Reference #: OST-1017-335457
Submit Date: 03/28/2002 10:21:21-0500

Novel Chemistry in Photoprotection - Benzotriazol and Hydroxyphenyltriazine

ABSTRACT:
Sunscreens were introduced some 70 years ago. Their major objective was to protect against sunburn, caused by UV-B radiation. Protection from UV-A radiation has become recognized as an important measure against photodamage of the skin over the last 10-20 years. In this period, only one new UV absorber, Butylmethoxy dibenzoylmethane (BMBM), has been added to the US FDA sunscreen monograph. In the same time several new filters that fulfilled the new need have been developed and approved in Europe, giving the European sunscreen manufacturers a much greater choice to formulate safe and effective sun protection products. Benzotriazol chemistry has led to the first broadband filters (UVB +UVA). The UV energy is dissipated into harmless thermal energy via an intramolecular isomerisation cycle (proton-transfer). The period of this Photo-tautomerism cycle is extremely short (order of 10^-12 seconds), thus not allowing radical formation or other undesired side reactions to take place. This efficient mechanism of energy dissipation also explains that this chemistry of UV absorbers is photostable. One representative of the Benzotriazol family, Methylene Bis Benzotriazolyl Tetramethylbutylphenol (MBBT), is unique in another sense. It is the first UV filter consisting of organic, microfine particles. Scattering of the UV radiation by the particles leads to an extended coverage of the UV-A range. A second new chemistry is called Hydroxyphenyltriazine. The first representative is Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine (BEMT). It also absorbs in UVB and UVA very efficiently and is also photostable. There is still a debate how the UVA protection provided by UVA- or broadband filters should be assessed. There are two countries with official standards so far; Australia with an in vitro transmittance method and Japan with an in vivo method based on Persistent Pigment Darkening (PPD). Other methods in discussion are the Critical wavelength and the UVA/UVB ratio. Examples with the new broadband filters MBBT and BEMT demonstrate the significance of these UVA methods in discussion. An advantage of all broadband filters is their substantial contribution to sunburn protection (SPF boosting). A desired level of SPF as well as good UVA protection can thus be achieved with lower amounts of UV absorber.

Keywords: Methylene Bis Benzotriazolyl Tetramethylbutylphenol (MBBT), , Ethylhexyloxyphenol Methoxyphenyl Triazine (BEMT), Broadband UV Absorber, Photostable

Reference #: MOY-1017-327311
Submit Date: 03/28/2002 08:13:55-0500

UVA photoprotection:clinical aspect

ABSTRACT:
Experimental findings show that UVA radiation can cause damages in human skin such as: genetic damage in cellular DNA, photoimmunosuppression, photoaging and photodermatosis like Polymorphous Light Eruption (PLE). Increasing concern about these effects has led to the developmentof sunscreens which effectively attenuate the UVA radiation reaching the skin. Sunscreens efficacy is currently evaluated by the sun protection factor (SPF)method using sunburn as endpoint.The action spectrum for sunburn is heavily weighted in the UVB range with a small contribution from the UVA. Due to the fact that UVA protection level can not be effectively assessed by the SPF, we have used the Persistent Pigment Darkening (PPD)method to select sunscreen products to study their efficacy in the prevention of PLE and photoimmunosuppression. We have shown a direct relationship between the PLE prevention and the PPD UVA-PF of the products. Maximal prevention was achieved by sunscreen providing a high protection throughout the entire UV spectrum and in particular in the UVA one. The efficacy of two products with a same SPF15 but with different UVA-PF (10.4 and 2.4)against the UV-induced immune suppression was compared using the delayed type hypersensitivity (DTH) reaction to recall antigens. They were found significantly different. Prevention of UV-immune suppression was achieved with the sunscreen having the higher UVA-PF, conversely a decrease of DTH reaction was observed after UV exposure with the lower UVA-PF suncreen. The UVA-PF assessed by the PPD method affords an important information in addition to the SPF value. Consequently we propose to complete the labelling of sunscreen products by using the SPF/UVA-PF ratio.

Keywords: UVA protection, Polymorphous Light Eruption, Photoimmunosuppression, SPF/UVA-PF

Reference #: YOU-1018-353748
Submit Date: 04/09/2002 06:11:13-0500

UVA protection; basic science aspects

ABSTRACT:
Terrestrial UVR is mostly (at least 95%) UVA (320-400nm) radiation. Action spectroscopy tells us that the small amount of UVB (~295-320nm) is very much more important from a biological point of view, at least for epidermal DNA photodamage and sunburn (human data), and immunosuppression, non-melanoma skin cancer and photoaging (mouse data). Mouse data can be applied to humans but this assumes comparable mechanisms of action. The role of UVA in immunosuppression in humans is controversial, especially as some mouse data suggest that UVA can abrogate the immunosuppressive effects of UVB. The role of UVA in malignant melanoma is an unanswered question. There is no evidence that UVA, which readily causes oxidative stress, is the prime cause of any type of acute normal damage by solar UVR. Thus, the main reason for considering UVA protection is the prevention of chronic damage. This could be in cases where action spectroscopy would indicate UVA as an important cause of damage, or due to increased cumulative UVA exposure relative to UVB where primarily UVB sunscreens have been routinely used.

Keywords: protection, UVA

Reference #: SPE-1018-030953
Submit Date: 04/05/2002 12:15:14-0500

Phototherapy with the 308nm Excimer Laser

ABSTRACT:
Phototherapy with the 308nm Excimer Laser Phototherapy with UVB light is a time honored and widely practiced modality in Dermatology. A number of skin diseases respond to therapy with ultraviolet light with excellent results. Drawbacks include a relatively lengthy course of treatment in most cases, and the exposure of non-lesional skin to UV radiation. Recently, the excimer laser has become available for phototherapy. This laser emits monochromatic light at 308nm, in the UVB range, and quite close to the wavelenght used for narrowband UVB phototherapy. Excimer stands for excited dimer and is a class of lasers rather than a single unit. The xenon chloride laser, in the excimer family, emits at 308nm. This laser emits a train of 30nansecond pulses that essentially functions as a continuous wave laser. High fluences can be directed to localized spots in short amounts of time. This has the simple advantage of being able to deliver a high dose of light to a localized area, such as a plaque of psoriasis, while sparing the surrounding skin from any effects of UV radiation. Besides simply being able to deliver high doses quickly, excimer laser has the theoretic potential of a unique light-tissue interaction that may enhance its effectiveness. For example, UVB in the form of laser light may penetrate more deeply than conventional incoherent UVB, and a dose-time effect is also possible. Clinical effectiveness has been demonstrated for psoriasis, atopic dermatitis, vitiligo, and hypopigmented scars, all in a much shorter amount of time than would be possible with conventional UVB.

Keywords: Phototherapy, laser, excimer

Reference #: H-1016-457895
Submit Date: 03/18/2002 06:25:09-0500

UVA1 Phototherapy

ABSTRACT:
UVA1 Phototherapy Phototherapy is well-known to be beneficial for the majority of atopic patients. However, UVB-therapy is of limited success in the chronic stage. PUVA therapy has to be used with caution because of its carcinogenic risk. Some patients profit from the combination of UVB plus UVA. Based on the latter observation pure UVA1 was tried to treat acute exacerbated atopic dermatitis. In a pilot study high dose UVA1 therapy was shown to be effective in such patients(5). Therapy consisted of 15 single daily doses of 130 J/cm2. In this pilot study, all patients responded well. In a follow up study, it turned out that, a proportion of patients does not respond. The efficacy of this treatment was confirmed in multicenter trial (6). Attempts to characterize these nonresponders remain controversial: While one study showed that the severer the exacerbation the better the response and found no correlation between IgE, eosinophilic cationic protein or soluble IL-2 receptor (4), another study found that nonresponders were characterized by a highly elevated atopic score and by high levels of IgE (8). More recent observations indicate that high doses as applied originally by Krutmann et al are not necessary. Abeck showed effective treatment with only 50 J/cm2, however, at the end of the 3-month posttreatment observation period the skin condition had reached the pretreatment level (1). An own study revealed similar results (11).UVA1 therapy has also been tried with some success in a variety of other dermatoses including localized scleroderma (3,9), chronic GvHD (2), urticaria pigmentosa (10) and cutaneous T-cell lymphoma (7,12) but this needs confirmation in larger patient series. References 1. Abeck D, et al.: J Am Acad Dermatol 2000; 42: 254-257 2. Grundmann-Kollmann M, et al.: J Am Acad Dermatol 2000; 42: 134-136 3. Kerscher M, et al: J Am Acad Dermatol 1998; 38: 21-26 4. Kowalzick L, et al: Acta Derm Venereol 1995; 75: 43-45 5. Krutmann J, et al: J Am Acad Dermatol 1992; 26: 225-230 6. Krutmann J et al. J Am Acad Dermatol 1998 38: 589-93 7. Plettenberg H et al J Am Acad Dermatol 1999; 41: 47-50 8. Schempp CM, et al: Hautarzt 1997; 48: 94-99 9. Stege H, et al: Lancet 1996; 347: 64 10. Stege H, et al: J Am Acad Dermatol 1997; 36: 938-944 11. Tzanewa S, et al: J Am Acad Dermatol, J Am Acad Dermatol 2001;45:503-7. 12. Zane C et al: J Am Acad Dermatol 2001; 44: 629-33

Keywords: UVA1, atopic dermatitis, phototherapy

Reference #: 081233
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