JP2018062499A - 外用組成物 - Google Patents
外用組成物 Download PDFInfo
- Publication number
- JP2018062499A JP2018062499A JP2016235795A JP2016235795A JP2018062499A JP 2018062499 A JP2018062499 A JP 2018062499A JP 2016235795 A JP2016235795 A JP 2016235795A JP 2016235795 A JP2016235795 A JP 2016235795A JP 2018062499 A JP2018062499 A JP 2018062499A
- Authority
- JP
- Japan
- Prior art keywords
- composition
- skin
- hyaluronic acid
- acid
- external use
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 69
- 229920002674 hyaluronan Polymers 0.000 claims abstract description 77
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims abstract description 66
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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 claims abstract description 24
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Abstract
Description
[項1] ヒアルロン酸、その誘導体、及びそれらの塩からなる群より選択される少なくとも1種を有効成分として含有する、皮膚への紫外線ダメージの予防又は改善のための外用組成物。
[項2] 皮膚への紫外線ダメージの予防又は改善が、紫外線曝露による皮膚の炎症を予防又は改善することを含む、項1に記載の外用組成物。
[項3] 紫外線が紫外線B波である、項1又は2に記載の外用組成物。
[項4] 皮膚への紫外線ダメージの予防又は改善が、紫外線曝露による皮膚の炎症に起因するメラニン産生の誘発を予防又は改善することを含む、項1〜3のいずれかに記載の外用組成物。
[項5] 皮膚への紫外線ダメージの予防又は改善が、紫外線曝露による表皮角化細胞におけるPGE2及びIL−1αからなる群より選択される少なくとも1種の産生を抑制することによるものである、項1〜4のいずれかに記載の外用組成物。
[項6] ヒアルロン酸の平均分子量が0.1〜700kDaである、項1〜5のいずれかに記載の外用組成物。
[項7] 更に、トラネキサム酸、その誘導体、及びそれらの塩からなる群より選択される少なくとも1種を有効成分として含有する、項1〜6のいずれかに記載の外用組成物。
[項8] ヒアルロン酸、その誘導体、及びそれらの塩からなる群より選択される少なくとも1種の成分の総量1重量部に対して、トラネキサム酸、その誘導体、及びそれらの塩からなる群より選択される少なくとも1種の成分の総量が0.05〜4000重量部である、項7に記載の外用組成物。
本発明の皮膚への紫外線ダメージの予防又は改善のための外用組成物は、ヒアルロン酸、その誘導体、及びそれらの塩からなる群より選択される少なくとも1種(以下、ヒアルロン酸類ともいう)を有効成分として含有することを特徴とする。
ヒアルロン酸は、酸性ムコ多糖類の一種であり、グルクロン酸とN−アセチルグルコサミンの二糖を構成単位として含む多糖類である。ヒアルロン酸は、鶏冠や、サメの皮、臍帯、眼球、皮膚、及び軟骨などの動物組織、ストレプトコッカス属微生物等のヒアルロン酸生産微生物、動物細胞もしくは植物細胞の培養物から抽出、回収することができる。また、市販品を購入することもできる。
本発明の外用組成物には、上記ヒアルロン酸類に加えて、トラネキサム酸、その誘導体、及びそれらの塩からなる群より選択される少なくとも1種(以下、トラネキサム酸類ともいう)を更なる有効成分として配合してもよい。とりわけ、ヒアルロン酸の平均分子量が350kDa以下である低分子ヒアルロン酸類を用いる場合には、トラネキサム酸類を組み合わせて用いることで両成分の作用が相俟って、より一層高い皮膚への紫外線ダメージ抑制効果が得られることが分かっている。
前述のように、ヒアルロン酸、その誘導体、及びそれらの塩からなる群より選択される少なくとも1種を有効成分として用いることにより、皮膚への紫外線ダメージを効果的に抑制できることが確認されている。
従って、本発明は更に別の観点から、皮膚への紫外線ダメージの予防又は改善のための外用組成物の製造における、ヒアルロン酸、その誘導体、及びそれらの塩からなる群より選択される少なくとも1種の使用をも提供する。特定の実施形態では、上記使用において、上記ヒアルロン酸類と共に、トラネキサム酸、その誘導体、及びそれらの塩からなる群より選択される少なくとも1種を併用することが好ましい。
より具体的に、上記の使用の態様において、使用される成分の種類やその配合割合、他に配合され得る他の成分やその配合割合、使用方法等については、上記「(1.外用組成物)」と同様である。
前述のように、ヒアルロン酸、その誘導体、及びそれらの塩からなる群より選択される少なくとも1種を有効成分として用いることにより、皮膚への紫外線ダメージを効果的に抑制できることが確認されている。
従って、本発明は更に別の観点から、ヒアルロン酸、その誘導体、及びそれらの塩からなる群より選択される少なくとも1種を皮膚に適用することにより、皮膚への紫外線ダメージを予防又は改善する方法をも提供する。特定の実施形態では、上記方法において、ヒアルロン酸類と共に、トラネキサム酸、その誘導体、及びそれらの塩からなる群より選択される少なくとも1種を併用することが好ましい。
より具体的に、上記の方法の態様において、使用される成分の種類やその配合割合、他に配合され得る他の成分やその配合割合、使用方法等については、上記「(1.外用組成物)」と同様である。
下記の方法に従い、UVB曝露後の表皮角化細胞におけるPGE2産生抑制効果について評価を行った。
まず、ヒト正常表皮角化細胞(NHEK)を、6ウェルカルチャープレート中で培養した。より詳細には、3.0×105細胞/ウェルの密度でプレートに播種し、37℃で、5%炭酸ガスおよび95%空気の環境下で1日間培養を行った。培養液としては、Humedia−KB2(倉敷紡績製)に10μg/mLのインスリン及び0.67μg/mLのハイドロコーチゾンを添加した培地を各ウェルあたり2mLずつ使用した。次いで、培養液を除去し、2mLのPBS(−)(コージンバイオ株式会社製)に培地交換した後、表皮角化細胞に対してUVBを照射した。UVB照射は、紫外線照射装置(デルマレイ−200;東芝医療用品株式会社製)を用いて、培養プレートの蓋を除去した状態で該培養プレートに25mJ/cm2でUVBを照射することで実施した。UVB照射後、PBS(−)を除去し、下記表1の実施例1〜3に示す各種のヒアルロン酸を0.001w/v%となるように添加して溶解した2mLの前記培養液に交換して3日間培養した。コントロール(比較例1)として、ヒアルロン酸を含まない以外は同様にして2mLの前記培養液に交換して培養したものを用意した。3日間培養した後、培養液を採取し、培養液中に分泌されたPGE2濃度を酵素結合免疫測定法(PGE2 high sensitivity ELISA kit;Enzo Life Sciences社製)で定量した。なお、下記表1に示す本試験例で用いた各ヒアルロン酸1〜3は全て、Aldrich製の試薬を用いた。この結果として、各実施例及び比較例の定量値から算出した平均値を、表1及び図1に示す。
上記試験例1と実質的に同様の方法で、UVB曝露後の表皮角化細胞におけるPGE2産生抑制試験を実施した。
本試験例では、下記表2に示す被験薬を用いて試験を行った。本試験例で用いた各ヒアルロン酸1〜3は、試験例1で使用したものと同じである。同じ平均分子量のヒアルロン酸をのみを含む実施例(実施例4、6、8)を用いた場合のPGE2産生量に対する、トラネキサム酸を組み合わせた場合の実施例(実施例5、7、9)を用いたときのPGE2産生量の割合を百分率(%)として、表2に結果を併せて示す。
下記の方法に従い、UVB曝露後の表皮角化細胞におけるIL−1α産生抑制効果について評価を行った。
まず、ヒト正常表皮角化細胞(NHEK)を、6ウェルカルチャープレート中で培養した。より詳細には、3.0×105細胞/ウェルの密度でプレートに播種し、37℃で、5%炭酸ガスおよび95%空気の環境下で1日間培養を行った。培養液としては、Humedia−KB2(倉敷紡績製)に10μg/mLのインスリン及び0.67μg/mLのハイドロコーチゾンを添加した培地を各ウェルあたり2mLずつ使用した。次いで、培養液を除去し、2mLのPBS(−)(コージンバイオ株式会社製)に培地交換した後、表皮角化細胞に対してUVBを照射した。UVB照射は、紫外線照射装置(デルマレイ−200;東芝医療用品株式会社製)を用いて、培養プレートの蓋を除去した状態で該培養プレートに25mJ/cm2でUVBを照射することで実施した。UVB照射後、PBS(−)を除去し、下記表3の実施例10〜12に示す各種のヒアルロン酸を0.001w/v%となるように添加して溶解した2mLの前記培養液に交換して3日間培養した。コントロール(比較例2)として、ヒアルロン酸を含まない以外は同様にして2mLの前記培養液に交換して培養したものを用意した。3日間培養した後、培養液を採取し、培養液中に分泌されたIL−1α濃度を酵素結合免疫測定法(Quantikine ELISA Human IL−1α/IL−1F1;R&D社製)で定量した。なお、下記表3に示す本試験例で用いた各ヒアルロン酸1〜3は、試験例1で使用したものと同じである。この結果として、各実施例及び比較例の定量値から算出した平均値を、表3に併せて示す。
下記の方法に従い、UVB曝露後の正常ヒト皮膚3次元モデルにおけるPGE2産生抑制効果について評価を行った。
まず、正常ヒト皮膚3次元モデル EPI−200(倉敷紡績製)を、6ウェルカルチャープレート中で培養した。より詳細には、培養液としてEPI−100NMM(倉敷紡績製)を各ウェルあたり5mLずつ使用し、37℃で、5%炭酸ガスおよび95%空気の環境下で1日間培養を行った。次いで、各ウェルあたり0.9mLのPBS(−)(コージンバイオ株式会社製)を入れた6ウェルカルチャープレートにヒト皮膚3次元モデルを移した後、UVBを照射した。UVB照射は、紫外線照射装置(デルマレイ−200;東芝医療用品株式会社製)を用いて、プレートの蓋を除去した状態で該培養プレートに120mJ/cm2でUVBを照射することで実施した。次いで、EPI−100NMM培養液を各ウェルあたり5mLずつ入れた新しい6ウェルカルチャープレートに、UVB照射後の各ヒト皮膚3次元モデルを移した。この角層側に、下記表4に示す各種の被験薬(実施例13〜15)を添加して溶解した200μLのPBS(+)(Aldrich製)を添加し、1日毎に被験薬溶液を交換して3日間培養した。コントロール(比較例3)として、被験薬を含まない以外は同様にして200μLのPBS(+)で1日毎に液交換して3日間培養したものも用意した。3日間培養後に培養液を採取し、培養液中に分泌されたPGE2濃度を酵素結合免疫測定法(PGE2 high sensitivity ELISA kit;Enzo Life Sciences社製)で定量した。なお、本試験例で用いたヒアルロン酸1は、試験例1で使用したものと同じである。各実施例及び比較例の定量値から算出した平均値の結果を表4に示す。
Claims (8)
- ヒアルロン酸、その誘導体、及びそれらの塩からなる群より選択される少なくとも1種を有効成分として含有する、皮膚への紫外線ダメージの予防又は改善のための外用組成物。
- 皮膚への紫外線ダメージの予防又は改善が、紫外線曝露による皮膚の炎症を予防又は改善することを含む、請求項1に記載の外用組成物。
- 紫外線が紫外線B波である、請求項1又は2に記載の外用組成物。
- 皮膚への紫外線ダメージの予防又は改善が、紫外線曝露による皮膚の炎症に起因するメラニン産生の誘発を予防又は改善することを含む、請求項1〜3のいずれかに記載の外用組成物。
- 皮膚への紫外線ダメージの予防又は改善が、紫外線曝露による表皮角化細胞におけるPGE2及びIL−1αからなる群より選択される少なくとも1種の産生を抑制することによるものである、請求項1〜4のいずれかに記載の外用組成物。
- ヒアルロン酸の平均分子量が0.1〜700kDaである、請求項1〜5のいずれかに記載の外用組成物。
- 更に、トラネキサム酸、その誘導体、及びそれらの塩からなる群より選択される少なくとも1種を有効成分として含有する、請求項1〜6のいずれかに記載の外用組成物。
- ヒアルロン酸、その誘導体、及びそれらの塩からなる群より選択される少なくとも1種の成分の総量1重量部に対して、トラネキサム酸、その誘導体、及びそれらの塩からなる群より選択される少なくとも1種の成分の総量が0.05〜4000重量部である、請求項7に記載の外用組成物。
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