A Commercially Available Skin Care Lotion with a pH of 4.5 and 10% Urea Improves Skin Surface pH, Stratum Corneum Hydration and Epidermal Barrier Function in Subjects with Dry Skin and Atopic Diathesis — Oak Academic Publishing
Research ArticleOpen AccessGoogle Scholar indexed
A Commercially Available Skin Care Lotion with a pH of 4.5 and 10% Urea Improves Skin Surface pH, Stratum Corneum Hydration and Epidermal Barrier Function in Subjects with Dry Skin and Atopic Diathesis
Department of Research & Development and Regulatory Affairs, Kneipp GmbH, Würzburg, Germany
,
Department of Research & Development and Regulatory Affairs, Kneipp GmbH, Würzburg, Germany
,
Department of Research & Development and Regulatory Affairs, Kneipp GmbH, Würzburg, Germany
,
Department of Research & Development and Regulatory Affairs, Kneipp GmbH, Würzburg, Germany
,
Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Osnabrück, Germany
,
Department of Research & Development and Regulatory Affairs, Kneipp GmbH, Würzburg, Germany
1 Department of Research & Development and Regulatory Affairs, Kneipp GmbH, Würzburg, Germany
2 Department of Research & Development and Regulatory Affairs, Kneipp GmbH, Würzburg, Germany
3 Department of Research & Development and Regulatory Affairs, Kneipp GmbH, Würzburg, Germany
4 Department of Research & Development and Regulatory Affairs, Kneipp GmbH, Würzburg, Germany
5 Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Osnabrück, Germany
6 Department of Research & Development and Regulatory Affairs, Kneipp GmbH, Würzburg, Germany
OBJECTIVE: The physiological skin surface pH is crucial for several epidermal barrier functions, like stratum corneum integrity, cohesion and restoration. Alterations of the “normal” acidic nature of the skin surface have been shown to correlate with specific skin conditions like aged or inflamed skin and are leading to impaired skin barrier function and formation. It is previously demonstrated that topical acidification in atopic dermatitis improves stratum corneum function, skin barrier structure and clinical signs in dermatitis. Against this background, we examined the impact of a slightly acidic skin care product containing urea on stratum corneum hydration, skin surface pH and epidermal barrier function in subjects with dry skin and atopic diathesis. METHODS: Stratum corneum hydration, skin surface pH and transepidermal water loss were biophysically measured before and after a 4-week treatment period with the test product (pH 4.5, 10% urea) compared to the reference product in 25 volunteers. In addition, dynamic epidermal barrier parameters like stratum corneum integrity, cohesion and recovery were investigated by using a previously described tape stripping approach. RESULTS: It was shown that the test product (pH 4.5, 10% urea) significantly elevated stratum corneum hydration and improved the acidic nature of the skin surface by lowering the skin surface pH to a greater extent compared to the reference product. After the 4-week treatment period a significant faster barrier restoration was detected on the test site treated with the test product compared to the reference product. Moreover, the test product strengthens the skin barrier integrity and cohesion. CONCLUSION: The present marketed skin care lotion was shown to increase epidermal barrier function after 4 weeks of application. Balancing and controlling the skin surface pH in subjects with dry and atopic-prone skin by application of the herein tested o/w emulsion with a given pH of 4.5, in combination with a 10% urea content seems to be effective and beneficial. The results are important for the formulation of topical products for dry and atopic-prone skin.
Elias, P.M. (2005) Stratum Corneum Defensive Functions: An Integrated View. Journal of Investigative Dermatology, 125, 183-200. https://doi.org/10.1111/j.0022-202X.2005.23668.x
Menon, G.K. and Kligman, A.M. (2009) Barrier Functions of Human Skin: A Holistic View. Skin Pharmacology and Physiology, 22, 178-189. https://doi.org/10.1159/000231523
Bosko, C.A. (2019) Skin Barrier Insights: From Bricks and Mortar to Molecules and Microbes. Journal of Drugs in Dermatology, 18, s63-s67.
Michaels, A.S., Chandrasekaran, S.K. and Shaw, J.E. (1975) Drug Permeation through Human Skin: Theory and in Vitro Experimental Measurement. AIChE Journal, 21, 985-996. https://doi.org/10.1002/aic.690210522
Johnson, M.E., Blankschtein, D. and Langer, R. (1997) Evaluation of Solute Permeation through the Stratum Corneum: Lateral Bilayer Diffusion as the Primary Transport Mechanism. Journal of Pharmaceutical Sciences, 86, 1162-1172. https://doi.org/10.1021/js960198e
Proksch, E., Folster-Holst, R. and Jensen, J.M. (2006) Skin Barrier Function, Epidermal Proliferation and Differentiation in Eczema. Journal of Dermatological Science, 43, 159-169. https://doi.org/10.1016/j.jdermsci.2006.06.003
Elias, P.M. and Menon, G.K. (1991) Structural and Lipid Biochemical Correlates of the Epidermal Permeability Barrier. Advances in Lipid Research, 24, 1-26. https://doi.org/10.1016/B978-0-12-024924-4.50005-5
Miajlovic, H., Fallon, P.G., Irvine, A.D. and Foster, T.J. (2010) Effect of Filaggrin Breakdown Products on Growth of and Protein Expression by Staphylococcus aureus. Journal of Allergy and Clinical Immunology, 126, 1184-1190. https://doi.org/10.1016/j.jaci.2010.09.015
Jensen, J.M., Schütze, S., Fürl, M., Krönke, M. and Proksch, E. (1999) Roles for Tumor Necrosis Factor Receptor p55 and Sphingomyelinase in Repairing the Cutaneous Permeability Barrier. Journal of Clinical Investigation, 104, 1761-1770. https://doi.org/10.1172/JCI5307
Sanford, J.A. and Gallo, R.L. (2013) Functions of the Skin Microbiota in Health and Disease. Seminars in Immunology, 25, 370-377. https://doi.org/10.1016/j.smim.2013.09.005
Nakatsuji, T., Chiang, H.I., Jiang, S.B., Nagarajan, H., Zengler, K. and Gallo, R.L. (2013) The Microbiome Extends to Subepidermal Compartments of Normal Skin. Nature Communications, 4, Article No. 1431. https://doi.org/10.1038/ncomms2441
Proksch, E., Brandner, J.M. and Jensen, J.M. (2008) The Skin: An Indispensable Barrier. Clinical and Experimental Dermatology, 17, 1063-1072. https://doi.org/10.1111/j.1600-0625.2008.00786.x
Eberlein-König, B., Schäfer, T., Huss-Marp, J., Darsow, U., Möhrenschlager, M., Herbert, O., Abeck, D., Krämer, U., Behrendt, H. and Ring, J. (2000) Skin Surface pH, Stratum Corneum Hydration, Trans-Epidermal Water Loss and Skin Roughness Related to Atopic Eczema and Skin Dryness in a Population of Primary School Children. Acta Dermato-Venereologica, 80, 188-191. https://doi.org/10.1080/000155500750042943
Seidenari, S. and Giusti, G. (1995) Objective Assessment of the Skin of Children Affected by Atopic Dermatitis: A Study of pH, Capacitance and TEWL in Eczematous and Clinically Uninvolved Skin. Acta Dermato-Venereologica, 75, 429-433.
Seite, S., Flores, G.E., Henley, J.B., Martin, R., Zelenkova, H., Aguilar, L. and Fierer, N. (2014) Microbiome of Affected and Unaffected Skin of Patients with Atopic Dermatitis before and after Emollient Treatment. Journal of Drugs in Dermatology, 13, 611-618.
Fluhr, J.W. and Elias, P.M. (2002) Stratum Corneum pH: Formation and Function of the “Acid Mantle”. Exogenous Dermatology, 1, 163-175. https://doi.org/10.1159/000066140
Segger, D., Aßmus, U., Brock, M., Erasmy, J., Finkel, P., Fitzner, A., Heuss, H., Kortemeier, U., Munke, S., Rheinländer, T., Schmidt-Lewerkühne, H. and Schneider, W. and Weser, G. (2007) Multicenter Study on Measurement of the Natural pH of the Skin Surface. IFSCC Magazine, 10, 107-110.
Lambers, H., Piessens, S., Bloem, A., Pronk, H. and Finkel, P. (2006) Natural Skin Surface pH Is on Average below 5, Which Is Beneficial for Its Resident Flora. International Journal of Cosmetic Science, 28, 359-370. https://doi.org/10.1111/j.1467-2494.2006.00344.x
Schade, H. and Marchionini, A. (1928) Der Säuremantel der Haut (nach Gaskettenmessungen). Journal of Molecular Medicine, 7, 12-14. https://doi.org/10.1007/BF01711684
Choi, E.H., Man, M.Q., Xu, P., Xin, S., Liu, Z., Crumrine, D.A., Jiang, Y.J., Fluhr, J.W., Feingold, K.R., Elias, P.M. and Mauro, T.M. (2007) Stratum Corneum Acidification Is Impaired in Moderately Aged Human and Murine Skin. Journal of Investigative Dermatology, 127, 2847-2856. https://doi.org/10.1038/sj.jid.5700913
Man, M.Q., Xin, S.J., Song, S.P., Cho, S.Y., Zhang, X.J., Tu, C.X., Feingold, K.R. and Elias, P.M. (2009) Variation of Skin Surface pH, Sebum Content and Stratum Corneum Hydration with Age and Gender in a Large Chinese Population. Skin Pharmacology and Physiology, 22, 190-199. https://doi.org/10.1159/000231524
Schreml, S., Zeller, V., Meier, R.J., Korting, H.C., Behm, B., Landthaler, M. and Babilas, P. (2012) Impact of Age and Body Site Adult Female Skin Surface pH. Dermatology, 224, 66-71. https://doi.org/10.1159/000337029
Blaak, J., Wohlfart, R. and Schürer, N.Y. (2011) Treatment of Aged Skin with a pH 4 Skin Care Product Normalizes Increased Skin Surface pH and Improves Barrier Function: Results of a Pilot Study. Journal of Cosmetics, Dermatological Sciences and Applications, 1, 50-58. https://doi.org/10.4236/jcdsa.2011.13009
Luebberding, S., Krueger, N. and Kerscher, M. (2014) Age-related Changes in Male Skin: Quantitative Evaluation of One Hundred and Fifty Male Subjects. Skin Pharmacology and Physiology, 27, 9-17. https://doi.org/10.1159/000351349
Sparavigna, A., Setaro, M. and Gualandri, V. (1999) Cutaneous pH in Children Affected by Atopic Dermatitis and in Healthy Children: A Multicenter Study. Skin Research and Technology, 5, 221-227. https://doi.org/10.1111/j.1600-0846.1999.tb00134.x
Rippke, F., Schreiner, V. and Schwanitz, H.J. (2002) The Acidic Milieu of the Horny Layer. New Findings on the Physiology and Pathophysiology of Skin pH. American Journal of Clinical Dermatology, 3, 261-272. https://doi.org/10.2165/00128071-200203040-00004
Maibach, H. and Levin, J. (2011) pH Buffering Considerations in Mature Skin. Cosmetics & Toiletries, 126, 422-428.
Elias, P.M. and Choi, E.H. (2005) Interactions among Stratum Corneum Defensive Functions. Experimental Dermatology, 14, 719-726. https://doi.org/10.1111/j.1600-0625.2005.00363.x
Borgono, C.A., Michael, I.P., Komatsu, N., Jayakumar, A., Kapadia, R., Clayman, G.L., Sotiropoulou, G. and Diamandis, E.P. (2007) A Potential Role for Multiple Tissue Kallikrein Serine Proteases in Epidermal Desquamation. The Journal of Biological Chemistry, 282, 3640-3652. https://doi.org/10.1074/jbc.M607567200
Caubet, C., Jonca, N., Brattsand, M., Guerrin, M., Bernard, D., Schmidt, R., Egelrud, T., Simon, M. and Serre, G. (2004) Degradation of Corneodesmosome Proteins by Two Serine Proteases of the Kallikrein Family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7. Journal of Investigative Dermatology, 122, 1235-1244. https://doi.org/10.1111/j.0022-202X.2004.22512.x
Brattsand, M., Stefansson, K., Lundh, C., Haasum, Y. and Egelrud, T. (2005) A Proteolytic Cascade of Kallikreins in the Stratum Corneum. Journal of Investigative Dermatology, 124, 198-203. https://doi.org/10.1111/j.0022-202X.2004.23547.x
Ovaere, P., Lippens, S., Vandenabeele, P. and Declercq, W. (2009) The Emerging Roles of Serine Protease Cascades in the Epidermis. Trends in Biochemical Sciences, 34, 453-463. https://doi.org/10.1016/j.tibs.2009.08.001
Mauro, T., Holleran, W.M., Grayson, S., Gao, W.N., Man, M.Q., Kriehuber, E., Behne, M., Feingold, K.R. and Elias P.M. (1998) Barrier Recovery Is Impeded at Neutral pH, Independent of Ionic Effects: Implications for Extracellular Lipid Processing. Archives of Dermatological Research, 290, 215-222. https://doi.org/10.1007/s004030050293
Holleran, W.M. and Takagi, Y. (2006) Stratum Corneum Lipid Processing: The Final Steps in Barrier Formation. In: Elias, P.M. and Feingold, K.R., Eds., Skin Barrier, Taylor & Francis, Abingdon, 231-259.
Elias, P.M. and Choi, E.H. (2005) Interactions among Stratum Corneum Defensive Functions. Experimental Dermatology, 14, 719-726. https://doi.org/10.1111/j.1600-0625.2005.00363.x
Blaak, J., Kaup, O., Hoppe, W., Baron-Ruppert, G., Langheim, H., Staib, P., Wohlfart, R., Lüttje, D. and Schürer, N.Y. (2015) A Long-Term Study to Evaluate Acidic Skin Care Treatment in Nursing Home Residents: Impact on Epidermal Barrier Function and Microflora in Aged Skin. Skin Pharmacology and Physiology, 28, 269-279. https://doi.org/10.1159/000437212
Behm, B., Kemper, M., Babilas, P., Abels, C. and Schreml, S. (2015) Impact of a Glycolic Acid-Containing pH 4 Water-in-Oil Emulsion on Skin pH. Skin Pharmacology and Physiology, 28, 290-295. https://doi.org/10.1159/000439030
Blaak, J., Dähnhardt, D., Dähnhardt-Pfeiffer, S., Bielfeldt, S., Wilhelm, K.P., Wohlfart, R. and Staib, P. (2017) A Plant Oil-containing pH 4 Emulsion Improves Epidermal Barrier Structure and Enhances Ceramide Levels in Aged Skin. International Journal of Cosmetic Science, 39, 284-291. https://doi.org/10.1111/ics.12374
Angelova-Fischer, I., Fischer, T.W., Abels, C. and Zillikens, D. (2018) Accelerated Barrier Recovery and Enhancement of the Barrier Integrity and Properties by Topical Application of a pH 4 vs. a pH 5·8 Water-in-Oil Emulsion in Aged Skin. British Journal of Dermatology, 179, 471-477. https://doi.org/10.1111/bjd.16591
Kilic, A., Masur, C., Reich, H., Knie, U., Dähnhardt, D., Dähnhardt-Pfeiffer, S. and Abels, C. (2019) Skin Acidification with a Water-in-Oil Emulsion (pH 4) Restores Disrupted Epidermal Barrier and Improves Structure of Lipid Lamellae in the Elderly. The Journal of Dermatology, 46, 457-465. https://doi.org/10.1111/1346-8138.14891
Hatano, Y., Man, M.Q., Uchida, Y., Crumrine, D., Scharschmidt, T.C., Kim, E.G., Mauro, T.M., Feingold, K.R., Elias, P.M. and Holleran, W.M. (2009) Maintenance of an Acidic Stratum Corneum Prevents Emergence of Murine Atopic Dermatitis. Journal of Investigative Dermatology, 129, 1824-1835. https://doi.org/10.1038/jid.2008.444
Sakai, T., Hatano, Y., Zhang, W. and Fujiwara, S. (2014) Defective Maintenance of pH of Stratum Corneum Is Correlated with Preferential Emergence and Exacerbation of Atopic-Dermatitis-Like Dermatitis in Flaky-Tail Mice. Journal of Dermatological Science, 74, 222-228. https://doi.org/10.1016/j.jdermsci.2014.01.012
Lee, H.J., Yoon, N.Y., Lee, N.R., Jung, M., Kim, D.H. and Choi, E.H. (2014) Topical Acidic Cream Prevents the Development of Atopic Dermatitis- and Asthma-Like Lesions in Murine Model. Experimental Dermatology, 23, 736-741. https://doi.org/10.1111/exd.12525
Jang, H., Matsuda, A., Jung, K., Karasawa, K., Matsuda, K., Oida, K., Ishizaka, S., Ahn, G., Amagai, Y., Moon, C., Kim, S.H., Arkwright, P.D., Takamori, K., Matsuda, H. and Tanaka A. (2016) Skin pH Is the Master Switch of Kallikrein 5-Mediated Skin Barrier Destruction in a Murine Atopic Dermatitis Model. Journal of Investigative Dermatology, 136, 127-135. https://doi.org/10.1038/JID.2015.363
Panther, D.J. and Jacob, S.E. (2015) The Importance of Acidification in Atopic Eczema: An Underexplored Avenue for Treatment. Journal of Clinical Medicine, 5, 970-978. https://doi.org/10.3390/jcm4050970
Denby, S.G. and Cork, M.J. (2018) pH in Atopic Dermatitis. Current Problems in Dermatology, 54, 95-107. https://doi.org/10.1159/000489523
Loden, M. (2009) Urea as a Moisturizing and Barrier-Enhancing Ingredient. In: Rawlings, A.V. and Leyden, J.J., Eds., Skin Moisturization, Informa Healthcare, London, 335-346. https://doi.org/10.3109/9781420070958.021
Grether-Beck, S., Felsner, I., Brenden, H., Kohne, Z., Majora, M., Marini, A., Jaenicke, T., Rodriguez-Martin, M., Trullas, C., Hupe, M., Elias, P.M. and Krutmann, J. (2012) Urea Uptake Enhances Barrier Function and Antimicrobial Defense in Humans by Regulating Epidermal Gene Expression. Journal of Investigative Dermatology, 132, 1561-1572. https://doi.org/10.1038/jid.2012.42
Celleno, L. (2018) Topical Urea in Skincare: A Review. Dermatologic Therapy, 31, e12690. https://doi.org/10.1111/dth.12690
Scheinfeld, N.S. (2010) Urea: A Review of Scientific and Clinical Data. Skinmed, 8, 102-106.
Pan, M., Heinicke, G., Bernado, S., Tsui, C. and Levitt, J. (2013) Urea: A Comprehensive Review of the Clinical Literature. Dermatology Online Journal, 19, Article ID: 20392.
Dähnhardt, D., Surber, C. and Dähnhardt-Pfeiffer, S. (2018) Influence of Topical Formulations: Lipid Lamella Organization and Lipid Composition of Stratum Corneum as a Surrogate Marker for Barrier Integrity. Current Problems in Dermatology, 54, 166-172. https://doi.org/10.1159/000489530
Wohlrab, J. and Gebert, A. (2018) pH and Buffer Capacity of Topical Formulations. Current Problems in Dermatology, 54, 123-131. https://doi.org/10.1159/000489526
Parra, J.L. and Paye, M. (2003) EEMCO Guidance for the in Vivo Assessment of Skin Surface pH. Skin Pharmacology and Physiology, 16, 188-202. https://doi.org/10.1159/000069756
Rogiers, V. (2001) EEMCO Guidance for the Assessment of Transepidermal Water Loss in Cosmetic Sciences. Skin Pharmacology and Physiology, 14, 117-128. https://doi.org/10.1159/000056341
Berardesca, E. (1997) EEMCO Guidance for the Assessment of Stratum Corneum Hydration: Electrical Methods. Skin Research and Technology, 3, 126-132. https://doi.org/10.1111/j.1600-0846.1997.tb00174.x
Pelc, J., Czarnecka-Operacz, M. and Adamski, Z. (2018) Structure and Function of the Epidermal Barrier in Patients with Atopic Dermatitis—Treatment Options. Part One. Advances in Dermatology and Allergology, 35, 1-5. https://doi.org/10.5114/ada.2018.73159
Bieber, T. (2010) Atopic Dermatitis. Annals of Dermatology, 22, 125-137. https://doi.org/10.5021/ad.2010.22.2.125
Elias, P.M. (2014) Lipid Abnormalities and Lipid-Based Repair Strategies in Atopic Dermatitis. Biochimica et Biophysica Acta, 1841, 323-330. https://doi.org/10.1016/j.bbalip.2013.10.001
Dähnhardt-Pfeiffer, S., Surber, C., Wilhelm, K.P., Dähnhardt, D., Springmann, G., Böttcher, M. and Fölster-Holst, R. (2012) Noninvasive Stratum Corneum Sampling and Electron Microscopical Examination of Skin Barrier Integrity: A Pilot Study with a Topical Glycerin Formulation for Atopic Dermatitis. Skin Pharmacology and Physiology, 25, 155-161. https://doi.org/10.1159/000336789
Rawlings, A.V. (2014) Molecular Basis for Stratum Corneum Maturation and Moisturization. British Journal of Dermatology, 171, 19-28. https://doi.org/10.1111/bjd.13303