性狀，並可抑制普拉洛芬及/或其鹽吸附於兩性離子性軟式隱形眼鏡。另外，本發明還關於一種抑制普拉洛芬及/或其鹽吸附於兩性離子性軟式隱形眼鏡之方法。The present invention relates to an ophthalmic composition for a zwitterionic soft contact lens, which has a clear and transparent appearance and can inhibit the adsorption of pranoprofen and / or its salt on a zwitterionic soft contact lens. In addition, the present invention also relates to a method for inhibiting adsorption of pranoprofen and / or a salt thereof on a zwitterionic soft contact lens.
普拉洛芬及/或其鹽具有抑制成為發炎或疼痛原因的前列腺素生合成的作用，在眼科領域被廣泛使用於眼睛充血或發癢等症狀的緩和、或眼瞼炎、結膜炎、包括上強膜炎的強膜炎、術後發炎、前眼部葡萄膜炎等的預防或治療的目的。另外，關於利用普拉洛芬及/或其鹽的眼科用組成物的製劑配方，也已經有了各種文獻報告。例如專利文獻1報告了一種含有普拉洛芬及/或其鹽與抗組織胺劑的局部用水性液劑，可發揮出優異的抗發炎作用及止癢作用。另外，專利文獻2報告了一種點眼劑，其係含有普拉洛芬及/或其鹽0.01~2.0w/v%與萘甲唑啉等的特定血管收縮劑0.0005~0.1w/v%，可有效地發揮除去或減輕外眼部充血的作用。Praprofen and / or its salts have the effect of inhibiting prostaglandin synthesis which is the cause of inflammation or pain, and are widely used in the ophthalmology field to alleviate symptoms such as eye congestion or itching, or blepharitis, conjunctivitis, including Shangqiang The purpose of prevention or treatment of meningitis, meningitis, postoperative inflammation, anterior uveitis, etc. In addition, various literature reports have been made on the formulation of ophthalmic compositions using pranoprofen and / or its salts. For example, Patent Document 1 reports a topical aqueous solution containing pranoprofen and / or a salt thereof and an antihistamine, which can exhibit an excellent anti-inflammatory effect and an antipruritic effect. In addition, Patent Document 2 reports an eye drop, which is a specific vasoconstrictor containing praziprofen and / or a salt thereof of 0.01 to 2.0 w / v% and naphthozoline, 0.0005 to 0.1 w / v%, Effectively removes or reduces external eye congestionRole.
另一方面，近年來開發出拋棄式或可長期連續配戴的軟式隱形眼鏡(以下也會有簡記為SCL的情形)，SCL的配戴者正在增加。另外，以往，SCL的材料大多採用呈現非離子性或陰離子性的材料，而近年來兩性離子性的材料也正在實用化以作為抑制淚液中的蛋白質、脂質、細胞斷片等堆積在SCL鏡片表面的材料。於是，為了提高兩性離子性SCL配戴者的便利性，正需要一種在配戴著兩性離子性SCL的狀態下可使用的點眼劑(兩性離子性SCL用點眼劑)。兩性離子性SCL用點眼劑必須調配成可發揮出所希望的藥效，而且不會對兩性離子性SCL造成不良影響。若兩性離子性SCL用點眼劑中的藥物吸附於SCL，則會造成鏡片變形、舒適感降低等，甚至還會有無法對眼睛黏膜發揮出所希望的藥理效果的情形，因此抑制藥物吸附於兩性離子性SCL，在兩性離子性SCL用點眼劑是特別重要的課題。On the other hand, in recent years, soft contact lenses that are disposable or can be continuously worn for a long time have been developed (hereinafter also referred to as SCL), and the number of SCL wearers is increasing. In addition, in the past, most of the materials of SCL are non-ionic or anionic materials. In recent years, zwitterionic materials are also being put into practical use as a method for inhibiting the accumulation of proteins, lipids, cell fragments, etc. in the tear fluid on the surface of SCL lenses. material. Therefore, in order to improve the convenience of a zwitterionic SCL wearer, there is a need for an eyedrop (zwitterionic SCL eyedrop) that can be used while wearing the zwitterionic SCL. The eyedrops for zwitterionic SCL must be formulated so that they can exhibit the desired efficacy without causing adverse effects on zwitterionic SCL. If the zwitterionic SCL eyedrops drug is adsorbed on SCL, it will cause lens deformation, reduced comfort, etc. It may even fail to exert the desired pharmacological effect on the mucous membrane of the eye, so inhibiting the drug from adsorbing on the zwitterionic Ionic SCL, eye drops for zwitterionic SCL are particularly important issues.
以往的SCL用點眼劑為了抑制藥物吸附於SCL，是採用選擇難以吸附於SCL的藥物、摻合了可抑制藥物吸附於SCL的成分等而成的製劑配方。例如在專利文獻3中報告了一種SCL用組成物，可抑制由具有2級或3級胺基的胺化合物所構成之鹼性藥物吸附在SCL，其製劑配方含有該鹼性藥物以及胺基酸、其鹽、酸性黏多糖、其鹽、或環糊精，並且將pH設定在3.5~4.8。In order to suppress the adsorption of a drug to the SCL, the conventional eye drops for SCL have been prepared by selecting a drug that is difficult to adsorb to the SCL and incorporating a component that inhibits the adsorption of the drug to the SCL. For example, Patent Document 3 reports a composition for SCL that can inhibit the adsorption of a basic drug composed of an amine compound having a secondary or tertiary amine group on the SCL, and its formulation contains the basic drug and an amino acid. , Its salt, acid mucopolysaccharide, its salt, or cyclodextrin, and the pH is set at 3.5 ~ 4.8.
[專利文獻1]日本特開2002-193805號公報[Patent Document 1] Japanese Patent Laid-Open No. 2002-193805
[專利文獻2]國際公開第01/87304號[Patent Document 2] International Publication No. 01/87304
[專利文獻3]國際公開第2007/77783號[Patent Document 3] International Publication No. 2007/77783
然而，專利文獻3是著眼於普拉洛芬及/或其鹽，關於其在兩性離子性SCL的吸附特性完全沒有作檢討。具有2級或3級胺基的胺化合物包括了各種藥物，而藥物在SCL的吸附特性也會因為胺基以外的構造而變動。甚至SCL的鏡片表面特性也會隨著離子性的有無、離子性的種類等而顯著不同，因此關於藥物在SCL的吸附特性，需要因應SCL的材料來作檢討。實際上，本發明人確認了兩性離子性SCL與非離子性SCL或陰離子性SCL相異，會有普拉洛芬及/或其鹽的吸附性極高這樣的特有課題(參照後述測試例1)。However, Patent Document 3 focuses on pranoprofen and / or a salt thereof, and has not reviewed the adsorption characteristics of zwitterionic SCL at all. The amine compound having a secondary or tertiary amine group includes various drugs, and the adsorption characteristics of the drug in SCL may also be changed due to the structure other than the amine group. Even the surface characteristics of SCL lenses will vary significantly with the presence or absence of ionicity, the type of ionicity, etc. Therefore, the adsorption characteristics of drugs in SCL need to be reviewed in accordance with the materials of SCL. In fact, the present inventors have confirmed that zwitterionic SCL is different from nonionic SCL or anionic SCL, and has a unique problem of extremely high adsorption of pranoprofen and / or its salt (see Test Example 1 described later) ).
此外，專利文獻3還依據必須將pH設定在4.8以下，然而本發明人確認了若將含有普拉洛芬及/或其鹽的SCL用眼科用組成物的pH調整在4.8以下的程度，則會有發生白濁而無法呈現可實用化的外觀性狀的問題(參照後述測試例2)。In addition, Patent Document 3 also requires that the pH be set to 4.8 or less. However, the inventors have confirmed that if the pH of an ophthalmic composition for SCL containing pranoprofen and / or its salt is adjusted to a level of 4.8 or less, There is a problem that white turbidity occurs and a practical appearance cannot be exhibited (see Test Example 2 described later).
以這樣的先前技術為背景，為了使含有普拉洛芬及/或其鹽的兩性離子性SCL用眼科用組成物實用化，需要充分考慮普拉洛芬及/或其鹽吸附於兩性離子性SCL的特性而設計出呈現澄清透明的外觀性狀的製劑配方。With such a prior art as a background, in order to put into practical use an amphoteric composition for zwitterionic SCL containing pranoprofen and / or a salt thereof, it is necessary to sufficiently consider that the adsorption of praziprofen and / or a salt thereof to amphoteric ion SCL characteristicsIn addition, a formulation formula showing a clear and transparent appearance is designed.
於是，本發明目的為提供一種技術，其係使含有普拉洛芬及/或其鹽的兩性離子性SCL用眼科用組成物呈現澄清透明的外觀性狀，並且抑制普拉洛芬及/或其鹽吸附於兩性離子性SCL。Then, an object of the present invention is to provide a technique for making a zwitterionic SCL ophthalmic composition containing pranoprofen and / or a salt thereof a clear and transparent appearance and suppressing pranoprofen and / or Salt is adsorbed on zwitterionic SCL.
本發明人為了解決前述課題潛心檢討，結果發現藉由在含有普拉洛芬及/或其鹽的兩性離子性SCL用眼科用組成物中摻合胺基丁三醇，並且將pH設定在5.5以上，可實現澄清透明的外觀性狀，而且可有效抑制普拉洛芬及/或其鹽吸附於兩性離子性SCL。本發明基於這樣的見解，進一步反覆檢討而完成。The present inventors conducted an intensive review in order to solve the aforementioned problems, and as a result, they found that aminobutytriol was added to a zwitterionic SCL ophthalmic composition containing pranoprofen and / or a salt thereof, and the pH was set to 5.5. As described above, a clear and transparent appearance property can be achieved, and the adsorption of pranoprofen and / or its salt on zwitterionic SCL can be effectively suppressed. The present invention was completed based on such findings and further review.
亦即本發明提供以下所揭示態樣的發明。That is, the present invention provides the inventions disclosed below.
1. 一種兩性離子性軟式隱形眼鏡用眼科用組成物，其特徵為：含有普拉洛芬及/或其藥學所容許的鹽與胺基丁三醇，且pH為5.5以上。2. 如第1項所記載之兩性離子性軟式隱形眼鏡用眼科用組成物，其中，含有胺基丁三醇0.0001~5w/v%。An ophthalmic composition for a zwitterionic soft contact lens, comprising: pranoprofen and / or a pharmaceutically acceptable salt thereof and aminobutanetriol; and a pH of 5.5 or more. 2. The ophthalmic composition for amphoteric ionic soft contact lenses according to item 1, which contains 0.0001 to 5 w / v% of aminobutanetriol.
3. 如第1或2項所記載之兩性離子性軟式隱形眼鏡用眼科用組成物，其pH為5.5~9。3. The ophthalmic composition for zwitterionic soft contact lenses according to item 1 or 2 whose pH is 5.5 to 9.
4. 如第1至3項中任一項所記載之兩性離子性軟式隱形眼鏡用眼科用組成物，其中，含有普拉洛芬及/或其藥學所容許的鹽0.001~0.5w/v%。4. The ophthalmic composition for amphoteric ionic soft contact lenses according to any one of items 1 to 3, which contains pranoprofen and / or a pharmaceutically acceptable salt thereof 0.001 to 0.5 w / v% .
5. 如第1至4項中任一項所記載之兩性離子性軟式隱形眼鏡用眼科用組成物，其為兩性離子性軟式隱形眼鏡用點眼劑。5. Zwitterionic soft contact eye as described in any one of items 1 to 4An ophthalmic composition for a mirror, which is an ophthalmic agent for a zwitterionic soft contact lens.
6.一種抑制普拉洛芬及/或其藥學所容許的鹽吸附於兩性離子性軟式隱形眼鏡之方法，其特徵為：在含有普拉洛芬及/或其藥學所容許的鹽的兩性離子性軟式隱形眼鏡用眼科用組成物中摻合胺基丁三醇，並且將pH調整至5.5以上。6. A method for inhibiting the adsorption of pravaprofen and / or a pharmaceutically acceptable salt thereof on a zwitterionic soft contact lens, characterized in that the method comprises: Ophthalmic composition is blended into the ophthalmic composition for soft soft contact lenses, and the pH is adjusted to 5.5 or more.
7.一種液劑用以製造兩性離子性軟式隱形眼鏡用眼科用組成物之用途，該液劑為含有普拉洛芬及/或其藥學所容許的鹽與胺基丁三醇，且pH為5.5以上者。7. A liquid preparation for manufacturing an ophthalmic composition for zwitterionic soft contact lenses, the liquid preparation comprising pranoprofen and / or a pharmaceutically acceptable salt thereof and aminobutanetriol, and the pH is 5.5 or above.
8.一種抑制普拉洛芬及/或其藥學所容許的鹽吸附於兩性離子性軟式隱形眼鏡之方法，其包括使含有普拉洛芬及/或其藥學所容許的鹽與胺基丁三醇且pH為5.5以上的液劑與兩性離子性軟式隱形眼鏡接觸之步驟。8. A method for inhibiting the adsorption of pravaprofen and / or a pharmaceutically acceptable salt thereof on a zwitterionic soft contact lens, comprising the step of combining praziprofen and / or a pharmaceutically acceptable salt thereof with aminobutane The step of contacting a liquid agent having an alcohol and a pH of 5.5 or more with a zwitterionic soft contact lens.
只要利用本發明之兩性離子性SCL用眼科用組成物，即可抑制普拉洛芬及/或其鹽吸附於兩性離子性SCL，因此不會對兩性離子性SCL造成不良影響，而能夠有效地發揮普拉洛芬及/或其鹽的藥效。另外，在本發明之兩性離子性SCL用眼科用組成物中，藉由摻合作為pH調整劑使用的胺基丁三醇以及調整pH，可抑制普拉洛芬及/或其鹽吸附於兩性離子性SCL，可任意地設定是否摻合其他藥理成分或添加劑，因此也有製劑配方上的限制少這樣的優點。By using the ophthalmic composition for zwitterionic SCL of the present invention, it is possible to inhibit the adsorption of praziprofen and / or its salt on zwitterionic SCL, and therefore it is not effective to adversely affect the zwitterionic SCL, and can be effectively used Exert the medicinal effect of pranoprofen and / or its salt. In addition, in the ophthalmic composition for zwitterionic SCL of the present invention, by incorporating aminobutanetriol used as a pH adjusting agent and adjusting the pH, it is possible to suppress the adsorption of pranoprofen and / or a salt thereof to the amphoteric The ionic SCL can be arbitrarily set to incorporate other pharmacological components or additives, and therefore has the advantage of having fewer restrictions on the formulation of the formulation.
另外，利用本發明之兩性離子性SCL用眼科用組成物，可在含有普拉洛芬及/或其鹽之同時，抑制將pH設定在4.8以下左右所產生的白濁，而能夠提供呈現澄清透明的外觀性狀的兩性離子性SCL用眼科用組成物。此外，在本說明書之中，「澄清透明」是指並未因為普拉洛芬及/或其鹽而發生白濁的狀態，其概念不限於無色澄清透明，還包括因為其他含有成分而呈色的有色澄清透明。In addition, by using the zwitterionic SCL ophthalmic composition of the present invention, it is possible to suppress the setting of the pH while containing pranoprofen and / or a salt thereof.It is white turbidity of about 4.8 or less, and can provide a zwitterionic SCL ophthalmic composition showing a clear and transparent appearance. In addition, in the present specification, "clear and transparent" refers to a state in which turbidity does not occur due to pranoprofen and / or its salt. The concept is not limited to colorless, clear and transparent, but also includes those that are colored due to other ingredients. Colored clear and transparent.
1.兩性離子性SCL用眼科用組成物1. Ophthalmic composition for zwitterionic SCL
本發明之兩性離子性SCL用眼科用組成物，其特徵為：含有普拉洛芬及/或其藥學所容許的鹽與胺基丁三醇，且pH為5.5以上。以下針對本發明之兩性離子性SCL用眼科用組成物作詳細敘述。此外，在本說明書之中，「兩性離子性SCL用眼科用組成物」是表示被使用於眼科領域，而且在與兩性離子性SCL接觸狀態下使用的組成物。另外，在本說明書之中，各成分的濃度的單位「w/v%」代表質量相對於容量的百分率，與g/100mL同義。The ophthalmic composition for zwitterionic SCL of the present invention is characterized in that it contains pranoprofen and / or a pharmaceutically acceptable salt thereof and aminobutanetriol, and has a pH of 5.5 or higher. Hereinafter, the ophthalmic composition for zwitterionic SCL of the present invention will be described in detail. In addition, in this specification, "an amphoteric composition for zwitterionic SCL" means the composition which is used in the ophthalmology field, and is used in contact with zwitterionic SCL. In addition, in this specification, the unit "w / v%" of the concentration of each component represents the percentage of mass to capacity, and is synonymous with g / 100mL.
本發明之兩性離子性SCL用眼科用組成物含有普拉洛芬及/或其鹽。普拉洛芬，亦被稱為α-甲基-5H-[1]苯并吡喃[2,3-b]吡啶-7-醋酸，在眼科領域是周知的具有消炎作用的化合物。The ophthalmic composition for zwitterionic SCL of the present invention contains pranoprofen and / or a salt thereof. Praprofen, also known as α-methyl-5H- [1] benzopyran [2,3-b] pyridine-7-acetic acid, is a well-known compound with anti-inflammatory effects in the ophthalmic field.
普拉洛芬之鹽在藥學所容許的限度內並不受特別限制，而可列舉例如鈉鹽、鉀鹽、鈣鹽、鎂鹽、鋁鹽等的金屬鹽；三乙胺鹽、二乙胺鹽、嗎啉鹽、哌嗪鹽等的有機鹼鹽等。這些普拉洛芬之鹽可單獨使用一種，或可組合兩種以上來使用。The salt of pranoprofen is not particularly limited within the pharmaceutically acceptable limit, and examples thereof include sodium, potassium, calcium, magnesium, and aluminum salts.Metal salts; organic base salts such as triethylamine salt, diethylamine salt, morpholine salt, piperazine salt, etc. These pravaprofen salts may be used singly or in combination of two or more kinds.
在本發明之兩性離子性SCL用眼科用組成物之中，可由普拉洛芬及其鹽之中選擇一種單獨使用，或可組合兩種以上來使用。普拉洛芬及其鹽之中，宜為例如普拉洛芬。Among the ophthalmic compositions for zwitterionic SCL of the present invention, one kind may be selected from pranoprofen and its salts and used alone, or two or more kinds may be used in combination. Among the pranoprofen and its salts, for example, pranoprofen.
在本發明之兩性離子性SCL用眼科用組成物之中，普拉洛芬及/或其鹽的濃度可因應該兩性離子性SCL用眼科用組成物的用途等適當地設定，而可列舉例如0.001~0.5w/v%，宜為0.01~0.2w/v%、更佳為0.01~0.1w/v%。In the zwitterionic SCL ophthalmic composition of the present invention, the concentration of pranoprofen and / or its salt can be appropriately set according to the application of the zwitterionic SCL ophthalmic composition, and examples thereof include, for example, 0.001 ~ 0.5w / v%, preferably 0.01 ~ 0.2w / v%, more preferably 0.01 ~ 0.1w / v%.
本發明之兩性離子性SCL用眼科用組成物進一步含有胺基丁三醇。胺基丁三醇，亦被稱為三羥甲基胺基甲烷，在眼科領域是周知的可作為緩衝劑使用的化合物。The zwitterionic SCL ophthalmic composition of the present invention further contains aminobutanetriol. Aminobutytriol, also known as trimethylolaminomethane, is a well-known compound that can be used as a buffer in the ophthalmic field.
本發明之兩性離子性SCL用眼科用組成物之中，胺基丁三醇的濃度可列舉例如0.0001~5w/v%。尤其從更進一步有效抑制普拉洛芬及/或其鹽吸附於兩性離子性SCL的觀點看來，胺基丁三醇的濃度宜為例如0.001~5w/v%、更佳為0.001~2w/v%。In the ophthalmic composition for zwitterionic SCL of the present invention, the concentration of aminobutanetriol may be, for example, 0.0001 to 5 w / v%. Especially from the viewpoint of further effectively inhibiting the adsorption of pranoprofen and / or its salt on zwitterionic SCL, the concentration of aminobutanetriol is preferably 0.001 to 5 w / v%, more preferably 0.001 to 2 w / v%.
本發明之兩性離子性SCL用眼科用組成物的pH設定在5.5以上。在本發明之兩性離子性SCL用眼科用組成物中，使前述普拉洛芬及/或其鹽與胺基丁三醇共存，並且將pH設定在這樣的範圍，藉此可抑制普拉洛芬及/或其鹽吸附於兩性離子性SCL，同時可抑制白濁，而呈現澄清透明的外觀性狀。The pH of the zwitterionic SCL ophthalmic composition of the present invention is set to 5.5 or more. In the ophthalmic composition for zwitterionic SCL of the present invention, the aforementioned pranoprofen and / or a salt thereof are coexisted with aminobutanetriol, and the pH is set to such a range, thereby suppressing the pranoprofen Fen and / or its salt is adsorbed on zwitterionic SCL, and at the same time, it can suppress white turbidity and appear clear and transparentAppearance properties.
從更進一步有效抑制普拉洛芬及/或其鹽吸附於兩性離子性SCL，同時具備澄清透明的外觀性狀的觀點看來，本發明之兩性離子性SCL用眼科用組成物的pH宜為例如5.5~9，較佳為6~8、更佳為6.5~8，特佳為6.5~7.5。From further effectively inhibiting the adsorption of pranoprofen and / or its salt onFrom the viewpoint that the zwitterionic SCL also has a clear and transparent appearance, the pH of the ophthalmic composition for zwitterionic SCL of the present invention is preferably 5.5 to 9, preferably 6 to 8, and more preferably 6.5 to 8, particularly good for 6.5 ~ 7.5.
為了將本發明之兩性離子性SCL用眼科用組成物的pH調整在前述範圍，只要在眼科用組成物中使用一般所使用的pH調整劑即可。pH調整劑可列舉例如氫氧化鈉、氫氧化鉀等的鹼；醋酸、檸檬酸、鹽酸、磷酸、酒石酸等的酸。這些pH調整劑可單獨使用一種，或可組合兩種以上來使用。In order to combine the ophthalmic composition for zwitterionic SCL of the present invention,The pH of the product is adjusted within the aforementioned range, and a pH adjuster generally used may be used in the ophthalmic composition. Examples of the pH adjusting agent include bases such as sodium hydroxide and potassium hydroxide; acids such as acetic acid, citric acid, hydrochloric acid, phosphoric acid, and tartaric acid. These pH adjusting agents may be used singly or in combination of two or more kinds.
本發明之兩性離子性SCL用眼科用組成物中含有可表現出緩衝作用的胺基丁三醇，因此即使不含其他緩衝劑也能夠具備緩衝能力，然而在不妨礙本發明效果的限度內，亦可因應必要含有其他緩衝劑。這種其他緩衝劑可列舉例如磷酸緩衝劑、硼酸緩衝劑、檸檬酸緩衝劑、酒石酸緩衝劑、醋酸緩衝劑、胺基酸等。這些緩衝劑可單獨使用一種，或可組合兩種以上來使用。The ophthalmic composition for zwitterionic SCL of the present invention containsThere is an aminoglycerol which can exhibit a buffering effect, and therefore it can have a buffering ability even if it does not contain other buffering agents. However, other buffering agents may be contained as necessary as long as the effect of the present invention is not hindered. Examples of such other buffering agents include phosphate buffering agents, boric acid buffering agents, citric acid buffering agents, tartaric acid buffering agents, acetate buffering agents, amino acids, and the like. These buffering agents may be used singly or in combination of two or more kinds.
在本發明之兩性離子性SCL用眼科用組成物中，除了前述成分以外，還可因應必要含有普拉洛芬及/或其鹽以外的藥理成分。這種藥理成分可列舉例如甘草酸二鉀、尿囊素、ε胺基己酸、溴芬酸、酮咯酸氨丁三醇、奈帕芬胺、小蘗鹼氯化物、硫酸小蘗鹼、薁磺酸鈉、硫酸鋅、乳酸鋅、溶菌酶鹽酸鹽等的消炎劑；氯菲安明馬來酸鹽、二苯安明鹽酸鹽等的抗組織胺劑；色甘酸鈉、酮替芬富馬酸鹽、阿扎司特、氨來呫諾、吡嘧司特鉀、曲尼司特、異丁司特等的抗過敏劑；諾氟沙星、氧氟沙星、洛美沙星、左旋氧氟沙星、紫菌素、加替沙星等的抗菌劑；抗壞血酸、黃素腺嘌呤二核苷酸鈉、氰基鈷胺素、吡哆醇鹽酸鹽、生育酚醋酸酯、視黃醇醋酸酯、視黃醇棕櫚酸酯、泛醇、泛酸鈣、泛酸鈉等的維生素類；天門冬醯胺酸、牛磺酸、硫酸軟骨素鈉等的胺基酸類、新斯狄格明硫酸甲酯等的抗膽鹼酯酶劑；萘甲唑啉、四氫唑啉、腎上腺素、麻黃素、脫羥腎上腺素、dl-甲基麻黃素等的血管收縮劑；玻尿酸鈉等的角結膜上皮障礙治療藥；磺胺嘧啶、磺胺異噁唑、磺胺異嘧啶、磺胺二甲氧基嘧啶、磺胺甲氧基噠嗪、磺胺甲噁唑、磺胺乙基噻二唑、磺胺甲氧甲嘧啶、磺胺苯吡唑、磺胺胍、酞醯基磺胺噻唑、琥珀醯基磺胺噻唑等的磺胺劑等。此處所例示的化合物在藥學所容許的限度內可為鹽的形態，或可為其他鹽的形態。這些藥理成分可單獨使用一種，或可組合兩種以上來使用。Ophthalmic composition for zwitterionic SCL in the present inventionIn addition to the aforementioned components, pharmacological components other than pranoprofen and / or a salt thereof may be contained as necessary. Examples of such pharmacological components include dipotassium glycyrrhizinate, allantoin, epsilon aminocaproic acid, bromfenac, ketorolac tromethamine, nepafenac, berberine chloride, berberine sulfate,薁 Anti-inflammatory agents such as sodium sulfonate, zinc sulfate, zinc lactate, lysozyme hydrochloride, etc .; clophenamine maleate,Antihistamines such as diphenhydramine hydrochloride; sodium cromoglycate, ketotifen fumarate, azalast, amretonol, pyridolast potassium, tranilast, ibudilast Special anti-allergic agents; Norfloxacin, Ofloxacin, Lomefloxacin, Levofloxacin, Shikonin, Gatifloxacin, etc .; Ascorbic acid, flavin adenine dinucleotide sodium Vitamins such as cyanocobalamin, pyridoxine hydrochloride, tocopheryl acetate, retinyl acetate, retinyl palmitate, panthenol, calcium pantothenate, sodium pantothenate; aspartic acid , Amino acids such as taurine, chondroitin sulfate, anticholinyl esterase agents such as neostigmine methyl sulfate; naphthozoline, tetrahydrozoline, epinephrine, ephedrine, and Vasoconstrictive agents such as hydroxyl adrenaline, dl-methylephedrine, etc .; corneal and conjunctival epithelial disorders such as sodium hyaluronate; sulfadiazine, sulfisoxazole, sulfadiazine, sulfadimethoxine, sulfamethoxine Pyridazine, Sulfamethoxazole, Sulfaethylthiadiazole, Sulfamethoxine, Sulfamethoxazole, Sulfaguanidine, Phthalosulfenyl Thiazole, succinic acyl sulfonamides thiazole sulfonamides and the like. The compound exemplified herein may be in the form of a salt, or may be in the form of another salt within the pharmaceutically acceptable limit. These pharmacological components may be used singly or in combination of two or more kinds.
這些藥理成分的濃度可因應藥理成分的種類或兩性離子性SCL用眼科用組成物的用途等適當地設定。The concentration of these pharmacological components can be appropriately set according to the type of the pharmacological component, the use of the ophthalmic composition for zwitterionic SCL, and the like.
另外，在本發明之兩性離子性SCL用眼科用組成物中，除了前述成分之外，還可因應必要含有等張化劑、溶解助劑、黏稠劑、螯合劑、清涼化劑、防腐劑、安定化劑、界面活性劑等的添加劑。In addition, in the ophthalmic composition for zwitterionic SCL of the present invention, in addition to the aforementioned components, an isotonicity agent, a dissolution aid, a thickener, a chelating agent, a cooling agent, a preservative, Additives such as stabilizers and surfactants.
等張化劑可列舉山梨醇、葡萄糖、甘露醇等的糖類；甘油、丙二醇等的多元醇類；氯化鈉等的鹽類；硼酸等。這些等張化劑可單獨使用一種，或可組合兩種以上來使用。Examples of the isotonicity agent include sugars such as sorbitol, glucose, and mannitol.Polyols such as glycerol and propylene glycol; salts such as sodium chloride; boric acid and the like. These isotonic agents may be used singly or in combination of two or more kinds.
溶解助劑可列舉例如聚氧乙烯去水山梨醇單油酸酯、聚氧乙烯硬化蓖麻油、泰洛沙伯、普朗尼克等的非離子性界面活性劑；甘油、聚乙二醇等的多元醇等。這些溶解助劑可單獨使用一種，或可組合兩種以上來使用。Examples of the dissolution aid include polyoxyethylene desorbate single oil.Acid esters, polyoxyethylene hardened castor oil, non-ionic surfactants such as tylosabell, plonic, etc .; polyols such as glycerin, polyethylene glycol, etc. These dissolution aids may be used singly or in combination of two or more kinds.
黏稠劑可列舉例如聚乙烯基吡咯烷酮、聚乙二醇、聚乙烯醇、羧乙烯基聚合物、黃原膠、硫酸軟骨素鈉、玻尿酸鈉等的水溶性高分子；羥丙基甲基纖維素、羥乙基纖維素、甲基纖維素、羥丙基纖維素、羥丙基甲基纖維素、羧甲基纖維素鈉等的纖維素類等。這些黏稠劑可單獨使用一種，或可組合兩種以上來使用。Examples of the thickener include polyvinylpyrrolidone, polyethyleneWater-soluble polymers such as alcohol, polyvinyl alcohol, carboxyvinyl polymer, xanthan gum, chondroitin sulfate, sodium hyaluronate, etc .; hydroxypropyl methyl cellulose, hydroxy ethyl cellulose, methyl cellulose, hydroxy Cellulose such as propyl cellulose, hydroxypropyl methyl cellulose, sodium carboxymethyl cellulose, and the like. These viscous agents may be used singly or in combination of two or more kinds.
螯合劑可列舉例如依地酸鹽、檸檬酸或其鹽等。這些螯合劑可單獨使用一種，或可組合兩種以上來使用。Examples of the chelating agent include edetate, citric acid or a salt thereof. These chelating agents may be used singly or in combination of two or more kinds.
清涼化劑可列舉例如l-薄荷醇、龍腦、樟腦、桉樹油等。這些清涼化劑可單獨使用一種，或可組合兩種以上來使用。Examples of the cooling agent include l-menthol, borneol, camphor, and eucalyptus oil. These cooling agents may be used singly or in combination of two or more kinds.
防腐劑可列舉例如山梨酸或其鹽、安息香酸或其鹽、對羥安息香酸甲酯、對羥安息香酸乙酯、對羥安息香酸丙基、氯丁醇、氯己定葡萄糖酸鹽、硼酸、去氫醋酸或其鹽、苯紮氯銨、苄索氯銨、苄醇、氯化鋅、對氯間二甲酚、氯甲酚、苯乙醇、泊利氯銨、硫汞撒、二丁基羥基甲苯等。這些防腐劑可單獨使用一種，或可組合兩種以上來使用。Examples of the preservative include sorbic acid or a salt thereof, benzoic acid or a salt thereof, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, chlorobutanol, chlorohexidine gluconate, and boric acid. , Dehydroacetic acid or a salt thereof, benzalkonium chloride, benzethonium chloride, benzyl alcohol, zinc chloride, p-chloro-xylenol, chlorocresol, phenethyl alcohol, polimonium chloride, thimerosal, dibutyl alcohol Hydroxytoluene and the like. These preservatives can be used alone or in combination of two or more.use.
安定化劑可列舉例如聚乙烯基吡咯烷酮、亞硫酸鹽、單乙醇胺、甘油、丙二醇、環糊精、聚葡萄糖、抗壞血酸、依地酸鹽、牛磺酸、生育酚、二丁基羥基甲苯等。這些安定化劑可單獨使用一種，或可組合兩種以上來使用。Examples of the stabilizer include polyvinylpyrrolidone, sulfite, monoethanolamine, glycerol, propylene glycol, cyclodextrin, polydextrose, ascorbic acid, edetate, taurine, tocopherol, and dibutylhydroxytoluene. These stabilizers may be used singly or in combination of two or more kinds.
界面活性劑可列舉例如泰洛沙伯、聚氧乙烯硬化蓖麻油、聚氧乙烯聚氧丙烯嵌段共聚物、聚氧乙烯去水山梨醇脂肪酸酯、辛基酚聚醚等的非離子性界面活性劑；烷基二胺乙基甘胺酸、月桂基二甲基胺基醋酸甜菜鹼等的兩性界面活性劑；烷基硫酸鹽、N-醯基牛磺酸鹽、聚氧乙烯烷醚磷酸鹽、聚氧乙烯烷醚硫酸鹽等的陰離子界面活性劑；烷基吡啶鎓鹽、烷基胺鹽等的陽離子界面活性劑等。這些界面活性劑可單獨使用一種，或可組合兩種以上來使用。Examples of the surfactant include nonionics such as tyloxamer, polyoxyethylene hardened castor oil, polyoxyethylene polyoxypropylene block copolymers, polyoxyethylene sorbitan fatty acid esters, and octylphenol polyether. Surfactants; Amphoteric surfactants such as alkyl diamine ethyl glycine, lauryl dimethyl amino acetate betaine; alkyl sulfate, N-fluorenyl taurine, polyoxyethylene alkyl ether Anionic surfactants such as phosphates and polyoxyethylene alkyl ether sulfates; cationic surfactants such as alkylpyridinium salts and alkylamine salts. These surfactants may be used singly or in combination of two or more kinds.
這些添加劑的濃度可因應添加劑的種類或兩性離子性SCL用眼科用組成物的用途等適當地設定。The concentration of these additives can be appropriately set in accordance with the type of the additive, the use of the ophthalmic composition for zwitterionic SCL, and the like.
本發明之兩性離子性SCL用眼科用組成物的製劑形態只要含有水作為基劑即可，例如可為水溶液狀、乳液狀等的任一者，而宜為例如水溶液狀。The formulation form of the ophthalmic composition for zwitterionic SCL of the present invention is sufficient as long as it contains water as a base, and it may be, for example, any of an aqueous solution and an emulsion, and is preferably an aqueous solution.
本發明之兩性離子性SCL用眼科用組成物，只要因應其用途，依據周知的調製法來製造即可，例如可採用第16改正日本藥典製劑總則所記載的方法來製造。The ophthalmic composition for zwitterionic SCL of the present invention may be produced according to a well-known preparation method in accordance with its use, and may be produced, for example, by the method described in the 16th revised Japanese Pharmacopoeia General Regulations.
本發明之兩性離子性SCL用眼科用組成物，可使用作為在配戴著兩性離子性SCL時可使用的點眼劑(兩性離子性SCL用點眼劑)；在配戴著兩性離子性SCL時可使用的洗眼劑(兩性離子性SCL用洗眼劑)；兩性離子性SCL用配戴液、兩性離子性SCL用多效保養液、兩性離子性SCL用洗淨液、兩性離子性SCL用保存液等的隱形眼鏡保養用品等。該等之中，宜為例如兩性離子性SCL用點眼劑、兩性離子性SCL用洗眼劑，更佳為兩性離子性SCL用點眼劑。The ophthalmic composition for zwitterionic SCL of the present invention can be used as an eye drop (zwitterionic) which can be used when wearing zwitterionic SCL.Eye drops for daughter SCL); eye wash for use with zwitterionic SCL (zwitterionic SCL eyewash); zwitterionic SCL wearing solution, zwitterionic SCL multi-effect maintenance Liquid, cleaning solution for zwitterionic SCL, preservation solution for zwitterionic SCL, etc. Among these, for example, an ophthalmic agent for zwitterionic SCL, an eyewash for zwitterionic SCL, and an eyedrop for zwitterionic SCL are more preferred.
作為本發明的適用對象的兩性離子性SCL，是指以含有具有陽離子性基的單體與具有陰離子性基的單體以作為離子性單體的聚合物為構成材料的SCL。兩性離子性SCL具體而言，可列舉以含有四級銨鹽等的陽離子性基與羧基、磺酸基、磷酸基等的陰離子性基的聚合物為構成材料的SCL，其材料或製法被記載於例如日本特開平10-197831號公報等。The zwitterionic SCL to which the present invention is applicable refers to an SCL comprising a monomer having a cationic group and a monomer having an anionic group and a polymer as an ionic monomer as a constituent material. Specific examples of the zwitterionic SCL include SCL which is composed of a polymer containing a cationic group such as a quaternary ammonium salt and an anionic group such as a carboxyl group, a sulfonic acid group, and a phosphate group, and the material or production method thereof is described. For example, Japanese Patent Application Laid-Open No. 10-197831.
另外，作為本發明之適用對象的兩性離子性SCL可為高含水率或低含水率之任一者，而宜為例如高含水率者，亦即美國食品醫藥品局(FDA)分類為群組IV者(離子性單體1莫耳%以上，含水率50%以上)。In addition, the zwitterionic SCL that is an object of application of the present invention may be any of a high water content or a low water content, and is preferably, for example, a high water content, that is, the US Food and Drug Administration (FDA) is classified into a group IV (1 mol% or more of ionic monomer, 50% or more water content).
2.抑制普拉洛芬及/或其鹽吸附於兩性離子性SCL的方法(1)另外，本發明提供一種抑制普拉洛芬及/或其鹽吸附於兩性離子性SCL的方法，其特徵為：在含有普拉洛芬及/或其藥學所容許的鹽的兩性離子性SCL用眼科用組成物中摻合胺基丁三醇，並且將pH調整在5.5以上。該吸附抑制方法在對於兩性離子性SCL用眼科用組成物賦予抑制普拉洛芬及/或其鹽吸附於兩性離子性SCL的作用上是有用的。2. Method for inhibiting adsorption of pranoprofen and / or its salt on zwitterionic SCL (1) In addition, the present invention provides a method for inhibiting adsorption of pranoprofen and / or its salt on zwitterionic SCL, which is characterized in that This is because aminobutytriol is blended in a zwitterionic SCL ophthalmic composition containing pranoprofen and / or a pharmaceutically acceptable salt thereof, and the pH is adjusted to 5.5 or more. This adsorption suppression method imparts inhibition of prazoprofen to a zwitterionic SCL ophthalmic composition and / orIts salt is useful for the adsorption of zwitterionic SCL.
在本發明的吸附抑制方法之中，所使用的普拉洛芬及/或其藥學所容許的鹽的種類或濃度、胺基丁三醇的濃度、兩性離子性SCL用眼科用組成物的pH、摻合至兩性離子性SCL用眼科用組成物的藥理成分或添加劑的種類、兩性離子性SCL用眼科用組成物的製劑形態或用途、作為適用對象的兩性離子性SCL的種類等，如前述「1.兩性離子性SCL用眼科用組成物」之欄所記載。In the adsorption suppression method of the present invention, praloxThe type or concentration of fen and / or its pharmaceutically acceptable salt, the concentration of aminobutanetriol, the pH of the ophthalmic composition for zwitterionic SCL, and the pharmacological component incorporated into the ophthalmic composition for zwitterionic SCL Or types of additives, the form or use of the zwitterionic SCL ophthalmic composition, or the type of zwitterionic SCL to be applied, etc., as described in the above section of "1. Zwitterionic SCL ophthalmic composition" Record.
3.抑制普拉洛芬及/或其鹽吸附於兩性離子性SCL的方法(2)另外，本發明提供一種抑制普拉洛芬及/或其鹽吸附於兩性離子性SCL之方法，其係包括含有普拉洛芬及/或其藥學所容許的鹽與胺基丁三醇且pH為5.5以上的液劑，與兩性離子性SCL接觸之步驟。3. Method for inhibiting adsorption of pranoprofen and / or its salt on zwitterionic SCL (2) In addition, the present invention provides a method for inhibiting adsorption of pranoprofen and / or its salt on zwitterionic SCL, which is The method comprises the step of contacting a liquid agent containing pranoprofen and / or a pharmaceutically acceptable salt thereof with aminobutanetriol and having a pH of 5.5 or higher, and contacting the zwitterionic SCL.
在本發明的吸附抑制方法中，所使用的普拉洛芬及/或其藥學所容許的鹽的種類或濃度、胺基丁三醇的濃度、液劑的pH、摻合至液劑的藥理成分或添加劑的種類、液劑的製劑形態或用途、作為適用對象的兩性離子性SCL的種類等，如前述「1.兩性離子性SCL用眼科用組成物」之欄所記載。另外，在本發明的吸附抑制方法之中，使前述液劑與兩性離子性SCL接觸之方法只要因應該液劑的用途適當地設定即可。例如在前述液劑為點眼劑的情況，只要將前述液劑滴在配戴著兩性離子性SCL的眼睛即可。In the adsorption inhibition method of the present invention, the type or concentration of pravaprofen and / or a pharmaceutically acceptable salt thereof, the concentration of aminobutanetriol, the pH of the liquid agent, and the pharmacology of the liquid agent The type of the component or additive, the form or use of the liquid preparation, the type of the zwitterionic SCL to be applied, and the like are described in the above-mentioned column of "1. Ophthalmic composition for zwitterionic SCL". In addition, in the adsorption suppression method of the present invention, the method of bringing the liquid agent into contact with the zwitterionic SCL may be appropriately set depending on the use of the liquid agent. For example, in a case where the liquid preparation is an eye drop, the liquid preparation may be dropped on an eye wearing a zwitterionic SCL.
以下列舉實施例，對本發明作具體說明，然而本發明完全不受該等所限定。此外，在以下的測試例之中，普拉洛芬是使用API Corporation股份有限公司製的產品，胺基丁三醇是使用日本藥典外的醫藥品規格的胺基丁三醇(UE-E)(關東化學股份有限公司製)或特級三(羥甲基)胺基甲烷(Nacalai Tesque股份有限公司製)。The following examples are given to specifically describe the present invention.The invention is not limited at all by these. In addition, in the following test examples, pranoprofen is a product manufactured by API Corporation, and aminobutytriol is an aminobutanetriol (UE-E) using a pharmaceutical standard other than the Japanese Pharmacopoeia. (Manufactured by Kanto Chemical Co., Ltd.) or special tris (hydroxymethyl) aminomethane (manufactured by Nacalai Tesque Co., Ltd.).
測試例1藉由常法混合表1所示的各成分而調製出測試液。藉由觀察所得到的各測試液的外觀，並且測定濁度(在660nm的吸光度)，以評估白濁的有無。In Test Example 1, each component shown in Table 1 was mixed by a conventional method to prepare a test solution. The presence or absence of white turbidity was evaluated by observing the appearance of each of the obtained test solutions and measuring the turbidity (absorbance at 660 nm).
另外，將各測試液2mL裝入樣品瓶，將一枚SCL浸漬於其中，在25℃下振盪2小時以上。另外，將各測試液2mL裝入樣品瓶，在沒有浸漬SCL的狀態並且在25℃下振盪2小時以上。振盪後，以液相層析測定各測試液中的普拉洛芬含量，依據下式計算出普拉洛芬吸附於SCL吸附量。此外還可確認若在測試液中浸漬SCL的條件下振盪，則在2小時以內，普拉洛芬吸附於SCL達到平衡狀態，因此只要將振盪時間設定在2小時以上，則對於普拉洛芬吸附於SCL的吸附量的測定值沒有影響。In addition, 2 mL of each test solution was put into a sample bottle, one SCL was immersed therein, and shaken at 25 ° C. for 2 hours or more. In addition, 2 mL of each test solution was put into a sample bottle, and the SCL was not immersed and shaken at 25 ° C. for 2 hours or more. After shaking, the content of pranoprofen in each test solution was measured by liquid chromatography, and the adsorption amount of pranoprofen on SCL was calculated according to the following formula. In addition, it can also be confirmed that if SCL is immersed in the test solution, pranoprofen will adsorb to SCL and reach equilibrium in less than 2 hours. Therefore, as long as the oscillation time is set to more than 2 hours, The measured value of the adsorption amount adsorbed on SCL has no effect.
[數1]普拉洛芬吸附在一枚SCL上的吸附量(μg)=(CC-CT)×V[Number 1] Adsorption amount of pranoprofen on an SCL (μg) = (CC-CT) × V
CC：並未浸漬SCL的測試液中的普拉洛芬含量(μg/mL)CC: Praprofen content in the test solution that is not impregnated with SCL (μg / mL)
CT：浸漬SCL的測試液中的普拉洛芬含量(μg/mL)CT: Praprofen content in test solution impregnated with SCL (μg / mL)
V：測試所使用的測試液的量(mL)V: The amount of test solution used in the test (mL)
此外，在此測試中使用下述4種SCL，求得普拉洛芬在各SCL的吸附量。In addition, the following four types of SCL were used in this test, and the adsorption amount of pranoprofen on each SCL was determined.
鏡片1：群組IV、商品名「SEED 1dayPure」(註冊商標)Seed公司股份有限公司製)、兩性離子性、鏡片材料：甲基丙烯酸2-羥乙酯(HEMA)、含4級銨基的甲基丙烯酸酯系化合物、含羧基的甲基丙烯酸酯系化合物、甲基丙烯酸甲酯(MMA)、乙二醇二甲基丙烯酸酯(EGDMA)Lens 1: Group IV, trade name "SEED 1dayPure" (registered trademark) Seed Co., Ltd.), zwitterionic, lens material: 2-hydroxyethyl methacrylate (HEMA), grade 4 ammonium group-containing Methacrylate compounds, carboxyl group-containing methacrylate compounds, methyl methacrylate (MMA), ethylene glycol dimethacrylate (EGDMA)
鏡片2：群組IV、商品名「SEED 1dayPure UP(加強濕潤)」(註冊商標)Seed公司股份有限公司製)、兩性離子性、鏡片材料：甲基丙烯酸2-羥乙酯(HEMA)、含有4級銨基的甲基丙烯酸酯系化合物、含羧基的甲基丙烯酸酯系化合物、甲基丙烯酸甲酯(MMA)、乙二醇二甲基丙烯酸酯(EGDMA)Lens 2: Group IV, trade name "SEED 1dayPure UP (Enhanced Wetness)" (registered trademark) manufactured by Seed Co., Ltd.), zwitterionic, lens material: 2-hydroxyethyl methacrylate (HEMA), containing Grade 4 ammonium methacrylate compound, carboxyl group-containing methacrylate compound, methyl methacrylate (MMA), ethylene glycol dimethacrylate (EGDMA)
鏡片3：群組IV、商品名「1-DayAcuvue(註冊商標)」(Johnson & Johnson medical公司製)、陰離子性、USAN名：etafilcon ALens 3: Group IV, trade name "1-DayAcuvue (registered trademark)" (manufactured by Johnson & Johnson medical), anionic, USAN name: etafilcon A
鏡片4：聚矽氧水凝膠隱形眼鏡、群組I、商品名AIR OPTIX 2week(註冊商標)」(CIBA Vision公司製)、USAN名：lotrafilcon BLens 4: Polysiloxane hydrogel contact lens, group I, trade name AIR OPTIX 2week (registered trademark) "(manufactured by CIBA Vision), USAN name: lotrafilcon B
將所得到的結果揭示於表1。由此結果可確認在pH7.5的情況，任一測試液皆為無色澄清透明，呈現良好的外觀性狀。另外，判明了在不含胺基丁三醇的測試液(比較例1)的情況中，普拉洛芬幾乎沒有吸附在陰離子性SCL及非離子性的SCL，相對於此，明顯觀察到普拉洛芬的吸附在兩性離子性SCL，普拉洛芬具有容易吸附在兩性離子性SCL這樣的特有性質。相對於此，含有普拉洛芬以及胺基丁三醇，且pH7.5的測試液(實施例1~5)可抑制普拉洛芬吸附於兩性離子性SCL。The obtained results are shown in Table 1. From this result, it was confirmed that at a pH of 7.5, any test solution was colorless, clear, and transparent, and exhibited good appearance properties. In addition, it was found that in the case of the test solution (Comparative Example 1) containing no aminobutanetriol, pranoprofen hardly adsorbed on the anionic SCL and the non-ionic SCL. In contrast, the general Laprofen is adsorbed on zwitterionic SCL, Praprofen is easily adsorbed on zwitterionic SCLSuch unique properties. In contrast, a test solution (Examples 1 to 5) containing pravaprofen and aminobutanetriol at pH 7.5 can inhibit the adsorption of prazoprofen on zwitterionic SCL.
表中各配方成分的摻合量的單位為「w/v%」。The unit of the blending amount of each formula ingredient in the table is "w / v%".
n.m.(1)表示未測定。n.m. (1) means not determined.
測試例2藉由常法混合表2所示的各成分而調製出測試液。藉由觀察所得到的各測試液的外觀，並且測定濁度(在660nm的吸光度)，以評估白濁的有無。另外，以與前述測試例1同樣的方法對於所得到的各測試液測定普拉洛芬吸附於兩性離子性SCL的吸附量。In Test Example 2, each component shown in Table 2 was mixed by a conventional method to prepare a test solution. The presence or absence of white turbidity was evaluated by observing the appearance of each of the obtained test solutions and measuring the turbidity (absorbance at 660 nm). In addition, the adsorption amount of pranoprofen to zwitterionic SCL was measured for each of the obtained test liquids in the same manner as in Test Example 1.
將所得到的結果揭示於表2。由此結果可確認，若pH在4.5以下，則觀察到測試液呈白濁，外觀性狀惡化，然而在pH為5.5以上的情況，會呈現澄清透明的外觀性狀。另外，隨著pH變高，還觀察到普拉洛芬吸附於兩性離子性SCL的吸附量有增加的傾向，然而含有胺基丁三醇的測試液可有效抑制普拉洛芬吸附於兩性離子性SCL。以上的結果確認了藉由含有普拉洛芬以及胺基丁三醇，並且將pH設定在5.5以上，可呈現澄清透明的外觀性狀，並且可抑制普拉洛芬吸附於兩性離子性SCL。The obtained results are shown in Table 2. From this result, it was confirmed that when the pH was 4.5 or less, the test solution was observed to be white and turbid, and the appearance properties were deteriorated. However, when the pH was 5.5 or more, the appearance was clear and transparent. In addition, as the pH became higher, the adsorption amount of pranoprofen on zwitterionic SCL also tended to increase. However, the test solution containing aminobutanetriol could effectively inhibit the adsorption of pranoprofen on zwitterions. Sexual SCL. The above results confirmed that by containing pranoprofen and aminobutanetriol and setting the pH to 5.5 or more, a clear and transparent appearance can be exhibited, and the adsorption of pranoprofen on zwitterionic SCL can be suppressed.
表中各配方成分的摻合量的單位為「w/v%」。The unit of the blending amount of each formula ingredient in the table is "w / v%".
n.m.(1)表示未測定。n.m. (1) means not determined.
n.m.(2)是因為白濁而未測定。n.m. (2) was not determined because of cloudiness.
測試例3藉由常法混合表3所示的各成分而調製出測試液。藉由觀察所得到的各測試液的外觀，並且測定濁度(在660nm的吸光度)，以評估白濁的有無。另外，對於所得到的各測試液，與前述測試例1同樣的方法，測定普拉洛芬吸附於兩性離子性SCL的吸附量。此外，在此測試中，兩性離子性SCL採用前述測試例1所使用的鏡片2(群組IV、兩性離子性)來進行測試。In Test Example 3, the components shown in Table 3 were mixed by a conventional method to prepare a test solution. The presence or absence of white turbidity was evaluated by observing the appearance of each of the obtained test solutions and measuring the turbidity (absorbance at 660 nm). In addition, for each of the obtained test liquids, the amount of adsorption of praziprofen on zwitterionic SCL was measured in the same manner as in Test Example 1 described above. In this test, the zwitterionic SCL was tested using the lens 2 (Group IV, zwitterionic) used in the aforementioned Test Example 1.
將所得到的結果揭示於表3。由表3明顯可知，使用胺基丁三醇以外的緩衝劑成分並無法充分降低普拉洛芬吸附於兩性離子性SCL的吸附量。亦即，由此測試結果判明了抑制普拉洛芬吸附於兩性離子性SCL，是藉由選擇胺基丁三醇作為所含的成分，並且將pH設定在5.5以上所觀察到的特有效果。The obtained results are shown in Table 3. It is clear from Table 3 that the use of buffer components other than aminobutanetriol cannot sufficiently reduce the adsorption amount of pranoprofen on zwitterionic SCL. That is, from this test result, it was determined that the inhibition of praziprofen adsorption on zwitterionic SCL is a unique effect observed by selecting aminobutanetriol as the contained component and setting the pH to 5.5 or more.
表中各配方成分的摻合量的單位為「w/v%」。The unit of the blending amount of each formula ingredient in the table is "w / v%".
#1 HEPES是指2-[4-(2-羥乙基)哌嗪-1-基]乙磺酸的簡稱。# 1 HEPES is an abbreviation for 2- [4- (2-hydroxyethyl) piperazin-1-yl] ethanesulfonic acid.
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| TWI623314Btrue TWI623314B (en) | 2018-05-11 |
| Application Number | Title | Priority Date | Filing Date |
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| TW103118779ATWI623314B (en) | 2013-05-30 | 2014-05-29 | Ophthalmic composition for zwitterionic soft contact lens |
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| CN (1) | CN105392481B (en) |
| HK (1) | HK1217901A1 (en) |
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| TW201517904A (en) | 2015-05-16 |
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| MM4A | Annulment or lapse of patent due to non-payment of fees |