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(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2014/053038 A2 10 April 2014 (10.04.2014) P O P C T (51) International Patent Classification: Not classified (74) Agent: DANNEMANN, SIEMSEN, BIGLER & IPAN- EMA MOREIRA; Caixa Postal 2142, Rua Marques de (21) International Application Number: Olinda, 70, Botafogo, 2225 1-040 - Rio de Janeiro - RJ PCT/BR2013/000388 (BR). (22) International Filing Date: (81) Designated States (unless otherwise indicated, for every 1 October 2013 (01 .10.2013) kind of national protection available): AE, AG, AL, AM, (25) Filing Language: English AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (26) Publication Language: English DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (30) Priority Data: HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KN, KP, KR, 61/708,266 1 October 2012 (01. 10.2012) US KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (71) Applicant: NATURA COSMETICOS S.A. [BR/BR]; OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, Rodovia Regis Bittencourt, Km 293 Edificio I, Potuvera, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, 06882-700 - Itapecerica da Serra - SP (BR). TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (72) Inventors: FERRARI, Cintia Rosa; Rua Sabino, 228, ZW. Cidade Ariston 3, Carapicuiba, 06390-500 Sao Paulo - SP (84) Designated States (unless otherwise indicated, for every (BR). ZIMBARDI, Daniela; Rua Bolivia, 218, Jd. belo kind of regional protection available): ARIPO (BW, GH, Horizonte, 13450-182 Santa Barbara d'Oeste - SP (BR). GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, PLACONA DINIZ, Gabriela Placona; Rua Guaiuba, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, 128, Cidade Dutra, 04810-1 10 Sao Paulo - SP (BR). DE TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, ASSIS SANTOS, Icaro; Rua Varzea, 569, apt. 94A, Jun- EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, ΓΓ, LT, LU, LV, diai - SP (BR). LORENCINI, Marcio; Rua Alcebiades MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, Plaisant, 1105, ap. 206, Bairro Agua Verde, 80620-270 TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, Curitiba - PR (BR). DA LUZ MOREIRA, Patricia; Rua KM, ML, MR, NE, SN, TD, TG). Fabia, n° 39, apto 32, Vila Romana, 0505 1-030 Sao Paulo - SP (BR). [Continued on nextpage] (54) Title: PLANT LIPID COMPOSITION FOR MODULATING FUNCTIONS OF KERATINOUS MATERIALS, METHOD FOR MODULATING SAID FUNCTIONS AND USE OF SAID PLANT LIPIDS (57) Abstract: The present invention is directed to cosmetic and/or pharmaceutical compositions Andiroba Buriti oil Passion Cocoa comprising at least one plant lipid, having as its oil fruit oil butter main application the treatment of keratinous ma 120 4 8 155 15 8 4 terials, particularly skin, hair, scalp, nails and eye lashes, by modulating the expression of genes re 119 46 154 † 13 63 sponsible for ROS metabolism, lipid metabolism, skin integrity, cell renewal, cell differentiation, 12 1 I 1 strengthening the skin barrier, calcium metabol ism, cell proliferation, tissue healing and/or repair, cell adhesion, carbohydrate metabolism, hydra tion, skin homeostasis/maintenance, skin defense and/or protection, remodeling and/or extracellular Cupuacu Murumuru Ucuuba Pataua butter butter butter butter matrix synthesis, skin peeling, tissue maintenance, cell signaling, normal development of the epi 108 8 2 dermis, epidermal barrier function, development t 74 97 19 of the skin, dermis-epidermis junction, anti-in < flammatory or antioxidant action in keratinous ∞ 26 I 1 I 11 I 63 materials, through the modulation of the expres sion of the genes involved in said functions. The o present invention also teaches methods of modu Figure 1 lating the expression of genes responsible for such o functions of keratinous materials and the use of said plant lipids in the preparation of said com o positions. o w o 2014/053038 A 2 1II 11 II II 11 III 11 llll I III III Published: — without international search report and to be republished upon receipt of that report (Rule 48.2(g)) "PLANT LIPID COMPOSITION FOR MODULATING FUNCTIONS OF KERATINOUS MATERIALS, METHOD FOR MODULATING SAID FUNCTIONS AND USE OF SAID PLANT LIPIDS" Field of the Invention The present invention is directed to cosmetic and/or pharmaceutical compositions comprising at least one plant lipid, having as main application the treatment of keratinous materials, particularly skin, hair, scalp, nails and eyelashes, by modulating the functions of said keratinous materials through the modulation of the expression of genes involved in these functions. The present invention also relates to methods for modulating the expression of genes responsible for such functions of keratinous materials and to the use of said plant lipids in the preparation of said compositions. Background of the Invention With the action of time and aging, the skin suffers from a reduction of both the structural proteins essential for its support and of the substances in which these fibers are layered, resulting in loss of firmness and filling. Several biological processes contribute to the aging of keratinous material; each of these processes is regulated by the expression of specific genes. Lipids are a group consisting of several organic compounds found in animals, plants and microorganisms that possess important energetic and metabolic functions in the organism. Due to the diversity of these compounds, lipids have broad applications in nutrition and in developing cosmetics and pharmaceuticals, and they can also be used in consumer goods industries (paints, detergents, etc.). Triglycerides, also known as esters of trihydroxy alcohols with three fatty acid molecules attached, are the major lipids found in vegetable oils and butters, which are widely used raw materials. Vegetable oils and butters are water- insoluble substances whose compositions and proportions of triglycerides and fatty acids vary with the species of origin of the material. The main difference between vegetable oils and butters is given by their state at room temperature: oils are liquid and butters are solid. These characteristics are strongly related to the composition of fatty acids in their triglyceride molecules (Alvarez and Rodriguez, 2000). The vegetable oils and butters are commonly used in cosmetic and pharmaceutical formulations as emollients, which are agents that moisturize the skin by promoting a reduction of transepidermal water loss (TEWL) (Leyden and Rawlings, 2002). However, there are very few scientific studies that show a biological effect promoted by vegetable oils and butters when inserted into topical compositions. The Applicant, through extensive scientific research, has found that plant lipids act directly on genes related to the functionality and maintenance of keratinous materials. Accordingly, the regulation of the expression of these genes via plant lipids represents a particularly novel technological approach for the treatment of keratinous materials. Brief Description of the Invention The object of the present invention is a cosmetic composition, particularly for topical application, which comprises at least one plant lipid and one cosmetically acceptable carrier. The present invention is further directed to a pharmaceutical composition, particularly for topical application, which comprises at least one plant lipid and one pharmaceutically acceptable carrier. The present invention further relates to the use of a plant lipid for the preparation of a cosmetic composition for treating keratinous materials through the modulation of specific genes related to the functioning and/or maintenance of keratinous materials. In addition, the present invention is directed to the use of a plant lipid for the preparation of a pharmaceutical composition for treating keratinous materials through the modulation of the expression of genes related to the functioning and/or maintenance of keratinous materials. The present invention also relates to a method of cosmetic or therapeutic treatment comprising applying the compositions of the present invention. A further object of the present invention is a method for modulating the expression of genes related to the functioning and/or maintenance of keratinous materials. Description of Drawings Figure 1 is a representative schematic showing the number of genes modulated by different plant lipids as disclosed in the present invention. The upwards arrows indicate the number of genes that had their expression increased relative to the control (control = 1), while the downward arrows indicate the number of genes that showed a reduction in their expression compared to the respective control (control = 1). Detailed Description of the Invention The present invention relates to a cosmetic and/or pharmaceutical composition, particularly directed to the treatment of keratinous materials, comprising at least one plant lipid and one cosmetically or pharmaceutically acceptable carrier. In the context of the present invention, "keratinous materials" means skin, hair, scalp and skin appendages (nails, eyelashes and eyebrows). Preferably, the compositions of the present invention comprise plant lipids selected from vegetable oils and butters obtained, for example, from plants of the genus Theobroma, Carapa, Euterpe, Mauritia, Passiflora, Astrocaryum, Oenocarpus, Elaeis and Virola.
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    TaqMan® Gene Signature Arrays TaqMan® Human and Rat Inflammation Arrays These arrays are part of a collection of TaqMan® Gene Signature Group Assays Human Gene Symbols Arrays that enable analysis of hundreds of TaqMan® Gene Channels 7 Expression Assays on a micro fluidic card with minimal effort. L-type calcium 5 CACNA1C, CACNA1D, CACNA2D1, CACNB2, CACNB4 Inflammation is the body’s response to infection, irritation Ligand gated 2 HTR3A, HTR3B or injury; characterized by redness, heat, swelling, pain and Enzymes and inhibitors 41 possible dysfunction of the organs involved. It can be defined Inhibitor 1 A2M Lipase 15 CES1, PLA2G1B, PLA2G2A, PLA2G5, as an innate immune response manifested by increased blood PLCB2–4, PLCD1, PLCG1, PLCG2, supply and vascular permeability. This allows fluid and white PLA2G7, PLA2G10, PLA2G4C, blood cells to leave the intravascular compartment and move PLA2G2D, PLCE1 Kinase 4 MAPK1, MAPK3, MAPK8, MAPK14 to the site of injury or infection. Nitric oxide synthase 1 NOS2A Phosphodiesterase 4 PDE4A–D Inflammation is associated with a wide range of disorders Prostaglandin metabolism 9 ALOX12, ALOX5, HPGD, LTA4H, including asthma, allergy, rheumatoid arthritis, gout, sepsis, LTC4S, PTGIS, PTGS1 (COX1), PTGS2 (COX2), TBXAS1 autoimmune disease, cardiovascular disease, diabetes, Protease 7 KLK3, CASP1, KLK1, KLK2, neurologic disease and cancer. Medications targeting KLKB1, KLK14, KLK15 inflammatory diseases include NSAIDS, corticosteroids, Factors 9 ANXA1, ANXA3, ANXA5, TNFSF5, H1-receptor antagonists and ß2-selective adrenergic drugs. IL13, KNG1, NFKB1, TNFSF13B, TNF Current treatments tend to have limited efficacy because Receptors 35 they target symptoms or impair the immune response. GPCR 18 ADRB1, ADRB2, BDKRB1, BDKRB2, CYSLTR1, HRH1–3, LTB4R, An increasing number of new drugs and protein therapies LTB4R2, MC2R (missing on rat are being developed.
  • Phosphodiesterase Inhibitors: Their Role and Implications

    Phosphodiesterase Inhibitors: Their Role and Implications

    International Journal of PharmTech Research CODEN (USA): IJPRIF ISSN : 0974-4304 Vol.1, No.4, pp 1148-1160, Oct-Dec 2009 PHOSPHODIESTERASE INHIBITORS: THEIR ROLE AND IMPLICATIONS Rumi Ghosh*1, Onkar Sawant 1, Priya Ganpathy1, Shweta Pitre1 and V.J.Kadam1 1Dept. of Pharmacology ,Bharati Vidyapeeth’s College of Pharmacy, University of Mumbai, Sector 8, CBD Belapur, Navi Mumbai -400614, India. *Corres.author: rumi 1968@ hotmail.com ABSTRACT: Phosphodiesterase (PDE) isoenzymes catalyze the inactivation of intracellular mediators of signal transduction such as cAMP and cGMP and thus have pivotal roles in cellular functions. PDE inhibitors such as theophylline have been employed as anti-asthmatics since decades and numerous novel selective PDE inhibitors are currently being investigated for the treatment of diseases such as Alzheimer’s disease, erectile dysfunction and many others. This review attempts to elucidate the pharmacology, applications and recent developments in research on PDE inhibitors as pharmacological agents. Keywords: Phosphodiesterases, Phosphodiesterase inhibitors. INTRODUCTION Alzheimer’s disease, COPD and other aliments. By cAMP and cGMP are intracellular second messengers inhibiting specifically the up-regulated PDE isozyme(s) involved in the transduction of various physiologic with newly synthesized potent and isoezyme selective stimuli and regulation of multiple physiological PDE inhibitors, it may possible to restore normal processes, including vascular resistance, cardiac output, intracellular signaling selectively, providing therapy with visceral motility, immune response (1), inflammation (2), reduced adverse effects (9). neuroplasticity, vision (3), and reproduction (4). Intracellular levels of these cyclic nucleotide second AN OVERVIEW OF THE PHOSPHODIESTERASE messengers are regulated predominantly by the complex SUPER FAMILY superfamily of cyclic nucleotide phosphodiesterase The PDE super family is large, complex and represents (PDE) enzymes.