BEMT: An Efficient Broad-Spectrum UV Filter

Transcription

1 TESTING METHODS SUN CARE TECHNOLOGIES INGREDIENTS FROM THE SEA CT BEMT: An Efficient Broad-Spectrum UV Filter Sebastien Mongiat, Bernd Herzog, Cyrille Deshayes, Peter König and Uli Osterwalder Ciba Specialty Chemicals, Basel, Switzerland Over the past decade the need for improved UVA protec tion became apparent. UV radiation has adverse effects, including sunburn, photoaging and skin cancer. These effects can only be prevented by protecting against the whole range of UV radiation, including UVA. On the other hand there is also a trend to limit the amount of chemicals on the skin. This means that very efficient UV absorbers should be available for the new requirement of broad UV protection. Bis-Ethylhexyloxyphenol methoxyphenyl triazine a (BEMT) has been designed to fulfill this requirement. It is photo-stable, oil-soluble, very efficient and covers the UVB and UVA range. 1 Its physical and chemical properties are shown in Table 1. In the year 2000, European authorities added BEMT to the positive list of cosmetic UV absorbers. 2 Design of BEMT Due to their molecular structure, hydroxyphenyltriazines (HPTs) exhibit a UV spectrum with two distinctive absorption bands. This is due to the presence of two electronic transitions with strong dipole moments, both of which are polarized perpendicular to each other (Figure 1). In order to obtain broad-spectrum absorbance, OH and a Tinosorb S, Ciba Specialty Chemicals Inc., Basel, Switzerland. Ciba and Tinosorb are registered trademarks of Ciba Specialty Chemicals. O-alkyl substituents have to be introduced at the three phenyl groups and positioned as shown in Figure 1. UVA: Two ortho-oh groups are required for efficient energy dissipation via intramolecular hydrogen bridges. In order to obtain strong absorption in the UVA, the para-positions of the two respective phenyl moieties should be substituted by O-alkyl, resulting in a bis-resorcinyl triazine chromophor. UVB: The remaining phenyl group attached to the triazine leads to UVB absorption. It can be demonstrated that maximal full spectrum performance is achieved with O-alkyl located in the para-position. 1 Without solubilizing substituents, HPTs are nearly insoluble in cosmetic oils. They exhibit the typical properties of pigments (e.g., high melting points). In order to increase solubility Key words sunscreen, bisethylhexyloxyphenol methoxyphenyl triazine, BEMT, broad-spectrum UV protection, hydroxyphenyltriazine chemistry, persistent pigment darkening, UVA assessment Abstract Efficient broadspectrum UV protection is provided by bisethylhexyloxyphenol methoxyphenyl triazine (BEMT), an oil-soluble, photostable UV absorber that offers improved UVA protection and synergy with UVB filters. Table 1. Physical and chemical properties of bis-ethylhexyloxyphenol methoxyphenyl triazine Chemical Name 2,4-Bis-{[4-(2-ethyl-hexyloxy)-2-hydroxy]-phenyl}-6-(4-methoxyphenyl)-(1,3,5)-triazine INCI name Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine (BEMT) CAS no Molecular formula C38H49N3O5 Molecular mass g/mol Melting point 80 C Photostability Stable over 50 MED according to the method of Berset et al 3,5 Appearance Light yellow powder Absorbance E (1%, 1 cm) 790 (in isopropanol, 341 nm) Use/concentration Sunscreen products/max. 10% /03/ $05.00/ Allured Publishing Corp. Cosmetics & Toiletries magazine/1

2 in oil phases, the structure of the UV filter has been modified accordingly. The introduction of two 2-ethyl-hexyl groups as shown in Figure 1 results in the formation of BEMT, a new oilsoluble UV filter with true broad-spectrum performance. In general the photostability of a UV filter depends on how well the molecule is able to release the absorbed energy to the environment in the form of heat. BEMT contains two intramolecular hydrogen bonds, which enables excited state intramolecular proton transfer (phototautomerism) after photoexcitation. This results in rapid radiationless internal conversion that ensures that the UV radiation, efficiently absorbed by the filter, is almost quantitatively transformed into harmless vibrational energy. The entire phototautomeric cycle only lasts seconds, leaving no time for undesirable side reactions, such as population of triplet states, formation of singlet oxygen or radical formation. 4 This explains the photostability of BEMT; in other words, more than 95% recovery of parent BEMT is observed analytically after UV irradiation of 50 minimal erythema doses (MED). 5 Efficacy of BEMT in UVA Protection Figure 1. Molecular structure (left) and UV-absorption spectrum of BEMT. (Arrows indicate the polarization of the UVA and UVB transitions.) Formula 1. O/W cream with 5% ethylhexyl methoxycinnamate and varying amounts of BEMT A. Cetearyl alcohol/ dicetyl phosphate/ ceteth-10 phosphate (Crodafos CES, Croda GmbH) 4.00%w/w C12-15 alkyl benzoate (Tegosoft TN, Goldschmidt) 6.0 Cetearyl octanoate/ isopropyl myristate (Crodamol CAP, Croda GmbH) 3.50 Caprylic/Capric triglyceride (Myritiol 318, Cognis) 2.00 Caprylyl pyrrolidone (Surfadone LP-100, ISP) 1.50 Stearic acid 1.50 Glyceryl stearate (Tegin M, Goldschmidt) 2.50 Bis-Ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S, Ciba) x Ethylhexyl methoxycinnamate (Tinosoft OMC, Ciba) 5.00 B. Water (aqua) qs C.Sodium acrylates copolymer (and) Glycine soja (and) PPG-1 trideceth-6 (Salcare AST, Ciba) 0.20 D. Diazolidinyl urea (and) iodopropynyl butylcarbamate (Gernall Plus, ISP) 0.15 Propylene glycol 3.50 Water (aqua) 5.00 E. Sodium hydroxide, 30% qs Procedure: Heat A and B separately to 75 C. Pour B into A under increased stirring; add C; homogenize 10 sec at 10,000 rpm. Add D around 40 C. Cool under stirring. At RT, adjust the ph and homogenize (10 sec at 16,000 rpm). Both in vitro and in vivo methods are used in the assessment of the UVA protection of a suncare formulation. UVA protection factors (PFA) of sunscreen formulations with ethylhexylmethoxycinnamate (EHMC) and different concentrations of BEMT (Formula 1) were measured using the method of persistent pigment darkening (PPD). 6,7 Irradiation of volunteers was performed with a UVA light source (320 to 400 nm). Two hours after irradiation, the minimal pigmenting dose of protected (MPDp) and unprotected (MPDu) skin was evaluated. Each formulation was tested on 10 panelists. The results were expressed as PFAs in analogy to the SPF. The reference sample of the Japanese UVA standard 8 was also measured for comparison, using the same procedure on 10 panelists. It contains 5% butylmethoxydibenzoylmethane (BMBM) and 3% EHMC. In our tests, the UVA protection factor (PFA) of this reference sample was only 4.5 (in agreement with the standard, 4.3). However, non-irradiated BMBM has a higher extinction in the UVA range than BEMT. In fact the same PFA can already be achieved with only 1% BEMT (Figure 2). This clearly demonstrates the difference in photostability. PA+++ is the highest category of UVA protection according to the Japanese standard (where PA+, PA++ and PA+++ are increasingly good grades indicating protection against UVA radiation). We found that PA+++ is already reached with about 3% BEMT alone or 2% BEMT plus 5% EHMT. Herzog et al. have shown 6 that this synergistic effect with EHMC in the UVA range is not observed with BMBM, nor is it seen when BMBM is stabilized with octocrylene. Formulating with BEMT The cosmetic formulators have to design systems that will remain stable over the 2/Cosmetics & Toiletries magazine

3 Table 2. Solubility of BEMT in selected solvents Figure 2. PFA of BEMT and BEMT/EHMC (PPD method) useful lifetime of the product. 9 This requires a good working knowledge about the characteristics of each part of an emulsion including the oil phase, the aqueous phase and the emulsifier. Incorporation of BEMT in oil phase: The product form of BEMT is a very fine yellow powder with a melting point of 80 C. It is easily solubilized in most lipophilic emollients (Table 2), especially those with a high surface tension, because they present the lowest surface tension gradient (interfacial tension) between the oil and water phases. The interfacial tension is used as a guide to the emollient s polarity; the more polar the oil, the lower its interfacial tension with water. With BEMT, the polarity of lipophilic oils used in the oil phase is an essential parameter to develop stable formulations. The oil surface tension has a significant impact on the spreadability and therefore on the SPF of the formulation. 10 To create an uninterrupted and uniform film, an oil phase with high surface tension is required. Handling of BEMT in a W/O system: Formulating a physico-chemically stable W/O emulsion requires a minimal quantity of nonpolar oils. On the other hand, BEMT solubilization requires a sufficient amount of polar oils. Therefore, the formulator has to compromise in order to guarantee a stable W/O emulsion with BEMT. A reasonable limit for the use of BEMT in W/O emulsions is 3%. The stability of W/O emulsions that are built with mainly polar oils can be improved by adding some structure to the emulsion system. 11 For this purpose, one can use ethoxylated dodecylglycol copolymer, waxes and clays. One can also use polyglyceryl esters, an emulsifier category that builds liquid lamellar phases. Combining BEMT with inorganic pigments: Formulators face a major challenge in stabilizing an emulsion containing significant quantities of particulate materials (such as microfine particles of TiO 2 or ZnO) while maintaining their efficacy and controlling the whitening effect on skin. 12 To help meet this challenge, the combination of BEMT with TiO 2 offers several advantages: Lower levels of organic sunscreens in end-products; Solvent Solubility Caprylylpyrrolidone 20% Ethylhexyl salicylate 20 Isodecyl salicylate 18 Ethylhexyl methoxycinnamate 17 C 12 -C 15 Alkylbenzoate 13 Butyloctyl salicylate 11 Diethylhexyl adipate 9 Diethylhexyl succinate 7 Isopropylmyristate 6 Hexyl laurate 6 Coco caprylate / caprate 5 Caprylic / Capric triglyceride 5 Isopropylpalmitate 5 Sesame oil 3 Mineral oil <1 Figure 3. Synergy of BEMT with UVB filters Less whitening effect and more elegant end-products; Synergistic effect on the sun protection efficacy. Synergy of BEMT with UVB Filters Synergy is present when a particular combination of UV filters gives an SPF that is higher than the sum of the SPFs of each of the filters measured alone assuming all SPFs are determined by the same method, such as that of COLIPA. 13 We determined the synergy of 3% BEMT combined with 4% organic UVB filter, or 4% or 5% inorganic UVB filter (Figure 3). The SPF values of BEMT, the UVB absorbers and all combination pairs were calculated using a calibrated step film model 14 that was first proposed by O Neill. 15 The calculations are in good agreement with in vivo data. Cosmetics & Toiletries magazine/3

4 Formula 2. Sun protection emulsion for hydrophilic dispersion (A) or lipophilic dispersion (B) A B Ingredient (%w/w) (%w/w) A. Polyglyceryl-3 methylglucose distearate (Tego Care 450, Degussa) Caprylic/Capric triglyceride (Tegosoft CT, Degussa) Myristyl myristate (Tegosoft MM, Degussa) Dimethicone (Abil 350, Degussa) Mineral oil (paraffinum liquidum) (Paraffin, Merck) Bis-Ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S, Ciba) Titanium dioxide (and) alumina (and) dimethicone (UV Titan M262, Kemira) Cetyl dimethicone (Abil Wax 9840, Degussa) B. Water (aqua) qs qs Glycerin Xanthan gum (Rhodicare S, Rhodia) Aqua (and) titanium dioxide (and) alumina (and) metaphosphate (and) phenoxyethanol (and) sodium methylparaben (Eusolex T-Aqua, Merck) C. Phenoxyethanol (and) methylparaben (and) ethylparaben (and) butylparaben (and) propylparaben (and) isobutylparaben (Phenonip, Clariant) Procedure: Heat A and B separately to 75 C under moderate stirring. Add A to B under stirring. Homogenize for 20 sec with Ultra Turrax at 11,000 rpm. Allow to cool to 40 C. Add C. Let cool to RT and adjust the ph value between 6.50 and Table 3. Experiments on the Ciba Sunscreen Simulator Formula F-1 F-2 F-3* F-4* F-5* SPF UVA Transmission nm 100% 58% 60% 40% 26% Ingredients EHMC 7% 7% 5% EHT** 2% 1% BP-3 3% ZnO 3% BMBM 2% BEMT*** 3% 3% 3% MBBT*** 3% Total percentage of UV filter 10% 10% 8% 7% 7% * These formulations cannot yet be used in the USA. ** Not yet approved in the USA; US application (TEA) under way. 18 *** Does not yet have five years non-us marketing experience that is required for TEA. 18 BEMT shows a very strong synergy with the two most efficient UVB filters (which are ethylhexyl triazone and diethylhexyl butamido triazone) and a slight synergy in combination with the most frequently used, but less efficient UVB filter (ethylhexyl methoxycinnnamate). BEMT also shows a strong synergy with the inorganic UVB filter (TiO 2 ) that is used in most high SPF (e.g. 30+) sunscreens today. The synergy was tested with O/W b Tego Care 450, Degussa.Care Specialties, Essen, Germany. Tego is a registered trademark of Degussa.Care Specialties. emulsion systems using a standard formula (Formula 2) built with polyglyceryl ester emulsifiers b at 4% and using the in vitro assessment with polymethylmethacrylate (PMMA) plates (1.2 mg/cm 2 ). Two grades of TiO 2 were used together with 3% BEMT. We tested the hydrophilic grade c at 4% active ingredient and a lipophilic grade d at 5%. One explanation for the synergy is that the scattering of light by physical sunscreens increases the optical path length through the film and increases the absorption of UV light by the organic filter (such as BEMT). As expected, the synergy with the lipophilic grade TiO 2 turned out to be lower than with the hydrophilic grade because in the latter case the filters are present in both the oil phase and the water phase. We also checked the synergy using the Kull equation 14 (raw data BEMT 3% = SPF 7, TiO 2 5% = SPF 6, combined = SPF 18). The results again confirmed synergy. Improved UVA Protection One would expect the addition of BEMT into a sunscreen or day cream would improve UVA protection. To illustrate and quantify the improvement, we carried out some calculations with different formulations using the Ciba Sunscreen Simulator Table 3 shows the compo- c Eusolex T-2000 from Merck, Darmstadt, Germany. The INCI name is Water (aqua) (and) titanium dioxide (and) alumina (and) metaphosphate (and) phenoxyethanol (and) sodium methylparaben. d UV-Titan M262 from Kemira Pigments Oy, Pori, Finland. The INCI name is Titanium dioxide (and) alumina (and) dimethicone. 4/Cosmetics & Toiletries magazine

5 Conclusion Efficient broad-spectrum UV protection is provided by bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT), an oil-soluble, photostable UV absorber. It is compatible with UVB filters and can thus cover all needs from daily care to special high SPF sunscreens, especially those providing improved UVA protection. Reproduction of all or part of this article in English or any other language is strictly prohibited. Figure 4. Improvement in UVA protection shown as reduction in UVA transmission due to new broad-spectrum filters, calculated by 2-step model. 15,16 Area below formula F-1 (EHMC plus benzophenone-3) was defined as 100%. sition of these formulations. They all had similar SPFs, meaning similar UVB protection. But they differed significantly in the amount of UVA protection they offered. In spite of great differences, all these formulations could make UVA or broadband claims. We also measured the amount of UVA ( nm) transmitted through selected sunscreen films. The amount of UVA radiation still reaching the skin through a layer of sunscreen is best seen from the transmission curve of that sunscreen. The transmission spectrum was calculated using a 2-step film model (Figure 4). 15 The sunscreen with the highest UVA transmission was F-1 with benzophenone-3. This area has arbitrarily been defined as 100%. Formula F-2 with ZnO reduces this UVA exposure through the sunscreen to below 60%. With formula F-5, using BEMT, and another new broad-spectrum filter called methylenebisbenzotriazolyl tetramethylbutylphenol (MBBT), 19,20 the UVA exposure is reduced to a quarter of the value achieved with the conventional formulation (F-1). The new broad-spectrum UV filter BEMT provides a means to further improve the UVA protection as well as the overall efficacy of sunscreens. This is best illustrated by calculations of the transmission spectrum and confirmed by in vivo measurements. The residual UVA radiation still reaching the skin can be reduced to a quarter of the value of a conventional sunscreen. The improved efficacy of BEMT in UVA protection is confirmed by the measurement of the in vivo PFA (UVA protection factor after the PPD method). With only 2% BEMT together with the UVB filter EHMC, the highest protection category of the Japanese Standard, PA+++, can be reached. References Address correspondence to Uli Osterwalder, c/o Editor, Cosmetics & Toiletries magazine, 362 South Schmale Road, Carol Stream, IL USA. 1. D Hueglin, B Herzog, S Mongiat, Hydroxyphenyltriazines: A new generation of cosmetic UV filters with superior photoprotection, Oral presentation at 22 nd IFSCC, Edinburgh, September Twenty Fourth Commission Directive 2000/6/EC of 29 February 2000, Council Directive 76/768/EC, Official Journal of the European Communities L56/42 (Mar 1, 2000) 3. G Berset, H Gonzenbach, R Christ, R Martin, A Deflandre, RE Mascotto, JDR Jolley, W Lowell, R Pelzer and T Stiehm, Int J Cosmet Sci (1996) 4. J-E Otterstedt, Photostability and molecular structure, J Phys Chem (1973) 5. B Herzog and K Sommer, Investigations on photostability of UV-absorbers for cosmetic sunscreens, Proceedings (CD-ROM): 21 st IFSCC Congress, Berlin, Poster P 60, September B Herzog, S Mongiat, C Deshayes, M Neuhaus, K Sommer and A Mantler, In vivo and in vitro assessment of UVA-protection by sunscreen formulations containing either butyl methoxy dibenzoyl methane, methylene bisbenzotriazolyl tetramethylbutylphenol, or microfine ZnO, Oral presentation at 22 nd IFSCC, Edinburgh, September A Chardon, D Moyal and C Hourseau, Persistent pigment-darkening response as a method for evaluation of ultraviolet A protection assays, In Sunscreens: Development, Evaluation, and Regulatory Aspects, NJ Lowe, NA Shaath and MA Pathak, 2 nd edn, New York: Marcel Dekker (1997) pp JCIA Measurement Standard for UVA Protection Efficacy, Minato-Ku Tokyo: Japan Cosmetic Industry Association (1995) p R Schueller and P Romanowski, Understanding emulsions, Cosmet Toil 113(9) (1998) 10. GH Dahms, Choosing emollients and emulsifiers for sunscreen products, Cosmet Toil 109(11) (1994) 11. JP Hewitt, The influence of emulsion structure on SPF in physical sunscreen formulations, Poster 22 nd IFSCC Congress, Edinburgh B Innes, Nanotechnology and the cosmetic chemist, 22 nd IFSCC Edinburgh, September COLIPA sun protection factor test method, ref. 94/289, Brussels, Belgium: The European Cosmetic Toiletry and Perfumery Association (Oct 1994) 14. B Herzog, Prediction of sun protection factors by calculation of transmissions with a calibrated step film model, J Cosmet Sci 53(1) (2002) 15. D Steinberg, Measuring synergy, Cosmet Toil 115(11) (2000) 16. JJ O Neill, Effect of film irregularities on sunscreen efficacy, J Pharm Sci (1984) 17. Ciba Specialty Chemicals, The Ciba Sunscreen Simulator, personalcare 18. S Onel, FDA finalizes rule that could expand OTC drug marketplace, UPDATE Food and Drug Law, Regulations and Education, issue 5 (Sep/Oct 2002) U Osterwalder, H Luther and B Herzog, UV-A protection with a new class of UV absorber, Proceedings of the 47th SEPAWA Kongress, Bad Durkheim: SEPAWA Vereinigung der Seifen-, Parfüm- und Waschmittelfachleute ev (2000) pp U Osterwalder, H Luther and B Herzog, New Class of UV absorber with excellent performance in UV-A region, In Cosmetics and Toiletries Manufacture Worldwide, Hemel Hempstead, UK: Aston Publishing Group (2001) pp CT Cosmetics & Toiletries magazine/5