TWI743066B - 眼科組成物 - Google Patents
眼科組成物 Download PDFInfo
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- TWI743066B TWI743066B TW105137722A TW105137722A TWI743066B TW I743066 B TWI743066 B TW I743066B TW 105137722 A TW105137722 A TW 105137722A TW 105137722 A TW105137722 A TW 105137722A TW I743066 B TWI743066 B TW I743066B
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
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- GEYJUFBPCGDENK-UHFFFAOYSA-M sodium;3,8-dimethyl-5-propan-2-ylazulene-1-sulfonate Chemical compound [Na+].CC(C)C1=CC=C(C)C2=C(S([O-])(=O)=O)C=C(C)C2=C1 GEYJUFBPCGDENK-UHFFFAOYSA-M 0.000 description 1
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- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 1
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- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
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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
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229910000406 trisodium phosphate Inorganic materials 0.000 description 1
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- 239000004474 valine Substances 0.000 description 1
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- 238000005406 washing Methods 0.000 description 1
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- 239000003871 white petrolatum Substances 0.000 description 1
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- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
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- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
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- 235000005074 zinc chloride Nutrition 0.000 description 1
- 229960001939 zinc chloride Drugs 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- 235000014692 zinc oxide Nutrition 0.000 description 1
Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/133—Amines having hydroxy groups, e.g. sphingosine
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L12/00—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor
- A61L12/08—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor using chemical substances
- A61L12/10—Halogens or compounds thereof
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- A—HUMAN NECESSITIES
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- A61L12/00—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor
- A61L12/08—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor using chemical substances
- A61L12/12—Non-macromolecular oxygen-containing compounds, e.g. hydrogen peroxide or ozone
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- A—HUMAN NECESSITIES
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L12/00—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor
- A61L12/08—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor using chemical substances
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- G—PHYSICS
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- G—PHYSICS
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Landscapes
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- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本發明係關於一種眼科組成物,其含有(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類。
Description
本發明係關於一種眼科組成物。
角膜因睡眠時之閉眼、隱形眼鏡之配戴等而被置於低氧狀態。對於處於此種低氧狀態之角膜,例如已知有於隱形眼鏡之卸除時等因角膜上之氧分壓急遽變化而產生自由基,從而產生由此所引起之角膜損傷(例如參照專利文獻1)。
專利文獻1:日本特開平7-291870號公報
然而,對於如上所述之角膜損傷,現狀為尚不存在可於治療或預防之方面令人充分滿意之有用之藥劑。
本發明之目的在於提供一種對於因低氧狀態所引起之角膜損傷之治療或預防有用之眼科組成物。
本發明人等為了解決上述課題而反覆進行努力研究,結果發
現:將(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上與(B)多糖類組合而成的眼科組成物可保護角膜細胞免受因低氧狀態產生之自由基所引起之氧化壓力。本發明基於該見解,且提供以下之各發明。
[1]一種眼科組成物,其含有(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類。
[2]如[1]中所記載之眼科組成物,其中,(A)成分選自由精胺酸及其鹽所組成之群中1種以上。
[3]如[1]或[2]中所記載之眼科組成物,其中,(B)成分為黏多糖類。
[4]如[1]至[3]中任一項所記載之眼科組成物,其進而含有(C)殺菌劑或防腐劑。
[5]如[1]至[4]中任一項所記載之眼科組成物,其用於隱形眼鏡。
本發明之眼科組成物由於含有(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中之1種以上、及(B)多糖類,故而發揮保護角膜細胞免受因低氧狀態產生之自由基所引起之氧化壓力之效果。藉此,可提供一種對於因低氧狀態所引起之角膜損傷之治療或預防有用之眼科組成物。
以下,對用以實施本發明之形態進行詳細說明。但是,本發明並不限定於以下之實施形態。
於本說明書中,只要未特別記載,則含量之單位「%」意指「w/v%」,與「g/100mL」含義相同。於本說明書中,只要未特別記載,則縮寫「POE」意指聚氧乙烯,縮寫「POP」意指聚氧丙烯。
[1.眼科組成物]
本實施形態之眼科組成物含有(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷(亦稱為胺丁三醇(trometamol))、2-胺基乙醇(亦稱為單乙醇胺)及該等之鹽所組成之群中1種以上(亦僅表述為「(A)成分」)、及(B)多糖類(亦僅表述為「(B)成分」)。
<(A)成分>
(A)成分係選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上。(A)成分可單獨使用1種,或者亦可將2種以上組合而使用。
精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷及2-胺基乙醇可為游離體,亦可為醫藥上、藥理學上(製藥上)或生理學上所容許之鹽。
作為精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷及2-胺基乙醇之鹽,具體而言,例如可列舉鹽酸鹽等無機酸鹽等。再者,精胺酸及其鹽為D體、L體、DL體均可,較佳為L體。
作為精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷及2-胺基乙醇之鹽,較佳為無機酸鹽,更佳為鹽酸鹽。
作為(A)成分,就更顯著地發揮本發明之效果之觀點而言,較佳為精胺酸及其鹽,更佳為精胺酸及其無機酸鹽,進而較佳為精胺酸及其鹽酸鹽,尤佳為精胺酸。
精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽亦可使用市售者。
本實施形態之眼科組成物中之(A)成分之含量並無特別限定,根據(A)成分之種類、其他摻合成分之種類及含量、眼科組成物之用途及製劑形態等而適當設定。作為(A)成分之含量,就更顯著地發揮本發明之效果之觀點而言,例如以眼科組成物之總量作為基準,(A)成分之總含量較佳為0.001~10w/v%,更佳為0.01~10w/v%,進而較佳為0.1~3w/v%,進而更佳為0.1~2w/v%。
<(B)成分>
(B)成分為多糖類。(B)成分可單獨使用1種,或者亦可將2種以上組合而使用。
多糖類包含葡聚糖、黏多糖類、三仙膠、結冷膠(gellan gum)、纖維素系高分子化合物及該等之鹽。多糖類可自公知之多糖類中適當選擇而使用。
作為葡聚糖之具體例,例如可列舉葡聚糖40及葡聚糖70。
作為黏多糖類之具體例,例如可列舉:玻尿酸、硫酸軟骨素、聚葡萄胺糖、肝素、乙醯肝素(heparan)、海藻酸、該等之衍生物(例如乙
醯化體)及該等之鹽等。
於黏多糖類中,就更顯著地發揮本發明之效果之觀點而言,較佳為玻尿酸、硫酸軟骨素及該等之鹽,進而較佳為玻尿酸或其鹽。作為玻尿酸之鹽、硫酸軟骨素之鹽,只要為醫藥上、藥理學上(製藥上)或生理學上所容許者,則並無特別限制。作為玻尿酸之鹽、硫酸軟骨素之鹽,例如較佳為鹼金屬鹽,更佳為鈉鹽、鉀鹽等,進而較佳為鈉鹽。於黏多糖類之鹽中,較佳為玻尿酸鈉、軟骨素硫酸鈉,進而較佳為玻尿酸鈉。
黏多糖類可單獨使用1種,或者亦可將2種以上組合而使用。
作為纖維素系高分子化合物,可使用藉由將纖維素之羥基利用其他官能基進行取代而獲得之纖維素系高分子化合物。作為取代纖維素之羥基之官能基,例如可列舉:甲氧基、乙氧基、羥基甲氧基、羥基乙氧基、羥基丙氧基、羧基甲氧基及羧基乙氧基。纖維素系高分子化合物亦可使用市售者。
作為纖維素系高分子化合物,例如可列舉:甲基纖維素、乙基纖維素、羥乙基纖維素、羥甲基纖維素、羥丙基纖維素、羥丙基甲基纖維素(羥丙甲纖維素(hypromellose))、羧甲基纖維素、羧乙基纖維素及該等之鹽。此處,作為鹽,只要為醫藥上、藥理學上(製藥上)或生理學上所容許者即可,其中較佳為鹼金屬鹽,更佳為鈉鹽、鉀鹽等。
於纖維素系高分子化合物中,就更顯著地發揮本發明之效果之觀點而言,較佳為甲基纖維素、羥乙基纖維素、羥丙基甲基纖維素(2208、2906、2910等)、羥丙基纖維素、羧甲基纖維素或該等之鹽,更佳為羥丙基甲基纖維素、羥乙基纖維素、或羧甲基纖維素鈉,進而更佳為羥丙基甲基
纖維素、羥乙基纖維素,進而更佳為羥丙基甲基纖維素,尤佳為羥丙基甲基纖維素2208、羥丙基甲基纖維素2906、羥丙基甲基纖維素2910,最佳為羥丙基甲基纖維素2906。
纖維素系高分子化合物可單獨使用1種,或者亦可將2種以上組合而使用。
作為多糖類,較佳為黏多糖類、纖維素系高分子化合物,更佳為玻尿酸、硫酸軟骨素、羥丙基甲基纖維素、羥乙基纖維素及該等之鹽,進而較佳為玻尿酸鈉、及軟骨素硫酸鈉,進而更佳為玻尿酸鈉。又,作為另一態樣,較佳為玻尿酸、羥丙基甲基纖維素及該等之鹽,更佳為玻尿酸鈉、羥丙基甲基纖維素。
多糖類亦可使用市售者。多糖類可單獨使用1種,或者亦可將2種以上組合而使用。
本實施形態之眼科組成物中之(B)成分之含量並無特別限定,根據(B)成分之種類、其他摻合成分之種類及含量、眼科組成物之用途及製劑形態等而適當設定。作為(B)成分之含量,就更顯著地發揮本發明之效果之觀點而言,例如以眼科組成物之總量作為基準,(B)成分之總含量較佳為0.0001~5w/v%,更佳為0.0005~1w/v%,進而較佳為0.001~0.75w/v%,進而更佳為0.001~0.5w/v%,尤佳為0.001~0.1w/v%。
於使用黏多糖類作為(B)成分之情形時,作為黏多糖類之含量,就進一步提高本發明之效果之觀點而言,例如以眼科組成物之總量作為基準,黏多糖類之總含量較佳為0.0001~1w/v%,更佳為0.0005~0.7w/v%,進而較佳為0.0005~0.6w/v%。
於使用玻尿酸鈉作為(B)成分之情形時,作為玻尿酸鈉之含量,就進一步提高本發明之效果之觀點而言,例如以眼科組成物之總量作為基準,玻尿酸鈉之總含量較佳為0.0001~0.5w/v%,較佳為0.0005~0.3w/v%,更佳為0.0005~0.1w/v%,進而較佳為0.001~0.05w/v%,進而更佳為0.001~0.02w/v%,尤佳為0.001~0.01w/v%。
於使用纖維素系高分子化合物作為(B)成分之情形時,作為纖維素系高分子化合物之含量,就進一步提高本發明之效果之觀點而言,例如以眼科組成物之總量作為基準,纖維素系高分子化合物之總含量通常為0.0001~1w/v%,較佳為0.0005~1w/v%,更佳為0.001~0.5w/v%,進而較佳為0.005~0.1w/v%,進而更佳為0.01~0.05w/v%。
本實施形態之眼科組成物中之(B)成分相對於(A)成分之含有比率並無特別限定,根據(A)成分及(B)成分之種類、其他摻合成分之種類及含量、眼科組成物之用途及製劑形態等而適當設定。作為(B)成分相對於(A)成分之含有比率,就更顯著地發揮本發明之效果之觀點而言,例如相對於本實施形態之眼科組成物中所含之(A)成分之總含量1質量份,(B)成分之總含量較佳為0.0005~5質量份,更佳為0.001~1質量份,進而較佳為0.005~0.5質量份,進而更佳為0.01~0.1質量份。
於使用黏多糖類作為(B)成分之情形時,相對於本實施形態之眼科組成物中所含之(A)成分之總含量1質量份,黏多糖類之總含量較佳為0.0001~50質量份,較佳為0.0005~10質量份,更佳為0.001~1質量份。
於使用玻尿酸鈉作為(B)成分之情形時,相對於本實施形
態之眼科組成物中所含之(A)成分之總含量1質量份,玻尿酸鈉之總含量較佳為0.00001~1質量份,較佳為0.0001~0.5質量份,更佳為0.0001~0.1質量份,進而較佳為0.0005~0.05質量份,進而更佳為0.001~0.01質量份。
於使用纖維素系高分子化合物作為(B)成分之情形時,相對於本實施形態之眼科組成物中所含之(A)成分之總含量1質量份,纖維素系高分子化合物之總含量較佳為0.0005~1質量份,較佳為0.001~0.5質量份,更佳為0.005~0.1質量份,進而較佳為0.01~0.05質量份。
<(C)成分>
本實施形態之眼科組成物較佳為進而含有(C)殺菌劑或防腐劑(亦僅表述為「(C)成分」)。藉由眼科組成物進而含有(C)成分,而更顯著地發揮本發明之效果。
殺菌劑或防腐劑係具有殺菌作用或抑菌作用之化合物及其鹽。防腐劑可自公知之防腐劑或抗菌劑中適當選擇而使用。
作為殺菌劑或防腐劑之具體例,例如可列舉:陽離子系殺菌劑(防腐劑)(苄烷銨、本索寧(benzethonium)、洛赫西定、阿來西定(alexidine)、聚己雙胍等)、烷基聚胺基乙基甘胺酸(alkylpolyaminoethylglycine)、苯甲酸、氯丁醇、山梨酸、脫氫乙酸、對羥基苯甲酸酯(例如對羥基苯甲酸甲酯、對羥基苯甲酸乙酯、對羥基苯甲酸丙酯及對羥基苯甲酸丁酯等對羥基苯甲酸酯)、羥基喹啉、苯乙醇、苄醇、聚四級銨鹽類(泊利氯銨(polidronium chloride)等)、Gurokiru(Rhodia公司製造,商品名)、鋅、磺胺異唑及磺胺甲異唑、以及該等之鹽。
作為殺菌劑或防腐劑之鹽之具體例,例如可列舉:鹽酸烷基
二胺基乙基甘胺酸、苯甲酸鈉、氯化苄烷銨、氯化本索寧、葡萄糖酸洛赫西定、山梨酸鉀、脫氫乙酸鈉、硫酸羥基喹啉、鹽酸聚己雙胍、氯化鋅、磺胺二甲嘧啶鈉及磺胺甲異唑鈉。
作為殺菌劑或防腐劑,較佳為陽離子系殺菌劑(防腐劑)、聚四級銨鹽類,更佳為氯化苄烷銨、葡萄糖酸洛赫西定、阿來西定、鹽酸聚己雙胍、泊利氯銨,進而較佳為鹽酸聚己雙胍、阿來西定、泊利氯銨,進而更佳為鹽酸聚己雙胍。
就更顯著地發揮本發明之效果之觀點而言,殺菌劑或防腐劑更佳為將2種以上組合而使用。其中,較佳為陽離子系殺菌劑(防腐劑)與聚四級銨鹽類之組合,更佳為泊利氯銨與陽離子系殺菌劑(防腐劑)之組合,進而較佳為泊利氯銨與鹽酸聚己雙胍、或泊利氯銨與阿來西定之組合。
殺菌劑或防腐劑亦可使用市售者。殺菌劑或防腐劑可單獨使用1種,或者亦可將2種以上組合而使用。
本實施形態之眼科組成物中之(C)成分之含量並無特別限定,根據(C)成分之種類、其他摻合成分之種類及含量、眼科組成物之用途及製劑形態等而適當設定。作為(C)成分之含量,就更顯著地發揮本發明之效果之觀點而言,例如以眼科組成物之總量作為基準,(C)成分之總含量較佳為0.00001~2w/v%,更佳為0.00001~1w/v%,進而較佳為0.00005~0.5w/v%,進而更佳為0.00005~0.1w/v%。
於殺菌劑或防腐劑為阿來西定、鹽酸聚己雙胍或泊利氯銨之情形時,以眼科組成物之總量作為基準,防腐劑之總含量較佳為0.000001
~0.01w/v%,其中較佳為0.000001~0.005w/v%,其中較佳為0.000005~0.002w/v%,其中較佳為0.000005~0.001w/v%,其中較佳為0.00001~0.0005w/v%,其中較佳為0.00005~0.0004w/v%,其中較佳為0.00007~0.0002w/v%。
本實施形態之眼科組成物中之(C)成分相對於(A)成分之含有比率並無特別限定,根據(A)成分及(C)成分之種類、其他摻合成分之種類及含量、眼科組成物之用途及製劑形態等而適當設定。作為(C)成分相對於(A)成分之含有比率,就更顯著地發揮本發明之效果之觀點而言,例如相對於本實施形態之眼科組成物中所含之(A)成分之總含量1質量份,(C)成分之總含量較佳為0.0000001~0.1質量份,更佳為0.000001~0.01質量份,進而較佳為0.000005~0.001質量份,進而更佳為0.00001~0.0005質量份。
就進一步提高本發明之效果之觀點而言,本實施形態之眼科組成物較佳為進而含有非離子界面活性劑。
作為非離子界面活性劑之具體例,例如可列舉:POE(20)山梨醇酐單月桂酸酯(聚山梨醇酯20)、POE(20)山梨醇酐單棕櫚酸酯(聚山梨醇酯40)、POE(20)山梨醇酐單硬脂酸酯(聚山梨醇酯60)、POE(20)山梨醇酐三硬脂酸酯(聚山梨醇酯65)、POE(20)山梨醇酐單油酸酯(聚山梨醇酯80)等POE山梨醇酐脂肪酸酯類;POE(5)氫化蓖麻油(聚氧乙烯氫化蓖麻油5)、POE(10)氫化蓖麻油(聚氧乙烯氫化蓖麻油10)、POE(20)氫化蓖麻油(聚氧乙烯氫化蓖麻油20)、POE(30)氫化蓖麻油(聚氧乙烯氫化蓖麻油30)、POE(40)氫化蓖麻油(聚氧乙烯氫化蓖麻油40)、POE(60)氫化蓖麻油(聚氧乙烯氫化蓖麻油60)、POE(80)氫化蓖麻油(聚氧乙烯氫化蓖麻油80)、
POE(100)氫化蓖麻油(聚氧乙烯氫化蓖麻油100)等POE氫化蓖麻油;POE(3)蓖麻油(聚氧乙烯蓖麻油3)、POE(10)蓖麻油(聚氧乙烯蓖麻油10)、POE(35)蓖麻油(聚氧乙烯蓖麻油35)、POE(70)蓖麻油(聚氧乙烯蓖麻油70)等POE蓖麻油;POE(9)月桂醚等POE烷基醚;POE(20)POP(4)鯨蠟基醚等POE-POP烷基醚;POE(20)POP(20)二醇(Pluronic L44)、POE(42)POP(67)二醇(Poloxamer403,Pluronic P123)、POE(54)POP(39)二醇(Poloxamer235,Pluronic P85)、POE(120)POP(40)二醇(Pluronic F87)、POE(160)POP(30)二醇(Poloxamer188,Pluronic F68)、POE(196)POP(67)二醇(Poloxamer407,Pluronic F127)、POE(200)POP(70)二醇等POE-POP二醇;硬脂酸聚烴氧10酯(polyoxyl stearate 10)、硬脂酸聚烴氧40酯等單硬脂酸聚乙二醇酯等。再者,於上述所例示之化合物中,括號內之數字表示加成莫耳數。
作為非離子界面活性劑,較佳為POE山梨醇酐脂肪酸酯類、聚氧乙烯氫化蓖麻油、聚氧乙烯蓖麻油、單硬脂酸聚乙二醇酯、POE-POP二醇,更佳為POE山梨醇酐脂肪酸酯類、聚氧乙烯氫化蓖麻油、POE-POP二醇,進而較佳為POE山梨醇酐脂肪酸酯類、聚氧乙烯氫化蓖麻油,進而更佳為聚山梨醇酯80、聚氧乙烯氫化蓖麻油60,尤佳為聚氧乙烯氫化蓖麻油60。
於使用POE-POP二醇作為非離子界面活性劑之情形時,較佳為POE(42)POP(67)二醇、POE(120)POP(40)二醇、POE(160)POP(30)二醇、POE(196)POP(67)二醇、POE(200)POP(70)二醇,更佳為POE(42)POP(67)二醇、POE(196)POP(67)二醇,進而較佳為POE(196)POP(67)二醇。
非離子界面活性劑亦可使用市售者。非離子界面活性劑可單
獨使用1種,或者亦可將2種以上組合而使用。
本實施形態之眼科組成物中之非離子界面活性劑之含量並無特別限定,根據非離子界面活性劑之種類、其他摻合成分之種類及含量、眼科組成物之用途及製劑形態等而適當設定。作為非離子界面活性劑之含量,就更顯著地發揮本發明之效果之觀點而言,例如以眼科組成物之總量作為基準,非離子界面活性劑之總含量較佳為0.0001~10w/v%,更佳為0.001~5w/v%,進而較佳為0.005~1w/v%,進而更佳為0.01~0.5w/v%,尤佳為0.01~0.1w/v%,特佳為0.01~0.05w/v%。
本實施形態之眼科組成物中之非離子界面活性劑相對於(A)成分之含有比率並無特別限定,根據(A)成分及非離子界面活性劑之種類、其他摻合成分之種類及含量、眼科組成物之用途及製劑形態等而適當設定。作為非離子界面活性劑相對於(A)成分之含有比率,就更顯著地發揮本發明之效果之觀點而言,例如相對於本實施形態之眼科組成物中所含之(A)成分之總含量1質量份,非離子界面活性劑之總含量較佳為0.0001~10質量份,更佳為0.0005~5質量份,進而較佳為0.001~3質量份,進而更佳為0.01~1重量份,尤佳為0.01~0.5質量份。
就進一步提高本發明之效果之觀點而言,本實施形態之眼科組成物較佳為進而含有緩衝劑。作為緩衝劑,只要為醫藥上、藥理學上(製藥上)或生理學上所容許者,則並無特別限制。作為此種緩衝劑,例如可列舉:硼酸緩衝劑、磷酸緩衝劑、碳酸緩衝劑、檸檬酸緩衝劑、乙酸緩衝劑、三羥甲基胺基甲烷緩衝劑。
作為硼酸緩衝劑,可列舉硼酸或其鹽(硼酸鹼金屬鹽、硼酸
鹼土金屬鹽等)。作為磷酸緩衝劑,可列舉磷酸或其鹽(磷酸鹼金屬鹽、磷酸鹼土金屬鹽等)。作為碳酸緩衝劑,可列舉碳酸或其鹽(碳酸鹼金屬鹽、碳酸鹼土金屬鹽等)。作為檸檬酸緩衝劑,可列舉檸檬酸或其鹽(檸檬酸鹼金屬鹽、檸檬酸鹼土金屬鹽等)。作為乙酸緩衝劑,可列舉乙酸或其鹽(乙酸鹼金屬鹽、乙酸鹼土金屬鹽等)。又,亦可使用硼酸鹽、磷酸鹽、碳酸鹽、檸檬酸鹽或乙酸鹽之水合物作為硼酸緩衝劑、磷酸緩衝劑、碳酸緩衝劑、檸檬酸緩衝劑或乙酸緩衝劑。關於更具體之例,可例示:作為硼酸緩衝劑之硼酸或其鹽(硼酸鈉、四硼酸鉀、偏硼酸鉀、硼酸銨、硼砂等);作為磷酸緩衝劑之磷酸或其鹽(磷酸氫二鈉、磷酸二氫鈉、磷酸二氫鉀、磷酸三鈉、磷酸三鉀、磷酸氫鈣、磷酸二氫鈣等);作為碳酸緩衝劑之碳酸或其鹽(碳酸氫鈉、碳酸鈉、碳酸銨、碳酸鉀、碳酸鈣、碳酸氫鉀、碳酸鎂等);作為檸檬酸緩衝劑之檸檬酸或其鹽(檸檬酸鈉、檸檬酸鉀、檸檬酸鈣、檸檬酸二氫鈉、檸檬酸二鈉等);作為乙酸緩衝劑之乙酸或其鹽(乙酸銨、乙酸鉀、乙酸鈣、乙酸鈉等)等。於該等緩衝劑中,較佳為硼酸緩衝劑(例如硼酸與硼砂之組合等)、磷酸緩衝劑(例如磷酸氫二鈉與磷酸二氫鈉之組合等),更佳為硼酸緩衝劑。
緩衝劑亦可使用市售者。緩衝劑可單獨使用1種,或者亦可將2種以上組合而使用。
於含有緩衝劑之情形時,作為本實施形態之眼科組成物中之緩衝劑之含量,就更顯著地發揮本發明之效果之觀點而言,例如以眼科組成物之總量作為基準,緩衝劑之總含量較佳為0.001~10w/v%,更佳為0.005~5w/v%,進而較佳為0.01~3w/v%,進而更佳為0.1~2w/v%。
本實施形態之眼科組成物中之緩衝劑相對於(A)成分之含有比率並無特別限定,根據(A)成分及緩衝劑之種類、其他摻合成分之種類及含量、眼科組成物之用途及製劑形態等而適當設定。作為緩衝劑相對於(A)成分之含有比率,就更顯著地發揮本發明之效果之觀點而言,例如相對於本實施形態之眼科組成物中所含之(A)成分之總含量1質量份,緩衝劑之總含量較佳為0.001~10質量份,更佳為0.0005~5質量份,進而較佳為0.01~3質量份,進而更佳為0.05~2質量份。
就進一步提高本發明之效果之觀點而言,本實施形態之眼科組成物較佳為進而含有螯合劑。
作為螯合劑,例如可列舉:乙二胺二乙酸(EDDA)、乙二胺三乙酸、乙二胺四乙酸(edetic acid,EDTA)、N-(2-羥基乙基)乙二胺三乙酸(HEDTA)、二伸乙基三胺五乙酸(DTPA)、及艾提壯酸(etidronic acid)等。作為螯合劑,就更顯著地發揮本發明之效果之觀點而言,較佳為乙二胺四乙酸。
螯合劑亦可使用市售者。螯合劑可單獨使用1種,或者亦可將2種以上組合而使用。
本實施形態之眼科組成物中之螯合劑之含量並無特別限定,根據螯合劑之種類、其他摻合成分之種類及含量、眼科組成物之用途及製劑形態等而適當設定。作為螯合劑之含量,就更顯著地發揮本發明之效果之觀點而言,例如以眼科組成物之總量作為基準,螯合劑之總含量較佳為0.001~1w/v%,更佳為0.005~0.5w/v%,進而較佳為0.01~0.2w/v%。
本實施形態之眼科組成物中之螯合劑相對於(A)成分之含
有比率並無特別限定,根據(A)成分及螯合劑之種類、其他摻合成分之種類及含量、眼科組成物之用途及製劑形態等而適當設定。作為螯合劑相對於(A)成分之含有比率,就更顯著地發揮本發明之效果之觀點而言,例如相對於本實施形態之眼科組成物中所含之(A)成分之總含量1質量份,螯合劑之總含量較佳為0.001~10質量份,更佳為0.005~5質量份,進而較佳為0.005~3質量份,進而更佳為0.01~1質量份,尤佳為0.01~0.5質量份。
就進一步提高本發明之效果之觀點而言,本實施形態之眼科組成物較佳為進而含有(A)成分以外之胺基酸類。
作為(A)成分以外之胺基酸類,例如可列舉:天冬胺酸、麩胺酸、胺基乙基磺酸(牛磺酸)、丙胺酸、天冬醯胺、麩醯胺、脯胺酸、甘胺酸、離胺酸、組胺酸、絲胺酸、甲硫胺酸、蘇胺酸、半胱胺酸、胺基乙酸、纈胺酸、色胺酸、苯丙胺酸、白胺酸、異白胺酸、及其等之鹽。作為(A)成分以外之胺基酸類,就更顯著地發揮本發明之效果之觀點而言,較佳為天冬胺酸、麩胺酸、胺基乙基磺酸、甘胺酸、及其等之鹽,較佳為天冬胺酸鉀、胺基乙基磺酸。
(A)成分以外之胺基酸類為D體、L體、DL體均可,較佳為L體。
(A)成分以外之胺基酸類亦可使用市售者。(A)成分以外之胺基酸可單獨使用1種,或者亦可將2種以上組合而使用。
本實施形態之眼科組成物中之(A)成分以外之胺基酸類之含量並無特別限定,根據(A)成分以外之胺基酸類之種類、其他摻合成分之種類及含量、眼科組成物之用途及製劑形態等而適當設定。作為(A)成
分以外之胺基酸類之含量,就更顯著地發揮本發明之效果之觀點而言,例如以眼科組成物之總量作為基準,(A)成分以外之胺基酸類之總含量較佳為0.001~5w/v%,更佳為0.01~2w/v%,進而較佳為0.1~1w/v%。
本實施形態之眼科組成物中,(A)成分以外之胺基酸相對於(A)成分之含有比率並無特別限定,根據(A)成分及(A)成分以外之胺基酸之種類、其他摻合成分之種類及含量、眼科組成物之用途及製劑形態等而適當設定。作為(A)成分以外之胺基酸相對於(A)成分之含有比率,就更顯著地發揮本發明之效果之觀點而言,例如相對於本實施形態之眼科組成物中所含之(A)成分之總含量1質量份,(A)成分以外之胺基酸之總含量較佳為0.001~5質量份,更佳為0.01~2質量份,進而較佳為0.1~1質量份。
就進一步提高本發明之效果之觀點而言,本實施形態之眼科組成物較佳為進而含有類萜。作為類萜,只要為醫藥上、藥理學上(製藥上)或生理學上所容許者,則並無特別限制。作為此種類萜,例如可列舉:薄荷腦、薄荷酮、樟腦、冰片、香葉草醇、桉樹腦、香茅醇、香旱芹酮、大茴香腦、丁香油酚、檸檬烯、沈香醇、乙酸沈香酯、該等之衍生物等。該等化合物為D體、L體或DL體均可。又,於本發明中,亦可使用含有上述化合物之精油作為類萜。作為此種精油,例如可列舉:桉葉油、佛手柑油、辣薄荷油(peppermint oil)、清涼薄荷油、綠薄荷油、薄荷油、茴香油、桂皮油、玫瑰油等。該等類萜可單獨使用1種,或者亦可將2種以上任意組合而使用。
於該等類萜中,較佳為薄荷腦、樟腦、冰片等,作為含有該
等之較佳之精油,可例示清涼薄荷油、辣薄荷油、薄荷油、樟腦油等。更佳為薄荷腦。
類萜亦可使用市售者。類萜可單獨使用1種,或者亦可將2種以上組合而使用。
於含有類萜之情形時,作為本實施形態之眼科組成物中之類萜之含量,就更顯著地發揮本發明之效果之觀點而言,例如以眼科組成物之總量作為基準,類萜之總含量較佳為0.00005~1w/v%,更佳為0.0001~0.5w/v%,進而較佳為0.001~0.1w/v%。
本實施形態之眼科組成物中之類萜相對於(A)成分之含有比率並無特別限定,根據(A)成分及類萜之種類、其他摻合成分之種類及含量、眼科組成物之用途及製劑形態等而適當設定。作為類萜相對於(A)成分之含有比率,就更顯著地發揮本發明之效果之觀點而言,例如相對於本實施形態之眼科組成物中所含之(A)成分之總含量1質量份,類萜之總含量較佳為0.00005~1質量份,更佳為0.0001~0.5質量份,進而較佳為0.001~0.1質量份。
就進一步提高本發明之效果之觀點而言,本實施形態之眼科組成物較佳為進而含有多元醇。
作為多元醇,例如可列舉:丙二醇、甘油、聚乙二醇(400、4000、6000等)等。作為多元醇,就更顯著地發揮本發明之效果之觀點而言,較佳為丙二醇。
多元醇亦可使用市售者。多元醇可單獨使用1種,或者亦可將2種以上組合而使用。
本實施形態之眼科組成物中之多元醇之含量並無特別限定,根據多元醇之種類、其他摻合成分之種類及含量、眼科組成物之用途及製劑形態等而適當設定。作為多元醇之含量,就更顯著地發揮本發明之效果之觀點而言,例如以眼科組成物之總量作為基準,多元醇之總含量較佳為0.01~5w/v%,更佳為0.05~2w/v%,進而較佳為0.1~1w/v%。
本實施形態之眼科組成物之pH只要為醫藥上、藥理學上(製藥上)或生理學上所容許之範圍內,則並無特別限定。作為本實施形態之眼科組成物之pH,例如可為4.0~9.5,較佳為4.0~9.0,更佳為4.5~9.0,進而較佳為4.5~8.5,進而更佳為5.0~8.5,尤佳為5.5~8.5。
本實施形態之眼科組成物可視需要調節為生物體所容許之範圍內之滲透壓比。適當之滲透壓比係根據應用部位、劑型等而異,例如可設為0.4~5.0,較佳為設為0.6~3.0,更佳為設為0.7~2.0。滲透壓之調整可使用無機鹽類、多元醇等,並利用該技術領域中已知之方法進行。滲透壓比係基於日本藥典第十六修訂版,設為試樣之滲透壓相對於286mOsm(0.9w/v%氯化鈉水溶液之滲透壓)之比,滲透壓可參考日本藥典中所記載之滲透壓測定法(凝固點降低法)而測定。再者,滲透壓比測定用標準液(0.9w/v%氯化鈉水溶液)可將氯化鈉(日本藥典標準試劑)於500~650℃乾燥40~50分鐘後,於乾燥器(矽膠)中放置冷卻,準確地稱量其0.900g,並溶解於精製水中而準確地製備成100mL,或者使用市售之滲透壓比測定用標準液(0.9w/v%氯化鈉水溶液)。
本實施形態之眼科組成物之黏度只要為醫藥上、藥理學上(製藥上)或生理學上所容許之範圍內,則並無特別限定。作為本實施形
態之眼科組成物之黏度,例如利用旋轉黏度計(RE550型黏度計,東產業公司製造,轉子:1°34'×R24)所測得之20℃下之黏度較佳為0.01~10000mPa.s,更佳為0.05~8000mPa.s,進而較佳為0.1~1000mPa.s,進而更佳為1~100mPa.s,尤佳為1~10mPa.s,尤佳為1~5mPa.s。
本實施形態之眼科組成物只要於無損本發明之效果之範圍內,則亦可除上述成分以外,將選自各種藥理活性成分及生理活性成分中之成分組合並含有適當量。該成分並無特別限制,例如可例示一般用醫藥品製造販賣承認基準2012年版(一般社團法人監管科學學會監修)中所記載之眼科用藥中之有效成分。作為眼科用藥中所使用之成分,具體而言,例如可列舉如下成分。
抗組織胺劑:例如異丙海汀(iproheptine)、鹽酸二苯胺(diphenhydramine hydrochloride)、馬來酸氯苯那敏(chlorpheniramine maleate)、富馬酸可多替芬(ketotifen fumarate)、鹽酸奧洛他定(olopatadine hydrochloride)、鹽酸左卡巴斯汀(levocabastine hydrochloride)等。
抗過敏劑:例如色甘酸鈉、曲尼司特(tranilast)、吡嘧司特鉀(potassium pemirolast)等。
類固醇劑:例如丙酸氟替卡松(fluticasone propionate)、糠酸氟替卡松、糠酸莫米松(mometasone furoate)、丙酸倍氯米松(beclomethasone dipropionate)、氟尼縮松(flunisolide)等。
消炎劑:例如甘草次酸、甘草酸二鉀、普拉洛芬(pranoprofen)、水楊酸甲酯、水楊酸乙二醇酯、尿囊素、傳明酸、ε-胺基己酸、黃連素、薁磺酸鈉(sodium azulene sulfonate)、氯化溶菌酶、硫酸鋅、乳酸鋅、甘草等。
充血去除劑:鹽酸四氫唑啉、硝酸四氫唑啉、鹽酸萘甲唑啉、硝酸萘甲唑啉、腎上腺素、鹽酸腎上腺素、鹽酸麻黃鹼、鹽酸去氧腎上腺素、dl-鹽酸甲基麻黃鹼等。
眼肌調節藥劑:例如具有與乙醯膽鹼類似之活性中心之抗膽鹼酯酶劑,具體而言為甲基硫酸新斯的明、托品醯胺(tropicamide)、土木香素(helenien)、硫酸阿托品等。
維生素類:例如黃素腺嘌呤二核苷酸鈉(flavin adenine dinucleotide sodium)、氰鈷胺、鹽酸吡哆醇、泛醇、泛酸鈣、泛酸鈉、棕櫚酸視黃醇酯、乙酸視黃醇酯、乙酸生育酚酯等。
無機鹽類:例如氯化鈣、氯化鎂、氯化鈉、氯化鉀、氯化銨等金屬之氯化物、硫酸鈣、硫酸鎂、硫酸鈉、硫酸鉀、硫酸銨等金屬之硫酸鹽等。
收斂劑:例如鋅白、乳酸鋅、硫酸鋅等。
局部麻醉劑:例如利多卡因、普魯卡因等。
其他:瑞巴派特(rebamipide)等。
於本實施形態之眼科組成物中,只要於無損本發明之效果之範圍內,則亦可根據其用途及製劑形態,按照常法適當選擇各種添加物,併用1種或其以上而含有適當量。作為此種添加物,例如可例示醫藥品添加物事典2007(日本醫藥品添加劑協會編輯)中所記載之各種添加物。作為代表性之成分,可列舉以下添加物。
載體:例如水、含水乙醇等之水性溶劑。
基劑:例如辛基十二烷醇、氧化鈦、溴化鉀、Plastibase、液態石蠟、輕質液態石蠟、精製羊毛脂、白凡士林等。
pH調節劑:鹽酸、乙酸、氫氧化鈉、氫氧化鉀、氫氧化鈣、氫氧化鎂、三乙醇胺、二異丙醇胺等。
糖類:例如單糖類、二糖類,具體而言為葡萄糖、麥芽糖、海藻糖、蔗糖、環糊精、木糖醇、山梨糖醇、甘露醇等。
穩定化劑:二丁基羥基甲苯、丁基羥基大茴香醚、甲醛次硫酸鈉(保險粉(rongalite))、亞硫酸氫鈉、焦亞硫酸鈉、單硬脂酸鋁、單硬脂酸甘油、環糊精等。
陰離子界面活性劑:聚氧乙烯烷基醚磷酸鹽、聚氧乙烯烷基醚硫酸鹽、烷基苯磺酸鹽、烷基硫酸鹽、N-醯基牛磺酸鹽等。
兩性界面活性劑:月桂基二甲胺基乙酸甜菜鹼等。
乙烯基系高分子:聚乙烯吡咯啶酮、聚乙烯醇、羧基乙烯基聚合物等。
再者,本實施形態之眼科組成物較佳為實質上不含有吡咯啶酮羧酸,更佳為不含有吡咯啶酮羧酸。
本實施形態之眼科組成物例如可藉由將(A)成分、(B)成分、及視需要之其他含有成分以成為所需含量之方式添加及混合而製備。具體而言,例如可藉由利用精製水使上述成分溶解或懸浮,調整為特定之pH及滲透壓,並藉由過濾滅菌等進行滅菌處理而製備。
本實施形態之眼科組成物可根據目的而採用各種劑型,例如可列舉:液劑、凝膠劑、半固體劑(軟膏等)等。該等之中,較佳為液劑。又,於液劑中,較佳為水性液劑。於將本實施形態之眼科組成物製成水性液劑之情形時,相對於眼科組成物之總量,例如水之含量為50w/v%以上,較佳為70w/v%以上,更佳為80w/v%以上,進而較佳為90w/v%以上,進
而更佳為95w/v%以上。作為本實施形態之眼科組成物中所使用之水,只要使用醫藥上、藥理學上(製藥上)或生理學上所容許之水即可,作為此種水,例如可列舉:蒸餾水、普通水、精製水、滅菌精製水、注射用水、注射用蒸餾水。
本實施形態之眼科組成物只要為眼科領域中所使用者,則其製劑形態並無限制。例如可列舉:滴眼劑(包括隱形眼鏡用滴眼劑(可於配戴隱形眼鏡之狀態下使用之滴眼劑))、洗眼劑(包括隱形眼鏡用洗眼劑(可於配戴隱形眼鏡之狀態下使用之洗眼劑))、隱形眼鏡配戴液、隱形眼鏡保養用液劑(隱形眼鏡消毒液、隱形眼鏡保存液、隱形眼鏡清洗液、隱形眼鏡清洗/保存液、及隱形眼鏡消毒/清洗/保存液(多用途溶液)等)等。
又,棘阿米巴(Acanthamoeba)角膜感染症於隱形眼鏡配戴者中罹患者最多,而對於隱形眼鏡配戴者強烈要求棘阿米巴之殺菌作用。因此,作為本實施形態之眼科組成物之較佳之製劑形態,可列舉:隱形眼鏡用滴眼劑(可於配戴隱形眼鏡之狀態下使用之滴眼劑)、隱形眼鏡用洗眼劑(可於配戴隱形眼鏡之狀態下使用之洗眼劑)、隱形眼鏡配戴液、隱形眼鏡保養用液劑等隱形眼鏡用眼科組成物,其中尤佳為列舉隱形眼鏡保養用液劑。
於使用本實施形態之眼科組成物作為隱形眼鏡用眼科組成物之情形時,成為應用對象之隱形眼鏡之種類並無特別限制,可將目前市售或將來市售之所有隱形眼鏡(包含軟性隱形眼鏡、硬性隱形眼鏡、及透氧性硬性隱形眼鏡之任一者。又,所謂軟性隱形眼鏡,包含離子性及非離子性之兩者,並且包含聚矽氧水凝膠隱形眼鏡及非聚矽氧水凝膠隱形眼鏡
之兩者)作為適用對象。
棘阿米巴角膜感染症於隱形眼鏡配戴者中多為軟性隱形眼鏡配戴者罹患,而對於軟性隱形眼鏡配戴者強烈要求棘阿米巴之殺菌作用。因此,作為本實施形態之眼科組成物之製劑形態,較佳為軟性隱形眼鏡用眼科組成物(即,適用對象鏡片為軟性隱形眼鏡之隱形眼鏡用眼科組成物)。
又,於使用本實施形態之眼科組成物作為軟性隱形眼鏡用眼科組成物之情形時,成為適用對象之軟性隱形眼鏡之含水率並無特別限制,例如可為90%以下,較佳為60%以下,更佳為50%以下。再者,軟性隱形眼鏡含有至少多於0%之水分。
本實施形態之眼科組成物係按照對應其製劑形態之使用方法而使用。例如於眼科組成物為滴眼劑(包括隱形眼鏡用滴眼劑)之情形時,只要對裸眼或配戴有隱形眼鏡之眼睛滴加適量之該滴眼劑即可。又,於眼科組成物為洗眼劑(包括隱形眼鏡用洗眼劑)之情形時,亦只要對裸眼或配戴有隱形眼鏡之眼睛將適量之該洗眼劑用於洗眼即可。又,於眼科組成物為隱形眼鏡配戴液之情形時,藉由於隱形眼鏡之配戴時使隱形眼鏡與適量之該配戴液接觸而使用。進而,若於眼科組成物為隱形眼鏡保養用液劑之情形時,則藉由使隱形眼鏡浸漬於適量之該保養用液劑中,或使隱形眼鏡與該保養用液劑接觸並擦洗等而使用。於使隱形眼鏡浸漬之情形時,浸漬時間通常為1分鐘以上即可,較佳為10分鐘以上,更佳為1小時以上,進而較佳為4小時以上。
作為收容本實施形態之眼科組成物之容器,可使用作為收容
眼科組成物之容器所通常使用之容器,可為玻璃製,又,亦可為塑膠製。於使用塑膠製作為收容本實施形態之眼科組成物之容器之情形時,該塑膠容器之構成材質並無特別限制,例如可列舉:聚萘二甲酸乙二酯、聚芳酯、聚對苯二甲酸乙二酯、聚丙烯、聚乙烯、聚醯亞胺、聚碳酸酯中之任一種、該等之共聚物、或2種以上之混合體。又,作為上述共聚物,可列舉以2,6-萘二甲酸乙二酯單位、芳酯單位、對苯二甲酸乙二酯單位、丙烯單位、乙烯單位、醯亞胺單位中之任一種作為主體且含有其他聚酯單位、醯亞胺單位的共聚物。再者,於本發明中,例如於記載為聚對苯二甲酸乙二酯製容器之情形時,只要相對於容器之構成材質整體之重量含有聚對苯二甲酸乙二酯即可,通常意指含有10w/w%以上、較佳為50w/w%以上。
又,關於收容本實施形態之眼科組成物之容器所具備之噴嘴等容器注入口周邊部,其構造、構成素材等亦並無特別限制。關於噴嘴等容器注入口周邊部之構造,只要為作為眼科組成物用容器(例如滴眼劑容器)之滴出口(例如噴嘴)所通常採用之構造即可,可與容器本體成形為一體,亦可與容器本體分別成形。關於注入口周邊部或是滴出口(例如噴嘴)之構成素材,例如可例示與上述塑膠容器之構成素材相同者。
尤其是就使柔軟性、成本方面及/或滴下量之不均抑制效果更良好之觀點而言,較佳為含有聚乙烯或聚丙烯作為構成素材之滴出口。
作為聚乙烯之種類,可列舉高密度聚乙烯、低密度聚乙烯等,其中,較佳為含有低密度聚乙烯作為構成素材之滴出口。又,作為滴出口,較佳為滴眼劑容器所使用之噴嘴。
作為收容本實施形態之眼科組成物之容器及容器注入口周
邊部之較佳組合,為聚對苯二甲酸乙二酯製容器與聚乙烯製容器注入口周邊部之組合,更佳為聚對苯二甲酸乙二酯製滴眼容器與聚乙烯製噴嘴之組合,尤佳為聚對苯二甲酸乙二酯製滴眼容器與低密度聚乙烯製噴嘴之組合。又,作為收容本實施形態之眼科組成物之容器及容器注入口周邊部之組合,亦較佳為聚對苯二甲酸乙二酯製容器與聚丙烯製噴嘴之組合、聚丙烯製容器與聚丙烯製噴嘴之組合。又,作為收容本實施形態之眼科組成物之容器及容器注入口周邊部之組合,亦較佳為聚乙烯製容器與聚乙烯製噴嘴之組合、或其一體成型之容器,其中尤佳為低密度聚乙烯製容器與低密度聚乙烯製噴嘴之組合、或其一體成型之容器。
[2.因低氧狀態所引起之角膜損傷之治療或預防]
本實施形態之眼科組成物對於因低氧狀態所引起之角膜損傷之治療或預防有用。因此,作為本發明之一實施形態,提供一種對眼科組成物賦予因低氧狀態所引起之角膜損傷之治療或預防作用之方法,其包含如下特徵:使眼科組成物含有(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類。
又,作為本發明之一實施形態,提供一種因低氧狀態所引起之角膜損傷之治療或預防劑,其由眼科組成物所構成,該眼科組成物含有(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類。
進而,作為本發明之一實施形態,提供一種(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該
等之鹽所組成之群中1種以上、及(B)多糖類之用途,其用於製造因低氧狀態所引起之角膜損傷之治療或預防用之眼科組成物。
再說,作為本發明之一實施形態,提供一種因低氧狀態所引起之角膜損傷之治療或預防方法,其係將(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上與(B)多糖類併用。
再者,關於上述各實施形態中之(A)成分之種類及含量等、其他成分之種類及含量等、眼科組成物之製劑形態及用途等,如[1.眼科組成物]中所說明。
[3.角膜細胞之活化]
本實施形態之眼科組成物發揮使角膜細胞活化之效果。因此,作為本發明之一實施形態,提供一種對眼科組成物賦予角膜細胞之活化作用之方法,其包含如下特徵:使眼科組成物含有(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類。
又,作為本發明之一實施形態,提供一種角膜細胞之活化劑,其由眼科組成物所構成,該眼科組成物含有(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類。
進而,作為本發明之一實施形態,提供一種(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類之用途,其用於製造角膜細
胞活化用之眼科組成物。
再說,作為本發明之一實施形態,提供一種使角膜細胞活化之方法,其係將(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上與(B)多糖類併用。
再者,關於上述各實施形態中之(A)成分之種類及含量等、其他成分之種類及含量等、眼科組成物之製劑形態及用途等,如[1.眼科組成物]中所說明。
[4.棘阿米巴之殺菌]
本實施形態之眼科組成物發揮將成為棘阿米巴角膜感染症之原因之棘阿米巴有效地殺菌之效果。
因此,作為本發明之一實施形態,提供一種對眼科組成物賦予將棘阿米巴殺菌之作用之方法,其包含如下特徵:使眼科組成物含有(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類。
又,作為本發明之一實施形態,提供一種棘阿米巴之殺菌劑,其由眼科組成物所構成,該眼科組成物含有(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類。
進而,作為本發明之一實施形態,提供一種(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類之用途,其用於製造棘阿米
巴之殺菌用之眼科組成物。
再說,作為本發明之一實施形態,提供一種將棘阿米巴殺菌之方法,其係將(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上與(B)多糖類併用。
再者,關於上述各實施形態中之(A)成分之種類及含量等、其他成分之種類及含量等、眼科組成物之製劑形態及用途等,如[1.眼科組成物]中所說明。
[5.棘阿米巴角膜感染症之預防]
本實施形態之眼科組成物發揮預防棘阿米巴角膜感染症之效果。
因此,作為本發明之一實施形態,提供一種對眼科組成物賦予預防棘阿米巴角膜感染症之作用之方法,其包含如下特徵:使眼科組成物含有(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類。
又,作為本發明之一實施形態,提供一種棘阿米巴角膜感染症之預防劑,其由眼科組成物所構成,該眼科組成物含有(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類。
進而,作為本發明之一實施形態,提供一種(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類之用途,其用於製造棘阿米巴角膜感染症預防用之眼科組成物。
再說,作為本發明之一實施形態,提供一種預防棘阿米巴角膜感染症之方法,其係將(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上與(B)多糖類併用。
再者,關於上述各實施形態中之(A)成分之種類及含量等、其他成分之種類及含量等、眼科組成物之製劑形態及用途等,如[1.眼科組成物]中所說明。
[7.角膜上皮損傷之預防]
本實施形態之眼科組成物發揮預防角膜染色等角膜上皮損傷之效果。
因此,作為本發明之一實施形態,提供一種對眼科組成物賦予預防角膜上皮損傷之作用之方法,其包含如下特徵:使眼科組成物含有(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類。
又,作為本發明之一實施形態,提供一種角膜上皮損傷之預防劑,其由眼科組成物所構成,該眼科組成物含有(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類。
進而,作為本發明之一實施形態,提供一種(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類之用途,其用於製造角膜上皮損傷預防用之眼科組成物。
再說,作為本發明之一實施形態,提供一種預防角膜上皮損
傷之方法,其包括如下步驟:使眼科組成物與隱形眼鏡接觸,該眼科組成物含有(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類之的步驟。該接觸步驟可於隱形眼鏡配戴中實施,亦可於隱形眼鏡未配戴中實施。
再者,關於上述各實施形態中之(A)成分之種類及含量等、其他成分之種類及含量等、眼科組成物之製劑形態及用途等,如[1.眼科組成物]中所說明。
[8.隱形眼鏡之配戴感之改善]
本實施形態之眼科組成物發揮改善隱形眼鏡之配戴感之效果。
因此,作為本發明之一實施形態,提供一種對眼科組成物賦予改善隱形眼鏡之配戴感之作用之方法,其包含如下特徵:使眼科組成物含有(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類。
又,作為本發明之一實施形態,提供一種隱形眼鏡之配戴感之改善劑,其由眼科組成物所構成,該眼科組成物含有(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類。
進而,作為本發明之一實施形態,提供一種(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類之用途,其用於製造隱形眼鏡之配戴感改善用的眼科組成物。
再說,作為本發明之一實施形態,提供一種改善隱形眼鏡之配戴感之方法,其包括如下步驟:使眼科組成物與隱形眼鏡接觸,該眼科組成物含有(A)選自由精胺酸、2-胺基-2-甲基-1,3-丙二醇、三(羥基甲基)胺基甲烷、2-胺基乙醇及該等之鹽所組成之群中1種以上、及(B)多糖類。該接觸步驟可於隱形眼鏡配戴中實施,亦可於隱形眼鏡未配戴中實施。
再者,關於上述各實施形態中之(A)成分之種類及含量等、其他成分之種類及含量等、眼科組成物之製劑形態及用途等,如[1.眼科組成物]中所說明。
[實施例]
以下,根據試驗例具體地說明本發明,但本發明並不限定於該等。
[試驗例1:對低氧後之氧化壓力之耐性評價]
按照表1中所記載之配方製備各試驗液(眼科組成物)。表1中之各成分量之單位為w/v%。
將永生化人類角膜上皮細胞(HCE-T)播種至6孔板,並於DMEM/F12培養基(對DMEM/F12培養基470mL添加Anti-anti 5mL、DMSO 2.5mL、EGF 0.5mL、胰島素0.6mL及FBS 25mL而成者)中進行培養直至融合。將各試驗液利用培養基稀釋10倍後,對各孔添加各2mL,於使用AnaeroPack-Kenki(三菱瓦斯化學公司製造)之低氧條件下,於37℃培養18小時。其後,使用QIAshredder & RNase Mini Kit(QIAGEN公司製造)自細胞提取RNA,並使用SuperScript II(Life technologies公司製造)反轉錄成cRNA後,利用ABI QuantStudio Real Time PCR(Thermo Fisher公司製造)進行q-PCR
(quantitative Polymerase Chain Reaction,定量聚合酶鏈反應),測量即時PCR法中之上升循環數(Ct)值。使用下述式求出相對於比較例1-1之HMOX1、GPX1、及GSTp1基因之相對表現比。使用18S基因(持家(House Keeping)基因)作為內部標準。
表現比=2-{(藉由試驗液處理所得之基因之Ct值)-(藉由試驗液處理所得之18S rRNA之Ct值)}/2-{(藉由比較例1-1處理所得之基因之Ct值)-(藉由比較例1-1處理所得之18S rRNA之Ct值)}
再者,已知HMOX1係保護細胞免受氧化壓力之基因,GPX1係抑制氧化壓力產生之基因,GSTp1作為對已受到損傷之細胞之修復發揮作用之基因。
將結果示於表1。
關於單獨摻合有玻尿酸鈉之比較例1-2之試驗液,與比較例1-1之試驗液相比,該等基因之表現量幾乎無變化。相對於此,關於摻合有精胺酸及玻尿酸鈉之實施例1-1及1-2之試驗液,意外地確認到該等基因之表現顯著增加。
根據以上之結果確認,即便於置於低氧條件下之情形時,藉由使用本發明之眼科組成物,亦會促進「對因低氧狀態所產生之氧化壓力有效地發揮作用之基因」之產生。因此,確認本發明之眼科組成物對於因低氧狀態所引起之角膜損傷之治療或預防有用。
[試驗例2:對於細胞活化作用之評價]
按照表2中所記載之配方製備各試驗液(眼科組成物)。表2中之各成分量之單位為w/v%。
將永生化人類角膜上皮細胞(HCE-T)以形成1×104個/孔之方式播種至96孔板,並進行培養直至融合。添加各試驗液各100μL,於37℃培養20分鐘。同時,準備如下者來代替各試驗液並設為對照,即,除添加100μL之DMEM/F12培養基以外進行相同之處理所獲得者。其後,使用細胞計數套組(Cell-counting kit)-8,求出相對於對照之各試驗液之細胞生存率(%)。繼而,使用下述式,算出相對於比較例2-1之各試驗液之細胞生存率之上升率(%)。
相對於比較例2-1之細胞生存率之上升率(%)={(各試驗液之細胞生存率-比較例2-1之細胞生存率)/比較例2-1之細胞生存率}×100
將結果示於表2。
關於單獨摻合有玻尿酸鈉之比較例2-2之試驗液,與比較例2-1之試驗液相比,幾乎未見細胞生存率上升。相對於此,關於摻合有精胺酸及玻尿酸鈉之實施例2-1~2-3之試驗液,確認到細胞生存率顯著上升。
根據以上之結果確認,藉由使用本發明之眼科組成物,細胞生存率顯著上升,因此即便於置於缺乏營養之狀態時,亦減輕細胞生存率之降低,即角膜細胞被活化。
[試驗例3:對棘阿米巴之殺菌力之評價]
按照表3所記載之配方製備各試驗液(隱形眼鏡消毒/清洗/保存液)。表3中之各成分量之單位為w/v%。對於剛製備後之各試驗液、及於60℃保管3週後之各試驗液,評價對棘阿米巴之滋養型、及胞囊型之殺菌力。
將棘阿米巴(Acanthamoeba castellanii)於PYG液體培養基中、32.5℃下培養3天,並利用1/4RS(氯化鈉0.215g/100mL,氯化鉀0.0075g/100mL,CaCl2.2H2O 0.0083g/100mL)清洗3次後,以成為約2×106~5×106cells/mL之方式進行調整,而獲得微生物液。以無菌方式取出試驗液(10mL)並置於3個已滅菌之試驗容器之各者中,並對其接種微生物液(0.1mL),
最終設為約2.0×104~5.0×104cells/mL。
將所獲得之含有微生物液之試驗液於25℃靜置4小時後,自該含有微生物液之試驗液取出0.5mL,將其添加至中和液(將PYG液體培養基與DNB(Dey-Engley Neutralizing Broth,戴伊恩格利中和培養液)以8:1混合而成者)(4.5mL)中將被試驗物質中和而製作10倍稀釋溶液。將其於96孔多孔板中加入各200μL。其後,對加入有PYG液體培養基各180μL之孔添加上述10倍稀釋溶液各20μL並充分混合,將上述操作重複進行4次(直至稀釋104倍),而獲得培養液。
將所獲得之培養液於25℃培養7天,於倒置式顯微鏡下確認有無試驗微生物之增殖。將可見增殖之孔數加以合計,藉由Spearman-Karber法算出棘阿米巴之滋養型生菌數。繼而,將即將培養前之生菌數與培養7天後之生菌數進行比較,將菌數之減少量設為對數減少值(Log reduction)而算出。又,使用將棘阿米巴於PYG液體培養基中進行培養後將PYG液體培養基變更為EM液體培養基並進而於25℃培養14天而獲得者,除此以外,藉由與滋養型相同之方法算出棘阿米巴之胞囊型生菌數及對數減少值。
對於棘阿米巴之滋養型、及胞囊型各者,使用下述式算出相對於比較例3-1之阿米巴殺菌力改善率(%)。
阿米巴殺菌力改善率(%)={(各試驗例之對數減少值-「比較例3-1」之對數減少值)/「比較例3-1」之對數減少值}×100
將所算出之阿米巴殺菌力改善率示於表3。
關於實施例3-1及3-2之試驗液,確認對於棘阿米巴之滋養型、及胞囊型顯示出優異之殺菌力。
[試驗例4:角膜染色之評價]
按照表4中所記載之配方製備各試驗液(隱形眼鏡消毒/清洗/保存液)。表4中之各成分量之單位為w/v%。使隱形眼鏡(Acuvue Advance(註冊商標),Johnson & Johnson公司製造)於各試驗液(3mL)中浸漬整夜後,讓4名健康人配戴。
於配戴隱形眼鏡2小時後,將眼球表面進行螢光素染色,並利用狹縫燈進行觀察。
依據參考文獻(Cornea,Vol.30,No.10,October 2011,p.1098-1104)中所記載之方法,將眼球表面劃分為5處區域,對各處分別按照下述評價基準進行評價,算出將5處區域之各得分合計所得者作為染色得分,求出平均值。
<評價基準>
0:完全無染色
1:有略微之染色
2:有中等程度之染色
3:有嚴重之染色
對於染色得分之平均值,將0分以上且未達2.5分之情形評價為「◎」,將2.5分以上且未達5分之情形評價為「○」,將5分以上且未達10分之情形評價為「△」,將10分以上且15分以下之情形評價為「×」,並示於表4。
關於實施例4-1~4-3之試驗液,確認到染色得分較低之傾向。即,顯示出浸漬於實施例4-1~4-3之試驗液之隱形眼鏡不易產生角膜染色。
[試驗例5:隱形眼鏡配戴感之評價]
按照表5中所記載之配方製備各試驗液(隱形眼鏡消毒/清洗/保存液)。表5中之各成分量之單位為w/v%。使隱形眼鏡(Acuvue Advance(註冊商標),Johnson & Johnson公司製造)於各試驗液(3mL)中浸漬整夜後,讓4名健康人配戴。
於剛配戴隱形眼鏡後、配戴2小時後、及配戴8小時後,藉由VAS(Visual analog scale:視覺評價尺度)對表5中所記載之各症狀之感覺進行評價。
藉由VAS之評價係以如下方式進行。於畫有100mm之線之自覺症狀調查表上,將完全感覺不到表5中所記載之各症狀之情形設為0mm,將強烈感覺到各症狀之情形設為100mm,請被試驗者於所感覺到之症狀之程度之處打勾。將該長度(mm)設為VAS值。即,VAS值越高,各症狀之自覺症狀得分越高。
又,使用下述式算出相對於比較例5-1之得分變化率(%)。
得分變化率(%)={(各試驗例之VAS值-「比較例5-1」之VAS值)/「比較例5-1」之VAS值}×100
將所算出之得分變化率示於表5。
於使用實施例5-1之試驗液之情形時,於進行評價之各時間點,與比較例5-1之試驗液相比,隱形眼鏡配戴感之良好性提高,異物感、刺痛感、及乾燥感之各知覺得分降低,因此確認自剛配戴後經過8小時後,不易感覺到不快感,配戴感得到改善。
[試驗例6:對低氧後之氧化壓力之耐性評價(2)]
按照表6中所記載之配方製備各試驗液(眼科組成物)。表6中之各成
分量之單位除表中有記載者以外均為(w/v%)。
將測定對象之基因僅設為HMOX1,及使用對照代替比較例1-1,除此以外,藉由與試驗例1相同之方法算出相對於對照之HMOX1基因之相對表現比。對照係除不含有玻尿酸鈉以外均與比較例6-1相同之配方。
算出各配方之表現比後,使用下述式算出相對於所對應之配方之表現比之上升率。
表現比之上升率(%)={(各試驗例之表現比-所對應之比較例之表現比)所對應之比較例之表現比}×100
此處,實施例6-1~6-3所對應之比較例為比較例6-1,實施例6-4及6-5所對應之比較例為比較例6-2。
將所算出之表現比之上升率示於表6。
確認於摻合有2-胺基-2-甲基-1,3-丙二醇或三(羥基甲基)胺基甲烷與多糖類之情形時,HMOX1基因之表現亦顯著增加。
[試驗例7:對低氧後之氧化壓力之耐性評價(3)]
按照表7中所記載之配方製備各試驗液(眼科組成物)。表7中之各成分量之單位為w/v%。
將永生化人類角膜上皮細胞(HCE-T)播種至6孔板,並於DMEM/F12培養基(對DMEM/F12培養基470mL添加Anti-anti 5mL、DMSO 2.5mL、EGF 0.5mL、胰島素0.6mL及FBS 25mL而成者)中進行培養直至融合。對各孔添加各試驗液各2mL,於使用AnaeroPack-Kenki(三菱瓦斯化學公司製造)之低氧條件下,於37℃培養18小時。其後,使用QIAshredder & RNase Mini Kit(QIAGEN公司製造)自細胞提取RNA,並使用SuperScript II(Life technologies公司製造)反轉錄成cRNA後,利用ABI QuantStudio Real Time PCR(Thermo Fisher公司製造)進行q-PCR,測量即時PCR法中之上升循環數(Ct)值。使用下述式求出相對於比較例7-1之HMOX1、GPX1、及GSTp1基因之相對表現比。使用18S基因(持家基因(House Keeping))作為內部標準。
表現比=2-{(藉由試驗液處理所得之基因之Ct值)-(藉由試驗液處理所得之18S rRNA之Ct值)}/2-{(藉由比較例7-1處理所得之基因之Ct值)-(藉由比較例7-1處理所得之18S rRNA之Ct值)}
將結果示於表7。
確認於摻合有2-胺基-2-甲基-1,3-丙二醇、2-胺基乙醇或三(羥基甲基)胺基甲烷與多糖類之情形時,上述基因之表現亦顯著增加。
[製劑例]
按照表8及9中所記載之配方製備眼科組成物,設為製劑例1~18。表中之單位除表中有記載者以外均為(w/v%)。
Claims (3)
- 一種眼科組成物,其含有(A)選自由精胺酸及其鹽所組成之群中1種以上、及(B)玻尿酸及/或其鹽(其中,不包含含有膠原蛋白酶抑制劑(the inhibitor of collagenase)及新膠原蛋白合成促進劑(the promoter of neocollagen synthesis)之眼科組成物;該膠原蛋白酶抑制劑係選自由半胱胺酸、N-乙醯半胱胺酸及EDTA鈣鹽所成之群,該新膠原蛋白合成促進劑係選自由脯胺酸及羥脯胺酸所成之群)。
- 如申請專利範圍第1項之眼科組成物,其進而含有(C)殺菌劑或防腐劑。
- 如申請專利範圍第1項之眼科組成物,其用於隱形眼鏡。
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