TWI527584B - UV damage mitigation composition - Google Patents
UV damage mitigation composition Download PDFInfo
- Publication number
- TWI527584B TWI527584B TW099109837A TW99109837A TWI527584B TW I527584 B TWI527584 B TW I527584B TW 099109837 A TW099109837 A TW 099109837A TW 99109837 A TW99109837 A TW 99109837A TW I527584 B TWI527584 B TW I527584B
- Authority
- TW
- Taiwan
- Prior art keywords
- cysteine
- glutamic acid
- proline
- ultraviolet
- damage
- Prior art date
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Description
本發明係關於一種包含選自由D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸、與該等之衍生物及/或鹽所組成之群中的1種或2種以上之化合物的紫外線傷害減輕組合物;包括投與選自由D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸、與該等之衍生物及/或鹽所組成之群中的1種或2種以上之化合物的步驟之由紫外線暴露所致之皮膚病及皮膚之美容狀態之改善方法;及包括投與上述化合物之步驟之治療及/或預防白內障之方法。
紫外線分類為長於約320 nm之長波段紫外線(UV-A)、約320~約280 nm之中波段紫外線(UV-B)、及短於約280 nm之短波段紫外線(UV-C)。其中因UV-C被臭氧層吸收,故不包含於到達地面上之太陽光中。UV-A不被臭氧層吸收,佔到達地面上之紫外線之大部分。又,UV-B被臭氧層吸收一部分,但以UV-A之1000分之1之光量引起皮膚傷害。因此,UV-A及UV-B一併作為皮膚傷害之主要原因而較為重要。根據非專利文獻1,與紫外線相關之疾病可列舉:皺紋、紅斑、著色性乾皮症、慢性光化性皮炎、鱗狀細胞癌、基底細胞癌、惡性黑色素瘤、Bowen病(鮑溫病)、日光性角化症、光敏性皮炎、種痘樣水皰病及光接觸性皮炎,根據非專利文獻2,可列舉:日光性皮炎、慢性光線皮膚症、光化性角化症、光化性唇炎、面部多發性黑頭粉刺淡黃色結節(Favre-Racouchot)病、光敏性皮炎、光接觸性皮炎、香料皮炎(berlock dermatitis)、光敏性藥疹、多形性日光疹、種痘樣水皰病、日光蕁麻疹、慢性光線過敏性皮膚炎、著色性乾皮症、雀斑、血卟啉病、癩皮病、遺傳性菸鹼酸缺乏(Hartnup)病、日光性角化症、皮肌炎、扁平苔癬、毛囊角化(Darier)病、毛孔性紅糠疹、酒渣鼻、異位性皮膚炎、肝斑、單純疱疹及紅斑性狼瘡等。
非專利文獻1:皮膚病最新之治療2005-2006(南江堂)
非專利文獻2:標準皮膚科學第7版(醫學書院)
先前之由紫外線所致之皮膚傷害之預防及/或治療劑,已知有阻礙皮膚吸收紫外線之氧化鈦之類的紫外線散射劑或對甲氧基肉桂酸2-乙基己酯之類的紫外線吸收劑、或者除去由紫外線所產生之自由基之抗氧化劑。然而,紫外線散射劑、紫外線吸收劑對於室外之防曬有效,但並非日常使用者。又,抗氧化劑之穩定性及安全性存在問題。進而,針對由紫外線所致之皮膚傷害的治療劑僅已知有對症療法劑。因此,有必要開發一種可日常使用、穩定且安全之紫外線傷害之預防及/或治療劑,與包含其之醫藥品、化妝品及食品。
本發明提供一種紫外線傷害減輕組合物,其包含選自由D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸、與該等之衍生物及/或鹽所組成之群中的1種或2種以上之化合物。
本發明之紫外線傷害減輕組合物有適合用作皮膚外用劑之情形。
於本發明之紫外線傷害減輕組合物中,有上述皮膚外用劑用作化妝品之情形。
於本發明之紫外線傷害減輕組合物中,有上述化妝品為抗皺劑之情形。
於本發明之紫外線傷害減輕組合物中,有上述化妝品為防曬劑之情形。
於本發明之紫外線傷害減輕組合物中,有上述皮膚外用劑用作皮膚病用醫藥品之情形。
有如下情形:上述皮膚病係選自由紅斑、日光性皮炎、慢性光線皮膚症、光化性角化症、光化性唇炎、面部多發性黑頭粉刺淡黃色結節病、光敏性皮炎、光接觸性皮炎、香料皮炎、光敏性藥疹、多形性日光疹、種痘樣水皰病、日光蕁麻疹、慢性光線過敏性皮膚炎、著色性乾皮症、雀斑、血卟啉病、癩皮病、遺傳性菸鹼酸缺乏病、日光性角化症、皮肌炎、扁平苔癬、毛囊角化病、毛孔性紅糠疹、酒渣鼻、異位性皮膚炎、肝斑、單純疱疹、紅斑性狼瘡、鱗狀細胞癌、基底細胞癌及鮑溫病所組成之群組。
於本發明之紫外線傷害減輕組合物中,有上述皮膚病用醫藥品為皮膚病用治療劑之情形。
於本發明之紫外線傷害減輕組合物中,有上述皮膚病用醫藥品為皮膚病用預防劑之情形。
本發明之紫外線傷害減輕組合物有用作食品之情形。
本發明之紫外線傷害減輕組合物有用作白內障用醫藥品之情形。
於本發明之紫外線傷害減輕組合物中,有上述白內障用醫藥品為白內障用治療劑或白內障用預防劑之情形。
本發明之紫外線傷害減輕組合物有用作滴眼藥之情形。
上述白內障有老人性白內障之情形。
本發明有如下情形:提供一種治療及/或預防由紫外線暴露所致之皮膚病之方法,其包括投與包含選自由D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸、與該等之衍生物及/或鹽所組成之群中的1種或2種以上之化合物之步驟。有如下情形:上述皮膚病係選自由紅斑、日光性皮炎、慢性光線皮膚症、光化性角化症、光化性唇炎、面部多發性黑頭粉刺淡黃色結節病、光敏性皮炎、光接觸性皮炎、香料皮炎、光敏性藥疹、多形性日光疹、種痘樣水皰病、日光蕁麻疹、慢性光線過敏性皮膚炎、著色性乾皮症、雀斑、血卟啉病、癩皮病、遺傳性菸鹼酸缺乏病、日光性角化症、皮肌炎、扁平苔癬、毛囊角化病、毛孔性紅糠疹、酒渣鼻、異位性皮膚炎、肝斑、單純疱疹、紅斑性狼瘡、鱗狀細胞癌、基底細胞癌及鮑溫病所組成之群組。
本發明有如下情形:提供一種皮膚之美容狀態之改善方法,其包括投與包含選自由D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸、與該等之衍生物及/或鹽所組成之群中的1種或2種以上之化合物的組合物之步驟。於上述皮膚之美容狀態之改善方法中,有如下情形:包含選自由上述D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸、與該等之衍生物及/或鹽所組成之群中的1種或2種以上之化合物的組合物為化妝品組合物或食品組合物。
於本發明之皮膚之美容狀態之改善方法中,有皮膚之美容狀態之改善係指抗皺及/或防曬之情形,但並不限定於該等。
本發明提供一種治療及/或預防白內障之方法,其包括投與包含選自由D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸、與該等之衍生物及/或鹽所組成之群中的1種或2種以上之化合物的組合物之步驟。
於本發明之治療及/或預防白內障之方法中,有上述白內障用醫藥品為滴眼藥之情形。
於治療及/或預防本發明之白內障之方法中,有上述白內障為老人性白內障之情形。
於本說明書中,所謂「鹽」,係指以不損害D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸之紫外線傷害之減輕效果為條件而含有的金屬鹽、胺鹽等之任一種鹽。上述金屬鹽有包含鹼金屬鹽、鹼土類金屬鹽等之情形。上述胺鹽有包含三乙胺鹽、苄胺鹽等之情形。
於本說明書中,所謂「該等之衍生物」,係指以不損害D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸之紫外線傷害之減輕效果為條件而於D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸、或胺基、或羧基、或側鏈上與任一原子團共價鍵結者。上述任一原子團包含N-苯基乙醯基、4,4'-二甲氧基三苯甲基(DMT)基等之類的保護基;蛋白質、肽、糖、脂質、核酸等之類的生物高分子;聚苯乙烯、聚乙烯(polyethylene)、聚乙烯(polyvinyl)、聚酯等之類的合成高分子;及酯基等之類的官能基;但並不限定於該等。上述酯基有包含例如甲基酯、乙基酯等脂肪族酯、或芳香族酯之情形。
胺基酸中,作為光學異構物,有L構型與D構型,天然之蛋白質係L-胺基酸進行肽結合而成者,除細菌之細胞壁等例外,其他係僅利用L-胺基酸,因此認為以人為代表之哺乳類僅存在L-胺基酸,僅利用L-胺基酸(木野內忠稔等人,蛋白質核酸酶,50:453-460(2005)、Lehninger Principles of Biochemistry[上]第2版pp 132-147(1993)廣川書店,Harper's Biochemistry原書22版pp 21-30(1991)丸善)。因此,先前在學術上及產業上胺基酸主要係僅使用L-胺基酸。
作為例外地使用D-胺基酸之情況,有用作細菌所產生之抗生素之原料之情形;及為節省自化學合成胺基酸時等量獲得之L-胺基酸與D-胺基酸混合物中僅分離L-胺基酸之成本,而直接使用D-胺基酸作為DL-胺基酸混合物之食品添加物之例。然而,先前沒有於產業上使用游離或者單體之D-胺基酸本身來作為具有生理活性之物質之例。
近年來,報告有於人體中D-絲胺酸、D-天冬醯胺酸具有生理作用,明確人體中亦存在D-絲胺酸消旋酶等,明確於哺乳類體內亦存在D-胺基酸且發揮生理作用,但於人體中報告有生理作用之D-絲胺酸與L-絲胺酸、D-天冬醯胺酸與L-天冬醯胺酸顯示出完全不同之生理作用,因此明確D-胺基酸應作為與L-胺基酸完全不同之物質來對待,先前已知之關於胺基酸之見解可理解為關於L-胺基酸之見解。
如以下實施例所示,L-脯胺酸不具有減輕紫外線傷害之效果,關於D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸,至今亦未知有減輕紫外線傷害之效果。因此,本發明之包含選自由D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸等所組成之群中的1種或2種以上之化合物的紫外線傷害減輕組合物為新穎之發明。
近年來,報告有:使ddY小鼠自由攝取10 mM之D-胺基酸水溶液2週後,測定各器官之D-胺基酸濃度,結果於松果體中,每1腺松果體為3~1000 pmol,於腦組織中,每1克濕重量為2~500 nmol(Morikawa,A.等人,Amino Acids,32:13-20(2007))。據此,計算出以下說明之本發明之組合物中所含有之L-或D-麩胺酸、D-脯胺酸、及L-或D-半胱胺酸之一日攝取量之下限。
本發明之L-及D-麩胺酸如以下實施例所示,以單體對於培養人角質形成細胞及纖維母細胞以0.1~100 μM之濃度範圍具有減輕紫外線傷害之效果。因此,關於包括本發明之醫藥品組合物、抗皺劑及防曬劑、化妝品組合物、及食品組合物之本發明之組合物中所含有之L-及/或D-麩胺酸之量,以將該濃度範圍之L-及/或D-麩胺酸單體送達至生物皮膚組織之角質形成細胞或纖維母細胞為條件,可為任意含量。本發明之組合物為外用劑之情形時之L-及/或D-麩胺酸之含量於本發明之組合物總量中為自0.000015重量%至10重量%或可調配之最大重量濃度為止之範圍即可。即,上述組合物為外用劑之情形時之L-及/或D-麩胺酸之含量期望為0.00003重量%~0.3重量%,最期望為0.0003重量%~0.03重量%。本發明之組合物為內服劑之情形時之L-及/或D-麩胺酸之含量為0.00001重量%~100重量%之範圍即可。本發明之組合物為內服劑之情形時之L-及/或D-麩胺酸之含量期望為0.00002重量%~80重量%,最期望為0.0002重量%~60重量%。再者,本發明之組合物中所含有之D-麩胺酸之一日攝取量之下限為每1 kg體重為0.01 ng即可,較好的是0.1 ng,更好的是1 ng。本發明之組合物中所含有之L-麩胺酸之一日攝取量之下限為少於臨床藥之投與量(每1 kg體重為80 mg以上)之量,每1 kg體重為0.1 mg即可,較好的是1 mg,更好的是10 mg。
本發明之D-脯胺酸如以下實施例所示,以單體對於培養人纖維母細胞以0.01~1 μM之濃度範圍具有減輕紫外線傷害之結果。因此,關於本發明之醫藥品組合物、抗皺劑及防曬劑、化妝品組合物、及食品組合物中所含有之D-脯胺酸之量,以將該濃度範圍之D-脯胺酸單體送達至生物皮膚組織之纖維母細胞為條件,可為任意含量。本發明之組合物為外用劑之情形時之D-脯胺酸之含量於本發明之組合物總量中為自0.000015重量%至50重量%或可調配之最大重量濃度為止之範圍即可。即,上述組合物為外用劑之情形時之D-脯胺酸之含量期望為0.00003重量%~30重量%,最期望為0.0003重量%~3重量%。本發明之組合物為內服劑之情形時之D-脯胺酸之含量為0.00001重量%~100重量%之範圍即可。本發明之組合物為內服劑之情形時之D-脯胺酸之含量期望為0.00002重量%~80重量%,最期望為0.0002重量%~60重量%。再者,本發明之組合物中所含有之D-脯胺酸之一日攝取量之下限為每1 kg體重為0.01 ng即可,較好的是0.1 ng,更好的是1 ng。
本發明之L-及D-半胱胺酸如以下實施例所示,以單體對於培養人角質形成細胞及纖維母細胞以0.1~100 μM之濃度具有減輕紫外線傷害之效果。因此,關於包括本發明之醫藥品組合物、抗皺劑及防曬劑、化妝品組合物、及食品組合物之本發明之組合物中所含有之L-及/或D-半胱胺酸之量,以將該濃度之L-及/或D-半胱胺酸單體送達至生物皮膚組織之角質形成細胞或纖維母細胞為條件,可為任意含量。本發明之組合物為外用劑之情形時之L-及/或D-半胱胺酸之含量於本發明之組合物總量中為自0.000015重量%至10重量%或可調配之最大重量濃度為止之範圍即可。即,上述組合物為外用劑之情形時之L-及/或D-半胱胺酸之含量期望為0.00003重量%~0.3重量%,最期望為0.0003重量%~0.03重量%。本發明之組合物為內服劑之情形時之L-及/或D-半胱胺酸之含量為0.00001重量%~100重量%之範圍即可。本發明之組合物為內服劑之情形時之L-及/或D-半胱胺酸之含量期望為0.00002重量%~80重量%,最期望為0.0002重量%~60重量%。再者,本發明之組合物中所含有之D-半胱胺酸之一日攝取量之下限為每1 kg體重為0.01 ng即可,較好的是0.1 ng,更好的是1 ng。本發明之組合物中所含有之L-半胱胺酸之一日攝取量之下限為少於臨床藥之投與量(每1 kg體重為3 mg以上)之量,為1 kg體重為0.01 mg即可,較好的是0.1 mg,更好的是1 mg。
本發明之醫藥品組合物有如下情形:除含有選自由D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸之單體,D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸之鹽,及於生物體內藉由藥物代謝酶等可釋放出D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸之衍生物所組成之群中的1種或2種以上之化合物以外,以不損害D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸之紫外線傷害之減輕效果為條件,進而含有1種或2種以上之藥學上允許之添加物。上述添加物包括稀釋劑及膨脹劑、結合劑及接著劑、潤滑劑、流動促進劑、塑化劑、崩解劑、載體溶劑、緩衝劑、著色料、香料、甜味劑、防腐劑及穩定化劑、吸附劑、及業者已知之其他醫藥品添加劑,但並不限定於該等。
本發明之抗皺劑及/或防曬劑亦可僅使用D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸之單體,D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸之鹽及/或於生物體內藉由藥物代謝酶等可釋放出D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸之衍生物作為有效成分而製備,通常於不損害本發明之效果之範圍內,可視需要適當調配包含準藥品之化妝品或醫藥品等皮膚外用劑等中所使用之其他成分。作為上述其他成分(任意調配成分),例如可列舉油分、界面活性劑、粉末、色材、水、醇類、增黏劑、螯合劑、矽類、抗氧化劑、紫外線吸收劑、保濕劑、香料、各種藥效成分、防腐劑、pH調整劑、中和劑等。
所謂本發明之皮膚外用劑及化妝品組合物,例如可為軟膏、霜劑、乳液、洗劑、敷劑、浴用劑等先前皮膚外用劑及化妝品組合物中所使用者之任一者,劑型並無限定。
以不損害D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸之紫外線傷害之減輕效果為條件,本發明之化妝品組合物可視需要適當調配包含準藥品之化妝品或醫藥品等皮膚外用劑等中所使用之其他成分。作為上述其他成分(任意調配成分),例如可列舉油分、界面活性劑、粉末、色材、水、醇類、增黏劑、螯合劑、矽類、抗氧化劑、紫外線吸收劑、保濕劑、香料、各種藥效成分、防腐劑、pH調整劑、中和劑等。
本發明之食品組合物有如下情形:除D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸之單體、D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸之鹽及/或於生物體內藉由藥物代謝酶等可釋放出D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸之衍生物以外,以不損害D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸之紫外線傷害之減輕效果為條件,而含有調味料、著色料、防腐劑等食品上允許之成分。
本發明之食品組合物例如可為清涼飲料、軟糖、糖果、模壓點心等先前食品組合物中所使用者之任一者,並不限定於上述例示。
一般認為紫外線曝露不僅為皮膚病之原因之一,亦為眼病、尤其是白內障之原因之一。已知小鼠長時間曝露於紫外線中會使晶狀體之前部皮質產生白濁,可於實驗上製作白內障模型(前里多佳美及岩田修造,「晶狀體 其生物化學結構」,318-323頁,岩田修造編,醫學葵出版,東京(1986))。又,認為老人性白內障之原因之一為紫外線(藤永豐,「白內障眼科MOOK No.17」,10頁,三島濟一等人編,金原出版,東京(1982)),Zigman等人藉由馬尼拉、坦帕及洛契斯特之疫學調查,發現紫外線之照射量與白內障之發生率相關,紫外線為白內障之風險因素(Zigman,S.等人,Invest. Ophthalmol. Visual Sci. 18:462-467(1979))。因此,根據該等見解與以下實施例,具有減輕紫外線傷害之效果之D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸及L-半胱胺酸對於白內障之預防或治療有效。
以下說明之本發明之實施例僅以例示為目的,並不限定本發明之技術範圍。本發明之技術的範圍僅由申請專利範圍之記載限定。
D-麩胺酸之紫外線傷害減輕效果
細胞
細胞係使用市售之人新生兒表皮角化細胞(Cryo NHEK-Neo,三光純藥)。以達到2×105個/mL之方式將上述細胞播種於以市售之膠原蛋白I型覆蓋之35 mm直徑之培養皿(COL1,Asahi Techno Glass Corporation)中,使用市售之無血清培養基(Defined Keratinocyte-SFM,Gibco公司,以下稱為「通常培養基1」)進行培養。每2日交換一次培養基,將上述細胞於37℃、5% CO2及飽和水蒸氣環境下培養5至7天,直至達到融合。
在研究於紫外線照射前添加麩胺酸之處理(以下,稱為「前處理」)之效果之情形時,於照射24小時前轉換為添加有0.1至100 μM之L-或D-麩胺酸之培養基。
紫外線照射
於UV-B照射前將培養基置換為PBS 1 mL。UV-B照射係使用自製之紫外光曝光裝置(紫外線螢光燈,Toshiba Medical Supply TOREX FL20S-E-30/DMR,2根),於除去培養皿之蓋之狀態下以75 J/cm2自該培養皿之40 cm上部照射280 nm至320 nm之紫外線而實施。紫外線量係使用UV RADIOMETER UVR-3036/S(TOPCON股份有限公司)來測定。
經紫外線照射處理之細胞放回至通常培養基1中於37℃、5% CO2及飽和水蒸氣環境下培養21小時。在研究於紫外線照射後添加麩胺酸之處理(以下,稱為「後處理」)之效果之情形時,於該21小時之培養之培養基中添加0.1至100 μM之L-或D-麩胺酸。
細胞傷害之定量
其後,以最終濃度達到10%之方式向培養基中添加alamarBlue(商標,Biosource,Biosource International),3小時後,根據Ahmed S. A.等人(J. Immunol. Method. 170,211-224(1994))及製造者之說明書,以激發波長544 nm、螢光波長590 nm測定上清液之螢光強度。
結果
於圖1中表示調查D-麩胺酸對於由UV-B 75 mJ/cm2之紫外線照射所致之角質形成細胞之細胞傷害的效果之實驗結果。各實驗條件之誤差棒表示於同一條件下重複8次之實驗結果之測定值之標準偏差。又,星號(**)表示於邦弗朗尼(Bonferroni)檢驗中P未滿1%。於未照射UV之情形時,alamarBlue(商標)之螢光強度約為22000,若藉由UV-B照射而引起細胞傷害,則下降至5000至7000。然而,若添加D-麩胺酸,則螢光強度增大,減輕細胞傷害。該細胞傷害之減輕效果與在UV照射之前或之後實施D-麩胺酸處理並無關係,但若提高D-麩胺酸之濃度,則減輕效果亦增大。藉由添加L-麩胺酸,並未發現細胞傷害之減輕效果(未圖示)。由以上之結果顯示,D-麩胺酸依存於濃度而減輕角質形成細胞由UV-B所致之細胞傷害。
D-脯胺酸之紫外線傷害減輕效果
細胞
細胞係使用市售之人新生兒真皮纖維母細胞(Cryo NHDF-Neo,三光純藥)。以達到2×105個/mL之方式將上述細胞播種於市售之35 mm直徑之培養皿(BD FALCON 353001,日本Becton,Dickinson and Company)中,使用於市售之細胞培養用培養基(D-MEM(1 g/L葡萄糖),和光純藥)中添加有10%牛胎兒血清之培養基(以下,稱為「通常培養基2」)進行培養。於37℃、5% CO2及飽和水蒸氣環境下將上述細胞培養約24小時。
其後將培養上述細胞之培養基轉換為添加有1×10-3%作為麩胱甘肽之生物合成抑制劑之BSO(L-buthionine-(S,R)-sulfoximine,和光純藥)之BSO培養基1 mL,於37℃、5% CO2及飽和水蒸氣環境下培養約24小時。上述BSO培養基係將於乙醇中溶解有0.2% BSO之保存用原液於上述通常培養基2中稀釋200倍而製備。
在研究於紫外線照射前添加脯胺酸之處理(以下,稱為「前處理」)之效果之情形時,於照射24小時前轉換為添加有0.1 μM之L-或D-脯胺酸之培養基。
紫外線照射用培養基
以達到2×10-3%之方式將氯化鐵(II)溶解於蒸餾水中,將該溶解液以稀釋200倍(終濃度1×10-5%)之方式利用含有鈣離子、鎂離子之磷酸緩衝液PBS(+)加以稀釋而製作培養基(以下,稱為「紫外線照射用培養基」),將該培養基預先加溫至37℃並加以使用。
紫外線照射
於UV-A照射前將培養基置換為上述紫外線照射用培養基1 mL。UV-A照射係使用紫外光均勻曝光裝置UVE-502S+EL-160(三永電機製作所),於除去培養皿之蓋之狀態下以15 J/cm2及22.5 J/cm2自該培養皿之約20 cm上部照射320 nm至400 nm之紫外線而實施。紫外線量係使用UV RADIOMETER UVR-3036/S(TOPCON股份有限公司)來測定。
於紫外線照射後添加脯胺酸之處理
紫外線照射處理後,放回上述通常培養基2中於37℃、5% CO2及飽和水蒸氣環境下培養21小時。在研究於紫外線照射後添加脯胺酸之處理(以下,稱為「後處理」)之效果之情形時,向該21小時之培養之培養基中添加0.01至1000 μM之L-或D-脯胺酸。
後處理時之細胞傷害之定量
其後,根據實施例1中說明之方法測定螢光強度。
後處理之結果
於圖2中表示調查D-脯胺酸對於由UV-A 15 J/cm2及22.5 J/cm2之紫外線照射所致之纖維母細胞之傷害的效果之實驗結果。各實驗條件之誤差棒表示於同一條件下重複4次之實驗結果之測定值之標準偏差。又,星號(*)表示於Bonferroni檢驗中p未滿5%。於未照射UV之情形時,alamarBlue(商標)之螢光強度約為12000,若藉由UV-A 15 J/cm2之照射而引起細胞傷害,則下降至約5000。又,若藉由UV-A 22.5 J/cm2之照射引起細胞傷害,則下降至約3000。然而,若添加D-脯胺酸,則螢光強度增大,減輕細胞傷害。
於表1中表示調查L-及D-脯胺酸對於由UV-A 12.5 J/cm2及15 J/cm2之紫外線照射所致之纖維母細胞之傷害的效果之實驗結果。各實驗條件之誤差棒表示於同一條件下重複4次至6次之實驗結果之測定值之標準偏差。此處,星號(*)1表示於Bonferroni檢驗中與對照相比較之p未滿0.1%,與L-脯胺酸相比較之p為0.1%。又,星號(*)2表示於Bonferroni檢驗中與對照相比較之p未滿0.1%,與L-脯胺酸相比較之p未滿5%。於未照射UV之情形時,alamarBlue(商標)之螢光強度約為12000,若藉由UV-A 12.5 J/cm2及UV-A 15 J/cm2之照射而引起細胞傷害,則下降至約2500及約1000。藉由添加L-脯胺酸,幾乎不會減輕細胞傷害。然而,若添加D-脯胺酸,則螢光強度增大,減輕細胞傷害。
前處理時之細胞傷害之定量
細胞傷害性係藉由以下方式定量:以0.25%胰蛋白酶-EDTA(GIBCO)處理5分鐘處理而進行細胞剝離後,進行離心並洗淨,利用0.2%台盼藍染色(GIBCO)確認生死。
前處理之結果
於圖3中表示調查D-脯胺酸對於由22.5 J/cm2之紫外線照射所致之纖維母細胞之傷害的效果之實驗結果。各實驗條件之誤差棒表示於同一條件下重複4次之實驗結果之測定值之標準偏差。又,星號(**)表示於Bonferroni檢驗中p未滿1。
於未照射UV之情形時,活細胞率約為95%,若藉由UV-A 22.5 J/cm2之照射而引起細胞傷害,則下降至約30%。然而,若添加D-脯胺酸,則活細胞率增大至約50%,減少細胞死亡。由以上之結果顯示,細胞傷害之減輕效果與在UV照射之前或之後實施D-脯胺酸處理並無關係。又,顯示出D-脯胺酸依存於濃度而減輕由纖維母細胞之UV-A所致之細胞傷害。
D-脯胺酸及D-麩胺酸之紫外線傷害減輕效果之比較方法
細胞係使用市售之人新生兒真皮纖維母細胞(Cryo NHDF-Neo,三光純藥),與實施例2中說明之方法同樣地培養。在研究於紫外線照射前添加D-脯胺酸或D-麩胺酸之處理之效果之情形時,於照射24小時前轉換為添加有0.1 μM之D-脯胺酸、或者1 μM之L-或D-麩胺酸之培養基。將不添加該等胺基酸之培養基下之紫外線照射作為對照。UV-A之紫外線照射(22.5 J/cm2)與利用alamarBlue(商標)之細胞傷害之定量與實施例2中說明之方法同樣地實施。
結果
於圖4中表示調查D-脯胺酸與L-或D-麩胺酸對於由UV-A 22.5 J/cm2之紫外線照射所致之纖維母細胞之傷害的效果之實驗結果。各實驗條件之誤差棒表示於同一條件下重複4次之實驗結果之測定值之標準偏差。又,星號(**)表示於Bonferroni/Dunn檢驗中p未滿1%。
螢光強度於對照中約為1100。又,添加D-脯胺酸、或者L-或D-麩胺酸之情形之螢光強度為約1750、約1100或約1700。由以上之結果顯示,D-脯胺酸及D-麩胺酸於統計學上有意義地減輕正常人真皮纖維母細胞由UV-A所致之細胞傷害。然而,L-麩胺酸未發現細胞傷害之減輕效果。再者顯示出,D-脯胺酸與D-麩胺酸相比較,以10分之1之濃度來減輕紫外線傷害。
L-及D-半胱胺酸之紫外線傷害減輕效果
細胞
細胞係使用市售之人新生兒表皮角化細胞(Cryo NHEK-Neo,三光純藥)。以達到1×105個/mL之方式將上述細胞播種於以市售之膠原蛋白I型覆蓋之35 mm直徑之培養皿(COL1,Asahi Techno Glass Corporation)中。於市售之無血清培養基(Defined Keratinocyte-SFM,Gibco公司,以下稱為「通常培養基3」)中添加增殖添加劑(Defined Keratinocyte-SFM Growth Supplement,Gibco公司)及抗生素(PSF:青黴素、鏈黴素及兩性黴素),於37℃、5% CO2及飽和水蒸氣環境下將上述細胞培養3天。其後,以添加有100 μM之D-丙胺酸、D-絲胺酸、D-羥基脯胺酸、D-天冬醯胺酸、D-半胱胺酸或L-半胱胺酸之2 mL之通常培養基3培養2天。作為對照,代替D-胺基酸將PBS添加至通常培養基3中。
紫外線照射
於UV-B照射前將培養基置換為PBS 1 mL。UV-B照射係使用自製之紫外光曝光裝置(紫外線螢光燈,Toshiba Medical Supply TOREX FL20S-E-30/DMR,2根),於除去培養皿之蓋之狀態下以25 J/cm2自該培養皿之40 cm上部照射280 nm至320 nm之紫外線而實施。紫外線量係使用UV RADIOMETER UVR-3036/S(TOPCON股份有限公司)來測定。
使用添加有100 μM之D-丙胺酸、D-絲胺酸、D-羥基脯胺酸、D-天冬醯胺酸、D-半胱胺酸或L-半胱胺酸之900 μL之通常培養基3,將經紫外線照射處理之細胞於37℃、5% CO2及飽和水蒸氣環境下培養24小時。
細胞傷害之定量
其後,根據實施例1中說明之方法測定螢光強度。
結果
於圖5中表示調查半胱胺酸對於由UV-B 25 mJ/cm2之紫外線照射所致之角質形成細胞之細胞傷害的效果之實驗結果。各實驗條件之誤差棒表示於同一條件下重複4次之實驗結果之測定值之標準偏差。又,星號(**)表示於學生t檢驗中p未滿1%。由UV-B照射所致之細胞傷害產生後之alamarBlue(商標)之螢光強度於添加有D-丙胺酸之情形約為570,於未添加D-丙胺酸之情形時約為550。添加有D-絲胺酸之情形之螢光強度約為490,未添加D-絲胺酸之情形之螢光強度約為500。添加有D-羥基脯胺酸之情形之螢光強度約為550,未添加D-羥基脯胺酸之情形之螢光強度約為550。添加有D-天冬醯胺酸之情形之螢光強度約為600,未添加D-天冬醯胺酸之情形之螢光強度約為600。添加有D-半胱胺酸之情形之螢光強度約為700,未添加D-半胱胺酸之情形之螢光強度約為600。添加有L-半胱胺酸之情形之螢光強度約為700,未添加L-半胱胺酸之情形之螢光強度約為600。由以上之結果顯示,半胱胺酸之L構型及D構型兩者均於統計學上有意義地減輕細胞傷害。
XP細胞中之紫外線傷害減輕效果
方法
使用自財團法人生命科學振興財團獲得之來源於著色性乾皮症(A群)之人真皮繊維芽細胞(XP30S(SVT),以下稱為「XP細胞」),與實施例3中說明之方法同樣地培養。0.1 μM之L-或D-麩胺酸、脯胺酸及半胱胺酸之前處理與細胞傷害之定量根據實施例3中說明之方法進行。又,UV-A照射係使用紫外光均勻曝光裝置UVE-502S+EL-160(三永電機製作所),於除去培養皿之蓋之狀態下以1 J/cm2自該培養皿之約20 cm上部照射320 nm至400 nm之紫外線而實施。紫外線量係使用UV RADIOMETER UVR-3036/S(TOPCON股份有限公司)來測定。
L-及D-麩胺酸之結果
於圖6中表示調查L-及D-麩胺酸對於由紫外線照射所致之纖維母細胞之傷害的效果之實驗結果。各實驗條件之誤差棒表示於同一條件下重複2次之實驗結果之測定值之標準偏差。
螢光強度於未照射紫外線且未添加胺基酸之條件(以下,稱為「紫外線非照射條件」)下約為690,於照射紫外線且未添加胺基酸之條件(以下,稱為「陰性對照」)下約為630。添加有0.1 μM之L-或D-麩胺酸之情形之螢光強度為約658或約675。由以上之結果顯示,L-及D-麩胺酸均減輕XP細胞之由UV-A所致之細胞傷害。
L-及D-脯胺酸之結果
於圖7中表示調查L-及D-脯胺酸對於由紫外線照射所致之纖維母細胞之傷害的效果之實驗結果。各實驗條件之誤差棒表示於同一條件下重複2次之實驗結果之測定值之標準偏差。
螢光強度於未照射紫外線之條件下約為690,於陰性對照中約為630。添加有0.1 μM之L-或D-脯胺酸之情形之螢光強度為約583或約664。由以上之結果顯示,D-脯胺酸減輕XP細胞之由UV-A所致之細胞傷害。
L-及D-半胱胺酸之結果
於圖8中表示調查L-及D-半胱胺酸對於由紫外線照射所致之纖維母細胞之傷害的效果之實驗結果。各實驗條件之誤差棒表示於同一條件下重複2次之實驗結果之測定值之標準偏差。
螢光強度於未照射紫外線之條件下約為690,於陰性對照中約為630。添加有0.1 μM之L-或D-半胱胺酸之情形之螢光強度為約688或約638。由以上之結果顯示,L-及D-半胱胺酸菌減輕XP細胞之由UV-A所致之細胞傷害。
根據本發明,包含選自由D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸或L-半胱胺酸等所組成之群中的1種或2種以上之化合物的乳液製劑、貼附劑、錠劑、軟膠囊、顆粒、飲料、糖果、曲奇、味噌、法式沙拉醬、蛋黃醬、法式麵包、醬油、酸乳飲料、香松、調味料‧納豆佐料汁、納豆、未過濾黑醋、霜劑、身體用潤膚霜、凝膠劑、撕除式面膜、含浸式面膜、乳液、化妝水及噴霧劑之調配例示於以下。該等調配例係以例示為目的而列舉者,並不限定本發明之範圍。
調配例1(乳液製劑)
調配例2(貼附劑)
調配例3(錠劑)
調配例4(錠劑)
調配例5(軟膠囊)
調配例6(軟膠囊)
調配例7(顆粒)
調配例8(飲料)
調配例9(基安蒂(Chianti))
調配例10(曲奇)
調配例10(曲奇)之製造方法
一邊攪拌奶油一邊緩緩添加砂糖,添加雞蛋及香料、與L-或D-麩胺酸鈉、或D-脯胺酸、或者L-或D-半胱胺酸並加以攪拌。充分地混合後,添加經均勻地振動之低筋麵粉並以低速攪拌,以塊狀於冰箱中醱酵。其後,成型並於170℃烘烤15分鐘而製成曲奇。
調配例11(味噌)
調配例11(味噌)之製造方法
將米麴與鹽充分地混合。將洗淨之大豆於3倍量之水中放置一晚後除去水,一邊添加新的水一邊煮,用笊籬過濾。收集煮汁(種水),以達到10% w/v之方式溶解L-或D-麩胺酸、或D-脯胺酸、或者L-或D-半胱胺酸。將煮熟的豆子立即磨碎,添加至混合有鹽之米麹中,一邊補充溶解有上述L-或D-麩胺酸、或D-脯胺酸、或者L-或D-半胱胺酸之種水,一邊均勻地混合直至達到黏土之堅硬程度。將團成團子狀者以無間隙之方式緊密地塞入桶之各個角落,整平表面且以保鮮膜覆蓋並密封。3個月後更換容器,整平表面並以保鮮膜覆蓋。再者,亦可使用產生較多L-或D-麩胺酸、或D-脯胺酸、或者L-或D-半胱胺酸之米麹來代替將L-或D-麩胺酸、或D-脯胺酸、或者L-或D-半胱胺酸添加至種水中。為獲得上述米麹,可藉由以日本專利特開2008-185558中記載之方法定量L-或D-麩胺酸、或D-脯胺酸、或者L-或D-半胱胺酸來挑選。又,亦可於市售之味噌中添加D-麩胺酸、L-麩胺酸、D-脯胺酸、D-半胱胺酸或L-半胱胺酸、或該等之鹽。
調配例12(法式沙拉醬)
調配例12(法式沙拉醬)之製造方法
向醋中添加氯化鈉與L-或D-麩胺酸、或D-脯胺酸、或者L-或D-半胱胺酸後,充分地攪拌並溶解。添加沙拉油並充分地攪拌,添加胡椒。
調配例13(蛋黃醬)
調配例13(蛋黃醬)之製造方法
向雞蛋黃(室溫)中添加醋、氯化鈉及胡椒與L-或D-麩胺酸、或D-脯胺酸、或者L-或D-半胱胺酸,利用起泡器充分地攪拌。一邊一點一點地添加沙拉油一邊繼續攪拌而製成乳劑。最後添加砂糖並攪拌。
調配例14(法式麵包)
調配例14(法式麵包)之製造方法
於溫水中放入砂糖1 g及乾酵母使之預備醱酵。將高筋麵粉、低筋麵粉、氯化鈉及砂糖5 g與L-或D-麩胺酸鈉、或D-脯胺酸、或者L-或D-半胱胺酸放入盆中,向其中加入經預備醱酵之酵母。充分地捏合後製成球狀,使之於30℃進行一次醱酵。再次捏合生麵團後使之醒置,其後整形為適當之形狀,使用電子醱酵機進行最終醱酵。切開並以220℃之烘箱烘烤30分鐘。
調配例15(醬油)
調配例16(醬油)
調配例15及16(醬油)之製造方法
於市售之醬油中添加L-或D-麩胺酸鈉、或D-脯胺酸、或者L-或D-半胱胺酸並充分地攪拌。又,亦可使用產生較多L-或D-麩胺酸鈉、或D-脯胺酸、或者L-或D-半胱胺酸之麹來代替添加L-或D-麩胺酸鈉、或D-脯胺酸、或者L-或D-半胱胺酸或其鹽,而釀造醬油。為獲得上述麹,可藉由以日本專利特開2008-185558中記載之方法定量L-或D-麩胺酸鈉、或D-脯胺酸、或者L-或D-半胱胺酸來挑選。又,亦可於市售之醬油中添加D-麩胺酸鈉、L-麩胺酸鈉、D-脯胺酸、D-半胱胺酸或L-半胱胺酸、或該等之鹽。
調配例17(酸乳飲料)
調配例17(酸乳飲料)之製造方法
使之於40℃~45℃醱酵。既可使用其他市售之種菌,亦可於市售之酸乳飲料中添加L-或D-麩胺酸鈉、或D-脯胺酸、或者L-或D-半胱胺酸。又,亦可使用產生較多L-或D-麩胺酸鈉、或D-脯胺酸、或者L-或D-半胱胺酸之菌來代替添加L-或D-麩胺酸鈉、或D-脯胺酸、或者L-或D-半胱胺酸或其鹽。為獲得上述菌,可藉由以日本專利特開2008-185558中記載之方法定量L-或D-麩胺酸鈉、或D-脯胺酸、或者L-或D-半胱胺酸來挑選。又,亦可於市售之酸乳飲料中添加D-麩胺酸鈉、L-麩胺酸鈉、D-脯胺酸、D-半胱胺酸或L-半胱胺酸、或該等之鹽。
調配例18(香松)
調配例19(調味料‧納豆佐料汁)
調配例20(調味料‧納豆佐料汁)
調配例21(納豆)
調配例21(納豆)之製造方法
於市售之納豆中添加L-或D-麩胺酸鈉、或D-脯胺酸、或者L-或D-半胱胺酸並充分地攪拌。亦可使用產生較多L-或D-麩胺酸鈉、或D-脯胺酸、或者L-或D-半胱胺酸之菌來代替添加L-或D-麩胺酸鈉、或D-脯胺酸、或者L-或D-半胱胺酸或其鹽,而製作納豆。為獲得上述菌,可藉由以日本專利特開2008-185558中記載之方法定量L-或D-麩胺酸鈉、或D-脯胺酸、或者L-或D-半胱胺酸來選拔。又,亦可於市售之納豆中添加D-麩胺酸鈉、L-麩胺酸鈉、D-脯胺酸、D-半胱胺酸或L-半胱胺酸、或該等之鹽。
調配例22(未過濾黑醋)
調配例23(未過濾黑醋)
調配例22及23(未過濾黑醋)之製造方法
於市售之未過濾黑醋中添加L-或D-麩胺酸、或D-脯胺酸、或者L-或D-半胱胺酸並充分地攪拌。亦可使用產生較多L-或D-麩胺酸、或D-脯胺酸、或者L-或D-半胱胺酸之菌來代替添加L-或D-麩胺酸、或D-脯胺酸、或者L-或D-半胱胺酸或其鹽,而製作醋、黑醋、醪糟。為獲得上述菌,可藉由日本專利特開2008-185558中記載之方法定量L-或D-麩胺酸、或D-脯胺酸、或者L-或D-半胱胺酸來挑選。又,亦可於市售之未過濾黑醋中添加D-麩胺酸、L-麩胺酸鈉、D-脯胺酸、D-半胱胺酸或L-半胱胺酸、或該等之鹽。
調配例24(霜劑)
調配例25(身體用潤膚霜)
調配例26(凝膠劑)
調配例27(撕除式面膜)
調配例28(含浸式面膜)
調配例29(乳液)
調配例30(乳液)
調配例31(化妝水)
調配例32(化妝水)
調配例33(噴霧尿素外用劑原液)
調配例34(噴霧尿素噴射劑)
調配例34(噴霧尿素噴射劑)之充填方法
將噴霧尿素外用劑原液及二甲醚填充至內面經特氟綸(註冊商標)塗佈處理之耐壓噴霧鋁罐中而製備噴霧劑。
圖1為表示正常人表皮角化細胞中之D-麩胺酸處理之效果之圖表。
圖2為表示正常人真皮纖維母細胞中之紫外線照射後之D-脯胺酸處理之效果之圖表。
圖3為表示正常人真皮纖維母細胞中之紫外線照射前之D-脯胺酸處理之效果之圖表。
圖4為表示正常人真皮纖維母細胞中之紫外線照射前之D-脯胺酸處理及麩胺酸處理之效果之圖表。
圖5為表示正常人表皮角化細胞中之半胱胺酸處理之效果之圖表。
圖6為表示XP細胞中之L-及D-麩胺酸處理之效果之圖表。
圖7為表示XP細胞中之L-及D-脯胺酸處理之效果之圖表。
圖8為表示XP細胞中之L-及D-半胱胺酸處理之效果之圖表。
(無元件符號說明)
Claims (4)
- 一種用於製造紫外線傷害減輕用組合物之化合物之用途,該化合物為選自由D-麩胺酸、D-脯胺酸、與該等之鹽所組成之群中的1種或2種以上之化合物。
- 如請求項1之用途,其中上述化合物包含選自由D-麩胺酸、與其鹽所組成之群中的1種或2種以上之化合物。
- 如請求項1或2之用途,其中上述紫外線傷害減輕用組合物為抗皺劑。
- 如請求項1或2之用途,其中上述紫外線傷害減輕用組合物為防曬劑。
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Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012057084A1 (ja) * | 2010-10-25 | 2012-05-03 | キリン協和フーズ株式会社 | 風味改良剤 |
CN104363772B (zh) * | 2012-05-01 | 2019-02-12 | Mc食品科技株式会社 | 风味改良剂 |
WO2014058084A1 (ko) * | 2012-10-09 | 2014-04-17 | 주식회사 바이오리더스 | 감마올리고펩타이드 또는 그 염을 함유하는 주름개선용 화장료 조성물 |
JP6346596B2 (ja) * | 2015-08-31 | 2018-06-20 | 株式会社ミルボン | 毛髪変形用第1剤、及び毛髪変形処理方法 |
WO2018114745A1 (en) | 2016-12-21 | 2018-06-28 | Unilever Plc | Personal care compositions comprising poorly soluble compounds |
CN110121330B (zh) | 2016-12-21 | 2022-04-29 | 联合利华知识产权控股有限公司 | 具有包含4-取代的间苯二酚和氨基酸的谷胱甘肽前体的个人护理组合物 |
EA201991185A1 (ru) | 2016-12-21 | 2020-01-13 | Юнилевер Н.В. | Композиции для личной гигиены, содержащие цистин |
CA3047495A1 (en) | 2016-12-21 | 2018-06-28 | Unilever Plc | Topical skin lightening additive and composition with amino acids and nicotinamide compounds |
EP3603612A4 (en) * | 2017-03-24 | 2020-08-12 | Ajinomoto Co., Inc. | AGENT IMPROVING THE FUNCTIONS OF THE CORNEAL LAYER |
JP6493703B1 (ja) * | 2017-09-28 | 2019-04-03 | ウシオ電機株式会社 | 殺菌方法、殺菌装置 |
JP7467138B2 (ja) | 2020-01-30 | 2024-04-15 | 株式会社 資生堂 | 腸管バリア改善剤 |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW222591B (zh) | 1991-08-30 | 1994-04-21 | Procter & Gamble | |
US5296500A (en) | 1991-08-30 | 1994-03-22 | The Procter & Gamble Company | Use of N-acetyl-cysteine and derivatives for regulating skin wrinkles and/or skin atrophy |
AU675778B2 (en) * | 1991-11-27 | 1997-02-20 | Bioresearch Inc. | Specific eatable taste modifiers |
US6197317B1 (en) * | 1997-08-11 | 2001-03-06 | Marvin E. Klein | Composition and method for the treatment of skin |
JPH11286442A (ja) | 1998-04-01 | 1999-10-19 | Ajinomoto Co Inc | 炎症因子活性化抑制剤 |
EP1120407B1 (en) | 1998-10-09 | 2013-02-20 | Ajinomoto Co., Inc. | Cystine derivatives |
JP2001097888A (ja) * | 1999-09-28 | 2001-04-10 | Hiroshi Ikeno | 外用組成物 |
JP2002047178A (ja) * | 2000-08-03 | 2002-02-12 | Noevir Co Ltd | I型マトリックスメタロプロテアーゼ産生阻害剤 |
JP3983003B2 (ja) * | 2001-03-15 | 2007-09-26 | 株式会社ファンケル | グルタチオン増強用組成物 |
EP1521735A2 (en) | 2001-05-25 | 2005-04-13 | Ceremedix, Inc | Single amino acid based compounds for counteracting effects of reactive oxygen species and free radicals |
WO2003088909A2 (en) | 2002-04-19 | 2003-10-30 | University Of Arizona | Methods for modulating phototoxicity |
JP2005343880A (ja) * | 2004-06-02 | 2005-12-15 | Ito:Kk | レドックス制御組成物 |
EP1815245B1 (en) | 2004-11-15 | 2010-04-21 | Erasmus MC | Prematurely ageing mouse models for the role of dna damage in ageing and intervention in ageing-related pathology |
KR100628413B1 (ko) * | 2005-12-29 | 2006-09-26 | 주식회사 바이오리더스 | 폴리감마글루탐산―비타민c 복합체를 함유하는 콜라게나제저해제 및 그 용도 |
US20080070993A1 (en) * | 2006-09-07 | 2008-03-20 | Janos Borbely | Additives for cosmetic products and the like |
JP4980740B2 (ja) | 2007-01-31 | 2012-07-18 | 株式会社 資生堂 | 2次元液体クロマトグラフィー分析方法および分取用流路切り替えユニット |
JP2008285472A (ja) * | 2007-04-16 | 2008-11-27 | Sapporo Breweries Ltd | 細胞外マトリックス分解酵素阻害剤 |
DE102007038413A1 (de) * | 2007-08-09 | 2009-02-12 | Beiersdorf Ag | Kosmetische Emulgatorkombination |
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2010
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- 2010-03-30 AU AU2010231598A patent/AU2010231598A1/en not_active Abandoned
- 2010-03-30 BR BRPI1009796A patent/BRPI1009796A2/pt not_active Application Discontinuation
- 2010-03-30 RU RU2011143736/15A patent/RU2519206C2/ru not_active IP Right Cessation
- 2010-03-30 TW TW099109837A patent/TWI527584B/zh not_active IP Right Cessation
- 2010-03-30 ES ES10758696.8T patent/ES2638046T3/es active Active
- 2010-03-30 WO PCT/JP2010/055648 patent/WO2010113925A1/ja active Application Filing
- 2010-03-30 EP EP10758696.8A patent/EP2415468B1/en active Active
- 2010-03-30 CN CN2010800141315A patent/CN102365086A/zh active Pending
- 2010-03-30 JP JP2011507201A patent/JP5727364B2/ja not_active Expired - Fee Related
- 2010-03-30 US US13/138,786 patent/US8735442B2/en active Active
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Also Published As
Publication number | Publication date |
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EP2415468A1 (en) | 2012-02-08 |
WO2010113925A1 (ja) | 2010-10-07 |
CN102365086A (zh) | 2012-02-29 |
US20120142941A1 (en) | 2012-06-07 |
US8735442B2 (en) | 2014-05-27 |
EP2415468A4 (en) | 2014-08-20 |
JP2015134790A (ja) | 2015-07-27 |
BRPI1009796A2 (pt) | 2016-08-23 |
JP5727364B2 (ja) | 2015-06-03 |
ES2638046T3 (es) | 2017-10-18 |
RU2011143736A (ru) | 2013-05-10 |
KR20120027156A (ko) | 2012-03-21 |
AU2010231598A1 (en) | 2011-11-10 |
JP5934405B2 (ja) | 2016-06-15 |
RU2519206C2 (ru) | 2014-06-10 |
EP2415468B1 (en) | 2017-07-05 |
JPWO2010113925A1 (ja) | 2012-10-11 |
TW201039858A (en) | 2010-11-16 |
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