BR102016011816A2 - COMPOSITION FOR THE MODULATION OF GENES RESPONSIBLE FOR GENERAL SKIN FUNCTIONS, METHOD FOR MODULATING EXPRESSION OF GENES RESPONSIBLE FOR GENERAL SKIN FUNCTIONS AND USE OF SYLVESTRIS CASES, SCHINUS TEREBINTHIFOLIUS AND PAEONIA ALBIFLORA - Google Patents

COMPOSITION FOR THE MODULATION OF GENES RESPONSIBLE FOR GENERAL SKIN FUNCTIONS, METHOD FOR MODULATING EXPRESSION OF GENES RESPONSIBLE FOR GENERAL SKIN FUNCTIONS AND USE OF SYLVESTRIS CASES, SCHINUS TEREBINTHIFOLIUS AND PAEONIA ALBIFLORA Download PDF

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BR102016011816A2
BR102016011816A2 BR102016011816-6A BR102016011816A BR102016011816A2 BR 102016011816 A2 BR102016011816 A2 BR 102016011816A2 BR 102016011816 A BR102016011816 A BR 102016011816A BR 102016011816 A2 BR102016011816 A2 BR 102016011816A2
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genes
genes responsible
composition
modulating
modulation
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BR102016011816-6A
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Portuguese (pt)
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Paes Fabiana
Capelas Romeu Clarissa
Alexandre De Oliveira Reis Eduardo
Panzarin Savietto Joice
Carollo Moncayo Priscila
Augusto Santos De Oliveira Ricardo
Andrea Emidio Simone
Baione De Moura Soraya
Tadini D'annolfo Kassandra
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Natura Cosméticos S.A.
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Priority to BR102016011816-6A priority Critical patent/BR102016011816A2/en
Priority to US16/304,544 priority patent/US20200315950A1/en
Priority to EP17801853.7A priority patent/EP3466407A4/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
Priority to MX2018014431A priority patent/MX2018014431A/en
Publication of BR102016011816A2 publication Critical patent/BR102016011816A2/en
Priority to MX2021003951A priority patent/MX2021003951A/en
Priority to MX2021003950A priority patent/MX2021003950A/en
Priority to CL2018003354A priority patent/CL2018003354A1/en
Priority to MX2021003953A priority patent/MX2021003953A/en
Priority to MX2021003959A priority patent/MX2021003959A/en
Priority to CL2020002641A priority patent/CL2020002641A1/en
Priority to CL2020002639A priority patent/CL2020002639A1/en
Priority to CL2020002647A priority patent/CL2020002647A1/en
Priority to CL2020002646A priority patent/CL2020002646A1/en
Priority to CL2020002642A priority patent/CL2020002642A1/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
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/65—Collagen; Gelatin; Keratin; Derivatives or degradation products 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
    • A61K8/72—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

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  • Animal Behavior & Ethology (AREA)
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Abstract

a presente invenção refere-se a composições para a modulação de genes responsáveis pelas funções gerais da pele compreendendo casearia sylvestris, schinus terebinthifolius e paeonia albiflora 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 terebinthifolius e paeonia albiflora 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 terebinthifolius and paeonia albiflora and cosmetically acceptable carrier, as well as a method for modulating expression of genes responsible for general skin functions. skin and use of casearia sylvestris, schinus terebinthifolius and paeonia albiflora in the preparation of a composition for the modulation of genes responsible for the general functions of the skin.

Description

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 TEREBINTHIFOLIUS E PAEONIA ALBIFLORA CAMPO DA INVENÇÃOCOMPOSITION 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 TEREBINTHIFOLIUS AND PAEORA ALBUS

[1] A presente invenção refere-se a composições para a modulação de genes responsáveis pelas funções gerais da pele compreendendo Casearia sylvestris, Schinus terebinthifolius e Paeonia albiflora e veiculo 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 terebinthifolius e Paeonia albiflora na preparação de uma composição para a modulação de genes responsáveis pelas funções gerais da pele.[1] The present invention relates to compositions for modulating genes responsible for general skin functions comprising Casearia sylvestris, Schinus terebinthifolius and Paeonia albiflora and cosmetically acceptable carrier, as well as a method for modulating expression of genes responsible for general skin functions and use of Casearia sylvestris, Schinus terebinthifolius and Paeonia albiflora in the preparation of a composition for the modulation of genes responsible for general skin functions.

FUNDAMENTO DA INVENÇÃOBACKGROUND OF THE INVENTION

[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.Considered the largest organ in the human body, the skin is the seat of many complex and dynamic processes. These processes include barrier and immunological functions, melanin production, vitamin D synthesis, sensations, thermal regulation, protection against ultraviolet and aesthetic injury.

[3] 0 bom funcionamento das funções gerais da pele pode ser associado a um grupo de genes que, uma vez modulados, pode ser estratégia interessante para o desenvolvimento de produtos com finalidade cosmética.[3] The proper functioning of general skin functions can be associated with a group of genes that, once modulated, can be an interesting strategy for the development of cosmetic products.

[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 in modulating genes associated with general skin functions.

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

BREVE DESCRIÇÃO DAS FIGURASBRIEF DESCRIPTION OF THE FIGURES

[6] As figuras 1 e 2 apresentam aumento da proteína colágeno I relativo à amostra controle não tratada, dado em medidas de fluorescência e porcentagem.[6] Figures 1 and 2 show increased collagen protein I relative to the untreated control sample, given in fluorescence and percentage measurements.

[7] As figuras 3 e 4 apresentam aumento da proteína elastina relativo à amostra controle não tratada, dado em medidas de fluorescência e porcentagem.[7] Figures 3 and 4 show increased elastin protein relative to the untreated control sample, given in fluorescence and percentage measurements.

[8] As figuras 5 e 6 apresentam aumento da proteína ácido hialurônico relativo à amostra controle não tratada, dado em medidas de fluorescência e porcentagem. DESCRIÇÃO DA INVENÇÃO[8] Figures 5 and 6 show increased hyaluronic acid protein relative to the untreated control sample, given in fluorescence and percentage measurements. DESCRIPTION OF THE INVENTION

[9] A presente invenção trata de uma composição para a modulação de genes responsáveis pelas funções gerais da pele compreendendo Casearia sylvestris, Schinus terebinthifolius, Paeonia albiflora e veículo cosmeticamente aceitável.[9] The present invention relates to a composition for modulating genes responsible for general skin functions comprising Casearia sylvestris, Schinus terebinthifolius, Paeonia albiflora and cosmetically acceptable carrier.

[10] Casearia sylvestris pertence à família das Flacourtiaceae, também conhecida por guaçatonga. Por Casearia sylvestris entende-se qualquer fração proveniente da mesma, particularmente extratos.[10] Casearia sylvestris belongs to the Flacourtiaceae family, also known as guaçatonga. Casearia sylvestris means any fraction derived therefrom, particularly extracts.

[11] Schinus terebinthifolius pertence à família das Anacardiaceae, também conhecida como aroeira. Por Schinus terebinthifolius entende-se qualquer fração proveniente da mesma, particularmente extratos.[11] Schinus terebinthifolius belongs to the Anacardiaceae family, also known as aroeira. Schinus terebinthifolius means any fraction thereof, particularly extracts.

[12] Paeonia albiflora pertence à família das Paeoniaceae, uma espécie de flores. Por Paeonia albiflora entende-se qualquer fração proveniente da mesma, particularmente extratos de suas raízes.[12] Paeonia albiflora belongs to the Paeoniaceae family, a species of flowers. Paeonia albiflora means any fraction derived from it, particularly extracts from its roots.

[13] De maneira individualizada, os efeitos terapêuticos e cosméticos de ambos componentes têm sido estudados.[13] Individually, the therapeutic and cosmetic effects of both components have been studied.

[14] Entretanto, de maneira surpreendente, a Depositante verificou que, de maneira combinada, em uma composição, Casearia sylvestris, Schinus terebinthifolius e Paeonia albiflora apresentam efeito na modulação de genes responsáveis pelas funções gerais da pele.[14] Surprisingly, however, the Depositor found that, in a combined manner, Casearia sylvestris, Schinus terebinthifolius and Paeonia albiflora have an effect on the modulation of genes responsible for overall skin functions.

[15] Tais genes incluem pelo menos um dos genes CAT, GPXl, MSRA, NOXl, PRDX6, S0D2, DSC2, IGFlR, ITGAl, ITGBl, LAMBÍ, LAMB3, DEFB4A, CDHl, CAMP, CLDNl, CLDN4, CLDN7, CDSN, DSG4, DSP, EL0VL3, GBA, ITGA6, ITGB4, KRT19, KRT10, KRT14, KRT16, KRT17, KRTl, KRT6A, OR2AT4, LAMA5, OCLN, PKPl, PLEC, TGM5, TGMl, RNASE7, SMPDl, SDC1, TJPl, VCL, BTC, FLTl, PDGFRA, HAS1, HAS2, SIRTl, SRD5A1, PRLR, HSD17B2, TPHl, AANAT, ASMT, MTNRlA, AR, ESR2, CYP19A1, HTR2A, HTR2B, MTOR, AQP3, CTSB, CTSE, CTSL, CD44, HAL, PADI3, PADIl, CASP14, FLG, ST14, IL13, IL18, IL19, ITGA2, IL1A, ILlB, IL22, IL17A, ILlRl, IL10, IL6, F2RL1, TRPVl, CALCA, ACACA, ASAHl, UGCG, SPTLC1, SREBF2, GLBl, ADAM9, MMPl, MMP10, MMP2, MMP3, MMP9, SERPINEl, TIMPl, TIMP2, TMPRSS6, FBLN5, FBNl, MMP12, MMP13, MMP14, TYR, GPNMB, MAP1LC3B, POMC, OPRMl, MC1R, MITF, CANX, HSPBl, HSPAlA, EGFR, TGFBl, TGFBRl, NGF, PDGFA, VEGFA, VEGFB, FGFRl, FGFR2, FGFl, FGF2, MMPll, HYALl, HYAL2, ELN, LOX, COLlAl, COL1A2, AC02, ANXA5.[15] Such genes include at least one of the CAT, GPX1, MSRA, NOX1, PRDX6, SOD2, DSC2, IGFlR, ITGA1, ITGB1, LAMBI, LAMB3, DEFB4A, CDH1, CAMP, CLDN1, CLDN7, CDDN, DSG4 genes. DSP, EL0VL3, GBA, ITGA6, ITGB4, KRT19, KRT10, KRT14, KRT16, KRT17, KRT1, KRT6A, OR2AT4, LAMA5, OCLN, PKP1, PLEC, TGM5, TGM1, RNASE7, SMPD1 , FLTl, PDGFRA, HAS1, HAS2, SIRTl, SRD5A1, PRLR, HSD17B2, TPH1, AANAT, ASMT, MTNRlA, AR, ESR2, CYR19A1, HTR2A, HTR2B, MTOR, AQP3, CTSB, CTSE, HTS3 , PADIl, CASP14, FLG, ST14, IL13, IL18, IL19, ITGA2, IL1A, IL1B, IL17A, IL1R, IL10, IL6, F2RL1, TRPV1, CALCA, ACACA, ASAH1, UGCG, SPTLC1, SREBF2, GLB1 , MMPl, MMP10, MMP2, MMP3, MMP9, SERPINEl, TIMP2, TIMP2, TMPRSS6, FBLN5, FBNl, MMP12, MMP14, TYR, GPNMB, MAP1LC3B, POMC, OPRMl, MC1R, MITF, CANX, HSPB, HSPB , TGFB1, TGFBR1, NGF, PDGFA, VEGFA, VEGFB, FGFR1, FGFR2, FGFR, FGF2, MMP11, HYAL1, HYAL2, ELN, LOX, COL1Al, COL1A2, AC02, ANXA5.

[16] De maneira ainda mais surpreendente, a Depositante verificou que, em quantidades de cerca de 0,05% de Casearia sylvestris, cerca de 0,0125 de Schinus terebinthifolius e cerca de 2% Paeonia albiflora, há modulação sinérgica em tais genes, particularmente na modulação da expressão de pelo menos uma das proteínas colágeno, elastina e ácido hialurônico.[16] Even more surprisingly, the Depositor has found that in amounts of about 0.05% Casearia sylvestris, about 0.0125 Schinus terebinthifolius and about 2% Paeonia albiflora, there is synergistic modulation in such genes, particularly in modulating the expression of at least one of collagen, elastin and hyaluronic acid proteins.

[17] 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 de Casearia sylvestris, Schinus terebinthifolius e Paeonia albiflora na preparação de uma composição para a modulação de genes responsáveis pelas funções gerais da pele.[17] The present invention also relates to a method for modulating expression of such genes responsible for general skin functions which comprises the step of administering a composition according to the present invention as well as the use of Casearia sylvestris, Schinus terebinthifolius and Paeonia albiflora in the preparation of a composition for the modulation of genes responsible for the general functions of the skin.

[18] Os genes de acordo com a presente invenção e sua correlação com as funções gerais da pele estão definidos na tabela a seguir.[18] The genes according to the present invention and their correlation with general skin functions are defined in the following table.

Tabela 1. Definição de genes e correlação com a função geral da pele.Table 1. Gene definition and correlation with overall skin function.

[19] Os veículos cosmeticamente aceitáveis de acordo com a presente invenção incluem, sem qualquer limitação, aqueles conhecidos da técnica.[19] Cosmetically acceptable vehicles according to the present invention include, without limitation, those known in the art.

[20] 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.[20] The following examples without limitation illustrate the present invention, particularly with regard to the effects on gene modulation associated with general skin functions.

EXEMPLOSEXAMPLES

Exemplo 1. Ensaio de atividade molecular [21] 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 [21] A large scale gene expression profile (PCR array) assay of 180 genes was performed on skin explants obtained after blepharoplasty surgery and subjected to independent treatments with the present invention.

[22] 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, C02 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.[22] Initially, eyelid skin explants were obtained from women aged 45 to 55 years, with 3 different donors for each. The explants were divided into two portions and inserted in triplicate from each donor immediately into culture medium and maintained for 24 hours (portion 1) and 72 hours (portion 2) in a humid atmosphere, 37 ° C, 5% CO2. During this period, the explants were submitted to treatments with 2mg / cm2 of each sample applied topically over the explants, without any dilution. In addition, a control condition was performed by maintaining the explants in triplicate of each donor in culture medium only. A prior feasibility analysis was performed to ensure tissue integrity throughout the study protocol for all investigated formulas.

[23] A porção (1) foi coletada e submetida à extração de RNA total. A qualidade do RNA extraído foi validada qualitativa (Bioanalyzer microcapillary electrophoresis) e quantitativamente (Nanodrop spectrophotometer) . A partir do RNA, foi confeccionado o cDNA e este foi submetido à etapa de RT-PCR (Polymerase-Chain 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). 0 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 = -loglO (p-value)] refletindo a probabilidade de esta rede ser gerada ao acaso e onde o p-value foi calculado pelo 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.[23] Portion (1) was collected and subjected to total RNA extraction. The quality of the extracted RNA was validated qualitatively (Bioanalyzer microcapillary electrophoresis) and quantitatively (Nanodrop spectrophotometer). From RNA, cDNA was made and submitted to real-time RT-PCR (Polymerase-Chain Reaction) for expression evaluation of 180 genes using the Taqman PCR Array custom platform (ThermoFisher). The genes tested were those listed in table 1 with the aid of StepOne Plus equipment (Life Technologies). Gene expression profile and selection of differentially expressed genes were performed with the help of Expression Suite Software v.1.0.3 (Life Technologies). ACt values for the GAPDH reference gene (glyceraldehyde-3-phosphate dehydrogenase) and the target gene were calculated by subtracting the values from the experimental groups. Subsequently, the ACt from the experimental group was subtracted from the control group (untreated skin explant) to obtain the AACt. Finally, the relative quantification of the target genes was determined by the equation: RQ = 2-AACt. Only genes with a threshold of 1.3, ie 30% increase or decrease compared to the control, were selected. Statistical significance was assessed by the t-test followed by the Benjamini-Hochberg (FDR) false discovery rate method, and p-value <0.05 was 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 road / network, a p-score [p-score = -log10 (p-value)] was generated reflecting the probability that this network will be generated at random and where p-value was calculated by Fisher's exact test. This means that if a pathway has a p-score of 10, the chance of this network being randomly generated is less than 1 in 1010. These results show the genes and functions modulated by the compositions and methods of the present invention.

[24] 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). 0 parâmetro avaliado foi a intensidade de fluorescência emitida pela marcação com anticorpo especifico. 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.[24] Portion (2) was collected, fixed in 4% paraformaldehyde (pH 7.4) for 24 hours and cryoprotected in 30% sucrose solution for 48 hours. Then, 10 pm serial sections were collected directly on silanized slides with the aid of Cryostat (Leica - CN1850). At the end of the collection of the cuts, they were submitted to washings with 0.1 M CP and incubated overnight with antibodies referring to selected proteins of interest. Then, the slides were analyzed in a Fluorescence Microscope (Leica - DM 1000) with the aid of LAS Software (Leica Application Suite). The parameter evaluated was the fluorescence intensity emitted by the specific antibody labeling. Statistical analysis was performed using analysis of variance (ANOVA). In all groups studied, those whose P values were less than 0.05 were considered statistically significant.

[25] Foram investigados o controle não tratado, uma composição de base cosmética isenta de princípios ativos, uma composição de base cosmética idêntica incluindo 0,05% de Casearia sylvestris e cerca de 0,0125 de Schinus terebinthifolius, uma composição de base cosmética idêntica incluindo 2% de Paeonia albiflora e uma base cosmética idêntica incluindo 0,05% de Casearia sylvestris, 0,0125% de Schinus terebinthifolius e 2% de Paeonia albiflora [26] Com relação à expressão gênica, em relação ao controle não tratado, observou-se que a amostra extrato de guaçatonga + extrato de aroeira foi capaz de modular 151 genes, a amostra Volunage foi capaz de modular 117 genes e a combinação de extrato de guaçatonga + extrato de aroeira + volunage foi capaz de modular 162 genes. Os principais mecanismos identificados foram firmeza, estímulo de fibras elásticas, preenchimento, hidratação, anti-inflamatório, coesão dermo-epiderme, formação do envelope cornificado e reforço de barreira.[25] Untreated control, an active ingredient-free cosmetic base composition, an identical cosmetic base composition including 0.05% Casearia sylvestris and about 0.0125 Schinus terebinthifolius, an identical cosmetic base composition, were investigated. including 2% Paeonia albiflora and an identical cosmetic basis including 0.05% Casearia sylvestris, 0.0125% Schinus terebinthifolius and 2% Paeonia albiflora [26] With respect to gene expression compared to untreated control, he noted. It was found that the guaçatonga extract + aroeira extract sample was able to modulate 151 genes, the Volunage sample was able to modulate 117 genes and the combination of guaçatonga extract + aroeira extract + volunage was able to modulate 162 genes. The main mechanisms identified were firmness, elastic fiber stimulation, filling, hydration, anti-inflammatory, dermo-epidermis cohesion, cornified envelope formation and barrier reinforcement.

[27] Com relação à expressão proteica, a combinação extrato de guaçatonga e extrato de aroeira e Volunage promoveu aumentos de 140,4% na expressão da proteína colágeno I (figura 1 e 2) , 34,1% na expressão da proteína elastina (figura 3 e 4) e de 27,8% na expressão da proteína ácido hialurônico (figura 6 e 6).[27] Regarding protein expression, the combination of guaçatonga extract and aroeira extract and Volunage promoted increases of 140.4% in the expression of collagen protein I (figures 1 and 2), 34.1% in the expression of elastin protein ( figures 3 and 4) and 27.8% in the expression of the hyaluronic acid protein (figures 6 and 6).

[28] 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 reivindicações anexas.[28] The person skilled in the art will readily appreciate, by the teachings contained in the text and the examples presented, advantages of the invention and propose variations and equivalent alternatives without departing from the scope of the invention as defined in the appended claims.

REIVINDICAÇÕES

Claims (8)

1. Composição para a modulação de genes responsáveis pelas funções gerais da pele caracterizada pelo fato de que compreende Casearia sylvestris, Schinus terebinthifolius, Paeonia albiflora e veiculo cosmeticamente aceitável.Composition for the modulation of genes responsible for the general functions of the skin characterized by the fact that it comprises Casearia sylvestris, Schinus terebinthifolius, Paeonia albiflora and cosmetically acceptable vehicle. 2. Composição, de acordo com a reivindicação 1, caracterizada pelo fato de ser para modulação de pelo menos um dos genes CAT, GPXl, MSRA, N0X1, PRDX6, S0D2, DSC2, IGFlR, ITGAl, ITGBl, LAMBÍ, LAMB3, DEFB4A, CDHl, CAMP, CLDN1, CLDN4, CLDN7, CDSN, DSG4, DSP, EL0VL3, GBA, ITGA6, ITGB4, KRT19, KRT10, KRT14, KRTl6, KRT17, KRTl, KRT6A, OR2AT4, LAMA5, OCLN, PKPl, PLEC, TGM5, TGMl, RNASE7, SMPDl, SDC1, TJP1, VCL, BTC, FLTl, PDGFRA, HAS1, HAS2, SIRTl, SRD5A1, PRLR, HSD17B2, TPHl, AANAT, ASMT, MTNRlA, AR, ESR2, CYP19A1, HTR2A, HTR2B, MTOR, AQP3, CTSB, CTSE, CTSL, CD44, HAL, PADI3, PADIl, CASP14, FLG, ST14, IL13, IL18, IL19, ITGA2, ILlA, ILlB, IL22, IL17A, ILlRl, IL10, IL6, F2RL1, TRPVl, CALCA, ACACA, ASAHl, UGCG, SPTLC1, SREBF2, GLBl, ADAM9, MMPl, MMP10, MMP2, MMP3, MMP9, SERPINEl, TIMPl, TIMP2, TMPRSS6, FBLN5, FBNl, MMP12, MMP13, MMPl4, TYR, GPNMB, MAP1LC3B, POMC, OPRMl, MC1R, MITF, CANX, HSPBl, HSPAlA, EGFR, TGFBl, TGFBRl, NGF, PDGFA, VEGFA, VEGFB, FGFRl, FGFR2, FGFl, FGF2, MMPll, HYALl, HYAL2, ELN, LOX, COLlAl, COL1A2, AC02, ANXA5.Composition according to Claim 1, characterized in that it is for modulating at least one of the CAT, GPX1, MSRA, NOX1, PRDX6, SO2D, DSC2, IGFlR, ITGA1, ITGB1, LAMBI, LAMB3, DEFB4A genes; CDH1, CAMP, CLDN1, CLDN4, CLDN7, CDSN, DSG4, DSP, EL0VL3, GBA, ITGA6, ITGB4, KRT19, KRT10, KRT14, KRT17, KRT1, KRT6A, OR2AT4, LAMA5, OCLM, P5K TGM1, RNASE7, SMPD1, SDC1, TJP1, VCL, BTC, FLT1, PDGFRA, HAS1, HAS2, SIRT1, SRD5A1, PRLR, HSD1B2, TPHl, AANAT, ASMT, MTNR1A, AR, ESR2, CYP19A1, HTR2 AQP3, CTSB, CTSE, CTSL, CD44, HAL, PADI3, PADI, CASP14, FLG, ST14, IL13, IL18, ITGA2, IL1A, IL1B, IL22, IL17A, IL1R1, IL10, IL6, F2RL1, TRPV1, CALCA, ACACA, ASAHl, UGCG, SPTLC1, SREBF2, GLB1, ADAM9, MMPl, MMP10, MMP2, MMP3, MMP9, SERPINEl, TIMP1, TMPRSS6, FBLN5, FBNl, MMP12, MMP13, MMP1, TYR3 OPRM1, MC1R, MITF, CANX, HSPB1, HSPA1A, EGFR, TGFB1, TGFBR1, NGF, PDGFA, VEGFA, VEGFB, FGFR1, FGFR2, FGFl, FGF2, MMP11, HYALl, HYAL2, ELN, LOX, COL1Al, COL1A2, AC02, ANXA5. 3. Composição, de acordo com a reivindicação 1, caracterizada pelo fato de compreender cerca de 0,05% de Casearia sylvestris, cerca de 0,0125% de Schinus terebinthifolius e cerca de 2% de Paeonia albiflora.Composition according to Claim 1, characterized in that it comprises about 0.05% Casearia sylvestris, about 0.0125% Schinus terebinthifolius and about 2% Paeonia albiflora. 4. Composição, de acordo com a reivindicação 1, caracterizada pelo fato de ser para modulação da expressão de pelo menos uma das proteínas colágeno, elastina e ácido hialurônico.Composition according to Claim 1, characterized in that it is for modulating the expression of at least one of the collagen, elastin and hyaluronic acid proteins. 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.A method for modulating expression of genes responsible for general skin functions comprising the step of administering a composition as defined in any one 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 menos um dos genes CAT, GPXl, MSRA, N0X1, PRDX6, S0D2, DSC2, IGFlR, ITGAl, ITGBl, LAMBÍ, LAMB3, DEFB4A, CDHl, CAMP, CLDNl, CLDN4, CLDN7, CDSN, DSG4, DSP, EL0VL3, GBA, ITGA6, ITGB4, KRT19, KRT10, KRT14, KRTl6, KRT17, KRTl, KRT6A, OR2AT4, LAMA5, OCLN, PKPl, PLEC, TGM5, TGMl, RNASE7, SMPDl, SDC1, TJP1, VCL, BTC, FLTl, PDGFRA, HAS1, HAS2, SIRTl, SRD5A1, PRLR, HSD17B2, TPHl, AANAT, ASMT, MTNRlA, AR, ESR2, CYP19A1, HTR2A, HTR2B, MTOR, AQP3, CTSB, CTSE, CTSL, CD44, HAL, PADI3, PADIl, CASP14, FLG, ST14, IL13, IL18, IL19, ITGA2, ILlA, ILlB, IL22, IL17A, ILlRl, IL10, IL6, F2RL1, TRPVl, CALCA, ACACA, ASAHl, UGCG, SPTLC1, SREBF2, GLBl, ADAM9, MMPl, MMP10, MMP2, MMP3, MMP9, SERPINEl, TIMPl, TIMP2, TMPRSS6, FBLN5, FBNl, MMP12, MMP13, MMPl4, TYR, GPNMB, MAP1LC3B, POMC, OPRMl, MC1R, MITF, CANX, HSPBl, HSPAlA, EGFR, TGFBl, TGFBRl, NGF, PDGFA, VEGFA, VEGFB, FGFRl, FGFR2, FGFl, FGF2, MMPll, HYALl, HYAL2, ELN, LOX, COLlAl, C0L1A2, AC02, ANXA5.Method according to claim 5, characterized in that it is for modulating at least one of the CAT, GPX1, MSRA, NOX1, PRDX6, SO2D, DSC2, IGFlR, ITGA1, ITGB1, LAMBI, LAMB3, DEFB4A genes; CDH1, CAMP, CLDN1, CLDN4, CLDN7, CDSN, DSG4, DSP, EL0VL3, GBA, ITGA6, ITGB4, KRT19, KRT10, KRT14, KRT17, KRT1, KRT6A, OR2AT4, LAMA5, OCLM, P5K TGM1, RNASE7, SMPD1, SDC1, TJP1, VCL, BTC, FLT1, PDGFRA, HAS1, HAS2, SIRT1, SRD5A1, PRLR, HSD1B2, TPHl, AANAT, ASMT, MTNR1A, AR, ESR2, CYP19A1, HTR2 AQP3, CTSB, CTSE, CTSL, CD44, HAL, PADI3, PADI, CASP14, FLG, ST14, IL13, IL18, ITGA2, IL1A, IL1B, IL22, IL17A, IL1R1, IL10, IL6, F2RL1, TRPV1, CALCA, ACACA, ASAHl, UGCG, SPTLC1, SREBF2, GLB1, ADAM9, MMPl, MMP10, MMP2, MMP3, MMP9, SERPINEl, TIMP1, TMPRSS6, FBLN5, FBNl, MMP12, MMP13, MMP1, TYR3 OPRM1, MC1R, MITF, CANX, HSPB1, HSPA1A, EGFR, TGFB1, TGFBR1, NGF, PDGFA, VEGFA, VEGFB, FGFR1, FGFR2, FGFl, FGF2, MMP11, HYAL1, HYAL 2, ELN, LOX, COLlAl, COL1A2, AC02, ANXA5. 7. Uso de Casearia sylvestris, Schinus terebinthifolius e Paeonia albiflora caracterizado pelo fato de ser para a preparação de uma composição para a modulação de genes responsáveis pelas funções gerais da pele.7. Use of Casearia sylvestris, Schinus terebinthifolius and Paeonia albiflora characterized by the fact that it is for the preparation of a composition for the modulation of genes responsible for the general functions of the skin. 8. Uso, de acordo com a reivindicação 7, caracterizado pelo fato dos genes serem selecionados de pelo menos um dentre CAT, GPXl, MSRA, N0X1, PRDX6, S0D2, DSC2, IGFlR, ITGAl, ITGB1, LAMBÍ, LAMB3, DEFB4A, CDHl, CAMP, CLDNl, CLDN4, CLDN7, CDSN, DSG4, DSP, EL0VL3, GB A, ITGA6, ITGB4, KRT19, KRT10, KRT14, KRT16, KRT17, KRTl, KRT6A, OR2AT4, LAMA5, OCLN, PKPl, PLEC, TGM5, TGMl, RNASE7, SMPDl, SDC1, TJP1, VCL, BTC, FLTl, PDGFRA, HAS1, HAS2, SIRTl, SRD5A1, PRLR, HSD17B2, TPHl, AANAT, ASMT, MTNR1A, AR, ESR2, CYP19A1, HTR2A, HTR2B, MTOR, AQP3, CTSB, CTSE, CTSL, CD44, HAL, PADI3, PADIl, CASP14, FLG, ST14, IL13, IL18, IL19, ITGA2, ILlA, ILlB, IL22, IL17A, ILlRl, IL10, IL6, F2RL1, TRPVl, CALCA, ACACA, ASAHl, UGCG, SPTLC1, SREBF2, GLBl, ADAM9, MMPl, MMP10, MMP2, MMP3, MMP9, SERPINEl, TIMPl, TIMP2, TMPRSS6, FBLN5, FBNl, MMP12, MMP13, MMPl4, TYR, GPNMB, MAP1LC3B, POMC, OPRMl, MClR, MITF, CANX, HSPBl, HSPAlA, EGFR, TGFBl, TGFBRl, NGF, PDGFA, VEGFA, VEGFB, FGFRl, FGFR2, FGFl, FGF2, MMPll, HYALl, HYAL2, ELN, LOX, COLlAl, COL1A2, AC02, ANXA5.Use according to claim 7, characterized in that the genes are selected from at least one of CAT, GPX1, MSRA, NOX1, PRDX6, SO2D, DSC2, IGFlR, ITGA1, ITGB1, LAMBI, LAMB3, DEFB4A, CDH1. , CAMP, CLDN1, CLDN4, CLDN7, CDSN, DSG4, DSP, EL0VL3, GB, ITGA6, ITGB4, KRT19, KRT10, KRT14, KRT16, KRT17, KRT1, KRT6A, OR2AT4, LAMA5, OCLN, PKP, TG5 TGM1, RNASE7, SMPD1, SDC1, TJP1, VCL, BTC, FLT1, PDGFRA, HAS1, HAS2, SIRTl, SRD5A1, PRLR, HSD1B2, TPH1, AANAT, ASMT, MTNR1A, AR, ESR2, CYP19A1, HTR2 AQP3, CTSB, CTSE, CTSL, CD44, HAL, PADI3, PADI, CASP14, FLG, ST14, IL13, IL18, ITGA2, IL1A, IL1B, IL22, IL17A, IL1R1, IL10, IL6, F2RL1, TRPV1, CALCA, ACACA, ASAHl, UGCG, SPTLC1, SREBF2, GLB1, ADAM9, MMPl, MMP10, MMP2, MMP3, MMP9, SERPINEl, TIMP1, TMPRSS6, FBLN5, FBNl, MMP12, MMP13, MMP1, TYR3 OPRM1, MClR, MITF, CANX, HSPB1, HSPA1A, EGFR, TGFB1, TGFBR1, NGF, PDGFA, VEGFA, VEGFB, FGFR1, FGFR2, FGFl, FGF2, MMP11, HYAL1, HYAL2 , ELN, LOX, COL1Al, COL1A2, AC02, ANXA5.
BR102016011816-6A 2016-05-24 2016-05-24 COMPOSITION FOR THE MODULATION OF GENES RESPONSIBLE FOR GENERAL SKIN FUNCTIONS, METHOD FOR MODULATING EXPRESSION OF GENES RESPONSIBLE FOR GENERAL SKIN FUNCTIONS AND USE OF SYLVESTRIS CASES, SCHINUS TEREBINTHIFOLIUS AND PAEONIA ALBIFLORA BR102016011816A2 (en)

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BR102016011816-6A BR102016011816A2 (en) 2016-05-24 2016-05-24 COMPOSITION FOR THE MODULATION OF GENES RESPONSIBLE FOR GENERAL SKIN FUNCTIONS, METHOD FOR MODULATING EXPRESSION OF GENES RESPONSIBLE FOR GENERAL SKIN FUNCTIONS AND USE OF SYLVESTRIS CASES, SCHINUS TEREBINTHIFOLIUS AND PAEONIA ALBIFLORA
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
EP17801853.7A EP3466407A4 (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
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.
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.
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.
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
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.
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)
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)
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)
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)
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)
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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