j. Soc. Cosmet. Chem., 41, 67-84 (January/February 1990) Efficacy of 4-methoxydibenzoylmethane-2-carboxylic acid as a new broad-spectrum sunscreen GENJI IMOKAWA, TORU TEJIMA, NORIHARU KIRII, and MICHIO KAWAI, Tochigi and Tokyo Research Laboratories, Kao Corporation, Tochigi and Tokyo, Japan. Received March 1, 1989. Synopsis 4-Methoxydibenzoylmethane-2-carboxylic acid (MDC) was developed as a new sunscreen agent that is characterized by varying UVA and UVB absorption spectra with the cationic metal compound, boehmite. For protection against UVA, MDC-boehmite complex demonstrates a remarkable preventive effect on PUVA-induced erythema and UVA-induced pigmentation. Further study on protection against UVB or natural sunlight reveals that MDC-boehmite complex also possesses a distinct protective effect against UVB- or sunlight-induced skin reactions including erythema, pigmentation, and immediate tanning, and that its protective effect is markedly enhanced in an optimal combination with the ordinary UVB sunscreen Parsol MCX. This preventive effect is corroborated by the fact that prostaglandin release induced in organ culture after PUVA or UVB (PUVA = 8-methoxypsoralen and ultraviolet-A radiation) exposure is also significantly suppressed by the application of MDC-boehmite complex. Based on these findings, MDC is found to be useful for preventing several adverse effects of exposure to sunlight. INTRODUCTION The UVA waveband has been an important subject of research on the protection of skin from damage caused by sunlight because several cutaneous effects of ultraviolet irradia- tion including wrinkles, pigmentation, and skin cancer are found to be attributable to not only UVB but also UVA exposure (1-4). It is well known that the best way of protecting skin from sun damage is to apply sunscreens. Many UVB filters are now commercially available, but very few UVA filters have been developed. Since it is not practical to use a UVA filter only, the combination of UVB and UVA filters is always recommended for sunscreen formulations. Thus, it is desirable to develop a UV filter that absorbs radiation in both UVB and UVA wavebands. For evaluation of the efficacy of sunscreens, many studies have focused on a sun protection factor that is mainly based on an erythematous reaction induced by UV irradiation. Since an erythematous reaction is a result of complex and elaborative biological reactions, it is also worthwhile to evaluate the beneficial effect of sunscreens on other biological events following UV exposure. In the present study, by measuring SPF values as well as the inhibitory effect on pigmentaion and prostaglandin synthesis, we evaluated the effectiveness of a broad- spectrum UV sunscreen that is capable of absorbing both UVB and UVA wavebands. 67

68 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS METHODS MATERIALS Groups of five to ten guinea pigs (albino Hartley strain and tortoiseshell guinea pigs) were used in the experiments. 4-Methoxydibenzoylmethane-2-carboxylic acid (MDC, •kma x = 344 nm, ½ = 30,300) was synthesized as described previously (5). SUNSCREEN PREPARATION MDC-boehmite complex was directly solubilized at indicated concentrations into aqueous solution or emulsified at indicated concentrations into W/O-type emulsion consisting of 3% o•-monomethyl heptadecyl glyceryl ether (GE Kao, Tokyo, Japan), 10% squalane, 3% petrolatum, and 10% octyl dodecyl myristate. PROTECTION AGAINST UVB EFFECT To test the effect of sunscreen agents on UVB-induced erythema, the experimental animals (guinea pigs, albino Hartley strain) were treated with samples on five separate areas and, ten minutes later, were irradiated once with 0.23-1.15 J/cm 2 of UVB light, emitted from a Toshiba FL20S'E30 lamp (SE lamp, Toshiba, Japan, 0.48 mW/cm 2, 1 MED = 7.9 minutes, 0.23 J/cm2). Test sites were observed 24 hours later to deter- mine the minimal erythema dose (MED), which is the smallest dose required to produce minimally visible erythema. Erythema was assessed according to the following scale: 0, no reaction _+, slight erythema 1 +, apparent erythema 2 +, moderate erythema with edema 3 +, crust or necrosis. The sun protection factors (SPF) were calculated by dividing the dose required to produce minimal erythema on the sunscreen-treated skin by the dose required to produce minimal erythema on untreated skin. In human volunteers, back skins were treated with samples and, ten minutes later, were irradiated with an SE lamp (290-320 nm) with energy of 62-311 mJ/cm 2 (0.41 mW/cm 2, 1 MED = 62 mJ/cm2), with an Osram lamp (0.41 mW/cm2), or under natural sunlight in summer. MED and SPF values were determined as described pre- viously. PROTECTION FROM UVA EFFECT For PUVA treatment, guinea pigs received a topical application of 0.6% 8-methoxy- psoralen in ethanol 30 minutes prior to UVA exposure (1.5-12 J/cm 2 at 365 nm) using a Toshiba FL20S-BLB lamp (BLB lamp). The samples were applied on five separate areas of the flank ten minutes prior to UVA exposure. Test sites were observed 48 hours later to determine the minimal phototoxic dose (MPD), which is the smallest dose required to produce a minimally visible phototoxic reaction consisting of erythema or edema. The SPF was determined as described above for UVB irradiation. PROTECTION FROM PIGMENTATION To test the effect of sunscreen agents on UVB- or UVA-induced pigmentation, the