New method for stabilising sunscreens
Phytoene and phytofluene, the colourless carotenoids, are the precursor carotenoids in the biosynthetic pathway of visibly coloured carotenoids. These molecules are colourless in the visible range; hence absorb light in the UV range only.
These molecules have effective and benefiting activities enhancing skin antiinflammatory capacity, protecting against UV and oxidative damage leading to premature ageing and other disorders. Effects on reduction of skin pigmentation were demonstrated, most likely related to the dual protection against UV irradiation, damage and inflammation. Phytoene and phytofluene, the colourless carotenoids are able to stabilise and boost other molecules; among them various sunscreens. Avobenzone, a broad spectrum sunscreen, is heavily degraded by daylight due to UV irradiation and radical generation. Free radical generation by TiO2 and ZnO, when exposed to UV, is known and is leading to increased instability of other components in formulas, as well as increasing the risk of oxidative damage from the free radicals generation. The colourless carotenoids, phytoene and phytofluene absorbing light in the UV range and being excellent hydroxyl radical quenchers are shown in the present study to reduce TiO2 free radical generation damage and stabilise avobenzone when exposed to UV light and free radical attack.
Avobenzone is an oil soluble, broad spectrum sunscreen product with an absorption maximum of 357 nm.6 The INCI name of avobenzone is: Butyl Methoxydibenzoylmethane. Avobenzone is significantly degraded by UV light and normal day light. Therefore, it will be drastically reduced over time during the course of normal use. Control degradation studies have shown that one hour of sunlight exposure reduces avobenzone absorbance by 36%.7-10,16 Avobenzone degrades faster when exposed to light in combination with physical sunscreens like zinc oxide and titanium dioxide. These compounds protect against UV irradiation by reflecting the light, however, this action also generates free radicals that can subsequently degrade the avobenzone.18 Stabilisation of avobenzone by free radical quenching and photo stabilisation is therefore needed to maintain the optimum protective activity from this sunscreen. A number of stabilisers to avobenzone are being claimed.11-15 The colourless carotenoids, phytoene and phytofluene demonstrate excellent hydroxyl radicals quenching capabilities.1-5 These unique and proprietary colourless carotenoids absorb light at the UVB and UVA range respectively (Fig. 1).1-5 Therefore, in the present study we investigated the capability of the colourless carotenoids to reduce TiO2 free radical generation damage and to stabilise avobenzone when exposed to UV light and free radicals attack. The colourless carotenoids have the ability to both absorb UV light and quench UV generated free radicals such as hydroxyl radicals and have been shown to stabilise oil soluble ingredients such as retinol and ?-carotene from photo-degradation. The observations have led us to study the ability of these photo stabilising agents to stabilise and protect other photo sensitive actives, among them avobenzone.
Results and discussion
Free radicals generation by TiO2 and ZnO when exposed to UV is known and leads to increased instability of other components in the formula as well as increasing the risk of oxidative damage from the free radicals generated.17-19 Avobenzone when formulated alone or in combination with the mineral sun screens is significantly unstable and easily decomposed when exposed to UV (especially UVA). The ability of phytoene and phytofluene to protect against free radicals generated by TiO2, following UV irradiation was initially investigated (Fig. 2). To study the protective effect of phytoene and phytofluene, phenol, a highly sensitive compound to free radical-induced decomposition was UV irradiated in the presence of TiO2 (0.25%), with increased levels of additional phytoene and phytofluene (TiO2 0.25%+ 0.01 mg/mL phytoene and phytofluene versus TiO2 0.25%+ 0.05 mg/mL phytoene and phytofluene). Increased levels of phytoene and phytofluene increased the stability and resistance of phenol to degradation by UV irradiated TiO2 (Fig. 2). To study the ability of phytoene and phytofluene to stabilise avobenzone, avobenzone 2% was dissolved in oil (polydecene) and exposed for 10 minutes to sunlight. The same concentration of avobenzone was mixed with increasing levels of phytoene and phytofluene (0%, 0.0037%, 0.0075% and 0.015%) in the polydecene solutions and exposed for 10 minutes to the sun. Levels of avobenzone were quantified using UV-VIS spectrophotometer and calculated based on Extinction Coefficient value 1618 of avobenzone in hexane at ?-350 nm. All samples were tested in parallel. Following 10 minutes of exposure to sunlight, avobenzone levels were reduced by 36%. In the presence of 0.015% phytoene and phytofluene photodecomposition of avobenzone was only 17%, retaining 50% more avobenzone than without stabiliser. These results show that phytoene and phytofluene, the colourless carotenoids were able to both stabilise avobenzone (Fig. 3) and quench the free radicals generated from irradiation of TiO2 (Fig. 2) thereby potentially increasing the sunscreen’s safety, stability and ultimate efficacy. Additional studies with 1.76% avobenzone with and without 0.0075% phytoene and phytofleune exposed to the sun for 10 minutes resulted in improved stability of the avobenzone as can be observed from Figure 4. Following the convincing results from the studies described above, a preliminary study with prepared basic cream containing 3% avobenzone labelled 703-1, to which phyto(flu)ene (0.0075%), was added and labelled 703-2, was conducted to determine the contribution of phyto(flu)ene to sun protection and photo stability of avobenzone under UVA following the Colipa 2009 in vitro Standard Guidelines. As appeared through this part of the study, the formula to which both the avobenzone and the phyto(flu)ene are formulated is extremely important. Therefore, only a fraction of the results are presented and formulation optimisation is under work.
Procedure brief: Approximately 1.7 mg/cm2 of each formula is applied to 5 PMMA plates (Helioplates-HD-6, Helioscreen, Source: Labsphere, North Sutton, NH), respectively, and allowed to equilibrate for at least 15 minutes. Absorbance spectra from five locations on each plate is measured using a UV2000 Sunscreen Analyzer (Labsphere, North Sutton, NH). Before and after irradiation with UVA doses of 10 J/cm2 administered using an Atlas Suntest CPS+ UV Irradiation System (Atlas Materials Testing, Inc. Chicago) [Fig. 5] which allowed measuring boost to SPF and UVA-PF due to the fact that the energy source of the SunTest lamp was not strong enough to degrade the avobenzone and only an addition to UVA-Pf with the phyto(flu)ene was measured. Plate temperatures are 25°C to 35°C. Mean UVA protection factors at each UV dose are then computed for each test product, using Colipa UVA Protection Factor Test Method Spreadsheet, and mean absorbance spectra from 290 nm to 400 nm is obtained.
Based on these studies, phytoene and phytofluene may function in stabilising avobenzone when exposed to sunlight as well as controlled UVA exposure similar to sunlight using Sun Test. Additionally, the colourless carotenoids, phytoene and phytofluene, prevent the oxidative damage generated by mineral sunscreens when irradiated with UV through quenching of the free radicals formed. An increase to mostly UVA-PF in the presence of the phytoene and phytofluene, colourless carotenoids, is observed too under Sun Test conditions. These observations support the potential increase in stability, safety and effectiveness of these sunscreens due to the presence of phytoene and phytofluene, the colourless carotenoids (Data as well as phytoene and phytofluene products are provided by IBR Ltd).
References 1 von Oppen-Bezalel L. Lightening, Boosting and Protecting with Colorless Carotenoids. Cosmet Toiletries, 124 (3), 66-75, (2009) 2 von Oppen-Bezalel L. Round-up: Colourless carotenoids may protect skin against inflammation and UV radiation. H&PC Today, n2/2008 p: 31-34. 3 von Oppen-Bezalel L. UVA, A Main Concern in Sun Damage: Protection from the Inside and Outside with Phytoene, Phytofluene, the Colorless Carotenoids and more. SÖFW-Journal, 11-2007. 4 von Oppen-Bezalel L., Shaish A. Application of the Colorless Carotenoids, Phytoene, and Phytofluene in Cosmetics, Wellness, Nutrition, and Therapeutics. In The alga Dunaliella: Biodiversity, Physiology, Genomics & Biotechnology, Eds. Ami Ben-Amotz, Juergen Polle, and Subba Rao, released May 2009 by Science Publishers, Enfield, NH, USA (2009). 5 von Oppen-Bezalel L., Lerner E., Kern D.G., Fuller B., Soudant E., Shaish A. IBR-CLC, Colorless Carotenoids: Phytoene and Phytofluene from Unicellular Algae – Applications in Cosmetics, Wellness and Nutrition. Fragrance Journal, 2006, Vol 34; Part 3, pages 48-53. PPCC 6 Vielhaber G., Grether-Beck S., Koch O., Johncock W., Krutmann J. Sunscreens with an absorption maximum of > or =360 nm provide optimal protection against UVA1-induced expression of matrix metalloproteinase-1, interleukin-1, and interleukin-6 in human dermal fibroblasts. Photochem Photobiol Sci, 5 (3), 275–82, (March 2006). 7 Chatelain E., Gabard B. Photostabilization of Butyl methoxydibenzoylmethane (Avobenzone) and Ethylhexyl methoxycinnamate by Bisethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S), a new UV broadband filter. Photochem Photobiol, 74 (3), 401-6, (September 2001). 8 Tarras-Wahlberg N., Stenhagen G., Larko O., Rosen A., Wennberg A.M., Wennerstrom O. Changes in ultraviolet absorption of sunscreens after ultraviolet irradiation. J Invest Dermatol, 113 (4), 547-53 (October 1999). 9 Wetz F., Routaboul C., Denis A., Rico-Lattes I. A new long-chain UV absorber derived from 4-tert-butyl-4’-methoxydibenzoylmethane: absorbance stability under solar irradiation, J Cosmet Sci, 56 (2), 135-48, (Mar-Apr 2005). 10 CTFA letter re: Tentative Final Monograph for OTC Sunscreen 11 Bonda C., Steinberg D.C. A new photostabilizer for full spectrum sunscreens. Cosmet Toiletries, 115 (6), 37-45, (2000). 12 http://www.dsm.com/en_US/downloads/ dnp/Parsol_SLX_Skin.pdf 13 Chaudhuri R.K., Lascu Z., Puccetti G., Deshpande A.A., Paknikar S.K. Design of a photostabilizer having built-in antioxidant functionality and its utility in obtaining broadspectrum sunscreen formulations. Photochem Photobiol, 82 (3), 823-8, (May-Jun 2006). 14 http://www.hallstar.com/techdocs/Polycrylene& CorapanTQAvobenzoneStabilization.pdf 15 Scalia S., Simeoni S., Barbieri A., Sostero S. Influence of hydroxypropyl-beta-cyclodextrin on photo-induced free radical production by the sunscreen agent, butyl-methoxydibenzoylmethane. J Pharm Pharmacol, 54 (11), 1553-8, (November 2002). 16 Warwick L. Morison M.D. Photosensitivity. The New England Journal of Medicine, 350, 1111-1117, (March 11, 2004). 17 Sunscreen Drug Products for Over-the-Counter use; Marketing Status of Products Containing Avobenzone; Enforcement Policy (PDF). US Food and Drug Administration. 1997-04-30. 23354. http://www.fda.gov/cder/otcmonographs/ Sunscreen/sunscreen_avobenzone_enforc_policy _19970420.pdf. Retrieved on 2007-06-03. 18 Stability Study of Avobenzone with Inorganic Sunscreens, Kobo Products Poster, 2001, Online version 19 Wakefield G., Lipscomb S., Holland E., Knowland J. The effects of manganese doping on UVA absorption and free radical generation of micronized titanium dioxide and its consequences for the photostability of UVA absorbing organic sunscreen components, Photochem Photobiol Sci, 3 (7), 648-52, (July 2004).