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 PDFInfo
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- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
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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 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.
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.
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
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.
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[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
23/3223/32
15/15 reivindicações anexas.15/15 attached claims.
24/3224/32
1/31/3
Claims (8)
Priority Applications (18)
Application Number | Priority Date | Filing Date | Title |
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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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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 |
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