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(12) United States Patent (10) Patent No.: US 7.999,008 B2 Bernard Et Al

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(12) United States Patent (10) Patent No.: US 7.999,008 B2 Bernard Et Al US007999008B2 (12) United States Patent (10) Patent No.: US 7.999,008 B2 Bernard et al. (45) Date of Patent: * Aug. 16, 2011 (54) UREACOMPOUNDS THAT PROMOTE OTHER PUBLICATIONS DESQUAMATION National Starch online retrieved from: http://news.nationalstarch. com/NewsStory.asp?newsltemld=416 on Mar. 20, 2009. Dec. 3, (75) Inventors: Dominique Bernard, Paris (FR); Lucie 2003. 3 pages.* Simonetti, Vincennes (FR); Pascale Formulating with Hydrovance online retrieved from: http://www. Pelletier, Antony (FR) personalcarepolymers.com/PCP/Products/ProductOverview. htm?id=95 on Mar. 20, 2009. May 17, 2005. 7 pages.* English language machine translation of DE2703185; Aug. 1978; 7 (73) Assignee: L'Oreal, Paris (FR) pages. Derivative online merriam websters online dictionary retrieved (*) Notice: Subject to any disclaimer, the term of this from http://.merriam-Webster.com/cgi-bin/ patent is extended or adjusted under 35 dictionary?book=dictionary&va-derivative; Jul. 5, 2008; 1 page.* U.S.C. 154(b) by 481 days. Anonymous: “pH Stability of Hydroxyalkylurea in Combination Either with One or More of a Cyclic (lactone) and/or Acylic Ester.” This patent is Subject to a terminal dis Dec. 22, 2004, IP. Com Journal, IP. Com. Inc., West Henrietta, NY, claimer. US, XPO 13022595. M. Ponec, et al. “Lack of Desquamation—the Achilles Heel of the (21) Appl. No.: 11/485,506 Reconstructed Epidermis' International Journal of Cosmetic Sci ence, 2002, vol. 24, (pp. 263-272). Sebastien Niamke, et al., “Physico-Chemical and Immunological (22) Filed: Jul. 13, 2006 Properties and Partial Amino Acid Sequencing of a New Metal loprotease: Endoprotease Thr-N” Biochimica et Biophysica Acta, (65) Prior Publication Data vol. 1623 (2003), (pp. 21-28), www.sciencedirect.com. D. Bernard, et al. "Analysis of Proteins with Caseinolytic Activity in US 2007/OO 14748A1 Jan. 18, 2007 a Human Stratum Corneum Extract Revealed a Yet Unidentified Cysteine Protease and Identified the So-Called “Stratum Corneum Related U.S. Application Data Thiol Protease” as Cathepsin L2” The Society for Investigative Der (60) Provisional application No. 60/724.951, filed on Oct. matology. Inc, vol. 120, No. 4 (Apr. 2003), (pp. 592-600). 11, 2005. * cited by examiner (30) Foreign Application Priority Data Primary Examiner — Ernst Arnold (74) Attorney, Agent, or Firm — Oblon, Spivak, Jul. 13, 2005 (FR) ...................................... O5521.89 McClelland, Maier & Neustadt, L.L.P. (51) Int. Cl. (57) ABSTRACT A6 IK 8/02 (2006.01) The invention relates to the use of at least one urea derivative A6 IK3I/7 (2006.01) of the following formula (I) AOIN 47/28 (2006.01) (52) U.S. Cl. ........................................ 514/588; 424/401 (I) (58) Field of Classification Search ........................ None R1 R4 See application file for complete search history. M A N-CO-N A V (56) References Cited R2 R3 U.S. PATENT DOCUMENTS in a composition containing a physiologically acceptable 2003/0O21379 A1 2/2003 Fein 2004/O197299 A1 * 10, 2004 Delattire et al. ............ 424/78.02 medium, as agent intended for stimulating descquamation of 2005/0113268 A1* 5/2005 Landa et al. .................. 510/130 the skin and/or the mucous membranes. It also relates to a method of cosmetic treatment and cosmetic agents containing FOREIGN PATENT DOCUMENTS it. EP 1535 607 A1 6, 2005 FR 2816837 5, 2002 18 Claims, 1 Drawing Sheet U.S. Patent Aug. 16, 2011 US 7.999,008 B2 FIG. I. Acid protease activity of SC in the presence of N-(2-hydroxyethyl)-urea dose effect 1O 5 time in hours Acid protease activity of SC in the presence of urea dose effect 10 15 time in hours US 7,999,008 B2 1. 2 UREACOMPOUNDS THAT PROMOTE and an extracellular matrix predominantly composed of col DESQUAMATION lagen, elastin and a substance called ground Substance. Leu kocytes, mastocytes or tissue macrophages are also present. REFERENCE TO PRIORAPPLICATIONS Finally, the dermis is crossed by blood vessels and nerve fibres. This application claims priority to U.S. provisional appli The cohesion between the epidermis and the dermis is cation 60/724,951 filed Oct. 11, 2005, and to French patent provided by the dermoepidermal junction. application 0552189 filed Jul. 13, 2005, both incorporated The epidermal homeostasis corresponds to an equilibrium herein by reference. between the keratinocytes entering into differentiation in the 10 deep layers of the epidermis and corneocytes removed from FIELD OF THE INVENTION the Surface of the epidermis in a process called descquamation. Normally, descquamation occurs corneocyte by corneocyte The present invention relates to novel desquamation-pro moting agents, and to their use in cosmetic orpharmaceutical, and remains imperceptible. in particular, dermatological, compositions. It also relates to 15 Desquamation has in the past been associated with cosmetic methods for treating the skin or its annexes, and mechanical actions. This so-called bricks and mortar theory, compositions allowing their use. the bricks being the corneocytes linked to each other by a lipid Additional advantages and other features of the present mortar (P. Elias, 1984), was contradicted only by the discov invention will be set forth in part in the description that ery of cohesive structures derived from the desmosomes follows and in part will become apparent to those having called corneodesmosomes linked to the horny envelope and to ordinary skill in the art upon examination of the following or the intermediate filaments of keratins (Chapman, Walsh et al. may be learned from the practice of the present invention. The 1991; Serre, Mils et al. 1991; Walsh and Chapman 1991). The advantages of the present invention may be realized and proteins which constitute these structures are the substrates obtained as particularly pointed out in the appended claims. for the descquamation enzymes. Indeed, the gradual appear As will be realized, the present invention is capable of other 25 ance of fragments of desmosomal proteins during differen and different embodiments, and its several details are capable tiation and the apparent ultrastructural modifications of the of modifications in various obvious respects, all without desmosome have led researchers in the direction of enzymes departing from the present invention. The description is to be responsible for these changes. regarded as illustrative in nature, and not as restrictive. The first, T. Egelrud (Egelrud, Hofer et al. 1988; Egelrud 30 and Lundstrom 1990; Egelrud and Lundstrom 1991), has BACKGROUND OF THE INVENTION demonstrated in the stratum corneum (SC) the existence of protease activities of the "trypsin-like” and especially "chy The skin has two compartments, one which is Superficial, motrypsin-like type associated with descquamation. These the epidermis, and one which is deeper, the dermis, which studies by T. Egelrud are part of the basic studies of any interact. The natural human epidermis is mainly composed of 35 research relating to the bio-chemistry of desquamation. Sub three types of cell which are the keratinocytes, which form the sequently, several cysteine and aspartic acid proteases were great majority, the melanocytes and the Langerhans' cells. implicated in this process, in particular the stratum corneum The epidermis is conventionally divided into a basal layer thiol protease (SCTP) or cathepsin L2, the stratum corneum of keratinocytes constituting the germinative layer of the cathepsin L-like (SCCL) and cathepsin D. epidermis, a so-called prickle cell layer consisting of several 40 In a number of situations, it may be desirable to stimulate layers of polyhedral cells arranged on the germinative layers, this desquamation mechanism in order to promote epidermal one to three so-called granular layers consisting of flattened renewal and improve the brightness of the complexion, cells containing distinct cytoplasmic inclusions, the kerato attenuate surface irregularities and Smoothe the skin, or to hyalin granules and finally the horny layer (or stratum cor promote the cleansing action and the removal of dead cells at neum), consisting of a set of layers of keratinocytes at the final 45 the Surface of the body. In physiological states, thickening of stage of their differentiation, called corneocytes. The corneo the horny layer is also observed which it is desired to limit, for cytes are anucleated cells mainly composed of a fibrous example in the case of callosites or after exposure to Sunlight. matrix containing cytokeratins, Surrounded by a very resis Moreover, in Some skin disorders, descquamation becomes tant structure 15 nm thick, called horny or hornified envelope. visible and it is large sized scales containing numerous cor The stacking of these corneocytes constitutes the horny layer 50 neocytes which are removed. Deregulations of descquamation which is responsible for the barrier function of the epidermis. are increasingly better described at the molecular level and During the normal desquamation process, the most Superfi associated with aspects of abnormal skin. cial corneocytes become detached from the surface of the Ichthyoses are generally examples of impaired epidermal epidermis. differentiation associated with abnormal descquamation. In Intercellular structures derived from desmosomes, called 55 psoriasis, an inflammatory skin disease, and atopic dermati corneosomes or corneodesmosomes, have been described in tis, it has also been possible to show disorders associated with the horny layer. They are of major importance in intercorneo abnormal descquamation. In the field of
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