JP4150501B2 - Composition with high efficiency skin protection from the damaging effects of ultraviolet light - Google Patents

Description

【００３０】
“シリコン”又は“ポリオルガノシロキサン”は、例えば、Remington(レミントン):「The Science and Practice of Pharmacy(調剤の科学と実技)」、第19版、第867-868頁に記載されるように、及び下記に示すように、酸素及びケイ素原子が交互に繰り返す鎖で、各ケイ素原子に付着する、メチル又はフェニルであることが多い、有機置換基を有する。
【化２】

【００３１】
特定の態様においては、乳化剤は非揮発性シリコン油、例えば、ポリシロキサンポリアルキルポリエーテル・コポリマーで、コポリオール類という名でも知られ、10,000から50,000の分子量を持ち、それらは、例えば、参考として本明細書に組み込む、米国特許第5,746,945号、及び次の
【化３】

(式中、R′基は、それぞれ、-H及びC_1-18アルキルから選ばれ、R″は、[CH₂CH₂O]_a[CH₂(CH₂)CHO]_bHであって、ここに、aは9から115、bは0から50、xは133-673で、yは0.25から25である。)に開示してある。特定の態様では、aは14、bは13、xは249で、yは1.25である。
【００３２】
乳化剤にはまた、米国特許出願第5,659,523号に開示され、これを参考として組み込むもののような、アルキル−及びアルコキシ−ジメチコンコポリオール類から選ばれるジメチコンが包含される。特に好ましいコポリオールは、T.H. GoldschmidtからAbil EM-90、又はAbil WE-90(これも、ポログリセリル-4-イソステアレート及びラウリン酸ヘキシルを含む)として入手し得るセチルジメチコンコポリオールである。
【００３３】
“水性”の用語は、組成物が実質的に非含水性ではないことを意味する。乳剤は、少なくとも2種の互いに混じり合わない液相を含む分散系である。水が分散相であり、油が分散媒体である乳剤は“油中水型”乳剤である。“水性乳剤”は水をその相の1種として含む乳剤を指す。
【００３４】
“日光遮蔽剤”は、(例えば)提案書に記載する方法で測定されるように、有効量において、紫外線への暴露を阻止することによって皮膚発赤の量を低減させる薬剤である。日光遮蔽剤は、UV-B型紫外放射又はUV-A型紫外線のいずれか、又は双方に対して保護し得る。特に開示する態様では、日光遮蔽剤は、有害な紫外線を効率的に吸収する芳香族化合物(オキシベンゾン及びケイ皮酸誘導体のようなもの)で、ZnO又はTiO₂、又は組成物中の抗酸化剤の安定性において有害作用を持つことがある他の金属酸化物のような粒状日焼け止め剤を実質的に含まない。組成物の特定の態様はまた、安定性に有害作用を持ち得る銅又は鉄をも排除する。
【００３５】
典型的に好適なUV-B型日光遮蔽剤には、置換パラアミノベンゾエート、例えば、N.J.(ニュージャージー州)07109、Belleville(ベルビル)所在のVan Dyk(バンダイク)& Co. Inc.(社)から、商品名Escalol(エスカロール)507の下で入手可能で、通常、約0から8重量%までの範囲(例えば1.5から8重量%まで)で存在するオクチルジメチルPABA；パラメトキシシナメートのアルキルエステル、例えば、N.J.07104、Clifton(クリフトン)所在のGivaudan Corp.(ギバウダン社)から、商品名Parasol(パラソル) MCXの下で入手可能で、通常、約0から7.5重量%まで(例えば、1.5から7.5重量%まで)の範囲で存在するオクチルパラメトキシシナメート；サリチル酸の一定のエステル、例えば、通常、約0から15重量%まで(例えば、4から15重量%まで)の範囲で存在するホモメンチルサリチレート又は通常、約0から5重量%まで(例えば、3から5重量%まで)の範囲で存在するオクチルサリチレートが包含される。(すべての重量%は総日焼け止め剤組成物の重量割合である。)
【００３６】
典型的に適切なUV-A型日光遮蔽剤には、ベンゾフェノン-3で、組成物中に通常、約0から6%までの範囲(例えば、0.5から6%まで)で存在し、及びN.J.07470、Wayne(ウェーン)所在のAmerican Cyanamid Co.(アメリカン・サイアナミッド社)から商品名Spectra-Sorb(スペクトラ・ソルブ) UV-9の下で入手可能なもの；ベンゾフェノン-8で、組成物中に通常、0から3重量%までの範囲(例えば、0.5から3重量%まで)で存在し、及びAmerican Cyanamid Co.から、商品名Spectra-Sorb UV-24の下で入手可能なもの；及びメンチルアントラニレートで、組成物中に通常、約0から5重量%まで(例えば、3.5から5重量%まで)の範囲で存在し、及びHaarmann and Reimer(ハールマン・アンド・ライマー)(N.J.)から商品名Sunarome(サンアロメ) UVAの下で入手可能なものが包含される。
【００３７】
本発明の組成物は好ましくは、少なくとも1種のUV-B型日光遮蔽剤及び少なくとも1種のUV-A型日光遮蔽剤を含む。本発明の組成物は更に、香料、防腐剤、染料、軟化剤、物理的反射剤及び他の抗酸化剤、並びにその存在が化粧上又は他にとって望ましい任意の他のクラスの物質をも含んでよい。
【００３８】
他の抗酸化剤には、没食子酸のプロピル、オクチル及びドデシルのエステル、ブチル化ヒドロキシアニソール(通常、オルト及びメタ異性体の混合物として)、ブチル化ヒドロキシトルエン及びノルジヒドログアヤレット酸が包含される。典型的に好適な防腐剤には、パラヒドロベンゾエート(パラベン)の低級アルキルエステル、特に、メチルパラベン、エチルパラベン、プロピルパラベン、ブチルパラベン、イソブチルパラベン及びそれらの混合物、及び安息香酸が包含される。典型的に好適な香料には、すべての油溶性香料又は芳香剤又は当業者に良く知られる香料又は芳香剤の混合物が包含される。典型的に好適な物理的反射剤には、タルク、カオリン、白亜、沈降シリカ、酸化亜鉛、及び二酸化チタンが包含される。
【００３９】
本発明の組成物は、液体、ゲル又は半固形の形であってよい。組成物の種類及び量の選定は、組成物の性質、即ちゲルや半固形によって定められるが、化粧品化学者の技量の範囲内にある。例えば、液体組成物物におけるよりもより一層大量のワックスが、本発明にかかる半固形組成物の中に含められる。
【００４０】
“少なくとも1種の防水剤の防水有効量”の用語は、ある防水剤を用いる場合に、その防水剤(防水剤群)が組成物中に少なくとも0.3%の濃度で、及び例えば、0.3-3%の範囲で存在することを意味する。典型的に好適な防水剤には、オクダデセン-1及び無水マレイン酸の重合から、例えば、米国特許第3,860,700号に開示されるような方法によって導かれる共重合体が包含される。特定の防水剤は、Chevron Chemicals Co.(シェブロン・ケミカルズ社)から商品名PA-18ポリアンヒドリド樹脂の下で商業上入手可能な共重合体である。他には、PVP/Epicosene(エピコセン)共重合体、PVP/Hexadecene(ヘキサデセン)共重合体、及びPVA/VA共重合体が包含され、いずれも、N.J、WayneのGAFから入手可能である。
【００４１】
典型的に好適な化粧ワックスには、オゾケライト、ラノリンアルコール、パラフィンワックス、ベイベリーワックス、ポリエチレンワックス、特に、N.J.、Morristown(モリスタウン)所在のAllied-Signal Corp.(アライドゥ-シグナル社) から入手可能なAC617；Polawax(ポーラワックス)[N.Y.(ニューヨーク州)10016、ニューヨーク所在のCroda, Inc.(クロダ社)から入手可能な高級脂肪アルコール及びエチレンオキシドの反応生成物]、トリヒドロキシステアリン、ラノリンワックス、蜜蝋、カンデリラワックス、微細結晶ワックス、カルナバワックス、セチルアルコール、ステアリルアルコール、鯨蝋、ココアバター、ラノリンの脂肪酸、モノ-、ジ-及びトリ-ベヘネート(ベヘン酸及びグリセリンのトリエステル)及びC₁₈-C₃₆酸トリグリセリド(C₁₈-C₃₆カルボン酸及びグリセリンのトリエステルの混合物)で、Croda, Inc、ニューヨーク、N.Y.から、それぞれ、商品名Syncowax(シンコワックス)HRC及びSyncowax HGL-Cの下で入手可能なもの、25℃で固形の脂肪エステル、メチルオクタデカンオキシポリシロキサン及びポリ(ジメチルシロキシ)ステアロキシシロキサンのようなシリコンワックス、ステアリルモノ-及びジ-エタノールアミン、ロージン、及びグリコール及びグリセロールのアビエテートのようなその誘導体、25℃で固化する水素化油、及びスクログリセリドが包含される。
【００４２】
さらに揮発性シリコン油を含む態様には、Dow Corning(ダウ・コーニング)344 Fluid(液)、Dow Corning 345液、Dow Corning 244液、及びDow Corning 245；並びにCT.(コネティカット州)、Danbury(ダンベリー)所在のUnion Carbide Corp.(ユニオン・カーバイド社)の商品名、Volatile Silicone(揮発性シリコン)7207のようなシクロメチコン、低粘度ジメチコン、即ち約50cst未満の粘度を持つジメチコン、特に、Dow Corning 0.5-200cst 液[Midland(ミッドランド)、ミシガン州]のようなジメチコンが包含される。シクロメチコン及びジメチコンは、それぞれ、環状ジメチルポリシロキサン化合物及びトリメチルシロキシ単位で末端ブロックされた完全メチル化直鎖シロキサン重合体に対して、CTFA化粧品成分辞書(Cosmetic Ingredient Dictionary)の第3版が与えた名称である。他の低い蒸発熱を持つ揮発性シリコン油で、General Electric Co.(ジェネラルエレクトリック社)、シリコン製品部、Waterford(ウォーターフォード)、N.Y.、およびMI(ミシガン州)、Adrian(エイドリアン)所在の、Stauffer Chemical Co.(スタウファー・ケミカル社)のSWSシリコン部から入手可能なもののようなものも、本発明の組成物において用いることができる。
【００４３】
典型的に好適な化粧用緩和剤には、鉱物油、特に、50から500 SUSの範囲の粘度を持つ鉱物油、ラノリン油、ココナツ油、ココアバター、オリーブ油、アーモンド油、マカデミアナッツ油、アロエ抽出物、ジョジョバ油、サフラワー油、コーン油、液状ラノリン、綿実油、及びピーナツ油が包含される。他の好適な化粧用緩和剤には、プルセリン油、ペルヒドロスクアレン、ヒマシ油、ポリブテン、無臭の鉱物精製油、甘アーモンド油、カロフィラム(テリハボク属)油、リチン油、ビタミンEアセテート、鉱物精製油、麦芽油のような穀粒胚芽油、エステル類で、例えば、パルミチン酸イソプロピル、ミリスチン酸イソプロプル、ミリスチン酸ブチル、ステアリン酸ヘキサデシル、オレイン酸デシル、アセチルグリセリド、(C₁₂-C₁₅)アルコールのオクタノエート及びベンゾエート、アルコール及びポリアルコールのオクタノエート及びデカノエート、例えば、グリコール及びグリセロールのもの、アルコール及びポリアルコールのオレイン酸リシン、例えば、アジピン酸イソプロピル、ラウリル酸ヘキシル及びドデカン酸オクチルのものが包含される。
【００４４】
周囲温度で固形又は半固形の化粧用緩和剤は、前述の化粧用緩和剤の1種以上と混ぜる場合、液状局所性組成物を提供するのに十分な量で用いてもよい。そのような固形又は半固形化粧用緩和剤には、水素化ラノリン、水酸化ラノリン、アセチル化ラノリン、ワセリン、ラノリン酸イソプロピル、ミリスチン酸セチル、ミリスチン酸ミリスチル、乳酸ミリスチル、セチルアルコール、イソステアリルアルコール及びラノリン酸イソセチルが包含される。
【００４５】
次の例の技術は、本発明の製造及び使用法のよりよき理解を与えることを意図している。処方技術に熟練したものであれば誰でも、処方に応用が可能な技術の他の可能な変形を容易に認識するであろう。したがって、これら例は、特許される技術を例示するのであって、その範囲の限定を意味しない。次の例示的例に用いる成分の定義及び供給者は、ワシントンD.C.20005の、Cosmetic, Toiletry and Fragrance Association, Inc.(コスメティック，トイレタリー・アンド・フレグランス・アソシエーション社)の出版するCTFA化粧品成分辞書、第3版、1982年に見出すことができる。別に示さない限り、全ての割合は重量%である。
【００４６】
[例1]
(細胞生存率定量)
本例は、抗酸化活性が細胞活性定量を用いてどのように測定されるかを説明する。個々の及びそれらの組合せの抗酸化物質の抗酸化活性は、MA.(マサチューセッツ州)Ashland(アシュランド)所在のMattek Corporation(マテック社)からのEpiderm Skin Model(エピダーム・スキン・モデル)(EPI-100)を用いて細胞培養において評価した。新生児包皮の細胞培養体を、製造者の指示に従って培養し、その細胞培養体によって摂取される3-(4,5-ジメチルタゾール-2-イル)-2,5-ジフェニルテトラゾリウムブロミド(MTT)染料の量を測定することによってパーセント細胞生存率を定量した。生細胞はこの染料を摂取し、これを、不溶のホルマジン結晶に変え、この結晶は、アルコールで抽出するまでは、細胞のミトコンドリアに留まる。抽出可能なホルマジン結晶に変換されたMTTの量は、細胞培養体の生存率に正比例する。MTTを分光光度法にて測定する。抗酸化剤成分又は混合物の存在下に、太陽光シミュレータ(フィルターを通し、290-400nmの範囲の波長を生成させる)により、1時間当り1平方cm当り1.5の最小発赤用量(MED)の割合でUV光に暴露した細胞を用いて、遊離基(フリーラジカル)の発生から細胞培養体を保護する抗酸化剤の作用を測定した。紫外光の全線量は31.5mJ/cm²だった。
【００４７】
実験のこの部分についての対照は、抗酸化剤を添加しない細胞培養体(陽性対照)であった。さらに、全ての細胞培養体を、UV光に暴露せず、及び抗酸化剤又は混合物(ブレンド)を含んでいない培養体と比較し、パーセント細胞生存率(陰性対照)を求めた。この後者の測定値を100%生存率に等しいと仮定した。3通りの細胞培養体を試験した各抗酸化剤成分、混合物又は対照標本について試行した。次に、これらの定量(アッセイ)についての結果を平均した。
【００４８】
[例2]
(PGE₂生産定量)
この例は、PGE₂定量法によってどのようにプロスタグランジンが測定されたかを記述する。細胞培養体について、MA.、ケンブリッジ所在のPerSpective Diagnostics(パースペクティブ・ダイアグノスティック)から入手した定量キットを用いてプロスタグランジンE₂(PGE₂)の生産を評価した。パーセント細胞生存率定量の場合と同様に、抗酸化剤成分、混合物又は対照の存在下、細胞を太陽光シミュレータにより1時間当り1平方cm当り1.5MEDの割合でUV光に暴露した。紫外光の全線量は31.5mJ/cm²であった。次に、この細胞培養体を正常な培養液中に24時間放置した。この時間の間増殖させた後、細胞培養体について、PerSpective Diagnostics製定量キットを用いて、PGE₂の生産を定量した。実験のこの部分についての対照は、同一線量の紫外線には暴露されるが、抗酸化剤は加えられていない培養体(陽性対照)であった。3通りの細胞培養体を、試験する各抗酸化剤成分、混合物又は対照標本について試行した。次に、これらの定量についての結果を平均した。
【００４９】
例1及び2からの試験の結果を表12及び表13に示す。表12に示す結果は、全ての抗酸化剤及びこれらの薬剤の混合物が、パーセント細胞生存率で測定するとき、紫外光誘発性遊離基からの有意な保護作用を呈することを示す。この活性は、抗酸化剤効果によるものでなければならない。なぜなら、これらの薬剤のいずれも、この太陽光紫外波長成分(290から400nm)において試験した濃度で何ら顕著な吸収を示さなかったからである。混合物Ａ、Ｂ及びＣにおける光暴露後のパーセント細胞生存率は、表14に提示したデータの中に見ることができる。個々の抗酸化剤成分間に若干の統計的有意差はあるけれども、主要な統計的差異は、薬剤の混合物及び混合物を構成する個々の薬剤の間に認められる。例えば、混合物Ｂは、ベータグルカン、DLパンテオール、ブドウ種子抽出物、リン酸アスコルビルマグネシウム及びスーパーオキシドジスムターゼから構成され、DLパンテノール以外のその個々の成分の各々に対し統計的に優れた保護作用を与える(データ示さず)。混合物は、DLパンテノールの標準偏差がもっと小さかったら、この抗酸化剤よりも統計的に優れていたかもしれない。混合物Ａは、ビタミンEアセテート及びビタミンAパルミテートから構成され、その構成成分と比較するとき、90%信頼度において、統計的に優れた保護作用を与える。
【００５０】
【表１２】

【００５１】
1. 統計的信頼度は、スチューデントのt-テストによる仮説検定に基づく。
2. これはビタミンCの安定形である(アスコルビン酸)。
3. 混合物ＡはビタミンAパルミテート及びビタミンEアセテートから構成する。
4. 混合物Ｂは、ベータグルカン、DLパンテノール、ブドウ種子抽出物、リン酸 アスコルビルマグネシウム及びスーパーオキシドジスムターゼから構成する。
5. この細胞培養体は抗酸化物質の添加なしにUV光に暴露された。
【００５２】
PGE₂生産定量データを表13に示す。この結果は、混合物Ａ及びＢが、PGE₂について定量した場合、紫外光からの統計的に有意な保護作用を与えることを示す。混合物Ａ、Ｂ及びＣにおける紫外光暴露によるPGE₂生産を表15に示す。混合物Ｂは、その構成組成物と比較すると、PEG₂生産からの統計的に優れた保護作用を与える。この結論は、混合物Ａについても正しい。混合物Ａ又はＢほど効果的ではないが、ブドウ種子抽出物及びリン酸アスコルビルマグネシウム単独でも、PEG₂生産は低くなることが認められた。
【００５３】
【表１３】

【００５４】
1. 統計的信頼度は、スチューデントのt-テストによる仮説検定に基づく。
2. これはビタミンCの安定形である(アスコルビン酸)。
3. 混合物ＡはビタミンAパルミテート及びビタミンEアセテートから構成する。
4. 混合物Ｂは、ベータグルカン、DLパンテノール、ブドウ種子抽出物、リン酸 アスコルビルマグネシウム及びスーパーオキシドジスムターゼから構成する。
5. この細胞培養体は抗酸化物質の添加なしにUV光に暴露された。
【００５５】
これらの成分の多くは、従来スキンケア製剤で用いられているものであるが、その併用が独特である。炎症媒介物(PGE₂のようなもの)の生産を妨げるか、又は紫外線暴露後に細胞生存率を向上させるベータグルカンの使用も独特だと考えられる。さらに、抗酸化剤のこれらの混合物が、互いに混合されると優れた保護作用を呈するという所見が予想外である。
【００５６】
混合物Ａ及びＢの組合せ、これは表14では混合物Ｃと表示されているが、これも、皮膚細胞培養体を用いる紫外光の傷害作用に対し統計的に有意な保護作用を与えることが判明した。抗酸化剤のこの混合物の比較は、その油及び水溶性成分混合物によって得られる保護作用レベルと近似していることが分かった。表12、13に示した結果に基づき、混合物Ｃがその成分原料よりも大きな保護作用を提供することが立証された。これらの試験から得られる結果を表14から17に示す。
【００５７】
【表１４】

【００５８】
1. 統計的信頼度は、スチューデントのt-テストによる仮説検定に基づく。
2. 混合物ＡはビタミンAパルミテート及びビタミンEアセテートから構成する。
3. 混合物Ｂは、ベータグルカン、DLパンテノール、ブドウ種子抽出物、リン酸 アスコルビルマグネシウム及びスーパーオキシドジスムターゼから構成する。
4. 混合物Ｃは混合物Ａ及びＢの混合物である。
【００５９】
【表１５】

【００６０】
1. 統計的信頼度は、スチューデントのt-テストによる仮説検定に基づく。
2. 混合物ＡはビタミンAパルミテート及びビタミンEアセテートから構成する。
3. 混合物Ｂは、ベータグルカン、DLパンテノール、ブドウ種子抽出物、リン酸 アスコルビルマグネシウム及びスーパーオキシドジスムターゼから構成する。
4. 混合物Ｃは混合物Ａ及びＢの混合物である。
【００６１】
【表１６】

【００６２】
1. この表に挙げた数値は、スチューデントのt-テストによる仮説検定に基づく 統計的信頼度である。
2. 混合物ＡはビタミンAパルミテート及びビタミンEアセテートから構成する。
3. 混合物Ｂは、ベータグルカン、DLパンテノール、ブドウ種子抽出物、リン酸 アスコルビルマグネシウム及びスーパーオキシドジスムターゼから構成する。
4. 混合物Ｃは混合物Ａ及びＢの混合物である。
5. この細胞培養体は抗酸化物質の添加なしにUV光に暴露された。
6. NSDは統計的有意差でないことの略語である。
【００６３】
表12及び13で示すように、混合物Ａ及びＢは、パーセント細胞生存率及びPGE₂生産定量の双方において、紫外光の傷害作用からの統計的に有意な保護を与える。さらに、表14及び15で示すように、混合物Ｃ(混合物Ａ及び混合物Ｂの双方の成分から構成される)も、同じ試験において、抗酸化剤を添加していない細胞培養体と比べると統計的に有意な保護作用を示した。
【００６４】
特に、表16に示すパーセント細胞生存率定量法で得られる結果に関しては、混合物Ａは、混合物Ｃよりも統計的に一層良好な保護作用を与えることが見出された。混合物Ａ及びＢは、この方法によって統計的に有意な差のレベルの保護を示さず、また、混合物Ｂ及びＣも、紫外光の傷害作用からの統計的に有意な差のレベルの保護を示さなかった。前の試験法において(表12参照)、同じ関係が、混合物Ａ及びＢに関して認められた。
【００６５】
特に、PGE₂生産定量法から得られた結果を表17に示し、これは、混合物Ｂが、混合物Ａよりも統計的に一層良好な保護を与えることが見出されたことを例証する。これは、前の試験で観察された結果(表13)と同じであり、そこでは、混合物Ｂは、混合物Ａよりも実質的に一層大きなPGE₂生産の低減を示した。表15及び17に示すように、混合物Ｃは、混合物Ａよりも統計的に一層良好な保護作用を与えることが認められた。しかし、混合物Ｂはまた、このPGE₂生産定量法によって、混合物Ｃよりも統計的に一層良好な保護を与えることが判明した。
【００６６】
【表１７】

【００６７】
1. この表に挙げた数値は、スチューデントのt-テストによる仮説検定に基づく 統計的信頼度である。
2. 混合物ＡはビタミンAパルミテート及びビタミンEアセテートから構成する。
3. 混合物Ｂは、ベータグルカン、DLパンテノール、ブドウ種子抽出物、リン酸 アスコルビルマグネシウム及びスーパーオキシドジスムターゼから構成する。
4. 混合物Ｃは混合物Ａ及びＢの混合物である。
5. この細胞培養体は抗酸化物質の添加なしにUV光に暴露された。
6. NSDは統計的有意差でないことの略語である。
【００６８】
パーセント細胞生存率定量において混合物Ａが最良の保護を示す一方で、PGE₂生産定量法において混合物Ｂが最良の保護を示すという事実は一見不統一に見える。しかし、これらの2種の定量法は別物である。紫外光によって生じる、及び各定量法によって検出される傷害を起こす反応性酸素種(ROS)は、恐らく異なる生物学的経路から発生するもので、それが異なる結果を招く。これは、なぜ、混合物Ｂ中に存在する水溶性抗酸化剤が、PGE₂生産定量法におけるより一層良好な保護を生じさせ、一方で、混合物Ａ中に存在する油溶性抗酸化剤が、パーセント細胞生存率定量法におけるより一層良好な保護を生じさせるかを説明する。
【００６９】
混合物Ａはまた、パーセント細胞生存率定量法において、混合物Ｃに比べ、統計的に一層良好な保護を提供することが見出されるが、一方で、混合物ＣはPGE₂生産定量について統計的に優れていることが見出された。同様に、混合物Ｂは、PGE₂生産定量においては混合物Ｃよりも統計的に一層良好な保護を与えるけれども、パーセント細胞生存率定量において混合物Ｃと統計的に有意差を持たない。
【００７０】
混合物Ｃと、その油溶性又は水溶性成分の混合物との間にはいくつかの統計的有意差が見られたが、混合物Ｃは、以前に試験した個々の成分と比べ有意な抗酸化剤活性を示した。
【００７１】
処方技術に熟練した者であれば誰でも、抗酸化剤薬剤のこれらの混合物を、どのようにして適切なスキンケア及び着色化粧品又は薬学的製品に簡単に組み込むかを知るであろう。したがって、この情報は、これらの抗酸化剤のすべての可能な組合せを、製品の処方において、種類又はそれらが販売される市場に関係無く包含されることを意図する。
【００７２】
(例3-10)
(皮膚保護組成物)
これらの例は、処方を記載し、スキンケア及び一般大衆向け(OTC)薬学的製剤において、本発明の皮膚保護組成物の典型的な使用を例示する。これらの処方は、使用可能な組成物の種類の例としてのみ挙げるもので、スキンケア及びOTC薬学的製剤における技術の可能な使用法のあらゆるものを含むものではない。処方技術に熟練したものであれば、この技術に関して、他の可能な使用を直ぐに見通すであろうし、及び本発明は、下記に挙げた処方の使用には限定されない。下記に挙げた処方の成分のすべては、重量％で示してある(%w/w)。
【００７３】
[例3]
(液状処方)
下記の例は組成物の液状調剤物についての一般的な処方である。
【表１８】

【００７４】
[例4]
下記の例は皮膚用整調剤として開発した処方である。
皮膚整調剤
【表１９】

【００７５】
[例5]
(水中油型(O/W)乳剤)
下記の例は本発明に従う組成物の水中油型乳剤についての一般的処方である。
【表２０】

【００７６】
[例6]
(皮膚保湿ローション)
下記の例は皮膚の保湿ローションとして開発した水中油型処方である。
【表２１】

【００７７】
[例7]
(油中水型(W/O)乳剤)
下記は本発明のいくつかの態様に従う油中水型乳剤の一般的処方である。
【表２２】

【００７８】
[例8]
(油中水型日光遮蔽処方)
下記の例は皮膚用日焼け止め剤製剤として開発した処方である。
【表２３】

【００７９】
[例9及び10]
(合成(保湿性)棒石鹸)
下記の例は保湿性石鹸の一般的処方である。
【表２４】

【００８０】
[例11及び12]
(防水性SPF20日焼け止め剤)
この例は、低レベルの日焼け止め剤及び抗酸化剤混合物を油中水型乳剤中で用いて開発した防水性のSPF20処方を記載する。例11は成分の一般的範囲の例を提供する一方で、例12は具体的処方を提供する。これらの例では、相Ａ及びＢは油溶性相を表わすが、相Ｃは水溶性相である。
【表２５】

1. q.s.は十分量(適量)を表わす略語。
【００８１】
混合法：Ａ相の成分を容器中で混合し、及びすべての油脂成分(ワックス)が溶解するまで、混ぜながら80から85℃までに加熱した。次に加熱を止め、混合物(ミクスチャ)を50から55℃までに冷却した。Ｂ相の成分も、緩徐に渦を形成しないよう混合することによって空気の取り込みを回避しながら、室温で均一になるまで容器中で混ぜた。Ｂ相の混合物をＡ相の混合物に加え、この場合も空気の取り込みを回避しながら、十分混ぜ合わせた。
【００８２】
Ｃ相の成分を適当な容器中で混ぜ、混合しながら、すべての固体物質が完全に溶解するまで、45から50℃までに加熱した。緩徐ではあるが十分に混ぜながら、ＡＢ相を、55から60℃で、45から50℃までのＣ相に添加した。添加完了後、バッチを、45から50℃までの温度に維持しながら均一にした。均一化後、30℃までの冷却を開始して混合を続行した。一旦室温に達したら、バッチを適当な容器に詰めた。
【００８３】
処方は、5名の被験者において17.9を超える防水性SPFを示した。日光遮蔽剤を含まないが、抗酸化剤を含む処方は、同じ5名の被験者において僅か2.8の防水性SPFしか示さなかった。日光遮蔽剤だけのこの組合せについての期待SPFは、正確な値は求めてないが、8未満であろう。日光遮蔽剤単独の期待SPFが抗酸化剤から得られるSPFに加えられる場合、その合計SPF(〜10.8)は、得られる製剤について見出されるものの僅か60%でしかない。
【００８４】
[例13]
(防水性SPF30日焼け止め剤)
本例は、低レベルの日焼け止め剤及び抗酸化剤の混合物を油中水型乳剤中で用いて開発した防水性SPF30処方を記載する。すべてのパーセント値は重量によるものである。相Ａ及びＢは油溶性相を表わし、相Ｃは水溶性である。
【表２６】

【００８５】
組成物は、例11、12に記載したものと同じやり方で混合した。
例13の処方は5名の被験者において32.1を超える防水性SPFを示した。抗酸化剤(ビタミンA、C及びE、ベータグルカン、ブドウ種子抽出物及びスーパーオキシドジスムターゼ)を含まない同じ処方は、5名の同じ被験者において19.6の防水性SPFを示した。日光遮蔽剤を含まないが、抗酸化剤を含む処方は、2.8の防水性SPFを示した。本製剤の個々の成分のSPF値合計(22.4)は、別に試験した完全製剤について観察されたSPF値の僅か約70%に過ぎなかった。この測定したSPF値はまた、期待された22.4SPFよりも40%上回った(32.1-22.4=9.7で、これは期待される22.4SPFの43%である)。
【００８６】
本発明は、皮膚を紫外線から保護する2種の皮膚薬剤、細胞生存率を増す保護剤のクラスからの1種の薬剤、及び皮膚においてPGE₂生産を減少させるクラスからの他のものを組み合わせるときに、例1の定量法で測定されるように見出される驚くべき優秀性を利用する。加えて、本発明はまた、抗酸化剤及び日光遮蔽剤の混合物が油中水型乳剤において協調的に組み合わされ、紫外線の有害作用に対し皮膚にとって予期し得ない優れた保護を提供するという結果をも利用する。本発明の組成物は、紫外線への暴露の前又は後双方に皮膚に適用でき、保護を提供するが、太陽への暴露前の適用が好ましい。皮膚保護剤は、太陽への暴露が予期されなくとも、毎日の塗布に使用して、皮膚におけるROSの老化作用を減退させることができる。本発明は、明らかなように、油中水型乳剤を伴うか、又は伴わないで、抗酸化剤の混合物を含む。
【００８７】
本明細書において用いるように、紫外線への暴露によって引き起こされる傷害の低減は、例1(上皮細胞性生存率の増加)又は例2(上皮細胞によるPGE₂生産の低減)の定量法によって測定されるように、傷害の低減を意味する。紫外線は、可視光の波長よりは短く、及びX線のものよりは長い波長を持つ電磁放射を指す。皮膚損傷は、細胞性生存率の減少又はPGE₂生産の増加、又は双方によって測定されるような細胞性傷害を指す。抗酸化剤は、除去(捕捉)するか、又はROSの低減か、又はROSの生産を妨げるかのいずれかによって、ROSの作用に対抗する物質である。
【００８８】
可能性のある界面活性剤には、脂肪性有機酸(ラウリン酸、パルミチン酸、ステアリン酸、オレイン酸及びミリスチン酸の諸塩のようなもの)のポリオキシエチレンソルビタンエステルで、様々のモル濃度のエチレンオキシド(一般に、ポリソルベート20、21、40、60、65、80、81及び85として挙げてあるもの)並びにこれらの成分の組合せが包含される。
【００８９】
可能性のある保湿剤には、糖類(ソルビトール、グルコース等のようなもの)、グリセリン(及びその重合体)、グリコール(プロプレングリコール、ブチレングリコール、及び各種分子量のポリエチレングリコール)、ヒアルロン酸(及びその塩)、ピロリドンカルボン酸(及びその塩)並びにこれらの成分の組合せが包含される。
【００９０】
可能性のある防腐剤には、パラベン(メチル、エチル、プロピル、イソプロピル、ブチル及びイソブチルのエステルのようなもの)、イミダゾリジニル尿素、ジアゾリジニル尿素、クアテルニウム-15、フェニルエチルアルコール、ベンジルアルコール、フェノキシエタノール、クロルフェネシン、クロルヘキシジンジグルコネート並びにこれらの成分の組合せが包含される。
【００９１】
可能性のある金属イオン封鎖剤には、エチレンジアミン四酢酸の各種塩(ナトリウム、カリウム、アミン及びアミノ酸の塩)が包含される。
リン酸アスコルビルマグネシウムはビタミンCの安定化形態である。
ビタミンAの安定化形態は、本発明の好適態様において、アルコールレチノール又はそのエステルのように用いることができる。他の形態(レチンAのようなもの)も用いることができるが、安定性はより一層低い。ビタミンEは好ましくは、アルコール形態(トコフェロール)、又は任意のそのエステル、又は他の安定化形態において用いる。
【００９２】
可能性のあるO/W型界面活性剤には、脂肪酸の塩(ステアリン酸、ミリスチン酸、オレイン酸、ラウリン酸又はパルミチン酸の、ナトリウム、カリウム、アミン又はアミノ酸の塩のようなもの)、前述のポリソルベートのような非イオン性界面活性剤、脂肪酸のソルビタンエステル(ステアリン酸、ミリスチン酸、オレイン酸、ラルリン酸及びパルミチン酸の諸塩のようなもの)、脂肪酸(ステアリン酸、ミリスチン酸、オレイン酸、ラウリン酸及びパルミチン酸の諸塩)のグリセリルエステル、ラノリン酸のポリオキシエチレンエステル、アルコール及び他のウールワックス成分、脂肪アルコール(ラウリル、セチル、オレイル及びステアリルのようなもの)のポリオキシエチレンエステル、脂肪酸(ラウリン酸、ステアリン酸、ミリスチン酸、オレイン酸、及びパルミチン酸の諸塩のようなもの)のポリエチレングリコールエステル、ポリオキシエチレンとポリオキシプロピレンのホモポリマー及び混合ブロックポリマー、脂肪酸のポリオキシプロピレンエステル、脂肪アルコールのポリオキシプロピレンエーテル類、脂肪酸の糖エステル(グルコース及びスクロースの脂肪酸エステルのようなもの)及び脂肪酸の4級アミン塩並びに水中油型乳剤をもたらすように選ばれるこれらの原料の組合せが包含される。
【００９３】
可能性のある緩和剤には、脂肪酸及び脂肪アルコールのエステル(パルミチン酸オクチル、ステアリン酸オクチル、ステアリン酸セテアリルのようなもの)、シリコン化合物(ジメチコン、シクロメチコン、フェニルトリメチコン等)、有機酸及び有機アルコールのエステル(C12-C15アルキルベンゾエート、オクチルドデカノール、乳酸セチル、トリデシルトリメリテート、オクチルドデシルネオペンタノエート等)、脂肪アルコール(セチルアルコール、ステアリルアルコール等)、ヒマシ油及びそれらの水素化誘導体並びにこれらの種類の成分の組合せが包含される。
【００９４】
可能性のある増粘剤には、アクリル酸ポリマー及びそれらの架橋ポリマー誘導体、ポリビニールピロリドンポリマー、自然ポリマー(ローカスビーンゴム、キサンタンゴム、アルギン酸及びその塩、デキストラン等のようなもの)、クレイ(ヘクトライト、モントモリロナイト等)並びにこれらの原料の組合せが包含される。
【００９５】
可能性のある油中水型(W/O)乳剤には、前述の水中油型乳剤の適切な組合せ、並びにセチルジメチコンコポリオール及び他の様々な他のジメチコンコポリオール、加えてこれらの原料の組合せが包含される。
【００９６】
可能性のある緩和剤及び日焼け止め剤には、前述の緩和剤、並びにジオキシベンゾン、ホモメンチルサリチレート、メンチルアントラニレート、オクトリレン、オクチルメトキシシナメート、オクチルパラアミノベンゾエート、オクチルサルチレート、オキシベンゾン、及びトロラミンサルチレートのような、任意の認められる日光遮蔽剤、並びにこれらの原料の組合せが包含される。
【００９７】
可能性のある塩には、塩化ナトリウム、塩化カリウム、塩化リチウム及び塩化マグネシウム又はこれらの原料の組合せが包含される。
【００９８】
可能性のある洗剤及び洗浄剤には、コシルイセチオネート、イソステアリルラクチレート塩(ナトリウム及びカリウムの塩のようなもの)、タロウ及びタロウ塩(ナトリウム、カリウム及びアンモニウムの塩のようなもの)、ラウリル硫酸及びラウレス硫酸の塩(ナトリウム、カリウム及びアンモニウムの塩のようなもの)、ベタイン及びスルタイン(コカミドプロピルベタイン又はスルタインのようなもの)及び脂肪酸の塩(ラウリン酸、ミリスチン酸、パルミチン酸、ステアリン酸、オレイン酸、ベヘン酸、リノリン酸及びリシノール酸のナトリウム又はカリウム塩のようなもの)、並びにこれらの原料の組合せが包含される。
【００９９】
可能性のある緩衝剤には、化学で用いられるすべての通常の緩衝系、特に、乳酸の塩(乳酸ナトリウムのようなもの)と、一定pH値を維持するのに適切な割合で組み合わせた乳酸が包含される。
【０１００】
可能性のある保湿剤及び皮膚コンディショナー剤には、前述の保湿剤、イソステアロイルラクチレートの塩(ナトリウム又はカリウムのようなもの)、4級化合物(ステアラミドプロピルジメチルアミンのようなもの)及びオート麦副産物(オート麦粉のようなもの)、並びにこれらの原料の組合せが包含される。
【０１０１】
可能性のある増粘剤及び着色剤には、前述の増粘剤(脚注8参照)、及び二酸化チタン、酸化鉄のような着色剤、FD&C及びD&C着色剤、ウルトラマリンブルー、カルミン、アンナット、クロロフィル及び他の天然又は人工着色剤、並びにこれらの原料の組合せが包含される。
【０１０２】
本発明者らの原理が適用され得る可能性のある態様が数多くあることに鑑み、例示した態様が本発明の単なる具体的な例に過ぎないことを認識すべきであり、及び本発明の範囲における制限と考えてはならない。むしろ、本発明の範囲は添付する特許請求の範囲によって規定される。したがって、本発明者らは、これらの特許請求の範囲の範囲及び精神内に入るすべてを、本発明者らの発明として求める。[0001]
(Field of Invention)
The present invention relates to topical antioxidant compositions for the protection and treatment of human skin, particularly skin exposed to harmful ultraviolet radiation.
[0002]
(Background of the invention)
The ultraviolet (UV) wavelength of sunlight can lead to sunburn (redness) and blisters (edema). Exposure to ultraviolet light can further cause the skin to feel dry and tight at moderate doses, and can cause skin detachment when exposed to higher doses. These acute or short-term effects can be immediately perceived. However, there are even more subtle acute effects that are not so easily recognized, such as light-induced immunosuppression, deoxyribonucleic acid (DNA) cross-linking reactions, sunburn cell formation, and disappearance of Langerhans cells. More serious long-term effects may occur, such as skin cancer and premature skin aging.
[0003]
Sunscreen formulations are known to protect the skin from some of the harmful effects of UV exposure. These formulations contain molecules that absorb the harmful wavelengths of ultraviolet light before they reach the skin. The absorbed light is converted to heat and quickly diffuses into the skin and the environment, whereby the molecule returns to a low energy state and subsequently absorbs another photon. In this way, the sunscreen agent can absorb a large number of photons of ultraviolet light in a relatively short time. By absorbing the harmful wavelengths of light, sunscreen formulations prevent many of the acute and chronic effects caused by ultraviolet light.
[0004]
However, sunscreen formulations are not perfect in their mode of action. No single sunscreen can absorb all of the harmful wavelengths that strike the skin. Advanced sun protection factor (SPF) formulas address this problem by including multiple sunscreens in the formula in combination. However, even when used in combination with multiple sunscreens, these formulations do not provide complete protection, especially from relatively long UV wavelengths. Although these relatively long wavelengths generally do not immediately induce much of the acute injury effects from ultraviolet light exposure, recent studies have pointed out that these wavelengths can cause free radicals in the skin. . These free radicals may cause premature skin aging, which is generally associated with UV light exposure.
[0005]
The skin has a defense mechanism against the generation of ROS (reactive oxygen species). Their defenses include enzymes such as superoxide dismutase, catalase, glutathione transferase, glutathione peroxidase and glutathione reductase, and antioxidants such as tocopherol, ubiquinone, ubiquinol, ascorbic acid and dehydroascorbic acid. . Unfortunately, since ultraviolet light that penetrates the skin can easily overwhelm these defense systems, the amount of superoxide dismutase and glutathione transferase in the skin is significantly attenuated by irradiation with sunlight approximated ultraviolet light. Simultaneously with the disappearance of these reductases, there is a dramatic increase in conjugated double bonds formed from linoleate present in the cell membrane in the skin. In addition, there is an increase in thiobarbituric acid reactants present in the skin, which represents a collection of molecules formed from ROS. Prostaglandins are inflammatory media believed to be generated by skin injury, and ROS may create conditions that promote the formation of prostaglandins and sunburn cells.
[0006]
The effect of the sunscreen is expressed as SPF value. The SPF value is the same minimum redness response in unprotected skin (with the radiation time required to produce a minimum redness reaction (sunburn) on sunscreened skin using a sun simulator ( Perceived as the ratio to the radiation time required to produce (sunburn). This study was conducted under clinical conditions according to the procedure described in the proposal for a formulation containing sunscreen (Proposed Monograph for Sunscreen Containing Drug Products, hereafter referred to as the proposal) and is based on the US Federal Register. Volume 43, August 25, 1978, Part 2, pages 38206-38269, published by the US Food and Drug Administration (FDA), which is incorporated by reference. As used herein, the term “SPF” or sun protection factor is defined according to the definition of the proposal. This same publication also describes the clinical test procedures necessary to determine whether a sunscreen formulation is waterproof, water resistant, and antiperspirant.
[0007]
The indicated SPF value is generally accepted to be between 2 and 50. This does not mean that SPF values above 50 are not feasible with conventional prescription techniques. However, the amount of sunscreen needed to achieve such a high SPF value is usually not cost-effective under current formulation techniques. The concentration of sunscreen needed to meet the “waterproof” label is particularly high because some drugs are washed out in tests that measure SPF for waterproofing compositions.
[0008]
The waterproof formulation shows its indicated SPF value after exposure to water for 80 minutes under conditions that simulate swimming. A water resistant formulation is defined similarly, but in this case it must withstand 40 minutes of water exposure. Although there is another test for antiperspirant nominal, the proposal allows formulations that have passed the waterproof or water resistance standards to assume the antiperspirant nominal.
[0009]
The most common sunscreen formulations on the market today are oil-in-water emulsions containing stearic acid neutralized with triethanolamine. The SPF values of such emulsions range from 2 to 50, but generally they contain ethylhexyl methoxycinnamate as a sunscreen. As the SPF of these formulations increases, they typically contain ethylhexyl salicylate, homosalate, octocrylene, and / or oxybenzone in addition to the aforementioned ethylhexyl methoxycinnamate. Alternatively, padimate O can be used in place of ethylhexyl methoxycinnamate or the aforementioned salicylate. Dioxybenzone, avobenzone or menthyl anthranilate can also be used instead of oxybenzone. If the formulation is not nominally effective against the skin (i.e. waterproof or water resistant), trolamine salicylate or DEA methoxycinnamate can be used instead of ethylhexyl methoxycinnamate, ethylhexyl salicylate or homosalate ( (Or in combination). In addition, soribenzone may be used in place of oxybenzone in such ineffective formulations. The proposal lists 21 active ingredients that can be used individually or in combination to achieve the desired formulation SPF.
[0010]
In addition to emulsion (lotion and / or cream) formulations, sunscreen preparations can be found in almost any form such as oils, sticks, gels, ointments and pastes. These forms of SPF also depend on the sunscreen used, the concentration and content of those screens in the formulation, and the type and amount of any volatile components (such as water, alcohol and volatile oils) in the formulation. Dependent.
[0011]
The most popular sunscreen formulations sold on the market today are TEA stearate oil-in-water lotion formulations that exhibit 15 or more SPFs. Many of the SPF 15 formulations contain about 7.5% ethylhexyl methoxycinnamate and 4.0% oxybenzone. By successfully modifying these SPF 15 formulations and by adding about 5.0% octyl salicylate to the sunscreen mixture, the SPF value can be increased to a value of about 30. With further improvements including the addition of 8.0% octocrylene, SPF values of up to 50 can be achieved.
[0012]
The emulsifier technology from Goldschmidt Chemical Company uses a silicon emulsifier. This emulsifier can be used to formulate a water-in-oil lotion formulation. An example of this emulsifier is Abil EM 90. This is a non-volatile silicone oil containing cetyl dimethicone copolyol. Another example of this emulsifier is Abil WE 09. This is a non-volatile silicone oil comprising polyglyceryl-4-isostearate, cetyl dimethicone copolyol and hexyl laurate. The chemical structure of these emulsifiers is disclosed in US Pat. No. 5,482,714, which is incorporated herein by reference, which describes the use of this emulsifier in skin protective emulsions. .
[0013]
US Pat. No. 5,447,715 can use volatile silicone oil to improve the SPF value of non-aqueous waterproof sunscreen compositions, but such non-aqueous formulations formulate aqueous emulsions It is disclosed that it is unsuitable.
Vitamins have been reported to have antioxidant properties. Antioxidants are substances that can block the biochemical tandem chain reaction of inflammatory mediators produced by free radicals. In sunscreen compositions, compositions comprising vitamin A or E or derivatives thereof are disclosed in US Pat. Nos. 4,454,112, 5,532,805, and 5,378,461. US Pat. No. 4,938,960 describes the use of vitamin C in combination with vitamins A, E, B and other drugs in skin protection compositions. An antioxidant formulation that is said to protect the skin against harmful ultraviolet radiation is disclosed in US Pat.No. 5,607,921, which includes vitamin C, vitamins A and E, and monosaccharides or amide precursors. Includes in combination. Sunscreen compositions containing panthenol and other agents are disclosed in US Pat. Nos. RE 33,845, 5,505,935, 5,445,823, and 5,573,754. The antioxidant effect of superoxide dismutase when applied externally to the skin to protect it from the action of ultraviolet light is also described in US Pat. No. 5,601,806.
[0014]
Despite recent advances in the protection of skin from harmful UV radiation, the prevalence of skin cancer and skin damage from this radiation has continued without mitigating. It is believed that the disappearance of the ozone layer due to environmental pollution has led to an increase in ambient ultraviolet light reaching the exposed skin. Many skin protection formulations that can prevent sun injury have unacceptable odors or textures that refrain from frequent use, and many of the currently available skin protection agents protect the skin from these many injuries. Insufficient protection from mechanism. Accordingly, there is an important public health need for a commercially acceptable and superior formulation that can be applied topically to human and animal skin to counteract the harmful effects of ultraviolet radiation.
[0015]
(Disclosure of the Invention)
The present invention provides a therapeutic or cosmetic composition comprising a novel antioxidant or an agent that reduces sun-induced skin damage and inflammation by abrogating the production of prostaglandins in the skin. This composition has an excellent therapeutic or cosmetic effect. Certain embodiments provide greater protection from the harmful effects of ultraviolet light without requiring the use of extreme concentrations of sunscreen in the protective formulation.
[0016]
The present invention includes compositions and methods for inhibiting UV-induced skin damage, which contains beta glucan or grape seed extract in an amount sufficient to protect the skin from UV damage. By applying the antioxidant composition topically to the skin. In disclosed aspects, the composition comprises panthenol, beta glucan, grape seed extract, vitamin C (and analogs thereof such as ascorbyl magnesium phosphate, ascorbyl palmitate, etc.), and superoxide dismutase, Cooperate to increase cell viability and inflammatory prostaglandin PGE in skin exposed to ultraviolet light ₂ Acts to lower the production of. The composition further includes vitamin A (analogues such as retinol and retinyl palmitate) and vitamin E (analogues thereof such as tocopherol and tocopheryl acetate), which in concert coordinate antioxidants in the skin. Acts as an agent. In addition, an additional aspect is that a mixture of one or more antioxidants and sunscreen agents in the emulsion, such as a water-in-oil (W / O, water-in-oil) emulsion, is harmful to the harmful effects caused by UV exposure. Take advantage of the surprising finding that it provides unexpected and superior protection of the skin.
[0017]
In certain embodiments, the composition comprises at least 0.005% beta glucan, 0.005% panthenol, 0.00001% grape seed extract, 0.0001% vitamin C, and 0.0001% superoxide dismutase. For example, the composition comprises 0.005-5.00% beta glucan, 0.005-5.00% panthenol, 0.00001-1.00% grape seed extract, 0.0001-3.00% vitamin C, and 0.0001-1.0000% superoxide dismutase. May include. Further, the composition may comprise at least 0.0005% vitamin A, and at least 0.05% vitamin E, such as 0.0005-0.50% vitamin A, and 0.05-30.00% vitamin E. In this specification, all component ratios are given by weight.
[0018]
In a more specific aspect, the topical composition is an amount sufficient to improve cell viability in the skin when applied topically before or after UV exposure of beta glucan and / or grape seed extract. , And at least one other skin protectant that reduces skin damage caused by ultraviolet light. When selecting beta-glucan, the skin protectant is selected from the group consisting of one or more panthenol, grape seed extract, vitamin C, superoxide dismutase, vitamin A or vitamin E, when applied topically PGE on the skin ₂ Sufficient to reduce the production of and increase cell viability. Vitamin C may be in the form of magnesium ascorbyl phosphate, while vitamin A may be in the form of vitamin A palmitate and vitamin E may be in the form of vitamin E acetate.
[0019]
The present invention further contemplates that the mixture of antioxidants and sunscreens in the emulsion, such as water-in-oil (W / O, water-in-oil) emulsions, may prevent the skin from adverse effects induced by UV exposure. Take advantage of the surprising finding that it provides the best protection you can't get. Accordingly, another aspect of this antioxidant composition is that an antioxidant, a sunscreen, and a non-volatile emulsifier (of an organic polysiloxane) in an amount sufficient to increase the sun protection factor (SPF) of the composition. Such as, for example, alkylpolysiloxanes, including polysiloxane polyalkyl polyether copolymers, such as alkyl dimethicone emulsifiers). The composition may contain, for example, a low concentration (level) of sunscreen (or group of drugs) in combination with a mixture of antioxidants in a water-in-oil organopolysiloxane and polyglycerol fatty acid ester emulsion. Good.
[0020]
In certain embodiments, the sunscreen agent is ethyl hexyl methoxycinnamate, DEA methoxycinnamate, padimate O, ethyl hexyl salicylate, homosalate, TEA salicylate, oxybenzone, dioxybenzone, soribenzone, avobenzone, octocrylene, titanium dioxide, zinc oxide or It contains one or more kinds of drug components selected from the group consisting of methyl anthranilate. In other embodiments, the sunscreen agent is at least one UVA sunscreen selected from the group consisting of oxybenzone, dioxybenzone, soribenzone, avobenzone or zinc oxide, and ethylhexyl methoxycinnamate, DEA methoxycinnamate, padimate O And at least one UVB sunscreen selected from the group consisting of ethylhexyl salicylate, homosalate, TEA salicylate, octocrylene, or titanium dioxide. In other specific embodiments, the sunscreen comprises at least oxybenzone and at least one ethylhexyl methoxycinnamate and octyl salicylate. The antioxidant in the composition may comprise a mixture of one or more of the aforementioned individual antioxidants.
[0021]
In a particular embodiment, the composition is a sun protection preparation in the form of an emulsion, the composition is at least 50% water, and the emulsifier comprises 1-12% of an emulsifying system comprising cetyl dimethicone copolyol; And the sunscreen and antioxidant are present in an amount sufficient to maintain the SPF of the composition at a value greater than about 15, or even 30 or greater. In certain embodiments, the sum of the SPF values of the antioxidant and sunscreen components tested separately is about 70% or less (e.g., 50% or 60% or less) of the SPF values of the sunscreen components tested together. It is.
[0022]
The present invention further comprises about 0.0002-4% fat-soluble antioxidant composition comprising vitamin A and vitamin C, about 0.004-5% water-soluble comprising vitamin C, beta glucan, grape seed extract, and superoxide dismutase. Including UV protection compositions containing an ingredient, a sunscreen ingredient containing less than about 12% sunscreen, and an emulsifier. In a particular embodiment of the composition, the emulsifier is a polyalkylsiloxane and may further comprise an ester such as hexyl laurate and polyglyceryl isostearate.
[0023]
The present invention further includes a method for improving the SPF value of a formulation that protects skin from the harmful effects of ultraviolet radiation, which comprises one or more antioxidants and one or more sunscreens in a water-in-oil type. Emulsions, e.g. emulsifiers such as organopolysiloxane emulsifiers, with a SPF value of the formulation that is higher than the sum of the SPF values of the antioxidant and sunscreen alone (e.g. By combining in the presence of enough to enhance (even beyond). The present invention further includes a method for protecting the skin from the effects of ultraviolet radiation, which comprises an emulsion of one or more sunscreens and one or more antioxidants on the skin prior to UV exposure. By applying.
[0024]
However, the compositions of the present invention may be supplied in many forms, such as aqueous or non-aqueous solutions, suspensions or emulsions (water-in-oil or oil-in-water). The composition may be a skin conditioning composition, a moisturizing lotion, a sunscreen composition, a skin cleanser, or any other skin treatment composition. The composition can further be used in a method for protecting the skin against the harmful effects of ultraviolet radiation, which can be used in PGE on the skin. ₂ By topically applying to the skin an amount of the composition effective to reduce the production of or improve cell viability. The composition may be applied before or after sun exposure, but is preferably applied before sun exposure, for example, just before sun exposure.
The above and other objects, features and advantages of the present invention will become more apparent from the following detailed description of some aspects.
[0025]
(Detailed description)
The combined use of antioxidants in the composition provides unexpectedly superior protection against the damaging effects of UV light exposure than those obtained from individual antioxidants. Furthermore, the present invention provides an excellent skin protection effect that is unexpectedly anticipated against the harmful effects of ultraviolet rays, wherein a mixture of one or more antioxidants and sunscreen agents is synergistically combined in a water-in-oil emulsion. Take advantage of the surprising finding that
[0026]
In some of the embodiments disclosed in the examples below, a mixture of antioxidants is shown to exhibit superior antioxidant activity than any of the individual antioxidants tested alone. In certain embodiments, this synergistic combination of antioxidants can also be incorporated into a water-in-oil emulsion formulation, which is expected from the low concentration of sunscreen present in the formulation. It is shown to exhibit SPF values far exceeding SPF values. The specific combination of antioxidant and low concentration sunscreen in this water-in-oil emulsion system is unexpectedly synergistic as measured by SPF values.
[0027]
The sunscreen employed in the formulation is the same combination used in some conventional formulations, such as ethylhexyl methoxycinnamate and oxybenzone. However, the levels of these sunscreens are significantly lower than those of the more conventional oil-in-water sunscreen formulations. Furthermore, the combination of antioxidants used in the formulations addressed by this technique is unique. Antioxidant combinations include a mixture of beta glucan, vitamin E acetate, vitamin A palmitate and ascorbyl magnesium phosphate (stabilized vitamin C), panthenol, grape seed extract and superoxide dismutase. The effect of this antioxidant combination on the skin is new and unexpected, as measured by its free radical scavenging activity and the low SPF of the emulsion when combined with a sunscreen.
[0028]
As used herein, an “antioxidant” is a compound that reduces the inflammatory biochemical stage reaction triggered by reactive oxygen species. Antioxidants include, for example, vitamin C and vitamin E (and their esters), magnesium ascorbyl phosphate, panthenol, beta glucan, grape seed extract, superoxide dismutase, and these individual antioxidant drugs. One or more mixtures are included.
[0029]
“Nonvolatile” siloxanes include organopolysiloxanes having a flash point of at least about 200 ° F. Thus, cetyl dimethicone polyols such as ABIL WE09 (having a flash point of 255 ° F.) are non-volatile siloxanes. “Siloxane” is a straight-chain compound (similar to paraffin hydrocarbons) that contains silicon atoms bonded to oxygen, but is arranged so that each silicon atom is bonded to four oxygen atoms.
[Chemical 1]

[0030]
“Silicon” or “polyorganosiloxane” is, for example, as described in Remington: “The Science and Practice of Pharmacy”, 19th Edition, pages 867-868, And, as shown below, oxygen and silicon atoms are alternating chains with organic substituents, often methyl or phenyl, attached to each silicon atom.
[Chemical 2]

[0031]
In a particular embodiment, the emulsifier is a non-volatile silicone oil, such as a polysiloxane polyalkyl polyether copolymer, also known as copolyols, having a molecular weight of 10,000 to 50,000, for example as a reference U.S. Pat.No. 5,746,945, incorporated herein, and
[Chemical 3]

Where R ′ groups are —H and C, respectively. _1-18 R ″ is selected from [CH ₂ CH ₂ O] _a [CH ₂ (CH ₂ ) CHO] _b H, where a is 9 to 115, b is 0 to 50, x is 133-673, and y is 0.25 to 25. ). In a particular embodiment, a is 14, b is 13, x is 249, and y is 1.25.
[0032]
Emulsifiers also include dimethicones selected from alkyl- and alkoxy-dimethicone copolyols, such as those disclosed in US Patent Application No. 5,659,523, incorporated herein by reference. Particularly preferred copolyols are cetyl dimethicone copolyols available from TH Goldschmidt as Abil EM-90, or Abil WE-90 (also including pologlyceryl-4-isostearate and hexyl laurate).
[0033]
The term “aqueous” means that the composition is not substantially free of water. An emulsion is a dispersion containing at least two liquid phases that are not miscible with each other. Emulsions where water is the dispersed phase and oil is the dispersion medium are “water-in-oil” emulsions. “Aqueous emulsion” refers to an emulsion containing water as one of its phases.
[0034]
A “sunscreen” is an agent that reduces the amount of skin redness by preventing exposure to ultraviolet radiation in an effective amount, as measured by the methods described in the proposal (for example). Sunscreens may protect against either UV-B ultraviolet radiation or UV-A ultraviolet radiation, or both. In a particularly disclosed embodiment, the sunscreen is an aromatic compound (such as oxybenzone and cinnamic acid derivatives) that efficiently absorbs harmful UV radiation, such as ZnO or TiO ₂ Or substantially free of particulate sunscreens such as other metal oxides that may have an adverse effect on the stability of the antioxidant in the composition. Certain embodiments of the composition also exclude copper or iron that can have a detrimental effect on stability.
[0035]
Typically suitable UV-B type sunscreens include substituted paraaminobenzoates such as NJ (NJ) 07109, Van Dyk & Co. Inc. located in Belleville. Octyl dimethyl PABA available under the name Escalol 507 and usually present in the range of about 0 to 8% by weight (eg 1.5 to 8% by weight); alkyl esters of paramethoxycinnamate, for example , NJ07104, available from Givaudan Corp., Clifton, under the trade name Parasol MCX, usually from about 0 to 7.5 wt% (e.g. from 1.5 to 7.5 wt%) Octylparamethoxycinnamate present in the range of); certain esters of salicylic acid, such as homomenthyl salicylate, typically present in the range of about 0 to 15% by weight (eg 4 to 15% by weight) Usually about 0-5% by weight In (e.g., from 3 to 5 wt%) octyl salicylate present in the range are included. (All weight percentages are weight percentages of total sunscreen composition.)
[0036]
Typically suitable UV-A sunscreens are benzophenone-3, usually present in the composition in the range of about 0 to 6% (e.g., 0.5 to 6%), and NJ07470, Available under the trade name Spectra-Sorb UV-9 from American Cyanamid Co. in Wayne; benzophenone-8, usually 0 in the composition In the range of from 3 to 3% by weight (eg 0.5 to 3% by weight) and available from American Cyanamid Co. under the trade name Spectra-Sorb UV-24; and in Menthyl anthranilate Present in the composition usually in the range of about 0 to 5% by weight (e.g. 3.5 to 5% by weight), and the trade name Sunarome (NJ) from Haarmann and Reimer (NJ). Included are those available under UVA.
[0037]
The composition of the present invention preferably comprises at least one UV-B type sunscreen and at least one UV-A type sunscreen. The compositions of the present invention further comprise fragrances, preservatives, dyes, softeners, physical reflectors and other antioxidants, as well as any other class of substances whose presence is desirable cosmetically or otherwise. Good.
[0038]
Other antioxidants include propyl gallate, esters of octyl and dodecyl, butylated hydroxyanisole (usually as a mixture of ortho and meta isomers), butylated hydroxytoluene and nordihydroguaialet acid. The Typically suitable preservatives include lower alkyl esters of parahydrobenzoate (paraben), in particular methylparaben, ethylparaben, propylparaben, butylparaben, isobutylparaben and mixtures thereof, and benzoic acid. Typically suitable fragrances include all oil-soluble fragrances or fragrances or mixtures of fragrances or fragrances well known to those skilled in the art. Typically suitable physical reflectors include talc, kaolin, chalk, precipitated silica, zinc oxide, and titanium dioxide.
[0039]
The composition of the present invention may be in liquid, gel or semi-solid form. The choice of composition type and amount is determined by the nature of the composition, ie gel or semi-solid, but is within the skill of the cosmetic chemist. For example, a much larger amount of wax than in a liquid composition is included in a semi-solid composition according to the present invention.
[0040]
The term “waterproofing effective amount of at least one waterproofing agent” means that when a waterproofing agent is used, the waterproofing agent (waterproofing agent group) is at a concentration of at least 0.3% in the composition and, It means to exist in the range of%. Typically suitable waterproofing agents include copolymers derived from the polymerization of Okudadecene-1 and maleic anhydride, for example, by methods such as those disclosed in US Pat. No. 3,860,700. A particular waterproofing agent is a copolymer commercially available from Chevron Chemicals Co. under the trade name PA-18 polyanhydride resin. Others include PVP / Epicosene copolymer, PVP / Hexadecene copolymer, and PVA / VA copolymer, all available from GAF of Wayne, NJ.
[0041]
Typically suitable cosmetic waxes are available from Allied-Signal Corp., Morristown, NJ, especially ozokerite, lanolin alcohol, paraffin wax, bayberry wax, polyethylene wax. AC617; Polawax (reaction product of higher fatty alcohol and ethylene oxide available from Croda, Inc., NY, New York 10016), trihydroxystearin, lanolin wax, beeswax , Candelilla wax, microcrystalline wax, carnauba wax, cetyl alcohol, stearyl alcohol, spermaceti, cocoa butter, fatty acids of lanolin, mono-, di- and tri-behenates (triesters of behenic acid and glycerin) and C ₁₈ -C ₃₆ Acid triglyceride (C ₁₈ -C ₃₆ A mixture of carboxylic acid and glycerol triesters, available under the trade names Syncowax HRC and Syncowax HGL-C from Croda, Inc, New York, NY, respectively, solid fat at 25 ° C Esters, silicone waxes such as methyloctadecanoxyoxypolysiloxane and poly (dimethylsiloxy) stearoxysiloxane, stearyl mono- and di-ethanolamine, rosin, and derivatives thereof such as glycolate and glycerol abiates, solidify at 25 ° C Hydrogenated oils and scroglycerides are included.
[0042]
Further embodiments containing volatile silicone oils include Dow Corning 344 Fluid, Dow Corning 345 Fluid, Dow Corning 244 Fluid, and Dow Corning 245; and CT. (Connecticut), Danbury (Danbury). ) Under the trade name of Union Carbide Corp., a cyclomethicone such as Volatile Silicone 7207, a low viscosity dimethicone, i.e. a dimethicone having a viscosity of less than about 50 cst, especially Dow Corning 0.5 Dimethicone such as -200cst fluid [Midland, Michigan] is included. Cyclomethicone and dimethicone were given by the third edition of the CTFA Cosmetic Ingredient Dictionary for fully methylated linear siloxane polymers end-blocked with cyclic dimethylpolysiloxane compounds and trimethylsiloxy units, respectively. It is a name. Other volatile silicone oils with low heat of vaporization, Stauffer, General Electric Co., Silicon Products Division, Waterford, NY, and MI, Michigan, Adrian Those available from the SWS silicon part of Chemical Co. (Staufer Chemical Company) can also be used in the compositions of the present invention.
[0043]
Typically suitable cosmetic emollients include mineral oils, especially mineral oils with viscosities ranging from 50 to 500 SUS, lanolin oil, coconut oil, cocoa butter, olive oil, almond oil, macadamia nut oil, aloe extract , Jojoba oil, safflower oil, corn oil, liquid lanolin, cottonseed oil, and peanut oil. Other suitable cosmetic emollients include: purserine oil, perhydrosqualene, castor oil, polybutene, odorless mineral refined oil, sweet almond oil, calophyllum oil, lysine oil, vitamin E acetate, mineral refined oil , Grain germ oils such as malt oil, esters such as isopropyl palmitate, isopropyl myristate, butyl myristate, hexadecyl stearate, decyl oleate, acetylglycerides, (C ₁₂ -C ₁₅ Included are octanoates and benzoates of alcohols, octanoates and decanoates of alcohols and polyalcohols, such as those of glycols and glycerol, lysine oleates of alcohols and polyalcohols, such as isopropyl adipate, hexyl laurate and octyl dodecanoate. Is done.
[0044]
Cosmetic emollients that are solid or semi-solid at ambient temperature may be used in an amount sufficient to provide a liquid topical composition when mixed with one or more of the aforementioned cosmetic emollients. Such solid or semi-solid cosmetic relaxants include hydrogenated lanolin, lanolin hydroxide, acetylated lanolin, petrolatum, isopropyl lanolinate, cetyl myristate, myristyl myristate, myristyl lactate, cetyl alcohol, isostearyl alcohol and Isocetyl lanolinate is included.
[0045]
The following example techniques are intended to provide a better understanding of the manufacture and use of the present invention. Anyone skilled in prescription techniques will readily recognize other possible variations of techniques that can be applied to prescriptions. Accordingly, these examples illustrate the patented technology and are not meant to limit its scope. Ingredient definitions and suppliers used in the following illustrative examples are the CTFA Cosmetic Ingredient Dictionary published by the Cosmetic, Toiletry and Fragrance Association, Inc., Washington, DC 20005, 3rd Edition, can be found in 1982. Unless otherwise indicated, all percentages are by weight.
[0046]
[Example 1]
(Quantification of cell viability)
This example illustrates how antioxidant activity is measured using cellular activity quantification. The antioxidant activity of the individual and combinations of antioxidants is determined by the Epiderm Skin Model (EPI--) from Mattek Corporation, Ashland, MA (Massachusetts). 100) was evaluated in cell culture. 3- (4,5-dimethyltazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT), cultured by neonatal foreskin cell culture according to the manufacturer's instructions and ingested by the cell culture Percent cell viability was quantified by measuring the amount of dye. Living cells take this dye and turn it into insoluble formazine crystals, which remain in the mitochondria of the cell until extracted with alcohol. The amount of MTT converted to extractable formazine crystals is directly proportional to the viability of the cell culture. MTT is measured spectrophotometrically. In the presence of an antioxidant component or mixture, a solar simulator (filtered to produce wavelengths in the range of 290-400 nm) at a rate of minimum redness dose (MED) of 1.5 per square centimeter per hour. Cells exposed to UV light were used to measure the effect of antioxidants that protect cell cultures from the generation of free radicals. Total dose of ultraviolet light is 31.5mJ / cm ² was.
[0047]
The control for this part of the experiment was a cell culture with no added antioxidant (positive control). In addition, all cell cultures were compared to cultures that were not exposed to UV light and did not contain antioxidants or mixtures (blends) to determine percent cell viability (negative control). This latter measurement was assumed to be equal to 100% survival. Triplicate cell cultures were run for each antioxidant component, mixture or control specimen tested. The results for these quantifications (assays) were then averaged.
[0048]
[Example 2]
(PGE ₂ Production quantification)
In this example, PGE ₂ Describe how prostaglandins were measured by quantitative methods. For cell cultures, prostaglandin E using a quantification kit obtained from PerSpective Diagnostics, MA., Cambridge. ₂ (PGE ₂ ) Production was evaluated. As with the percent cell viability quantification, cells were exposed to UV light at a rate of 1.5 MED per square centimeter per hour by a solar simulator in the presence of antioxidant components, mixtures or controls. Total dose of ultraviolet light is 31.5mJ / cm ² Met. Next, this cell culture was left in a normal culture solution for 24 hours. After growing for this time, the cell cultures were analyzed with PGE using the PerSpective Diagnostics quantification kit. ₂ The production of was quantified. The control for this part of the experiment was a culture (positive control) that was exposed to the same dose of UV light but no antioxidant was added. Triplicate cell cultures were run for each antioxidant component, mixture or control specimen tested. The results for these quantifications were then averaged.
[0049]
The results of the tests from Examples 1 and 2 are shown in Table 12 and Table 13. The results shown in Table 12 show that all antioxidants and mixtures of these drugs exhibit significant protection from ultraviolet light-induced free radicals when measured in percent cell viability. This activity must be due to an antioxidant effect. This is because none of these agents showed any significant absorption at the concentrations tested in this solar ultraviolet wavelength component (290 to 400 nm). The percent cell viability after light exposure in mixtures A, B and C can be seen in the data presented in Table 14. Although there are some statistically significant differences between the individual antioxidant components, major statistical differences are observed between the mixture of drugs and the individual drugs that make up the mixture. For example, Mixture B is composed of beta glucan, DL pantheol, grape seed extract, magnesium ascorbyl phosphate and superoxide dismutase, and has a statistically superior protective effect on each of its individual components other than DL panthenol. (Data not shown). The mixture may be statistically superior to this antioxidant if the standard deviation of DL panthenol was smaller. Mixture A is composed of Vitamin E acetate and Vitamin A palmitate and provides statistically superior protection at 90% confidence when compared to its constituents.
[0050]
[Table 12]

[0051]
1. Statistical confidence is based on hypothesis testing by Student's t-test.
2. This is a stable form of vitamin C (ascorbic acid).
3. Mixture A consists of vitamin A palmitate and vitamin E acetate.
4. Mixture B consists of beta glucan, DL panthenol, grape seed extract, magnesium ascorbyl phosphate and superoxide dismutase.
5. The cell culture was exposed to UV light without the addition of antioxidants.
[0052]
PGE ₂ Table 13 shows production quantitative data. This result shows that mixtures A and B are PGE ₂ When it is quantified, it shows that it provides a statistically significant protective effect from ultraviolet light. PGE by exposure to UV in mixtures A, B and C ₂ Production is shown in Table 15. Mixture B is PEG compared to its constituent composition. ₂ Provides statistically superior protection from production. This conclusion is also true for mixture A. Although not as effective as Mixture A or B, grape seed extract and magnesium ascorbyl phosphate alone are ₂ Production was observed to be low.
[0053]
[Table 13]

[0054]
1. Statistical confidence is based on hypothesis testing by Student's t-test.
2. This is a stable form of vitamin C (ascorbic acid).
3. Mixture A consists of vitamin A palmitate and vitamin E acetate.
4. Mixture B consists of beta glucan, DL panthenol, grape seed extract, magnesium ascorbyl phosphate and superoxide dismutase.
5. The cell culture was exposed to UV light without the addition of antioxidants.
[0055]
Many of these ingredients are traditionally used in skin care formulations, but their combination is unique. Inflammatory mediator (PGE ₂ The use of beta-glucan that interferes with the production of (such as) or improves cell viability after UV exposure is also considered unique. Furthermore, the finding that these mixtures of antioxidants exhibit excellent protective effects when mixed together is unexpected.
[0056]
The combination of mixtures A and B, which is labeled as mixture C in Table 14, has also been found to provide a statistically significant protective effect against the damaging effects of ultraviolet light using skin cell cultures. . A comparison of this mixture of antioxidants has been found to approximate the level of protection provided by the oil and water soluble ingredient mixture. Based on the results shown in Tables 12 and 13, it was proved that Mixture C provides a greater protective effect than its component ingredients. The results obtained from these tests are shown in Tables 14-17.
[0057]
[Table 14]

[0058]
1. Statistical confidence is based on hypothesis testing by Student's t-test.
2. Mixture A consists of vitamin A palmitate and vitamin E acetate.
3. Mixture B consists of beta glucan, DL panthenol, grape seed extract, magnesium ascorbyl phosphate and superoxide dismutase.
4. Mixture C is a mixture of Mixtures A and B.
[0059]
[Table 15]

[0060]
1. Statistical confidence is based on hypothesis testing by Student's t-test.
2. Mixture A consists of vitamin A palmitate and vitamin E acetate.
3. Mixture B consists of beta glucan, DL panthenol, grape seed extract, magnesium ascorbyl phosphate and superoxide dismutase.
4. Mixture C is a mixture of Mixtures A and B.
[0061]
[Table 16]

[0062]
1. The numbers listed in this table are statistical confidence based on hypothesis testing by Student's t-test.
2. Mixture A consists of vitamin A palmitate and vitamin E acetate.
3. Mixture B consists of beta glucan, DL panthenol, grape seed extract, magnesium ascorbyl phosphate and superoxide dismutase.
4. Mixture C is a mixture of Mixtures A and B.
5. The cell culture was exposed to UV light without the addition of antioxidants.
6. NSD is an abbreviation for not statistically significant.
[0063]
As shown in Tables 12 and 13, Mixtures A and B are the percent cell viability and PGE ₂ It provides statistically significant protection from the damaging effects of ultraviolet light in both production quantification. In addition, as shown in Tables 14 and 15, Mixture C (consisting of both components of Mixture A and Mixture B) is also statistically compared to cell cultures without added antioxidants in the same test. Showed a significant protective effect.
[0064]
In particular, with respect to the results obtained with the percent cell viability quantification method shown in Table 16, Mix A was found to provide a statistically better protective effect than Mix C. Mixtures A and B do not show a statistically significant difference level of protection by this method, and mixtures B and C also do not show a statistically significant difference level of protection from the damaging effects of ultraviolet light. There wasn't. In the previous test method (see Table 12), the same relationship was observed for mixtures A and B.
[0065]
In particular, PGE ₂ The results obtained from the production quantification method are shown in Table 17, which illustrates that Mixture B was found to provide statistically better protection than Mixture A. This is the same as the result observed in the previous test (Table 13), where mixture B is substantially larger in PGE than mixture A. ₂ It showed a reduction in production. As shown in Tables 15 and 17, Mixture C was found to provide statistically better protection than Mixture A. However, mixture B also has this PGE ₂ The production quantification method was found to provide statistically better protection than Mixture C.
[0066]
[Table 17]

[0067]
1. The numbers listed in this table are statistical confidence based on hypothesis testing by Student's t-test.
2. Mixture A consists of vitamin A palmitate and vitamin E acetate.
3. Mixture B consists of beta glucan, DL panthenol, grape seed extract, magnesium ascorbyl phosphate and superoxide dismutase.
4. Mixture C is a mixture of Mixtures A and B.
5. The cell culture was exposed to UV light without the addition of antioxidants.
6. NSD is an abbreviation for not statistically significant.
[0068]
While Mix A shows the best protection in percent cell viability quantification, PGE ₂ The fact that Mixture B shows the best protection in the production quantification method appears inconsistent. However, these two quantification methods are different. Reactive oxygen species (ROS) caused by ultraviolet light and causing injury detected by each quantification method are probably generated from different biological pathways, which lead to different results. This is why the water soluble antioxidant present in mixture B is PGE ₂ Explain whether oil-soluble antioxidants present in Mixture A give better protection in the production quantification method, while better protection in the percent cell viability quantification method.
[0069]
Mixture A is also found to provide statistically better protection in comparison to Mixture C in the percent cell viability quantification method, while Mixture C is PGE ₂ It was found to be statistically superior for production quantification. Similarly, mixture B is PGE ₂ Although it provides statistically better protection than Mixture C in production quantification, it does not statistically differ from Mixture C in percent cell viability quantification.
[0070]
Although there were some statistically significant differences between Mix C and its oil-soluble or water-soluble component mixtures, Mix C had significant antioxidant activity compared to the individual components tested previously. showed that.
[0071]
Anyone skilled in the formulation art will know how to easily incorporate these mixtures of antioxidant drugs into suitable skin care and coloring cosmetic or pharmaceutical products. This information is therefore intended to include all possible combinations of these antioxidants in the formulation of the product, regardless of the type or market in which they are sold.
[0072]
(Example 3-10)
(Skin protection composition)
These examples describe formulations and illustrate typical use of the skin protection compositions of the present invention in skin care and general public (OTC) pharmaceutical formulations. These formulations are given only as examples of the types of compositions that can be used and do not include all possible uses of the technology in skin care and OTC pharmaceutical formulations. Those skilled in the formulation art will readily appreciate other possible uses for this technology, and the invention is not limited to the use of the formulations listed below. All of the ingredients listed below are given in weight percent (% w / w).
[0073]
[Example 3]
(Liquid formulation)
The following example is a general formulation for a liquid formulation of the composition.
[Table 18]

[0074]
[Example 4]
The following example is a formulation developed as a skin conditioner.
Skin conditioner
[Table 19]

[0075]
[Example 5]
(Oil-in-water (O / W) emulsion)
The following example is a general formulation for an oil-in-water emulsion of a composition according to the invention.
[Table 20]

[0076]
[Example 6]
(Skin moisturizing lotion)
The following example is an oil-in-water formulation developed as a skin moisturizing lotion.
[Table 21]

[0077]
[Example 7]
(Water-in-oil (W / O) emulsion)
The following is a general formulation of a water-in-oil emulsion according to some embodiments of the present invention.
[Table 22]

[0078]
[Example 8]
(Water-in-oil sunscreen)
The following example is a formulation developed as a skin sunscreen preparation.
[Table 23]

[0079]
[Examples 9 and 10]
(Synthetic (moisturizing) bar soap)
The following example is a general formula for moisturizing soap.
[Table 24]

[0080]
[Examples 11 and 12]
(Waterproof SPF 20 sunscreen)
This example describes a waterproof SPF20 formulation developed using low levels of sunscreen and antioxidant mixtures in a water-in-oil emulsion. Example 11 provides an example of the general range of ingredients, while Example 12 provides a specific formulation. In these examples, phases A and B represent an oil soluble phase, while phase C is a water soluble phase.
[Table 25]

1. qs is an abbreviation for sufficient quantity.
[0081]
Mixing method: Phase A ingredients were mixed in a container and heated to 80-85 ° C. with mixing until all the fat component (wax) was dissolved. The heating was then stopped and the mixture (mixture) was cooled to 50-55 ° C. Phase B ingredients were also mixed in the container until uniform at room temperature while avoiding air entrainment by mixing to avoid slow vortex formation. The phase B mixture was added to the phase A mixture and again mixed well, avoiding air entrainment.
[0082]
The ingredients of Phase C were mixed in a suitable container and heated to 45-50 ° C. with mixing until all solid material was completely dissolved. With slow but thorough mixing, Phase AB was added to Phase C at 55-60 ° C and 45-50 ° C. After the addition was complete, the batch was homogenized while maintaining the temperature from 45 to 50 ° C. After homogenization, cooling to 30 ° C. was started and mixing was continued. Once at room temperature, the batch was packed into a suitable container.
[0083]
The prescription showed a waterproof SPF of over 17.9 in 5 subjects. Formulas containing no sunscreen but containing antioxidants showed only 2.8 waterproof SPFs in the same 5 subjects. The expected SPF for this combination of sunscreens alone will not be exact, but will be less than 8. When the expected SPF of the sunscreen alone is added to the SPF obtained from the antioxidant, the total SPF (˜10.8) is only 60% of that found for the resulting formulation.
[0084]
[Example 13]
(Waterproof SPF30 sunscreen)
This example describes a waterproof SPF30 formulation developed using a mixture of low levels of sunscreen and antioxidant in a water-in-oil emulsion. All percentage values are by weight. Phases A and B represent an oil soluble phase and phase C is water soluble.
[Table 26]

[0085]
The composition was mixed in the same manner as described in Examples 11,12.
The formulation of Example 13 showed a waterproof SPF of over 32.1 in 5 subjects. The same formulation without antioxidants (vitamins A, C and E, beta glucan, grape seed extract and superoxide dismutase) showed a waterproof SPF of 19.6 in 5 same subjects. The formulation without sunscreen, but with antioxidants showed a waterproof SPF of 2.8. The total SPF value (22.4) for the individual components of this formulation was only about 70% of the SPF value observed for the complete formulation tested separately. This measured SPF value was also 40% higher than the expected 22.4 SPF (32.1-22.4 = 9.7, which is 43% of the expected 22.4 SPF).
[0086]
The present invention relates to two skin agents that protect the skin from ultraviolet light, one agent from the class of protective agents that increase cell viability, and PGE in the skin. ₂ Take advantage of the surprising excellence found as measured by the quantitative method of Example 1 when combining others from the class that reduces production. In addition, the present invention also results in a mixture of antioxidants and sunscreens being cooperatively combined in a water-in-oil emulsion to provide unexpected protection for the skin against the harmful effects of ultraviolet radiation. Is also used. The compositions of the present invention can be applied to the skin both before and after exposure to ultraviolet light and provide protection, but application prior to sun exposure is preferred. Skin protectants can be used for daily application, even if no sun exposure is expected, to reduce the aging effects of ROS in the skin. As will be apparent, the present invention includes a mixture of antioxidants with or without a water-in-oil emulsion.
[0087]
As used herein, the reduction in injury caused by exposure to ultraviolet radiation can be seen in Example 1 (increased epithelial cell viability) or Example 2 (PGE by epithelial cells). ₂ It means a reduction in injury as measured by the quantitative method of (reduction of production). Ultraviolet radiation refers to electromagnetic radiation having a wavelength shorter than that of visible light and longer than that of X-rays. Skin damage is a decrease in cellular viability or PGE ₂ Refers to cellular injury as measured by increased production or both. Antioxidants are substances that counteract the action of ROS, either by removing (trapping), reducing ROS, or preventing ROS production.
[0088]
Possible surfactants include polyoxyethylene sorbitan esters of fatty organic acids (such as the salts of lauric acid, palmitic acid, stearic acid, oleic acid and myristic acid) in various molar concentrations. Ethylene oxide (generally listed as polysorbates 20, 21, 40, 60, 65, 80, 81 and 85) and combinations of these components are included.
[0089]
Potential moisturizers include saccharides (such as sorbitol, glucose, etc.), glycerin (and polymers thereof), glycols (propylene glycol, butylene glycol, and polyethylene glycols of various molecular weights), hyaluronic acid (and Salts thereof), pyrrolidone carboxylic acids (and salts thereof) and combinations of these components.
[0090]
Possible preservatives include parabens (such as methyl, ethyl, propyl, isopropyl, butyl and isobutyl esters), imidazolidinyl urea, diazolidinyl urea, quaternium-15, phenylethyl alcohol, benzyl alcohol, phenoxyethanol, chloro. Phenesin, chlorhexidine digluconate and combinations of these components are included.
[0091]
Possible sequestering agents include various salts of ethylenediaminetetraacetic acid (sodium, potassium, amine and amino acid salts).
Ascorbyl magnesium phosphate is a stabilized form of vitamin C.
A stabilized form of vitamin A can be used in the preferred embodiment of the invention, such as alcohol retinol or its ester. Other forms (such as Retin A) can also be used but are less stable. Vitamin E is preferably used in the alcohol form (tocopherol), or any of its esters, or other stabilized forms.
[0092]
Possible O / W surfactants include fatty acid salts (such as sodium, potassium, amine or amino acid salts of stearic acid, myristic acid, oleic acid, lauric acid or palmitic acid), as described above. Nonionic surfactants such as polysorbates of fatty acids, sorbitan esters of fatty acids (such as stearic acid, myristic acid, oleic acid, larlic acid and palmitic acid salts), fatty acids (stearic acid, myristic acid, oleic acid) Glyceryl esters of lauric acid and palmitic acid), polyoxyethylene esters of lanolinic acid, alcohol and other wool wax components, polyoxyethylene esters of fatty alcohols (such as lauryl, cetyl, oleyl and stearyl) , Fatty acids (lauric acid, stearic acid, myristic acid, olein Polyethylene glycol esters, polyoxyethylene and polyoxypropylene homopolymers and mixed block polymers, fatty acid polyoxypropylene esters, fatty alcohol polyoxypropylene ethers, fatty acid polyoxypropylene ethers, and the like. Included are sugar esters (such as fatty acid esters of glucose and sucrose) and quaternary amine salts of fatty acids and combinations of these ingredients selected to yield an oil-in-water emulsion.
[0093]
Possible relaxation agents include esters of fatty acids and fatty alcohols (such as octyl palmitate, octyl stearate, cetearyl stearate), silicon compounds (dimethicone, cyclomethicone, phenyltrimethicone, etc.), organic acids and Esters of organic alcohol (C12-C15 alkyl benzoate, octyldodecanol, cetyl lactate, tridecyl trimellitate, octyldodecyl neopentanoate, etc.), fatty alcohol (cetyl alcohol, stearyl alcohol, etc.), castor oil and their hydrogen As well as combinations of these types of ingredients.
[0094]
Possible thickeners include acrylic acid polymers and their crosslinked polymer derivatives, polyvinylpyrrolidone polymers, natural polymers (such as locust bean gum, xanthan gum, alginic acid and its salts, dextran, etc.), clay ( Hectorite, montmorillonite, etc.) as well as combinations of these ingredients.
[0095]
Possible water-in-oil (W / O) emulsions include an appropriate combination of the aforementioned oil-in-water emulsions, as well as cetyl dimethicone copolyol and various other dimethicone copolyols, plus these ingredients. Combinations are included.
[0096]
Possible relaxation agents and sunscreens include the aforementioned relaxation agents and dioxybenzone, homomenthyl salicylate, menthyl anthranilate, octrylene, octyl methoxycinnamate, octyl paraaminobenzoate, octyl saltylate, oxybenzone. And any recognized sunscreens, such as trolamine salicylate, and combinations of these ingredients.
[0097]
Possible salts include sodium chloride, potassium chloride, lithium chloride and magnesium chloride or combinations of these ingredients.
[0098]
Possible detergents and cleaning agents include cosyl isethionate, isostearyl lactylate salts (such as sodium and potassium salts), tallow and tallow salts (such as sodium, potassium and ammonium salts). , Lauryl sulfate and laureth sulfate salts (such as sodium, potassium and ammonium salts), betaine and sultain (such as cocamidopropyl betaine or sultain) and fatty acid salts (lauric acid, myristic acid, palmitic acid) , Stearic acid, oleic acid, behenic acid, linolinic acid and ricinoleic acid sodium or potassium salts), and combinations of these ingredients.
[0099]
Potential buffers include all the usual buffer systems used in chemistry, especially lactic acid in combination with a salt of lactic acid (such as sodium lactate) in an appropriate proportion to maintain a constant pH value. Is included.
[0100]
Possible moisturizers and skin conditioners include the aforementioned moisturizers, salts of isostearoyl lactylate (such as sodium or potassium), quaternary compounds (such as stearamide propyldimethylamine) and auto Included are wheat by-products (such as oat flour), as well as combinations of these ingredients.
[0101]
Possible thickeners and colorants include the aforementioned thickeners (see footnote 8), and colorants such as titanium dioxide, iron oxide, FD & C and D & C colorants, ultramarine blue, carmine, annut, Chlorophyll and other natural or artificial colorants and combinations of these ingredients are included.
[0102]
In view of the many aspects in which the inventors' principles may be applied, it should be recognized that the illustrated aspects are merely specific examples of the invention, and the scope of the invention Should not be considered a limitation in Rather, the scope of the present invention is defined by the appended claims. Accordingly, we seek all that come within the scope and spirit of these claims as our invention.

Claims (12)

A composition comprising:
An antioxidant comprising a fat-soluble component and a water-soluble component;
Sunscreens; and
Emulsifier emulsifying a sufficient amount of antioxidant and sunscreen to provide a sun protection composition
Including
A composition wherein the antioxidant comprises a mixture of antioxidants comprising vitamin A and vitamin E or esters thereof, ascorbyl magnesium phosphate, DL panthenol, beta glucan, grape seed extract and superoxide dismutase . A UV-protective composition comprising, by weight, 0.0002-4% fat-soluble sunscreen ingredients containing vitamin A and vitamin C; vitamin C, beta glucan, grape seed extract, and superoxide dismutase A composition comprising 0.004-5% of a water-soluble sunscreen component containing; an emulsifier; and a sunscreen component containing less than 12% non-particulate sunscreen . The composition of claim 2, wherein the sunscreen component is substantially free of metal oxides. The composition of claim 2, wherein the emulsifier comprises a polyalkylsiloxane . The composition of claim 2, wherein the emulsifier further comprises a fatty alcohol . The composition of claim 2, wherein the emulsifier comprises polyglyceryl-4-isostearate, cetyl dimethicone copolyol, and hexyl laurate . Composition by weight:

Including
A composition wherein the primary emulsifier comprises cetyl dimethicone copolyol . 8. The composition of claim 7, wherein by weight

Or

Including
The composition wherein the primary emulsifier further comprises polyglyceryl-4-isostearate and hexyl laurate . 8. The composition of claim 7, wherein the primary emulsifier comprises polyglyceryl-4-isostearate, cetyl dimethicone copolyol and hexyl laurate . A composition comprising:
(A)

Or (b)

Or (c)

Or (d)

Or (e)

Or (f)

Or (g)

A composition comprising: A skin sunscreen formulation, which:

Sunscreen formulation containing 12. The composition of any of claims 10 further comprising a sunscreen and a water-in-oil emulsion of polyorganosiloxane that increases the SPF of the composition .