廣譜防曬劑光穩(wěn)定和防曬增效作用的機(jī)理研究

1、PCHi 2013, Guangzhou廣譜防曬劑“雙乙基己氧苯酚甲氧苯基三嗪”(Bemotrizinol, BMT) 光穩(wěn)定和防曬增效作用的機(jī)理研究Study on Photostabilization and SPF Boosting of Bemotrizinol in Sunscreen瞿欣，趙小敏，陳志華，李亞男，凌峰亞什蘭公司, 特種添加劑部門, 上海研發(fā)中心, 上海, 中國QU Xin, ZHAO Xiao-min, CHEN Zhi-hua, Li Ya-nan, Ling FengASI Shanghai Technical Center, Ashland Inc., Sha

2、nghai, 200233, ChinaPage 2Electric wavesRadio wavesInfra RedVisible SpectrumUltravioletX-raysGamma raysmnmnm10510-101010-510-15UVPhoto Chemical EffectsLight EffectsHeat Effects800400100Visible LightUVAUVBUVC400320280100Position and classification of UV Radiation with the electromagnetic spectrum陽光輻射

3、Sunlight Irradiation 能量（能量（Energy level）: UVB UVA 皮膚穿透（皮膚穿透（Penetration level）: UVA UVBPage 3紫外光對皮膚的危害Ultraviolet Hazards老化Ageing皺紋Wrinkling過敏Skin allergies曬傷Sun burn皮膚癌Skin cancerPage 4 消費(fèi)者和相關(guān)的管理機(jī)構(gòu)越來越多的意識到UVA輻射對皮膚和健康的危害。Consumers are becoming more aware of the damage to skin and health from UVA rad

4、iation, focus now includes road spectrum protection.廣譜高效的抗紫外防護(hù)通常是通過復(fù)配不同的紫外吸收劑來實(shí)現(xiàn)有效的UVA防護(hù)，達(dá)到光穩(wěn)定性。Effective UVA protection requires “photo-stability”, which is often achieved by combining different UV filters.越來越高SPF值的防曬產(chǎn)品得到有關(guān)機(jī)構(gòu)的認(rèn)證并供消費(fèi)者選擇。Higher and higher SPF products recognized by regulatory agencie

5、s and selected by consumers. 紫外吸收劑被添加到各種各樣的護(hù)膚品和化妝品中：化妝品的雅致勢在必行。UV filters are increasingly finding their way into virtually every type of skin care and cosmetic product: cosmetic elegance is a requirement!市場情況 Market SituationPage 5研究的紫外吸收劑（UV Absorbers Studied）INCI/USP名INCI/USP name 化學(xué)結(jié)構(gòu)Chemical St

6、ructure商品名Trade Name特性PropertiesButyl MethoxydibenzoylmethaneUSP: Avobenzone (AVB)中文名：阿伏苯宗，丁基甲氧基二苯甲酰甲烷Escalol 517 (Ashland)Parsol 1785 (Roche)Eusolex 9020 (Merck)Uvinul BMBM (BASF)Full UVA coverageNo skin irritationMost widely usedUV unstableNeed stabilizersEthylhexyl Methoxycinnamate USP: Octinoxat

7、e (OMC)中文名：肉桂酸酯Escalol 557 (Ashland)Eusolex 2292 (Merck)Uvinul MC80 (BASF)Most widely usedUVB absorberBis-Ethylhexyloxyphenol Methoxyphenyl Triazine USP: Bemotrizinol (BMT)中文名：雙乙基己氧苯酚甲氧苯基三嗪Escalol S (Ashland)UVA/UVB coverageUV stabilizerSPF boostingOil solublePage 6酮式結(jié)構(gòu) (Keto Form)烯醇結(jié)構(gòu)(Enol Form)+hv

8、hvAVB光不穩(wěn)定的途徑（Pathways for AVB Decay ）阿伏苯宗(AVB)肉桂酸酯(OMC)+hvD. Dondi, A. Albinia, N. Serpone., Interactions between different solar UVB/UVA filters contained in commercial suncreams and consequent loss of UV protection, Photochem. Photobio. Sci., 2006, 5, 835-843影響AVB光不穩(wěn)定的因素 (Influence Factors):溶劑 (So

9、lvents), 乳化體系 (Emulsion types), 無機(jī)防曬劑 (Inorganic filters), 其他紫外吸收劑 (other UV absorbers).旋轉(zhuǎn)異構(gòu)體(Rotamer)環(huán)化加成反應(yīng)(2+2 Cycloaddition)光降解(photodegradation) 異構(gòu)化 振動(dòng)松弛Page 7阿伏苯宗(AVB )分子吸收紫外光，從基態(tài)躍遷到單重激發(fā)態(tài)，產(chǎn)生熒光，部分分子會通過異構(gòu)化，裂解，生成光化化合物的方式衰退。 (AVB absorbs UV radiation, emit fluroresence at singlet state, and decays

10、through tautomerization, fragmentation and photoproduct formation.)紫外吸收劑的能量躍遷 (Cycle of Photostability)基態(tài)(Ground State)單重激發(fā)態(tài)(Singlet State)- short lived無輻射弛豫Radiationless Deactivation三重激發(fā)態(tài)(Triplet State)- long lived磷光Phosphorescence熒光(Fluorescence)AVBBMTBMT (Escalol S) 分子吸收紫外光，從基態(tài)躍遷到激發(fā)態(tài)。通過分子間異構(gòu)化內(nèi)部轉(zhuǎn)化

11、、振動(dòng)弛豫的方式把能量以熱的形式發(fā)散，不產(chǎn)生熒光。BMT absorbs UV radiation, dissipates the energy through cycles of internal conversion followed by vibronic relaxation in the form of heat.輻射弛豫Radiation DeactivationPage 8熒光淬滅 (Fluorescence Quenching)y = -905.56x + 85.395R = 0.9908y = -63.49x + 88.154R = 0.6548304050607080901

12、000%1%2%3%4%5%6%光強(qiáng)度 （Luminance）BMT濃度（Concentration，%W/W）線性 (BMT)線性 (368)y = -943.20 x + 84.245R = 0.9851y = -79.17x + 86.349R = 0.8787304050607080900%1%2%3%4%5%6%光強(qiáng)度 （Luminance）BMT濃度 （Concentration，%W/W）線性 (BMT)線性 (368)*Ethylhexyl pamitate (EHP) 是作為陰性對照的惰性溶劑。（Inert to quench AVB as negative control

13、）* Modified method from Craigs article “Research Pathways to Photostable Sunscreens” C&T, Vol.123, No.22, P49-60, 2008Page 9激發(fā)態(tài)猝滅（能量轉(zhuǎn)移）Excited State Quenching (Energy Transfer)D*ADA*D* - 能量供能量供給給體，激體，激發(fā)態(tài)發(fā)態(tài)（Donor ，the molecule in the excited state）A - 能量接受體，基能量接受體，基態(tài)態(tài)（Acceptor ，starting out the groun

14、d state）偶極子偶極子機(jī)理，(Frster quenching) 熒光共振能量轉(zhuǎn)移，F(xiàn)RET(Fluorescence Resonance Energy Transfer) 單重激發(fā)態(tài)淬滅的主要機(jī)理(Primary mechanism for singlet quenching)電荷轉(zhuǎn)移機(jī)理，(aka Dexter exchange) 三重激發(fā)態(tài)淬滅的主要機(jī)理(Dominant mechanism for triplet quenching)兩種淬滅機(jī)理（Two Important Mechanisms）Page 10熒光共振能量轉(zhuǎn)移FRET (Fluorescence Resonanc

15、e Energy Transfer)020000400006000080000290340390440BMT absorptionAVB fluorescence供體和受體的偶極子的相對方位。 Transition dipole orientations must be approximately parallel供體的發(fā)射光譜與受體 的吸收光譜有一定的重疊。Acceptor absorption spectrum must overlap donor fluorescence spectrum供體與受體之間距離合適。Action at a distance (typically 10-100

16、 ) Page 11紫外吸收劑的光穩(wěn)定實(shí)驗(yàn)（Photo Stability Tests）溶劑中 (In Solvent) 溶劑 (Solvents): Phenethyl Benzoate (苯乙醇苯甲酸脂), C12-15 Alkyl Benzoate (C12-15醇苯甲酸脂） 紫外吸收劑 (UV absorbers): 1% AVB, 2% OMC, 2% BMT 混合物 (Combinations): 1% AVB + 1% OMC, 1% AVB + 1% BMT, 1% AVB + 1% OMC + 1% BMT乳液中 (In Emulsion) 乳液體系 (Systems): 硬

17、脂醇聚醚 ( Steareth-2 & Steareth-21), Prolipid 141 systems 溶劑 (Solvents): Phenethyl Benzoate (苯乙醇苯甲酸脂), C12-15 Alkyl Benzoate (C12-15醇苯甲酸脂） 紫外吸收劑 (UV absorbers): 5% AVB + 5% OMC, 5% AVB + 5% OMC + 1% BMT, 3%BMT, and 5% BMTPage 12光穩(wěn)定實(shí)驗(yàn)步驟(Test Procedure)Q-sun chamberUV spectrophotometer PMMA 板 (plate)樣品 (

18、Samples)(In Emulsions & In Solvents)涂抹樣品 (Apply sample)Dry for 15minUV transmittance/SPF(290nm -400nm)紫外光照射1小時(shí)(UV irradiation)41J/m2, 1 hourUV spectrophotometer UV transmittance/SPF(290nm -400nm)防曬指數(shù)對比(SPF Value)comparison未紫外光照射的樣品Pre-irradiationSample紫外光照射后的樣品Post-irradiationSamplePage 1387%83%108%

19、80%103%97%37%77%106%56%86%83%1%AVB2%OMC2%BMT1%AVB+1%OMC1%AVB+1%BMT1%AVB+1%OMC+1%BMTPhenethyl benzoateC12-15 Alkyl benzoate溶劑中 的光穩(wěn)定實(shí)驗(yàn) (Photo Stability in Oils)經(jīng)過1小時(shí)紫外照射后紫外吸收劑的剩余比例 (%) 紫外吸收劑剩余比例 (UV Absorbers Residue) %苯乙醇苯甲酸脂C12-15醇苯甲酸脂Page 14乳液體系 I (System I, Steareth-2 & Steareth-21, 硬脂醇聚醚 )成分 (Ing

20、redients)INCI名稱(INCI Name)無BMT成分(Series 1)有BMT成分(Series 2)供應(yīng)商(Supplier)Phase ADeionized waterWater70.3569.35GlycerineGlycerine2.002.00CognisStabileze QMPVM/MA Decadiene crosspolymer0.300.30AshlandDisodium EDTADisodium EDTA0.100.10Phase BBrij 72Steareth-22.552.55CrodaBrij 721Steareth-211.651.65CrodaA

21、VB (517)Butyl methoxydibenzoylmethane5.005.00AshlandBMT (S)Bis-ethylhexyloxyphenol methoxyphenyl triazine1.00/3.00/5.00AshlandOMC (557)Ethylhexyl methoxycinnamate5.005.00AshlandSolvent (Xtend 226/Finsolv TN)Phenethyl benzoate/Blend/C12-15 alkyl benzoate10.0010.00Ashland/InnospecPhase CAMP-95Aminomet

22、hyl Propanol0.350.35DowPhase DLiquapar OptimaPhenoxyethanol/methylparaben,etc.1.251.25AshlandPage 15乳液體系 II (System II, Prolipid 141, 層狀凝膠乳化劑)成分 (Ingredients)INCI名稱(INCI Name)有BMT成分無BMT成分供應(yīng)商(Supplier)Phase ADeionized waterWateraq. 100aq.100STABILEZE QMPVM/MA Decadiene crosspolymer0.30 0.30 AshlandGl

23、ycerineGlycerine2.00 2.00 CognisDisodium EDTADisodium EDTA0.10 0.10 Phase BProlipid 141Glyceryl stearate/behenyl alcohol/palmitic acid/stearic acid, etc.5.00 5.00 AshlandOMC (557)Ethylhexyl methoxycinnamate5.00 5.00 AshlandBMT (S)Bis-ethylhexyl oxyphenol methoxyphenyl triazine1.00 /3.00/5.00AshlandA

24、VB (517)Butyl methoxydibenzoyl methane5.00 5.00 AshlandSolvent (X-tend 226/Finsolv TN)Phenethyl benzoate/blend/C12-C15 alkyl benzoate10.00 10.00 Ashland/InnospecPhase CNaOH 10% solutionSodium dioxide0.70 0.70 Deionized waterwater5.00 5.00 Phase DLiquid OptimaPhenoxyethynol, propylparaben,etc1.00 1.0

25、0 AshlandPage 1615.920.524.727.1 11.920.625.136.0 -35.0-25.0-15.0-5.05.015.025.035.0Pre-SPFPost-SPFPhotodegradation%苯乙醇苯甲酸脂Phenethyl Benzoate(Xtend 226)乳液體系 I (硬脂醇聚醚) 中的光穩(wěn)定實(shí)驗(yàn)Photo Stability in Emulsion I (Steareth-2&Steareth-21)AVB:OMC:BMT5:5:05:5:15:5:35:5:5Page 1715.717.419.522.09.112.318.125.3-20

26、.0-10.00.010.020.030.040.0Pre-SPFPost-SPFPhotodegradation%乳液體系 I (硬脂醇聚醚) 中的光穩(wěn)定實(shí)驗(yàn)Photo Stability in Emulsion I (Steareth-2&Steareth-21)C12-15醇苯甲酸脂C12-15 Alkyl BenzoateAVB:OMC:BMT5:5:05:5:15:5:35:5:5Page 1832.531.535.642.719.231.137.247.0-10.00.010.020.030.040.050.0Pre-SPFPost-SPFPhotodegradation%乳液體系

27、 II 中的光穩(wěn)定實(shí)驗(yàn)Photo stability in Emulsion II (Prolipid 141)AVB:OMC:BMT5:5:05:5:15:5:35:5:5苯乙醇苯甲酸脂Phenethyl Benzoate(Xtend 226)Page 1925.429.934.947.68.513.221.039.60.010.020.030.040.050.060.070.0Pre-SPFPost-SPFPhotodegradation%AVB:OMC:BMT5:5:05:5:15:5:35:5:5乳液體系 II 中的光穩(wěn)定實(shí)驗(yàn)Photo stability in Emulsion II

28、 (Prolipid 141)C12-15醇苯甲酸脂C12-15 Alkyl Benzoate323136433130516925346880276279100防曬指數(shù) 未輻照 (SPF value - Pre irradiation)Page 20樣品穩(wěn)定性測試 (3個(gè)月) - 乳液體系 II，苯乙醇苯甲酸脂(3 months Stability Study Emulsion II, Phenethyl Benzoate)193137471620456213216180145087100防曬指數(shù) - 輻照后SPF value - Post irradiationIntRT445 595153

29、52 9966 63 80 105 8789109 10990100 99防曬指數(shù) 剩余比(%)Residual SPF Value %AVB:OMC:BMT5:5:05:5:15:5:35:5:5Page 2125303548293144592431615826466383防曬指數(shù) 未輻照 (SPF value - Pre irradiation)913214010142335812253310182843防曬指數(shù) - 輻照后SPF value - Post irradiationOriginal 25445343335374445 404060 53 40 44 835957 52防曬指數(shù) 剩余比(%)Residual SPF Value %樣品穩(wěn)定性測試 (3個(gè)月) - 乳液體系 II，C12-15醇苯甲酸脂(3 months Stability Study Emulsion II, C12-15 Alkyl Benzoate)AVB:OMC:BMT5:5:05:5:15:5:35:5:5Page 22結(jié)論 (Conclusions)u阿伏苯宗 (AVB)是最廣泛使用的UVA紫外吸收劑之一，但在紫外光照射