Topical urea in EFA-base vehicle most effective barrier

July 1, 2006

National report - A novel product formulating 40 percent urea in an essential fatty acid (EFA) vehicle (Umecta, JSJ Pharmaceuticals) appears to be a good choice for treating skin conditions associated with hyperkeratosis, scaling and compromised barrier function, according to Peter M. Elias, M.D., professor of dermatology, University of California, San Francisco, and a staff physician at the Veterans Administration Medical Center, San Francisco.

National report - A novel product formulating 40 percent urea in an essential fatty acid (EFA) vehicle (Umecta, JSJ Pharmaceuticals) appears to be a good choice for treating skin conditions associated with hyperkeratosis, scaling and compromised barrier function, according to Peter M. Elias, M.D., professor of dermatology, University of California, San Francisco, and a staff physician at the Veterans Administration Medical Center, San Francisco.

In a poster presented at the meeting, Dr. Elias and coauthors reported the results of a randomized, double-blind clinical study designed to objectively investigate the effects of the product and its unique vehicle on barrier performance.

Putting up a barrier

The analyses of those data indicated treatment with the urea/EFA product significantly improved the barrier characteristics compared with application of the vehicle alone or no treatment. However, application of the vehicle itself also had significant benefits compared with no treatment.

"Products containing a high concentration of urea have been used in dermatology for many years to promote hydration and desquamation. The formulation of urea in this EFA vehicle results in an enhanced preparation that is useful not only for eliminating the bad cells from the top layer of the stratum corneum, but that simultaneously further improves the skin's barrier by enabling better functioning of the residual stratum corneum cells," Dr. Elias says.

The clinical study included results from 12 adult subjects who applied the EFA vehicle to one volar forearm and the urea/EFA product contralaterally twice a day for four days. At the end of the study, stratum corneum was removed from the vehicle-treated, urea/EFA-treated and untreated sites using five adhesive discs at each site. Each disc was then analyzed for its protein content and the average was calculated for each treatment. In addition, barrier perturbation was evaluated through comparisons of TEWL measurements performed at baseline, after treatment completion, immediately after the tape-stripping and three hours after tape-stripping.

The final analysis

The analysis of removed stratum corneum protein showed a significant benefit of the urea/EFA product for increasing barrier cohesion compared with both vehicle alone and no treatment, but also showed the EFA vehicle by itself had a significant benefit compared to no treatment.

Mean protein removed from the urea/EFA-treated sites was about 50 mcg; it was approximately twofold greater from the EFA vehicle-treated skin and fourfold greater from skin receiving no treatment.

Analysis of results of TEWL measurements obtained prior to and immediately after tape-stripping showed significant benefits of treatment with the urea/EFA product for improving stratum corneum integrity, while the data from the three-hour post-tape stripping assessments demonstrated significantly faster recovery from the mechanical trauma. Again, the EFA vehicle exhibited significant activity for barrier enhancement as it significantly reduced barrier damage three hours post-tape stripping compared to baseline.

Multimodal mechanisms

Dr. Elias explains that with its high urea content, application of the urea/EFA product promotes shedding of the stratum disjunctum, the outermost layer of the stratum corneum.

The functionally competent stratum compactum that is left behind affords a much better barrier. However, the omega-6 enriched, EFA vehicle provides additional benefits.

"It has been known for decades that EFA-deficiency is associated with abnormalities of epidermal permeability barrier function and differentiation. Treatment with this vehicle provides the essential fatty acids that are required in the membranes of the cells that form the permeability barrier," Dr. Elias says.

In addition, the omega-6 fatty acids, and particularly the linoleic acid that is one component of the EFA vehicle system, acidify the stratum corneum. That action provides an effect that is similar to alpha-hydroxy acids.

"Lowering the pH of the stratum corneum results in inactivation of the serine proteases that mediate normal desquamation, and that leads to a more coherent stratum corneum that provides better barrier function," Dr. Elias explains.