BR102016022682A2 - COMPOSITION FOR MODULATION OF GENES RESPONSIBLE FOR GENERAL SKIN FUNCTIONS, METHOD FOR MODULATING EXPRESSION OF GENES RESPONSIBLE FOR SKIN GENERAL FUNCTIONS AND USE OF SYLVESTRIS, SCHINUS TEREBINTHFOLIUS AND HYNURIC ACID - Google Patents

COMPOSITION FOR MODULATION OF GENES RESPONSIBLE FOR GENERAL SKIN FUNCTIONS, METHOD FOR MODULATING EXPRESSION OF GENES RESPONSIBLE FOR SKIN GENERAL FUNCTIONS AND USE OF SYLVESTRIS, SCHINUS TEREBINTHFOLIUS AND HYNURIC ACID Download PDF

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BR102016022682A2
BR102016022682A2 BR102016022682-1A BR102016022682A BR102016022682A2 BR 102016022682 A2 BR102016022682 A2 BR 102016022682A2 BR 102016022682 A BR102016022682 A BR 102016022682A BR 102016022682 A2 BR102016022682 A2 BR 102016022682A2
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Prior art keywords
skin
composition
genes
genes responsible
modulation
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BR102016022682-1A
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Portuguese (pt)
Inventor
Paes Fabiana
Carollo Moncayo Priscila
Alexandre De Oliveira Reis Eduardo
Augusto Santos De Oliveira Ricardo
Tadini D?Annolfo Kassandra
Zimbardi Daniela
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Natura Cosméticos S.A.
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Priority to BR102016022682-1A priority Critical patent/BR102016022682A2/en
Priority to MX2018014431A priority patent/MX2018014431A/en
Priority to US16/304,544 priority patent/US20200315950A1/en
Priority to MX2021003952A priority patent/MX2021003952A/en
Priority to PCT/BR2017/050128 priority patent/WO2017201597A1/en
Priority to BR112018074219-8A priority patent/BR112018074219A2/en
Publication of BR102016022682A2 publication Critical patent/BR102016022682A2/en
Priority to CL2018003354A priority patent/CL2018003354A1/en
Priority to MX2021003953A priority patent/MX2021003953A/en
Priority to MX2021003951A priority patent/MX2021003951A/en
Priority to MX2021003959A priority patent/MX2021003959A/en
Priority to MX2021003950A priority patent/MX2021003950A/en
Priority to CL2020002641A priority patent/CL2020002641A1/en
Priority to CL2020002647A priority patent/CL2020002647A1/en
Priority to CL2020002639A priority patent/CL2020002639A1/en
Priority to CL2020002642A priority patent/CL2020002642A1/en
Priority to CL2020002646A priority patent/CL2020002646A1/en
Priority to CL2020002643A priority patent/CL2020002643A1/en
Priority to CL2020002644A priority patent/CL2020002644A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations

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  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
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  • Epidemiology (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Cosmetics (AREA)

Abstract

a presente invenção refere-se a composições para a modulação de genes responsáveis pelas funções gerais da pele compreendendo casearia sylvestris, schinus terebinthfolius e ácido hialurônico e veículo cosmeticamente aceitável, bem como de um método para a modulação da expressão de genes responsáveis pelas funções gerais da pele e uso de casearia sylvestris, schinus terebinthfolius e ácido hialurônico na preparação de uma composição para a modulação de genes responsáveis pelas funções gerais da pele.The present invention relates to compositions for modulating genes responsible for general skin functions comprising casearia sylvestris, schinus terebinthfolius and hyaluronic acid and cosmetically acceptable carrier, as well as a method for modulating expression of genes responsible for general functions of skin. skin and use of casearia sylvestris, schinus terebinthfolius and hyaluronic acid in the preparation of a composition for the modulation of genes responsible for the general functions of the skin.

Description

(54) Título: COMPOSIÇÃO PARA A MODULAÇÃO DE GENES RESPONSÁVEIS PELAS FUNÇÕES GERAIS DA PELE,(54) Title: COMPOSITION FOR THE MODULATION OF GENES RESPONSIBLE FOR GENERAL SKIN FUNCTIONS,

MÉTODO PARA A MODULAÇÃO DA EXPRESSÃO DE GENES RESPONSÁVEIS PELAS FUNÇÕES GERAIS DA PELE E USO DE CASEARIA SYLVESTRIS, SCHINUS TEREBINTHFOLIUS E ÁCIDO HIALURÔNICO (51) Int. Cl.: A61K 8/97; A61K 8/73; A61Q 19/08 (52) CPC: A61K 8/97,A61K 8/735,A61Q 19/08 (57) Resumo: A presente invenção refere-se a composições para a modulação de genes responsáveis pelas funções gerais da pele compreendendo Casearia sylvestris, Schinus terebinthfolius e ácido hialurônico e veículo cosmeticamente aceitável, bem como de um método para a modulação da expressão de genes responsáveis pelas funções gerais da pele e uso de Casearia sylvestris, Schinus terebinthfolius e ácido hialurônico na preparação de uma composição para a modulação de genes responsáveis pelas funções gerais da pele.METHOD FOR MODULATING THE EXPRESSION OF GENES RESPONSIBLE FOR GENERAL SKIN FUNCTIONS AND THE USE OF SYLVESTRIS, SCHINUS TEREBINTHFOLIUS AND HYALURONIC ACID (51) Int. Cl .: A61K 8/97; A61K 8/73; A61Q 19/08 (52) CPC: A61K 8/97, A61K 8/735, A61Q 19/08 (57) Abstract: The present invention relates to compositions for the modulation of genes responsible for the general functions of the skin comprising Casearia sylvestris , Schinus terebinthfolius and hyaluronic acid and cosmetically acceptable vehicle, as well as a method for modulating the expression of genes responsible for the general functions of the skin and the use of Casearia sylvestris, Schinus terebinthfolius and hyaluronic acid in the preparation of a composition for modulating genes responsible for the general functions of the skin.

(73) Titular(es): NATURA COSMÉTICOS S.A.(73) Holder (s): NATURA COSMÉTICOS S.A.

(72) Inventor(es): FABIANA PAES; PRISCILA CAROLLO MONCAYO; EDUARDO ALEXANDRE DE OLIVEIRA REIS; RICARDO AUGUSTO SANTOS DE OLIVEIRA; KASSANDRATADINI D7ANNOLFO; DANIELA ZIMBARDI bJ (74) Procurador(es): RENATA DOS SANTOS DE CAMPOS(72) Inventor (s): FABIANA PAES; PRISCILA CAROLLO MONCAYO; EDUARDO ALEXANDRE DE OLIVEIRA REIS; RICARDO AUGUSTO SANTOS DE OLIVEIRA; KASSANDRATADINI D7ANNOLFO; DANIELA ZIMBARDI bJ (74) Attorney (s): RENATA DOS SANTOS DE CAMPOS

Guaçatonea 0,1% + Aroeira 0,025% a Atído Hialurônico 5%Guaçatonea 0.1% + Aroeira 0.025% to Hyaluronic Acid 5%

Guaçatonca 0,1% + Aroeira 0,025% * Áddo hialurônico 5%Guaçatonca 0.1% + Aroeira 0.025% * Hyaluronic acid 5%

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COMPOSIÇÃO PARA A MODULAÇÃO DE GENES RESPONSÁVEIS PELAS FUNÇÕES GERAIS DA PELE, MÉTODO PARA A MODULAÇÃO DA EXPRESSÃO DE GENES RESPONSÁVEIS PELAS FUNÇÕES GERAIS DA PELE E USO DE CASEARIA SYLVESTRIS, SCHINUS TEREBINTHFOLIUS E ÁCIDO HIALURÔNICOCOMPOSITION FOR THE MODULATION OF GENES RESPONSIBLE FOR GENERAL SKIN FUNCTIONS, METHOD FOR MODULATING THE EXPRESSION OF GENES RESPONSIBLE FOR GENERAL SKIN FUNCTIONS AND THE USE OF SYLVESTRIS, SCHINUS TEREBINTHFOLIUS AND HYALIUM ACID

CAMPO DA INVENÇÃO [1] A presente invenção refere-se a composições para a modulação de genes responsáveis pelas funções gerais da pele compreendendo Casearia sylvestris, Schinus terebinthfolius e ácido hialurônico e veículo cosmeticamente aceitável, bem como de um método para a modulação da expressão de genes responsáveis pelas funções gerais da pele e uso de Casearia sylvestris, Schinus terebinthfolius e ácido hialurônico na preparação de uma composição para a modulação de genes responsáveis pelas funções gerais da pele.FIELD OF THE INVENTION [1] The present invention relates to compositions for the modulation of genes responsible for the general functions of the skin comprising Casearia sylvestris, Schinus terebinthfolius and hyaluronic acid and cosmetically acceptable vehicle, as well as a method for modulating the expression of genes responsible for general skin functions and use of Casearia sylvestris, Schinus terebinthfolius and hyaluronic acid in the preparation of a composition for the modulation of genes responsible for general skin functions.

FUNDAMENTO DA INVENÇÃO [2] Considerada o maior órgão do corpo humano, a pele é sede de muitos processos complexos e dinâmicos. Entre esses processos estão funções de barreira e imunológicas, produção de melanina, síntese de vitamina D, sensações, regulação térmica, proteção contra lesões por radiação ultravioleta e estética.BACKGROUND OF THE INVENTION [2] Considered the largest organ in the human body, the skin is home to many complex and dynamic processes. Among these processes are barrier and immunological functions, melanin production, vitamin D synthesis, sensations, thermal regulation, protection against injuries by ultraviolet radiation and aesthetics.

[3] O bom funcionamento [3] The proper functioning das funções of functions gerais general da gives pele pode skin can ser associado a um grupo be associated with a group de genes que of genes that , uma , an vez turn modulados, modulated, pode ser estratégia can be strategy interessante interesting para for o O

desenvolvimento de produtos com finalidade cosmética.development of products for cosmetic purposes.

[4] Entretanto, há um número limitado de compostos que efetivamente atuem na modulação de genes associados às funções gerais da pele.[4] However, there are a limited number of compounds that effectively act on the modulation of genes associated with general skin functions.

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2/15 [5] Portanto existe a necessidade de uma composição que atue na modulação de tais genes, fornecendo um tratamento efetivo para cuidado da pele.2/15 [5] Therefore, there is a need for a composition that acts on the modulation of such genes, providing an effective treatment for skin care.

BREVE DESCRIÇÃO DAS FIGURAS [6] As figuras 1A e 1B apresentam aumento da proteína colágeno I relativo à amostra controle não tratada após 3 dias de tratamento, dado em medidas de fluorescência e porcentagem.BRIEF DESCRIPTION OF THE FIGURES [6] Figures 1A and 1B show an increase in the collagen I protein relative to the untreated control sample after 3 days of treatment, given in fluorescence and percentage measurements.

[7] As figuras 2A e 2B apresentam aumento da proteína elastina relativo à amostra controle não tratada após 3 dias de tratamento, dado em medidas de fluorescência e porcentagem.[7] Figures 2A and 2B show an increase in elastin protein relative to the untreated control sample after 3 days of treatment, given in fluorescence and percentage measurements.

[8] As figuras 3A e 3B apresentam aumento da proteína ki-67 relativo à amostra controle não tratada após 3 dias de tratamento, dado em medidas de fluorescência e porcentagem.[8] Figures 3A and 3B show an increase in ki-67 protein relative to the untreated control sample after 3 days of treatment, given in fluorescence and percentage measurements.

[9] [9] As figuras The figures 4A e 4A and 4B apresentam 4B feature aumento increase da gives proteína protein involucrina involucrine relativo relative à amo s t ra the sample controle control não not tratada treated após after 3 dias 3 days de in tratamento, dado treatment, given em in medidas measures de in

fluorescência e porcentagem.fluorescence and percentage.

DESCRIÇÃO DA INVENÇÃO [10] A presente invenção trata de uma composição para a modulação de genes responsáveis pelas funções gerais da pele compreendendo Casearia sylvestris, Schinus terebinthfolius e ácido hialurônico e veículo cosmeticamente aceitável.DESCRIPTION OF THE INVENTION [10] The present invention deals with a composition for the modulation of genes responsible for the general functions of the skin comprising Casearia sylvestris, Schinus terebinthfolius and hyaluronic acid and cosmetically acceptable vehicle.

[11] Por Casearia sylvestris (popularmente conhecida de guaçatonga) ou Schinus terebinthfolius (popularmente conhecida como aroeira) entende-se qualquer fração proveniente das mesmas.[11] Casearia sylvestris (popularly known as guaçatonga) or Schinus terebinthfolius (popularly known as aroeira) means any fraction from them.

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3/15 [12] De maneira individualizada, os efeitos terapêuticos e cosméticos desses três componentes, Casearia sylvestris, Schinus terebinthfolius e ácido hialurônico, têm sido estudados.3/15 [12] Individually, the therapeutic and cosmetic effects of these three components, Casearia sylvestris, Schinus terebinthfolius and hyaluronic acid, have been studied.

[13] Entretanto, de maneira surpreendente, a Depositante verificou que, de maneira combinada, em uma composição, Casearia sylvestris, Schinus terebinthfolius e ácido hialurônico apresentam efeito na modulação de genes responsáveis pelas funções gerais da pele.[13] However, surprisingly, the Depositor found that, in a combined manner, in a composition, Casearia sylvestris, Schinus terebinthfolius and hyaluronic acid have an effect on the modulation of genes responsible for the general functions of the skin.

[14] Tais genes incluem pelo menos um dos genes[14] Such genes include at least one of the genes

CAT, GPX1, MSRA, NOX1, PRDX6 CAT, GPX1, MSRA, NOX1, PRDX6 , SOD2, , SOD2, DSC2, DSC2, IGF1R, IGF1R, I T GA1 , I T GA1, ITGB1, LAMB1, LAMB3, DEFB4A, ITGB1, LAMB1, LAMB3, DEFB4A, CDH1, CDH1, CAMP, CAMP, CLDN1, CLDN1, CLDN4, CLDN4, CLDN7, CDSN, DSG4, DSP, ELOVL3, GBA, CLDN7, CDSN, DSG4, DSP, ELOVL3, GBA, I T GA6, I T GA6, ITGB4, ITGB4, KRT19, KRT19, KRT10, KRT14, KRT16, KRT17, KRT10, KRT14, KRT16, KRT17, KRT1, KRT6A, KRT1, KRT6A, OR2AT4, OR2AT4, LAMA5, LAMA5, OCLN, PKP1, PLEC, TGM5, TGM1, OCLN, PKP1, PLEC, TGM5, TGM1, RNASE7 RNASE7 , SMPD1, SDC1, , SMPD1, SDC1, T JP1 , T JP1, VCL, BTC, FLT1, PDGFRA, HAS1, VCL, BTC, FLT1, PDGFRA, HAS1, HAS2, HAS2, SIRT1, SIRT1, S RD5 A1 , S RD5 A1, PRLR, PRLR, HSD17B2, TPH1, AANAT, ASMT, HSD17B2, TPH1, AANAT, ASMT, MTNR1A, MTNR1A, AR, AIR, ESR2, CYP19A1, ESR2, CYP19A1,

HTR2A, HTR2A, HTR2B HTR2B , MTOR, , MTOR, AQP3, AQP3, CTSB, CTSB, CTSE, CTSL, CD44 CTSE, CTSL, CD44 , HAL, , HAL, PADI3, PADI3, PADI1, PADI1, CASP14 CASP14 , FLG, , FLG, ST14, ST14, IL13, IL18, IL19, IL13, IL18, IL19, I T GA2 , I T GA2, IL1A, IL1A, IL1B, IL1B, I L2 2 , I L1 7 A, I L2 2, I L1 7 A, IL1R1, IL1R1, IL10, IL6, F2RL1, IL10, IL6, F2RL1, T RPV1 , T RPV1, CALCA, PANTS, ACACA THE HUNT , ASAH1, , ASAH1, UGCG UGCG , SPTLC1, SREBF2, GLB1, , SPTLC1, SREBF2, GLB1, ADAM9, ADAM9, MMP1, MMP1, MMP10, MMP10, MMP2 , MMP2, MMP3, MMP3, MMP9, MMP9, SERPINE1, TIMP1, SERPINE1, TIMP1, TIMP2, TIMP2,

TMPRSS6, FBLN5, FBN1, MMP12, MMP13, MMP14, TYR, GPNMB, MAP1LC3B, POMC, OPRM1, MC1R, MITF, CANX, HSPB1, HSPA1A, EGFR, TGFB1, TGFBR1, NGF, PDGFA, VEGFA, VEGFB, FGFR1, FGFR2, FGF1, FGF2, MMP11, HYAL1, HYAL2, ELN, LOX, COL1A1, COL1A2, ACO2, ANXA5.TMPRSS6, FBLN5, FBN1, MMP12, MMP13, MMP14, TYR, GPNMB, MAP1LC3B, POMC, OPRM1, MC1R, MITF, CANX, HSPB1, HSPA1A, EGFR, TGFB1, TGFBR1, NGF, PDGFA, FGF, FGF, VEGFA, VEGFA, FGF1, FGF2, MMP11, HYAL1, HYAL2, ELN, LOX, COL1A1, COL1A2, ACO2, ANXA5.

[15] De maneira ainda mais surpreendente, a Depositante verificou que, em quantidades de cerca de 0,1% de Casearia sylvestris, cerca de 0,025% de Schinus[15] Even more surprisingly, the Depositor found that, in amounts of about 0.1% of Casearia sylvestris, about 0.025% of Schinus

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4/15 terebinthfolius e cerca de 5% de ácido hialurônico, há modulação sinérgica em tais genes, particularmente na modulação da expressão das proteínas proteínas colágeno I, elastina, ki-67 e involucrina, propiciando seu uso em aplicações cosméticas na pele em geral.4/15 terebinthfolius and about 5% hyaluronic acid, there is synergistic modulation in such genes, particularly in the modulation of the expression of proteins proteins collagen I, elastin, ki-67 and involucrine, enabling its use in cosmetic applications on the skin in general.

[16] A presente invenção também está relacionada a um método para a modulação da expressão de tais genes responsáveis pelas funções gerais da pele, o qual compreende a etapa de administrar uma composição de acordo com a presente invenção, bem como uso da combinação de Casearia sylvestris, Schinus terebinthfolius e ácido hialurônico na preparação de uma composição para a modulação de genes responsáveis pelas funções gerais da pele.[16] The present invention is also related to a method for modulating the expression of such genes responsible for the general functions of the skin, which comprises the step of administering a composition according to the present invention, as well as using the combination of Casearia sylvestris, Schinus terebinthfolius and hyaluronic acid in the preparation of a composition for the modulation of genes responsible for the general functions of the skin.

[17] Os genes de acordo com a presente invenção e sua correlação com as funções gerais da pele estão definidos na tabela a seguir.[17] The genes according to the present invention and their correlation with the general functions of the skin are defined in the following table.

Tabela 1. Definição de genes e correlação com a função geral da pele.Table 1. Definition of genes and correlation with the general function of the skin.

Nome do gene Gene name Símbolo Symbol Função geral General function Catalase Catalase CAT CAT Defesa antioxidante Antioxidant defense Glutathione peroxidase 1 Glutathione peroxidase 1 GPX1 GPX1 Defesa antioxidante Antioxidant defense methionine sulfoxide reductase A methionine sulfoxide reductase A MSRA MSRA Defesa antioxidante Antioxidant defense NADPH oxidase 1 NADPH oxidase 1 NOX1 NOX1 Defesa antioxidante Antioxidant defense peroxiredoxin 6 peroxiredoxin 6 PRDX6 PRDX6 Defesa antioxidante Antioxidant defense Superoxide dismutase 2, mitochondrial Superoxide dismutase 2, mitochondrial SOD2 SOD2 Defesa antioxidante Antioxidant defense desmocollin 2 desmocollin 2 DSC2 DSC2 Adesão / ancoramento Adhesion / anchoring Insulin like growth factor 1 receptor Insulin like growth factor 1 receptor IGF1R IGF1R Adesão / ancoramento Adhesion / anchoring integrin, alpha 1 integrin, alpha 1 ITGA1 ITGA1 Adesão / ancoramento Adhesion / anchoring integrin, beta1 integrin, beta1 ITGB1 ITGB1 Adesão / ancoramento Adhesion / anchoring laminin, beta 1 laminin, beta 1 LAMB1 LAMB1 Adesão / ancoramento Adhesion / anchoring

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laminin, beta 3 laminin, beta 3 LAMB3 LAMB3 Adesão / ancoramento Adhesion / anchoring b-defensin 2, beta 4 b-defensin 2, beta 4 DEFB4A DEFB4A Atividade bactericida Activity bactericidal Cadherin-1 Cadherin-1 CDH1 CDH1 Função de barreira / coesão Barrier / cohesion function Cathelicidin antimicrobial peptide Cathelicidin antimicrobial peptide CAMP CAMP Função de barreira / coesão Barrier / cohesion function Claudin-1 Claudin-1 CLDN1 CLDN1 Função de barreira / coesão Barrier / cohesion function Claudin-4 Claudin-4 CLDN4 CLDN4 Função de barreira / coesão Barrier / cohesion function Claudin-7 Claudin-7 CLDN7 CLDN7 Função de barreira / coesão Barrier / cohesion function Corneodesmosin Corneodesmosin CDSN CDSN Função de barreira / coesão Barrier / cohesion function Desmoglein-4 Desmoglein-4 DSG4 DSG4 Função de barreira / coesão Barrier / cohesion function Desmoplakin Desmoplakin DSP DSP Função de barreira / coesão Barrier / cohesion function elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 3 elongation of very long chain fatty acids (FEN1 / Elo2, SUR4 / Elo3, yeast) -like 3 ELOVL3 ELOVL3 Função de barreira / coesão Barrier / cohesion function Glucosylceramidase Glucosylceramidase GBA GBA Função de barreira / coesão Barrier / cohesion function Integrin alpha-6 Integrin alpha-6 ITGA6 ITGA6 Função de barreira / coesão Barrier / cohesion function Integrin beta-4 Integrin beta-4 ITGB4 ITGB4 Função de barreira / coesão Barrier / cohesion function Keratin 19 Keratin 19 KRT19 KRT19 Função de barreira / coesão Barrier / cohesion function Keratin-10 Keratin-10 KRT10 KRT10 Função de barreira / coesão Barrier / cohesion function Keratin-14 Keratin-14 KRT14 KRT14 Função de barreira / coesão Barrier / cohesion function Keratin-16 Keratin-16 KRT16 KRT16 Função de barreira / coesão Barrier / cohesion function Keratin-17 Keratin-17 KRT17 KRT17 Função de barreira / coesão Barrier / cohesion function Keratin-1 Keratin-1 KRT1 KRT1 Função de barreira / coesão Barrier / cohesion function

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6/156/15

Keratin-6 Keratin-6 KRT6A KRT6A Função de barreira / coesão Barrier function / cohesion Olfactory receptor, family 2, subfamily AT, member 4 Olfactory receptor, family 2, subfamily AT, member 4 OR2AT4 OR2AT4 Cicatrização de feridas Healing of wounds Laminin subunit alpha-5 Laminin subunit alpha-5 LAMA5 LAMA5 Função de barreira / coesão Barrier function / cohesion Occludin Occludin OCLN OCLN Função de barreira / coesão Barrier function / cohesion Plakophilin 1 Plakophilin 1 PKP1 PKP1 Função de barreira / coesão Barrier function / cohesion Plectin-1 Plectin-1 PLEC PLEC Função de barreira / coesão Barrier function / cohesion Transglutaminase-5 Transglutaminase-5 TGM5 TGM5 Função de barreira / coesão Barrier function / cohesion Transglutaminase 1 Transglutaminase 1 TGM1 TGM1 Função de barreira / coesão Barrier function / cohesion RNase A family, 7 RNase A family, 7 RNASE7 RNASE7 Função de barreira / coesão Barrier function / cohesion Acid sphingomyelinase Acid sphingomyelinase SMPD1 SMPD1 Função de barreira / coesão Barrier function / cohesion Syndecan 1 Syndecan 1 SDC1 SDC1 Função de barreira / coesão Barrier function / cohesion Tight junction protein 1 Tight junction protein 1 TJP1 TJP1 Função de barreira / coesão Barrier function / cohesion Vinculin Vinculin VCL VCL Função de barreira / coesão Barrier function / cohesion Betacellulin Betacellulin BTC BTC Crescimento celular Cell growth Vascular permeability factor receptor Vascular permeability factor receptor FLT1 FLT1 Crescimento celular Cell growth Platelet-derived growth factor (PDGF) receptor A Platelet-derived growth factor (PDGF) receptor A PDGFRA PDGFRA Proliferação celular Cell proliferation Hyaluronan synthase 1 Hyaluronan synthase 1 HAS1 HAS1 Adesão da matriz celular Matrix adhesion cell phone Hyaluronan synthase 2 Hyaluronan synthase 2 HAS2 HAS2 Adesão da matriz celular Matrix adhesion cell phone Sirtuin 1 Sirtuin 1 SIRT1 SIRT1 histone deacetylase histone deacetylase Steroid-5-alpha- reductase Steroid-5-alpha- reductase SRD5A1 SRD5A1 Metabolismo hormonal Hormonal metabolism Prolactin receptor Prolactin receptor PRLR PRLR Metabolismo hormonal Hormonal metabolism Hydroxysteroid (17-beta) Hydroxysteroid (17-beta) HSD17B2 HSD17B2 Metabolismo hormonal Hormonal metabolism

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dehydrogenase 2 dehydrogenase 2 Tryptophan hydroxilase 1 Tryptophan hydroxylase 1 TPH1 TPH1 Metabolismo hormonal Hormonal metabolism Aralkylamine Nacetyltransferase Aralkylamine Nacetyltransferase AANAT AANAT Metabolismo hormonal Hormonal metabolism Hydroxyindole Omethyltransferase Hydroxyindole Omethyltransferase ASMT ASMT Metabolismo hormonal Hormonal metabolism Melatonin receptor 1a Melatonin receptor 1 to MTNR1A MTNR1A Metabolismo hormonal Hormonal metabolism Androgen receptor Androgen receptor AR AIR Metabolismo hormonal Hormonal metabolism Estrogen receptor Estrogen receptor ESR2 ESR2 Metabolismo hormonal Hormonal metabolism Cytochrome P450, family 19, subfamily A, polypeptide 1 / Aromatase Cytochrome P450, family 19, subfamily A, polypeptide 1 / Aromatase CYP19A1 CYP19A1 Metabolismo hormonal Hormonal metabolism 5-hydroxytryptamine (serotonin) receptor 2a 5-hydroxytryptamine (serotonin) 2a receptor HTR2A HTR2A Metabolismo hormonal Hormonal metabolism 5-hydroxytryptamine (serotonin) receptor 2B 5-hydroxytryptamine (serotonin) 2B receptor HTR2B HTR2B Metabolismo hormonal Hormonal metabolism Mechanistic target of rapamycin Mechanistic target of rapamycin MTOR MTOR Aquaporin-3 Aquaporin-3 AQP3 AQP3 Hidratação Hydration Cathepsin B Cathepsin B CTSB CTSB Hidratação Hydration Cathepsin E Cathepsin E CTSE CTSE Hidratação Hydration Cathepsin L1 Cathepsin L1 CTSL CTSL Hidratação Hydration CD44 antigen CD44 antigen CD44 CD44 Hidratação Hydration Histidine ammonia-lyase Histidine ammonia-lyase HAL HAL Hidratação Hydration Protein-arginine deiminase type-3 Protein-arginine deiminase type-3 PADI3 PADI3 Hidratação Hydration Peptidyl-arginine deiminase, type I Peptidyl-arginine deiminase, type I PADI1 PADI1 Hidratação Hydration Caspase-14 Caspase-14 CASP14 CASP14 Hidratação/ diferenciação/ formação de barreira Hydration / differentiation / barrier formation Filaggrin Filaggrin FLG FLG Hidratação/ diferenciação/ formação de barreira Hydration / differentiation / barrier formation Serine protease 14/Matriptase Serine protease 14 / Matriptase ST14 ST14 Hidratação/ diferenciação/ formação de barreira Hydration / differentiation / barrier formation Interleukin-13 Interleukin-13 IL13 IL13 Resposta imune Immune response Interleukin-18 Interleukin-18 IL18 IL18 Resposta imune Immune response Interleukin-19 Interleukin-19 IL19 IL19 Resposta imune Immune response

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Integrin, alpha 2 Integrin, alpha 2 ITGA2 ITGA2 Inflamação Inflammation Interleukin 1, alpha Interleukin 1, alpha IL1A IL1A Inflamação Inflammation Interleukin 1, beta Interleukin 1, beta IL1B IL1B Inflamação Inflammation Interleukin 22 Interleukin 22 IL22 IL22 Inflamação Inflammation Interleukin 17a Interleukin 17 a IL17A IL17A Inflamação Inflammation Interleukin-1 receptor type I Interleukin-1 type I receiver IL1R1 IL1R1 Inflamação Inflammation Interleukin-10 Interleukin-10 IL10 IL10 Inflamação Inflammation interleukin 6 interleukin 6 IL6 IL6 Inflamação Inflammation Protease-activated receptor 2 (kallikrein receptor) Protease-activated receiver 2 (kallikrein receiver) F2RL1 F2RL1 Descamação Flaking Activation of vanilloid receptor-1 Activation of vanilloid receiver-1 TRPV1 TRPV1 Prurido Itching Calcitonin gene-related peptide Calcitonin gene-related peptide CALCA PANTS Prurido Itching Acetyl-CoA carboxylase 1 Acetyl-CoA carboxylase 1 ACACA THE HUNT Síntese de lipídeo Lipid synthesis Acid ceramidase Acid ceramidase ASAH1 ASAH1 Síntese de lipídeo Lipid synthesis Ceramide glucosyltransferase Ceramide glucosyltransferase UGCG UGCG Síntese de lipídeo Lipid synthesis Serine palmitoyltransferase 1 Serine palmitoyltransferase 1 SPTLC1 SPTLC1 Síntese de lipídeo Lipid synthesis Sterol regulatory element-binding protein 2 Sterol regulatory element-binding protein 2 SREBF2 SREBF2 Síntese de lipídeo Lipid synthesis Galactosidase, beta 1 Galactosidase, beta 1 GLB1 GLB1 Hidrolase lipossomal Liposomal hydrolase ADAM metallopeptidase domain 9 ADAM metallopeptidase domain 9 ADAM9 ADAM9 Remodelagem de matriz Remodeling of matrix Matrix metallopeptidase 1 (interstitial collagenase) Matrix metallopeptidase 1 (interstitial collagenase) MMP1 MMP1 Remodelagem de matriz Remodeling of matrix Matrix metallopeptidase 10 (stromelysin 2) Matrix metallopeptidase 10 (stromelysin 2) MMP10 MMP10 Remodelagem de matriz Remodeling of matrix Matrix metallopeptidase 2 (gelatinase A, type IV collagenase) Matrix metallopeptidase 2 (gelatinase A, type IV collagenase) MMP2 MMP2 Remodelagem de matriz Remodeling of matrix Matrix metallopeptidase 3 (stromelysin 1, progelatinase) Matrix metallopeptidase 3 (stromelysin 1, progelatinase) MMP3 MMP3 Remodelagem de matriz Remodeling of matrix Matrix metallopeptidase 9 (gelatinase B, type IV Matrix metallopeptidase 9 (gelatinase B, type IV MMP9 MMP9 Remodelagem de matriz Remodeling of matrix

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collagenase) collagenase) Serpin peptidase inhibitor Serpin peptidase inhibitor SERPINE1 SERPINE1 Remodelagem matriz Remodeling matrix de in TIMP metallopeptidase TIMP metallopeptidase TIMP1 TIMP1 Remodelagem Remodeling de in inhibitor 1 inhibitor 1 matriz matrix TIMP metallopeptidase TIMP metallopeptidase TIMP2 TIMP2 Remodelagem Remodeling de in inhibitor 2 inhibitor 2 matriz matrix Transmembrane protease, serine 6 Transmembrane protease, serine 6 TMPRSS6 TMPRSS6 Remodelagem matriz Remodeling matrix de in Fibulin 5 Fibulin 5 FBLN5 FBLN5 Remodelagem matriz Remodeling matrix de in Fibrilin 1 Fibrilin 1 FBN1 FBN1 Remodelagem matriz Remodeling matrix de in Matrix metallopeptidase 12 Matrix metallopeptidase 12 MMP12 MMP12 Remodelagem de matriz/ cicatrização de feridas Matrix remodeling / healing of wounds Matrix metallopeptidase 13 Matrix metallopeptidase 13 MMP13 MMP13 Remodelagem de matriz/ cicatrização Remodeling of matrix / healing de feridas of wounds Matrix metallopeptidase 14 Matrix metallopeptidase 14 MMP14 MMP14 Remodelagem de matriz/ cicatrização Remodeling of matrix / healing de feridas of wounds Tyrosinase Tyrosinase TYR TYR Síntese de melanina Melanin synthesis Glycoprotein (transmembrane) nmb Glycoprotein (transmembrane) nmb GPNMB GPNMB Adesão de melanócitos a queratinócitos Adhesion of melanocytes to keratinocytes MAP1LC3B microtubule- associated protein 1 light chain 3 beta MAP1LC3B microtubule- associated protein 1 light chain 3 beta MAP1LC3B MAP1LC3B Autofagia Autophagy Proopiomelanocortin Proopiomelanocortin POMC POMC Metabolisto de neuropeptídeo Metabolist of neuropeptide Opioid receptor Opioid receptor OPRM1 OPRM1 Metabolisto neuropeptídeo Metabolist neuropeptide de in Melanocortin 1 receptor Melanocortin 1 receptor MC1R MC1R Metabolisto neuropeptídeo Metabolist neuropeptide de in Microphthalmiaassociated transcription factor Microphthalmiaassociated transcription factor tn-| H 1—1 _2_ tn- | H 1—1 _2_ Regulador de melanócitos Regulator melanocytes Calnexin Calnexin CANX CANX Folding de proteínas Protein folding Heat shock 27kDa Heat shock 27kDa HSPB1 HSPB1 Folding de proteínas Protein folding Heat shock 72kDa Heat shock 72kDa HSPA1A HSPA1A Folding de proteínas Protein folding

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10/1510/15

Epidermal growth factor receptor Epidermal growth factor receptor EGFR EGFR Transdução de sinal Signal transduction Transforming growth factor, beta 1 Transforming growth factor, beta 1 TGFB1 TGFB1 Transdução de sinal Signal transduction Transforming growth factor, beta receptor I Transforming growth factor, beta receptor I TGFBR1 TGFBR1 Transdução de sinal Signal transduction Nerve Growth Factor Nerve Growth Factor NGF NGF Cicatrização de feridas Wound healing Platelet-derived Growth Factor A Platelet-derived Growth Factor A PDGFA PDGFA Cicatrização de feridas Healing of wounds Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor A VEGFA VEGFA Cicatrização de feridas Healing of wounds Vascular Endothelial Growth Factor B Vascular Endothelial Growth Factor B VEGFB VEGFB Cicatrização de feridas Healing of wounds Fibroblast growth factor receptor 1 Fibroblast growth factor receptor 1 FGFR1 FGFR1 Cicatrização de feridas Healing of wounds Fibroblast growth factor receptor 2 Fibroblast growth factor receptor 2 FGFR2 FGFR2 Cicatrização de feridas Healing of wounds Fibroblast growth factor 1 (acidic) Fibroblast growth factor 1 (acidic) FGF1 FGF1 Cicatrização de feridas Healing of wounds Fibroblast growth factor 2 (basic) Fibroblast growth factor 2 (basic) FGF2 FGF2 Cicatrização de feridas Healing of wounds Matrix metallopeptidase 11 Matrix metallopeptidase 11 MMP11 MMP11 Cicatrização de feridas Healing of wounds Hyaluronidase 1 Hyaluronidase 1 HYAL1 HYAL1 Hidratação Hydration Hyaluronidase 2 Hyaluronidase 2 HYAL2 HYAL2 Hidratação Hydration Elastin Elastin ELN ELN Remodelação de matriz Remodeling of matrix Lysyl oxidase Lysyl oxidase LOX LOX Remodelação de matriz Remodeling of matrix Collagen, type I, alpha 1 Collagen, type I, alpha 1 COL1A1 COL1A1 Remodelação de matriz Remodeling of matrix Collagen, type I, alpha 2 Collagen, type I, alpha 2 COL1A2 COL1A2 Remodelação de matriz Remodeling of matrix Aconitase 2, mitochondrial Aconitase 2, mitochondrial ACO2 ACO2 Defesa antioxidante Antioxidant defense Annexin A5 Annexin A5 ANXA5 ANXA5 Crescimento celular/ diferenciação Cell growth / differentiation

[18] Os veículos cosmeticamente aceitáveis de acordo com a presente invenção incluem, sem qualquer[18] Cosmetically acceptable vehicles according to the present invention include, without any

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11/15 limitação, aqueles conhecidos da técnica.11/15 limitation, those known in the art.

[19] Os exemplos a seguir, sem impor qualquer limitação, ilustram a presente invenção, particularmente no que diz respeito aos efeitos na modulação de genes associados às funções gerais da pele.[19] The following examples, without imposing any limitation, illustrate the present invention, particularly with regard to the effects on the modulation of genes associated with the general functions of the skin.

EXEMPLOSEXAMPLES

Exemplo 1. Ensaio de atividade molecular [20] Foi realizado ensaio em larga escala do perfil de expressão gênica (por PCR array) de 180 genes em explantes de pele obtidas após cirurgia de blefaroplastia e submetidos a tratamentos independentes com a presente invenção.Example 1. Molecular activity assay [20] A large scale assay of the gene expression profile (by PCR array) of 180 genes was performed on skin explants obtained after blepharoplasty surgery and subjected to independent treatments with the present invention.

[21] Inicialmente, foram obtidos explantes de pele de pálpebras de mulheres com idades entre 45 e 55 anos, sendo 3 doadores diferentes para cada. Os explantes foram divididos em duas porções e inseridos, em triplicata de cada doador, imediatamente em meio de cultura e mantidos por 24 horas (porção 1) e 72 horas (porção 2) em atmosfera úmida, 37°C, CO2 5%. Durante esse período, os explantes foram submetidos aos tratamentos com 2mg/cm2 de cada amostra aplicados topicamente sobre os explantes, sem qualquer diluição. Além disso, uma condição controle foi realizada pela manutenção dos explantes, em triplicata de cada doador, em meio de cultura somente. Uma análise de viabilidade prévia foi realizada para garantir a integridade dos tecidos durante todo o protocolo do estudo para todas as fórmulas investigadas.[21] Initially, eyelid skin explants were obtained from women between the ages of 45 and 55, with 3 different donors for each. The explants were divided into two portions and inserted, in triplicate of each donor, immediately in culture medium and maintained for 24 hours (portion 1) and 72 hours (portion 2) in a humid atmosphere, 37 ° C, 5% CO 2 . During this period, the explants were subjected to treatments with 2mg / cm 2 of each sample applied topically over the explants, without any dilution. In addition, a control condition was performed by maintaining the explants, in triplicate from each donor, in culture medium only. A previous viability analysis was performed to guarantee the integrity of the tissues throughout the study protocol for all investigated formulas.

[22] A porção (1) foi coletada e submetida à extração de RNA total. A qualidade do RNA extraído foi validada qualitativa (Bíoanalyzer mícrocapíllary[22] Portion (1) was collected and subjected to extraction of total RNA. The quality of the extracted RNA was validated qualitatively (Bíoanalyzer microcapíllary

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12/15 electrophoresis) e quantitativamente (Nanodrop spectrophotometer). A partir do RNA, foi confeccionado o cDNA e este foi submetido à etapa de RT-PCR (PolymeraseChaín Reaction) em tempo real para avaliação da expressão de 180 genes utilizando a plataforma customizada Taqman PCR Array (ThermoFisher). Os genes testados foram aqueles listados na tabela 1 com o auxílio do equipamento StepOne Plus (Life Technologies). O perfil de expressão gênica e seleção dos genes diferencialmente expressos foram realizados com o auxílio do Expression Suite Software v.1.0.3 (Life Technologies). Os valores de ACt para o gene referência GAPDH (glyceraldehyde-3-phosphate dehydrogenase) e o gene alvo foram calculados pela subtração dos valores dos grupos experimentais. Posteriormente, o ACt do grupo experimental foi subtraído do grupo controle (explante de pele sem tratamento) para a obtenção do AACt. Por fim, a quantificação relativa dos genes alvos foi determinada pela equação: RQ = 2-AACt. Foram selecionados apenas os genes que apresentaram um threshold de 1,3, ou seja, 30% de aumento ou redução em relação ao controle. A significância estatística foi avaliada pelo teste-t acompanhado do método de Benjamini-Hochberg (FDR - false discovery rate), sendo que p-value < 0,05 foram considerados significantes. Os valores detectados como estatisticamente significantes foram carregados no software Ingenuity Pathway Analysis (IPA) (http://www.ingenuity.com) Para investigar as relações funcionais entre os genes identificados. Para cada via/rede estabelecida foi gerado um p-score [p-score = -log10 (p-value)] refletindo a probabilidade de esta rede ser gerada ao acaso e onde o p-value foi calculado pelo12/15 electrophoresis) and quantitatively (Nanodrop spectrophotometer). From the RNA, the cDNA was made and submitted to the RT-PCR (PolymeraseChaín Reaction) step in real time to evaluate the expression of 180 genes using the customized Taqman PCR Array (ThermoFisher) platform. The tested genes were those listed in Table 1 with the aid of the StepOne Plus equipment (Life Technologies). The profile of gene expression and selection of differentially expressed genes were performed with the aid of Expression Suite Software v.1.0.3 (Life Technologies). The ACt values for the reference gene GAPDH (glyceraldehyde-3-phosphate dehydrogenase) and the target gene were calculated by subtracting the values of the experimental groups. Subsequently, the ACt of the experimental group was subtracted from the control group (skin explant without treatment) to obtain the AACt. Finally, the relative quantification of the target genes was determined by the equation: RQ = 2-AACt. Only genes that had a threshold of 1.3, that is, 30% increase or decrease in relation to the control, were selected. Statistical significance was assessed by the t-test accompanied by the Benjamini-Hochberg method (FDR - false discovery rate), with p-value <0.05 being considered significant. The values detected as statistically significant were loaded into the Ingenuity Pathway Analysis (IPA) software (http://www.ingenuity.com) to investigate the functional relationships between the identified genes. For each established route / network, a p-score was generated [p-score = -log10 (p-value)] reflecting the probability that this network will be generated at random and where the p-value was calculated by

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Fisher's exact test. Isso significa que se uma via tem um p-score de 10, a chance de esta rede ser gerada ao acaso é menos do que 1 em 1010. Esses resultados mostram os genes e funções moduladas pelas composições e métodos da presente invenção.Fisher's exact test. This means that if a pathway has a p-score of 10, the chance of this network being generated at random is less than 1 in 1010. These results show the genes and functions modulated by the compositions and methods of the present invention.

[23] A porção (2) foi coletada, fixadas em paraformaldeído 4% (pH 7,4) por 24 horas e crioprotegidas em solução de sacarose 30% por 48 horas. Em seguida, cortes seriados de 10 pm foram coletados diretamente em lâminas silanizadas com o auxílio de Criostato (Leica - CN1850). Ao término da coleta dos cortes, os mesmos foram submetidos a lavagens com PB 0,1 M e incubados overnight com anticorpos referentes a proteínas de interesse selecionadas. Em seguida, as lâminas foram analisadas em Microscópio de Fluorescência (Leica - DM 1000) com auxílio do Software LAS (Leica Application Suíte). O parâmetro avaliado foi a intensidade de fluorescência emitida pela marcação com anticorpo específico. Para análise estatística foi utilizada a análise de variância (ANOVA). Em todos os grupos estudados, foram considerados estatisticamente significativos aqueles cujos valores de P foram inferiores a 0,05.[23] Portion (2) was collected, fixed in 4% paraformaldehyde (pH 7.4) for 24 hours and cryoprotected in a 30% sucrose solution for 48 hours. Then, 10 pm serial cuts were collected directly on silanized slides with the aid of cryostat (Leica - CN1850). At the end of the collection of the cuts, they were subjected to washes with 0.1 M PB and incubated overnight with antibodies to selected proteins of interest. Then, the slides were analyzed using a Fluorescence Microscope (Leica - DM 1000) with the aid of the LAS Software (Leica Application Suite). The evaluated parameter was the fluorescence intensity emitted by the labeling with specific antibody. For statistical analysis, analysis of variance (ANOVA) was used. In all groups studied, those whose P values were less than 0.05 were considered statistically significant.

[24] Foram investigados o controle não tratado, placebo, uma composição cosmética contendo a combinação de Casearia sylvestris, Schinus terebinthfolius e ácido hialurônico (preenchedor), combinação de Casearia sylvestris, Schinus terebínthfolíus (guaçatonga 1% + aroeira 0,025%) , ácido hialurônico 5% e a combinação de Casearia sylvestris, Schinus terebinthfolius e ácido hialurônico (guaçatonga 1% + aroeira 0,025% + ácido[24] The untreated placebo control, a cosmetic composition containing the combination of Casearia sylvestris, Schinus terebinthfolius and hyaluronic acid (filler), combination of Casearia sylvestris, Schinus terebínthfolíus (1% guaçatonga + 0.025% mastic), was investigated. 5% and the combination of Casearia sylvestris, Schinus terebinthfolius and hyaluronic acid (guaçatonga 1% + mastic 0.025% + acid

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14/15 hialurônico 5%).14/15 hyaluronic 5%).

[25] No que diz respeito à expressão gênica, em relação ao controle não tratado, observou-se que a amostra Guaçatonga e Aroeira foi capaz de modular 153 genes, a amostra Ácido Hialurônico foi capaz de modular 162 genes e a combinação de Guaçatonga e Aroeira e Ácido Hialurônico foi capaz de modular 144 genes. Observou-se que a combinação de acordo com a presente invenção apresentou efeito uma vez superior em relação ao controle não tratado na claudina I (mecanismo de comunicação célula-célula) e no ki-67 (mecanismo de proliferação - renovação celular), duas vezes superiores na elastina (estimulo de fibras elásticas), SOD2 (mecanismo do sistema antioxidante endógeno) e integrina B1 ou B4 (mecanismo de coesão dermeepiderme), quatro vezes superior no IL-10 (mecanismo antiinflamatório) e sete vezes superior em relação à involucrina (mecanismo de diferenciação celular).[25] Regarding gene expression, in relation to the untreated control, it was observed that the Guaçatonga and Aroeira sample was able to modulate 153 genes, the Hyaluronic Acid sample was able to modulate 162 genes and the combination of Guaçatonga and Aroeira and Hyaluronic Acid was able to modulate 144 genes. It was observed that the combination according to the present invention had an effect once superior in relation to the untreated control on claudin I (cell-cell communication mechanism) and ki-67 (proliferation mechanism - cell renewal), twice superior in elastin (stimulation of elastic fibers), SOD2 (mechanism of the endogenous antioxidant system) and integrin B1 or B4 (dermeepiderm cohesion mechanism), four times higher in IL-10 (anti-inflammatory mechanism) and seven times higher in relation to involucrine ( differentiation mechanism).

[26] Em relação à expressão proteica, a combinação da presente invenção promoveu aumentos de 31,4% na expressão da proteína colágeno I (Figuras 1A e 2B), de 130% na expressão da proteína elastina (Figura 2A e 2B) e de 56% na expressão da proteína ki-67 (Figuras 3A e 3B). Para a proteína involucrina, foi observado que a combinação de acordo com a presente invenção promoveu aumento de 111,3% na expressão da proteína (Figura 4A e 4B).[26] Regarding protein expression, the combination of the present invention promoted increases of 31.4% in the expression of collagen I protein (Figures 1A and 2B), of 130% in the expression of elastin protein (Figures 2A and 2B) and of 56% in ki-67 protein expression (Figures 3A and 3B). For the involucrine protein, it was observed that the combination according to the present invention promoted an increase of 111.3% in the expression of the protein (Figures 4A and 4B).

[27] O homem da técnica saberá prontamente avaliar, por meio dos ensinamentos contidos no texto e nos exemplos apresentados, vantagens da invenção e propor variações e alternativas equivalentes de realização, sem fugir ao escopo da invenção, conforme definido nas[27] The man of the art will readily evaluate, through the teachings contained in the text and in the examples presented, the advantages of the invention and propose variations and equivalent alternatives of realization, without departing from the scope of the invention, as defined in the

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15/15 reivindicações anexas.15/15 attached claims.

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Claims (8)

REIVINDICAÇÕES 1. COMPOSIÇÃO PARA A MODULAÇÃO DE GENES RESPONSÁVEIS PELAS FUNÇÕES GERAIS DA PELE caracterizada pelo fato de que compreende Casearia sylvestris , Schinus terebinthfolius, ácido hialurônico e veículo cosmeticamente aceitável.1. COMPOSITION FOR THE MODULATION OF GENES RESPONSIBLE FOR GENERAL SKIN FUNCTIONS characterized by the fact that it comprises Casearia sylvestris, Schinus terebinthfolius, hyaluronic acid and cosmetically acceptable vehicle. 2. COMPOSIÇÃO, de acordo com a reivindicação 1, caracterizada pelo fato de ser para modulação de pelo menos2. COMPOSITION, according to claim 1, characterized by the fact that it is for modulation of at least um dos one of the genes genes CAT, CAT, GPX1, MSRA, NOX1, PRDX6, GPX1, MSRA, NOX1, PRDX6, SOD2, SOD2, DSC2 DSC2 IGF1R, IGF1R, I T GA1 , I T GA1, ITGB1 ITGB1 , LAMB1, LAMB3, DEFB4A, , LAMB1, LAMB3, DEFB4A, CDH1, CDH1, CAMP CAMP CLDN1, CLDN1, CLDN4, CLDN4, CLDN7, CLDN7, CDSN, DSG4, DSP, ELOVL3 CDSN, DSG4, DSP, ELOVL3 , GBA, , GBA, I TGA6 I TGA6 ITGB4, ITGB4, KRT19, KRT19, KRT10 KRT10 , KRT14, KRT16, KRT17, , KRT14, KRT16, KRT17, KRT1, KRT1, KRT6A KRT6A OR2AT4, OR2AT4, LAMA5, LAMA5, OCLN, OCLN, PKP1, PLEC, TGM5, TGM1, RNASE7, PKP1, PLEC, TGM5, TGM1, RNASE7, SMPD1 SMPD1
SDC1, TJP1, VCL, BTC, FLT1, PDGFRA, HAS1, HAS2, SIRT1, SRD5A1, PRLR, HSD17B2, TPH1, AANAT, ASMT, MTNR1A, AR, ESR2, CYP19A1, HTR2A, HTR2B, MTOR, AQP3, CTSB, CTSE, CTSL, CD44, HAL, PADI3, PADI1, CASP14, FLG, ST14, IL13, IL18, IL19,SDC1, TJP1, VCL, BTC, FLT1, PDGFRA, HAS1, HAS2, SIRT1, SRD5A1, PRLR, HSD17B2, TPH1, AANAT, ASMT, MTNR1A, AR, ESR2, CYP19A1, HTR2A, HTR2B, CTR, MT, CTSL, CD44, HAL, PADI3, PADI1, CASP14, FLG, ST14, IL13, IL18, IL19, ITGA2, IL1A, IL1B, IL22, IL17A, IL1R1, IL10, IL6, F2RL1, TRPV1, CALCA, ACACA, ASAH1, UGCG, SPTLC1, SREBF2, GLB1, ADAM9, MMP1, MMP10, MMP2, MMP3, MMP9, SERPINE1, TIMP1, TIMP2, TMPRSS6, FBLN5, FBN1, MMP12, MMP13, MMP14, TYR, GPNMB, MAP1LC3B, POMC, OPRM1, MC1R, MITF, CANX, HSPB1, HSPA1A, EGFR, TGFB1, TGFBR1, NGF, PDGFA, VEGFA, VEGFB, FGFR1, FGFR2, FGF1, FGF2, MMP11, HYAL1, HYAL2, ELN, LOX, COL1A1, COL1A2, ACO2, ANXA5.ITGA2, IL1A, IL1B, IL22, IL17A, IL1R1, IL10, IL6, F2RL1, TRPV1, CALCA, ACACA, ASAH1, UGCG, SPTLC1, SREBF2, GLB1, ADAM9, MMP1, MMP10, MMP2, MMP3, MMP9, TIMP2, TMPRSS6, FBLN5, FBN1, MMP12, MMP13, MMP14, TYR, GPNMB, MAP1LC3B, POMC, OPRM1, MC1R, MITF, CANX, HSPB1, HSPA1A, EGFR, TGFB1, TGFBR1, NGF, FGG, VG FGFR2, FGF1, FGF2, MMP11, HYAL1, HYAL2, ELN, LOX, COL1A1, COL1A2, ACO2, ANXA5. 3. COMPOSIÇÃO, de acordo com a reivindicação 1, caracterizada pelo fato de compreender de cerca de 0,1% de Casearia sylvestris, cerca de 0,025% de Schinus terebinthfolius e cerca de 5% de ácido hialurônico.3. COMPOSITION, according to claim 1, characterized by the fact that it comprises about 0.1% of Casearia sylvestris, about 0.025% of Schinus terebinthfolius and about 5% of hyaluronic acid. 4. COMPOSIÇÃO, de acordo com a reivindicação 1,4. COMPOSITION, according to claim 1, 25/3225/32 2/3 caracterizada pelo fato de ser para modulação da expressão de pelo menos uma das proteínas colágeno I, elastina, ki-67 e involucrina.2/3 characterized by the fact that it modulates the expression of at least one of the proteins collagen I, elastin, ki-67 and involucrine. 5. MÉTODO PARA A MODULAÇÃO DA EXPRESSÃO DE GENES RESPONSÁVEIS PELAS FUNÇÕES GERAIS DA PELE caracterizado pelo fato de que compreende a etapa de administrar uma composição como definida em qualquer uma das reivindicações 1 a 4 a um indivíduo.5. METHOD FOR MODULATING THE EXPRESSION OF GENES RESPONSIBLE FOR GENERAL SKIN FUNCTIONS characterized by the fact that it comprises the step of administering a composition as defined in any of claims 1 to 4 to an individual. 6. MÉTODO, de acordo com a reivindicação 5, caracterizado pelo fato de ser para modulação de pelo menos6. METHOD, according to claim 5, characterized by the fact that it is for modulation of at least um dos one of the genes genes CAT, GPX1, MSRA, NOX1, CAT, GPX1, MSRA, NOX1, PRDX6, PRDX6, SOD2, SOD2, DSC2, DSC2, IGF1R, IGF1R, I T GA1 , I T GA1, ITGB1, LAMB1, LAMB3, ITGB1, LAMB1, LAMB3, DEFB4A, DEFB4A, CDH1, CDH1, CAMP, CAMP, CLDN1, CLDN1, CLDN4, CLDN4, CLDN7, CDSN, DSG4, DSP, CLDN7, CDSN, DSG4, DSP, ELOVL3 ELOVL3 , GBA, , GBA, I T GA6 , I T GA6, ITGB4, ITGB4, KRT19, KRT19, KRT10, KRT14, KRT16, KRT10, KRT14, KRT16, KRT17, KRT17, KRT1, KRT1, KRT6A, KRT6A,
OR2AT4, LAMA5, OCLN, PKP1, PLEC, TGM5, TGM1, RNASE7, SMPD1, SDC1, TJP1, VCL, BTC, FLT1, PDGFRA, HAS1, HAS2, SIRT1, SRD5A1, PRLR, HSD17B2, TPH1, AANAT, ASMT, MTNR1A, AR, ESR2, CYP19A1, HTR2A, HTR2B, MTOR, AQP3, CTSB, CTSE, CTSL, CD44, HAL, PADI3, PADI1, CASP14, FLG, ST14, IL13, IL18, IL19,OR2AT4, LAMA5, OCLN, PKP1, PLEC, TGM5, TGM1, RNASE7, SMPD1, SDC1, TJP1, VCL, BTC, FLT1, PDGFRA, HAS1, HAS2, SIRT1, SRD5A1, PRLR, HSD17B2, TR1, MTN AR, ESR2, CYP19A1, HTR2A, HTR2B, MTOR, AQP3, CTSB, CTSE, CTSL, CD44, HAL, PADI3, PADI1, CASP14, FLG, ST14, IL13, IL18, IL19, ITGA2, IL1A, IL1B, IL22, IL17A, IL1R1, IL10, IL6, F2RL1, TRPV1, CALCA, ACACA, ASAH1, UGCG, SPTLC1, SREBF2, GLB1, ADAM9, MMP1, MMP10, MMP2, MMP3, MMP9, SERPINE1, TIMP1, TIMP2, TMPRSS6, FBLN5, FBN1, MMP12, MMP13, MMP14, TYR, GPNMB, MAP1LC3B, POMC, OPRM1, MC1R, MITF, CANX, HSPB1, HSPA1A, EGFR, TGFB1, TGFBR1, NGF, PDGFA, VEGFA, VEGFB, FGFR1, FGFR2, FGF1, FGF2, MMP11, HYAL1, HYAL2, ELN, LOX, COL1A1, COL1A2, ACO2, ANXA5.ITGA2, IL1A, IL1B, IL22, IL17A, IL1R1, IL10, IL6, F2RL1, TRPV1, CALCA, ACACA, ASAH1, UGCG, SPTLC1, SREBF2, GLB1, ADAM9, MMP1, MMP10, MMP2, MMP3, MMP9, TIMP2, TMPRSS6, FBLN5, FBN1, MMP12, MMP13, MMP14, TYR, GPNMB, MAP1LC3B, POMC, OPRM1, MC1R, MITF, CANX, HSPB1, HSPA1A, EGFR, TGFB1, TGFBR1, NGF, FGG, VG FGFR2, FGF1, FGF2, MMP11, HYAL1, HYAL2, ELN, LOX, COL1A1, COL1A2, ACO2, ANXA5. 7. USO DE CASEARIA SYLVESTRIS, SCHINUS TEREBINTHFOLIUS E ÁCIDO HIALURÔNICO caracterizado pelo fato de ser para a preparação de uma composição para a modulação7. USE OF SYLVESTRIS HOUSEHOLD, SCHINUS TEREBINTHFOLIUS AND HYALURONIC ACID characterized by the fact that it is for the preparation of a composition for modulation 26/3226/32 3/3 de genes responsáveis pelas funções gerais da pele.3/3 of genes responsible for general skin functions. 8. USO, de acordo com a reivindicação 7, caracterizado pelo fato dos genes serem selecionados de pelo menos um dentre CAT, GPX1, MSRA, NOX1, PRDX6, SOD2, DSC2, IGF1R, ITGA1, ITGB1, LAMB1, LAMB3, DEFB4A, CDH1, CAMP, CLDN1, CLDN4, CLDN7, CDSN, DSG4, DSP, ELOVL3, GBA, ITGA6, ITGB4, KRT19, KRT10, KRT14, KRT16, KRT17, KRT1, KRT6A, OR2AT4, LAMA5, OCLN, PKP1, PLEC, TGM5, TGM1, RNASE7, SMPD1, SDC1, TJP1, VCL, BTC, FLT1, PDGFRA, HAS1, HAS2, SIRT1, SRD5A1, PRLR, HSD17B2, TPH1, AANAT, ASMT, MTNR1A, AR, ESR2, CYP19A1, HTR2A, HTR2B, MTOR, AQP3, CTSB, CTSE, CTSL, CD44, HAL, PADI3, PADI1, CASP14, FLG, ST14, IL13,8. USE, according to claim 7, characterized in that the genes are selected from at least one among CAT, GPX1, MSRA, NOX1, PRDX6, SOD2, DSC2, IGF1R, ITGA1, ITGB1, LAMB1, LAMB3, DEFB4A, CDH1 , CAMP, CLDN1, CLDN4, CLDN7, CDSN, DSG4, DSP, ELOVL3, GBA, ITGA6, ITGB4, KRT19, KRT10, KRT14, KRT16, KRT17, KRT1, KRT6A, OR2AT4, LAMA5, OCLN, PKM1, TGM, TGM1 , RNASE7, SMPD1, SDC1, TJP1, VCL, BTC, FLT1, PDGFRA, HAS1, HAS2, SIRT1, SRD5A1, PRLR, HSD17B2, TPH1, AANAT, ASMT, MTNR1A, AR, ESR2, CYP19A1, HQ2, HTR2 , CTSB, CTSE, CTSL, CD44, HAL, PADI3, PADI1, CASP14, FLG, ST14, IL13, IL18, IL19, ITGA2, IL1A, IL1B, IL22, IL17A, IL1R1, IL10,IL18, IL19, ITGA2, IL1A, IL1B, IL22, IL17A, IL1R1, IL10, IL6, F2RL1, TRPV1, CALCA, ACACA, ASAH1, UGCG, SPTLC1, SREBF2, GLB1, ADAM9, MMP1, MMP10, MMP2, MMP3, MMP9, SERPINE1, TIMP1, TIMP2, TMPRSS6, FBLN5, FBN1, MMP12, MMP13, MMP14, TYR, GPNMB, MAP1LC3B, POMC, OPRM1, MC1R, MITF, CANX, HSPB1, HSPA1A, EGFR, TGFB1, TGFBR1, NGF, PDGFA, VEGFA, VEGFB, FGFR1, FGFR2, FGF1, FGF2, MMP11, HYAL1, HYAL2, ELN, LOX, COL1A1, COL1A2, ACO2, ANXA5.IL6, F2RL1, TRPV1, CALCA, ACACA, ASAH1, UGCG, SPTLC1, SREBF2, GLB1, ADAM9, MMP1, MMP10, MMP2, MMP3, MMP9, SERPINE1, TIMP1, TIMP2, TMPRSS6, FBLN5, MMP, MMP, TYR, GPNMB, MAP1LC3B, POMC, OPRM1, MC1R, MITF, CANX, HSPB1, HSPA1A, EGFR, TGFB1, TGFBR1, NGF, PDGFA, VEGFA, VEGFB, FGFR1, FGFR2, FGF1, FGFY, HMP, LOX, COL1A1, COL1A2, ACO2, ANXA5. 27/3227/32 1/41/4 25.000 ** « *25,000 ** «* 20.00020,000 15.000 âú o15,000 ° 10.000° 10,000 5.0005,000 Conirole Placebo Preenchedot Ousça longa 0,1% + Arpei ra 0.025% Ácido HialurÒnko 5% Guaça longa 0,1% + Aioeira 0.025% + Ácido makjfftnico S%Conirole Placebo Preenchedot Longness 0.1% + Arpei ra 0.025% HialurÒnko Acid 5% Long Sleeve 0.1% + Aioeira 0.025% + Makjfftnico Acid S%
BR102016022682-1A 2016-05-24 2016-09-29 COMPOSITION FOR MODULATION OF GENES RESPONSIBLE FOR GENERAL SKIN FUNCTIONS, METHOD FOR MODULATING EXPRESSION OF GENES RESPONSIBLE FOR SKIN GENERAL FUNCTIONS AND USE OF SYLVESTRIS, SCHINUS TEREBINTHFOLIUS AND HYNURIC ACID BR102016022682A2 (en)

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BR102016022682-1A BR102016022682A2 (en) 2016-09-29 2016-09-29 COMPOSITION FOR MODULATION OF GENES RESPONSIBLE FOR GENERAL SKIN FUNCTIONS, METHOD FOR MODULATING EXPRESSION OF GENES RESPONSIBLE FOR SKIN GENERAL FUNCTIONS AND USE OF SYLVESTRIS, SCHINUS TEREBINTHFOLIUS AND HYNURIC ACID
MX2018014431A MX2018014431A (en) 2016-05-24 2017-05-24 Composition for modulating the genes responsible for general skin functions, method for modulating the expression of genes responsible for general skin functions, and use of a plant extract.
US16/304,544 US20200315950A1 (en) 2016-05-24 2017-05-24 Composition for modulating the genes responsible for general skin functions, method for modulating the expression of genes responsible for general skin functions, and use of a plant extract
MX2021003952A MX2021003952A (en) 2016-05-24 2017-05-24 Composition for modulating the genes responsible for general skin functions, method for modulating the expression of genes responsible for general skin functions, and use of a plant extract.
PCT/BR2017/050128 WO2017201597A1 (en) 2016-05-24 2017-05-24 Composition for modulating the genes responsible for general skin functions, method for modulating the expression of genes responsible for general skin functions, and use of a plant extract
BR112018074219-8A BR112018074219A2 (en) 2016-05-24 2017-05-24 composition for modulating genes responsible for general skin functions, method for modulating expression of genes responsible for general skin functions and use of a plant extract
MX2021003950A MX2021003950A (en) 2016-05-24 2018-11-23 Composition for modulating the genes responsible for general skin functions, method for modulating the expression of genes responsible for general skin functions, and use of a plant extract.
MX2021003951A MX2021003951A (en) 2016-05-24 2018-11-23 Composition for modulating the genes responsible for general skin functions, method for modulating the expression of genes responsible for general skin functions, and use of a plant extract.
MX2021003953A MX2021003953A (en) 2016-05-24 2018-11-23 Composition for modulating the genes responsible for general skin functions, method for modulating the expression of genes responsible for general skin functions, and use of a plant extract.
CL2018003354A CL2018003354A1 (en) 2016-05-24 2018-11-23 Composition to modulate genes responsible for the general functions of the skin, method to modulate the expression of genes responsible for the general functions of the skin and use of a plant extract
MX2021003959A MX2021003959A (en) 2016-05-24 2018-11-23 Composition for modulating the genes responsible for general skin functions, method for modulating the expression of genes responsible for general skin functions, and use of a plant extract.
CL2020002641A CL2020002641A1 (en) 2016-05-24 2020-10-13 Composition to modulate genes responsible for the general functions of the skin, comprising a plant extract of cichorium intybus and ceramides of passionflower (divisional of application 03354-2018)
CL2020002647A CL2020002647A1 (en) 2016-05-24 2020-10-13 Composition to modulate genes responsible for the general functions of the skin, comprising the combination of acmella oleracea extract and hyaluronic acid (divisional application 03354-2018)
CL2020002639A CL2020002639A1 (en) 2016-05-24 2020-10-13 Composition to modulate genes responsible for the general functions of the skin, comprising at least one plant extract selected from the group consisting of extracts of casearia sylvestris, schinus terebinthifolius and paeonia albiflora (divisional of application 03354-2018)
CL2020002642A CL2020002642A1 (en) 2016-05-24 2020-10-13 Composition to modulate genes responsible for the general functions of the skin, comprising at least one plant extract of schinus terebinthifolius and caffeine (divisional application 03354-2018)
CL2020002646A CL2020002646A1 (en) 2016-05-24 2020-10-13 Composition to modulate genes responsible for the general functions of the skin, comprising at least one selected plant extract of casearia sylvestris and schinus terebinthfolius and hyaluronic acid (divisional of application 03354-2018)
CL2020002643A CL2020002643A1 (en) 2016-05-24 2020-10-13 Composition to modulate genes responsible for the general functions of the skin, comprising at least one plant extract selected from hymenaea courbaril, paeonia albiflora, secale cereale and avena sativa (divisional application 03354-2018)
CL2020002644A CL2020002644A1 (en) 2016-05-24 2020-10-13 Composition to modulate genes responsible for the general functions of the skin, comprising the combination of an extract of hymenaea courbaril and a mixture of sodium and sarcosine cocoylamino acids and potassium aspartate and magnesium aspartate (divisional application 03354-2018)

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