(19) TZZ ¥_T (11) EP 2 588 593 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 8/46 (2006.01) A61K 8/49 (2006.01) 23.08.2017 Bulletin 2017/34 A61Q 19/08 (2006.01) A61K 8/97 (2017.01) (21) Application number: 11804011.2 (86) International application number: PCT/US2011/040157 (22) Date of filing: 13.06.2011 (87) International publication number: WO 2012/005876 (12.01.2012 Gazette 2012/02) (54) COMPOSITIONS AND METHODS FOR STIMULATING MAGP-1 TO IMPROVE THE APPEARANCE OF SKIN ZUSAMMENSETZUNGENUND VERFAHREN ZUR MAGP-1-STIMULATION ZUR VERBESSERUNG DES ERSCHEINUNGSBILDES DER HAUT COMPOSITIONS ET PROCÉDÉS DE STIMULATION DE MAGP-1 POUR AMÉLIORER L’ASPECT DE LA PEAU (84) Designated Contracting States: (56) References cited: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB WO-A1-2007/093839 WO-A1-2012/005872 GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO WO-A2-2006/068778 JP-A- 2002 087 973 PL PT RO RS SE SI SK SM TR JP-A- 2006 069 954 JP-A- 2010 090 069 US-A1- 2003 207 818 US-A1- 2006 134 231 (30) Priority: 30.06.2010 US 360083 P US-A1- 2007 161 625 US-A1- 2008 274 453 US-A1- 2009 012 273 (43) Date of publication of application: 08.05.2013 Bulletin 2013/19 • MICOR JOSERENE L. ET AL.: "BiologicalActivity of Bignay [Antidesma bunius (L.) Spreng] Crude (73) Proprietor: Avon Products, Inc. Extract in Artemia Salina", JOURNAL OF New York, NY 10017 (US) MEDICAL SCIENCES, vol. 5, no. 3, 1 September 2005 (2005-09-01), pages 195-198, XP002741400, (72) Inventors: ISSN: 1682-4474 • ZHENG, Qian • CHOI E M ET AL: "Screening of Indonesian Morris Plains medicinal plants for inhibitor activity on nitric New Jersey 07950 (US) oxide production of RAW264.7 cells and • CHEN, Siming W. antioxidant activity", FITOTERAPIA, IDB Parsippany HOLDING, MILAN, IT, vol. 76, no. 2, 1 March 2005 New Jersey 07054 (US) (2005-03-01), pages194-203, XP027752362, ISSN: • SANTHANAM, Uma 0367-326X [retrieved on 2005-03-01] Tenafly • JOTHI G.J. ET AL.: "Glimpses of Tribal Botanical New Jersey 07670 (US) Knowledge of Tirunveli Hills, Western Ghats, • LYGA, John W. India", ETHNOBOTANICAL LEAFLETS, vol. 12, 4 Basking Ridge March 2008 (2008-03-04), pages 118-126, New Jersey 07920 (US) XP002741401, (74) Representative: Dr. Weitzel & Partner Patent- und Rechtsanwälte mbB Friedenstrasse 10 89522 Heidenheim (DE) Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 2 588 593 B1 Printed by Jouve, 75001 PARIS (FR) (Cont. next page) EP 2 588 593 B1 • FUJIMOTO NORIHIRO ET AL: "Expression of • DATABASE GENBANK 15 December 2009 microfibril-associated glycoprotein-1 (MAGP-1) FARACO ET AL.: ’RecName: in human epidermal keratinocytes", ARCHIVES Full=Microfibrillar-associated protein 2; OFDERMATOLOGICAL RESEARCH, SPRINGER, Short=MFAP-2; AltName: INTERNATIONAL, BERLIN, DE, vol. 292, no. 1, 1 Full=Microfibrilassociated glycoprotein 1; January 2000 (2000-01-01), pages 21-26, Short=MAGP;Short=MAGP-1; Flags: Precursor.’, XP002436049, ISSN: 0340-3696, DOI: XP008162517 Database accession no. P55001 10.1007/PL00007456 • WEINBAUM ET AL.: ’Deficiency in • Y. TATANO ET AL: "Significant Decrease in microfibril-associated glycoprotein-1 leads to Tropoelastin Gene Expression in Fibroblasts complex phenotypes in multiple organ systems.’ from a Japanese Costello Syndrome Patient with J. BIOL. CHEM. vol. 283, no. 37, 12 September Impaired Elastogenesis and Enhanced 2008, pages 25533 - 25543, XP008162542 Proliferation", JOURNAL OF BIOCHEMISTRY, vol. 140, no. 2, 1 August 2006 (2006-08-01), pages 193-200, XP055198321, ISSN: 0021-924X, DOI: 10.1093/jb/mvj146 • DATABASE GNPD [Online] MINTEL; October 2011 (2011-10), "Treatment Cream", XP002746747, Database accession no. 1646948 2 EP 2 588 593 B1 Description RELATED APPLICATIONS 5 [0001] This application claims priority to U.S. Provisional Patent Application Serial No. 61/360,083, filed June 30, 2010. FIELD OF INVENTION [0002] The present invention relates generally to methods of improving the aesthetic appearance of human skin and/or 10 improving the appearance of aged and/or photodamaged skin by applying compounds to the skin which stimulate the expression of the extracellular matrix protein MAGP-1 and provide benefits to the skin. BACKGROUND OF THE INVENTION 15 [0003] There is an increasing demand in the cosmetics industry to develop products that may be applied topically to the skin that improve the condition and appearance of skin. Consumers are interested in mitigating or delaying the dermatological signs of chronologically- or hormonally- aged skin, as well as skin aging due to the environmental stress, such as fine lines, wrinkles, sagging skin and other conditions due to a progressive loss of cell growth, proliferation and functionality in the epidermal and dermal skin layers. During the aging process, the complexion of the skin, i.e., the color 20 and appearance of the skin, deteriorates slowly from aging and/or exposure to environmental stress, e.g., sunlight. [0004] There remains a general need in the cosmetics industry for products that retard or counter the aging effects on the skin, and more specifically for products that produce such effects without undesirable side effects. In particular, there remains a need for topically applied cosmetic compositions that provide anti-aging and skin texture benefits using natural plant materials as active components. 25 [0005] Active ingredients or components derived or extracted from plants and plant seeds have commonly been employed for a myriad of medicinal, therapeutic and cosmetic purposes. Such actives may be obtained from the entire plant or various parts of a plant, such as seeds, needles, leaves, flowers, roots, bark, cones, stems, rhizomes, callus cells, protoplasts, and meristems. Active ingredients or components are incorporated in compositions in a variety of forms. Such forms include a pure or semi-pure component, a solid or liquid extract or derivative, or a solid natural plant 30 material. Plant material may be incorporated in a variety of subforms such as whole, minced, ground or crushed, or otherwise physically modified for incorporation into a composition. [0006] Examples of skin beautifying products comprising plant extracts are US 2006/134231 A1 (Amorphophallus), JP 2010 090069 A (Ixora chinensis) and WO 2006/068778 A1 (Sapindus rarak and Thumbergia laurifolia). A peptide- based ingredient (KTFK) is disclosed in WO 2007/093839). 35 [0007] MAGP-1 (Microfibril-associated glycoprotein 1) is a small glycine rich acidic protein in extra-cellular matrix (ECM). MAGP-1 is a 30-33 kDa member of the microfibril associated glycoprotein family of proteins. It was found to be a key component of microfibrils and elastic fibers in skin. MAGP-1 forms complexes with other microfibril proteins such as fibrillin. Besides providing structural support for skin elastic fiber formation, MAGP-1 is also essential for vascular integrity, wound healing, and proper body fat deposition, possibly through regulating TGF-beta signaling, based on 40 animal studies. MAGP-1 apparently mediates the release of Notch extracellular domain and also likely binds to type IV collagen and contributes to elastin fiber formation. [0008] The present invention identifies a particular compound to be active at simulating expression of the extracellular matrix protein MAGP-1. This compound is an N-substituted sulfonyloxybenzylamine having the following structure (I): 45 50 [0009] The N-substituted sulfonyloxybenzylamine as disclosed above has not been known previously for topical ap- 55 plication to skin to improve the skin’s aesthetic appearance. [0010] Antidesma bunius is a species of fruit tree in the spurge family. It is native to Southeast Asia, the Philippines, and northern Australia. Its common Philippine name and other names include bignay, bugnay or bignai and currant tree. This is a variable plant which may be short and shrubby or tall and erect, approaching 30 meters in height. It has large 3 EP 2 588 593 B1 oval shaped leathery evergreen up to about 20 centimeters long and seven wide. The leaves are sudorific and employed in treating snakebite, in Asia. (Morton, J. 1987. Bignay. p. 210-212. In: Fruits of warm climates. Julia F. Morton, Miami, FL.) . [0011] Operculina turpethum is a plant in the morning glory family, (syn. Ipomoea turpethum) and is known commonly as turpeth, fue vao, and St. Thomas lidpod. It is one of many plants mentioned in the literature having claims of activity 5 against liver disorders. Vasudesan, N,V., Indian Medicinal Plants, Vol. IV, Orient Longman Ltd, Chennai, 1995, 172. It also has anthelmintic expectorant, antipyretic, anti-inflammatory and purgative properties. Id. [0012] Ixora chinensis is a fairly small, bushy shrub, usually only 5-10ft tall. There are dwarf varieties that are much smaller. Ixora will flower when only a few inches high. It is commonly used a hedge or small garden plant. The plant is mainly grown as ornamental but its flowers are believed to have some medicinal uses including treatment for hypertension 10 and for treating rheumatism, abscesses, bruises and wounds. The plant is native to India and Sri Lanka [0013] Clerodendron lindleyi are shrubs, lianas, and small trees, usually growing to 1-12 m tall, with opposite or whorled leaves. The genus is native to tropical and warm temperate regions of the world, with most of the species occurring in tropical Africa and southern Asia, but with a few in the tropical Americas and northern Australasia, and a few extending north into the temperate zone in eastern Asia.