BR102021019891A2 - REPAIRING COSMETIC COMPOSITION - Google Patents

Abstract

The present invention relates to a restorative cosmetic composition for daily use or after aesthetic procedures, comprising a regenerating complex and a pharmaceutically acceptable vehicle, the regenerating complex being composed of alpha-glucan oligosaccharide; niacinamide; alpha-bisabolol; dexpanthenol; low and high molecular weight hyaluronic acid and vitamin E.

Description

REPAIRING COSMETIC COMPOSITION FIELD OF THE INVENTION

[001] . The present invention relates to a restorative cosmetic composition for daily use or after aesthetic procedures, comprising a regenerating complex and a pharmaceutically acceptable vehicle, the regenerating complex being composed of alpha-glucan oligosaccharide; niacinamide; alpha-bisabolol; dexpanthenol; low and high molecular weight hyaluronic acid and vitamin E.

STATE OF THE TECHNIQUE

[002] . Several factors can sensitize the skin, from external factors such as cold and heat, to performing aesthetic procedures such as microneedling, laser treatments and tattoo removal. Such procedures affect the integrity of the epidermis and require a treatment that effectively assists in the recovery of this injured skin.

[003] . After an injury, it is necessary for the body to start repairing, and this process is called healing. Healing is a dynamic process and is traditionally divided into 3 stages that occur simultaneously: inflammation, proliferation and remodeling. The purpose of these processes is to restore the integrity of the skin so that it returns to the same appearance and functionality as before. Topical products that act in these three phases of skin restoration are useful for use on sensitized, irritated and sensitive skin and/or that have suffered some type of injury, as in the case of aesthetic procedures. (Gorski J, Proksch E, Baron JM, Schmid D, Zhang L. Dexpanthenol in Wound Healing after Medical and Cosmetic Interventions (Postprocedure Wound Healing). Pharmaceuticals. 2020; 13(7):138 ). Another important point to be highlighted is the importance of preserving the cutaneous microbiota, which is essential for maintaining the functional and structural integrity of the skin. While the stratum corneum acts as a mechanical barrier, protecting the skin against external aggressions, the saprophytic microbial flora, also known as Ecoflora, forms a defense barrier against microbiological infections. Prebiotic molecules act favoring the development and maintenance of saprophytic flora, beneficial to our microbiota, to the detriment of pathogenic and/or opportunistic microorganisms. Such molecules are agents and substances that serve as nutrients for our saprophytic flora, helping in its maintenance and development.

[004] . Most of the existing products do not act concomitantly in the three phases of skin recovery and in the reestablishment and maintenance of the skin microbiota, so the market lacks a restorative formulation, of dermatological safety, for daily use or after aesthetic procedures, restorative of the skin barrier, maintaining skin hydration, which soothes sensitized skin and sensitive skin and also restores and maintains the healthy skin microbiota.

[005] . To make up for the lack of a repairing formulation that acts simultaneously in the three phases of skin healing and in restoring and maintaining the cutaneous microbiota, an innovative repairing formulation has been developed for daily use or after aesthetic procedures, comprising a regenerating complex and a pharmaceutically acceptable vehicle, being that the regenerator complex is composed of alpha-glucan oligosaccharide; niacinamide; alpha-bisabolol; dexpanthenol; low and high molecular weight hyaluronic acid and vitamin E.

DESCRIPTION OF FIGURES

[006] . Figure 1 is an image demonstrating the unstimulated control.

[007] . Figure 2 is an image demonstrating the 8-day reconstituted human epidermis stimulated with 0.6% lactic acid.

[008] . Figure 3 is an image demonstrating 8-day reconstituted human epidermis stimulated with 0.6% lactic acid treated with the restorative cosmetic composition of the present invention.

[009] . Figure 4 is a graph representing the intensity of corneodesmosin staining related to the area of the epidermis.

[0010] . Figure 5 is a graph representing the percentage increase in skin hydration of the participants when using the restorative cosmetic composition of the present invention.

[0011] . Figure 6 is a graph depicting the participants' TEWL rate reduction percentage when using the restorative cosmetic composition of the present invention.

[0012] . Figure 7 is a graph representing the mean values of the corneometry test.

[0013] . Figure 8 is an image with the water map, where the colors in blue show high hydration after 21 days of using the product.

[0014] . Figure 9 is a graph representing the average pH values obtained throughout the study.

[0015] . Figure 10 is a graph depicting the average improvement in overall skin appearance of participants using the restorative cosmetic composition of the present invention.

[0016] . Figure 11 is a graph depicting the average improvement in skin smoothness of participants using the restorative cosmetic composition of the present invention.

[0017] . Figure 12 is a graph depicting the average improvement in skin erythema of participants using the restorative cosmetic composition of the present invention.

[0018] . Figure 13 is a comparative graph between the restorative cosmetic composition of the present invention and the control.

[0019] . Figure 14 is a graph depicting the improvement in the skin of participants using the restorative cosmetic composition of the present invention.

[0020] . Figure 15 is a comparative graph between the restorative cosmetic composition of the present invention and the control.

[0021] . Figure 16 is a graph depicting the improvement in the skin barrier of participants using the repairing cosmetic composition of the present invention.

[0022] . Figure 17 is a graph depicting the improvement in the skin's oily sheen of the participants when using the restorative cosmetic composition of the present invention.

[0023] . Figure 18 is a photo of one of the participants evaluating the oiliness shine control.

[0024] . Figure 19 is a graph depicting the stratum corneum recovery of participants using the cosmetic repair composition of the present invention.

[0025] . Figure 20 is a graph depicting the increase in the depth of the dermal papillae of the participants when using the repairing cosmetic composition of the present invention.

[0026] . Figure 21 is an MCR image demonstrating dermal papillae. In the region inside the red circle, it is possible to notice that in TO, well-defined and larger papillae are not observed, as observed in T14. These changes indicate better structure in the basal layer.

[0027] . Figure 22 is a graph representing the best organization of the participants' keratinocytes when using the repairing cosmetic composition of the present invention.

[0028] . Figure 23 is a graph depicting the increase in reflectance of the granular layer of the participants when using the restorative cosmetic composition of the present invention.

[0029] . Figure 24 is an MCR image demonstrating the brightness of the granulosa layer and keratinocyte morphology. In the region inside the red circle, it is possible to observe that in T14 the keratinocytes are better delimited, forming a honeycomb pattern. Greater delimitation is evidenced by greater reflectance (clearer regions around the keratinocyte) indicating greater cellular hydration and nutrition.

[0030] . Figure 25 is a graph depicting significant reduction in the participants' surface roughness parameter when using the restorative cosmetic composition of the present invention.

[0031] . Figure 26 is an MCR image demonstrating surface uniformity. In the region inside the red circle, it is possible to observe in TO less surface uniformity, with structures at different heights. At T14, the surface is more uniform, demonstrating greater cohesion in the stratum corneum.

[0032] . Figures 27 and 28 are graphs representing the percentage of positive responses from participants when using the restorative cosmetic composition of the present invention.

[0033] . Figure 29 is a graph representing the percentage of positive responses regarding product attributes.

[0034] . Figure 30 is a graph representing the distribution of the main phyla, showing the microbiota composition of the participants at times TO and T14.

SHORT DESCRIPTION OF THE PRESENT INVENTION

[0035] . The present invention provides a cosmetic composition to restore the skin barrier, maintaining skin hydration, in addition to calming sensitized, irritated and/or sensitive skin and ensuring the restoration and maintenance of the skin microbiota, comprising (i) a regenerating complex and ( ii) a pharmaceutically acceptable vehicle, where: (i) the regenerating complex is composed of alpha-glucan oligosaccharide in the range of 2% p.p. at 4% p.p.; niacinamide in the range of 3% p.p. at 7% p.p.; alpha-bisabolol in the range of 0.05% p.p. at 2% p.p.; dexpanthenol in the range of 0.05% p.p. at 2% p.p.; low molecular weight hyaluronic acid in the range of 0.01% p.p to 1% p.p; high molecular weight hyaluronic acid in the range of 0.01% p.p to 1% p.p; and vitamin E (racealphatocopheryl acetate) in the range of 0.5% p.p. to 2% p.p., where the range is based on 100% of the total weight of the composition.

[0036] . The composition of active ingredients proposed here acts in the different stages of recovery of skin that has suffered some type of injury: inflammation, proliferation and remodeling. Furthermore, the present composition has a prebiotic action that helps in the maintenance and recovery of the skin's microbiota and also reinforces the natural defenses by stimulating the production of antimicrobial peptides, beta-defensins, key markers of immunity. This protection becomes even more important in injured skin, since in this situation, the skin is not intact, thus reducing the mechanical barrier of protection.

[0037] . The composition is a prebiotic lotion indicated for maintenance, recovery and regeneration of the skin barrier. It acts in the immediate relief of signs and/or symptoms of irritated skin (redness, itching, burning, itching and flaking), has a calming and healing effect, restores and maintains the integrity of the skin barrier, increases and maintains skin hydration, in addition to to act in the preservation of the cutaneous microbiota, an essential factor for the maintenance of the functional and structural integrity of the skin. The cosmetic composition uses active ingredients that act in all stages of recovery of sensitized, irritated and/or sensitive skin; dexpanthenol, niacinamide, bisabolol, hyaluronic acid of different molecular weights and vitamin E, in addition to presenting a prebiotic in its composition, the alpha-glucan oligosaccharide, which acts in the maintenance and recovery of the skin's microbiota.

[0038] . The alpha-glucan oligosaccharide is a prebiotic molecule obtained from natural sugars through an enzymatic synthesis process involving a transferase enzyme. As it is a prebiotic, it favors the development of our saprophytic flora beneficial to the skin microbiota to the detriment of unwanted, opportunistic and/or pathogenic bacteria. This happens because our saprophytic flora manages to hydrolyze specific bonds (α-(1-6) and α-(1-2)) present in this molecule, while the pathogenic and opportunistic flora does not carry out this process easily. Due to this qualitative bio selection for the skin flora, where it benefits the saprophytic flora to the detriment of the pathogenic one, this oligosaccharide rebalances the bacterial landscape and thus strengthens the microbiological barrier of the skin. Due to its protective power, it also reinforces our body's natural defenses by stimulating the production of antimicrobial peptides, beta-defensins 2 and 3, key markers of immunity. Preservation of the microbiota is essential for maintaining the functional and structural integrity of the skin.

[0039] . The alpha-glucan oligosaccharide is present in this composition in an amount ranging from 1% wt to 5% wt, and preferably 3% wt, based on the total weight of the composition.

[0040] . Niacinamide strengthens the skin barrier function, as it increases the synthesis of ceramides, glucosyl-ceramide, sphingomyelin, cholesterol, free fatty acids and decreases transepidermal water loss, thus keeping the skin more hydrated and intact (Tanno O, Ota Y, Kitamura N, Katsube T et al. Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrier. Br J Dermatol. 2000;143(3):524-531 ). It also increases the production of keratin, filaggrin and involucrin (Oblong JE, Bissett DL, Ritter JL, Kurtz KK, Schnicker MS. Effect of Niacinamide on Collagen Synthesis and Markers of Keratinocyte Differentiation. 60th Annual Meeting of the American Academy of Dermatology, New Orleans. 2002), which help retain water in the skin. Niacinamide also has anti-inflammatory action, inhibiting important mediators of the inflammatory process, such as IL-12, TNF-α, IL-1. ( Ungerstedt JS, Blömback M, Söderström T. Nicotinamide is a potent inhibitor of proinflammatory cytokines. Clin Exp Immunol. 2003; 131(1):48-52 ). It also has antioxidant action (Kamat, J.P.; Devasagayam, T.P. Nicotinamide (vitamin B3) as an effective antioxidant against oxidative damage in rat brain mitochondria. Redox Rep. 1999, 4, 179-184; Kwak, J.Y.; Ham, H.J.; Kim , C.M.; Hwang, E.S. Nicotinamide exerts antioxidative effects on senescent cells. Mol. Cells 2015, 38, 229-235) and induces autophagy in keratinocytes, a cell renewal process, which helps maintain skin homeostasis (Oblong JE, DeAngelis YM, Jarrold BB, et al. Optimized low pH formulation of niacinamide enhances induction of autophagy marker ATG5 gene expression and protein levels in human epidermal keratinocytes. J Eur Acad Dermatol Venereol. 2020; 34Suppl 3:3-11). Lastly, it also increases fibroblast proliferation, thereby increasing collagen synthesis and aiding angiogenesis.

[0041] . Niacinamide is present in this composition in an amount ranging from 3% w.w. to 7% w.w., and preferably 5% w.w., based on the total weight of the composition.

[0042] . Alpha-bisabolol is an asset known for its calming properties. It has anti-inflammatory properties by inhibiting pro-inflammatory cytokines. In addition, it has antiseptic, bactericidal, antimycotic and healing action, being indicated in cases of small skin lesions, mild inflammation and burns. Its anti-inflammatory action is related to its action in inhibiting the enzyme 5-lipoxygenase (5-LOX), which has a central role in the biosynthesis of leukotrienes, important mediators of the inflammatory process.

[0043] . Alpha-bisabolol is present in this composition in an amount ranging from 0.05% wt to 2% wt, and preferably 1% wt, based on the total weight of the composition.

[0044] . Dexpanthenol is a precursor to vitamin B5. When applied topically, it is absorbed by the skin and quickly converted into pantothenic acid, a component of coenzyme A, essential for the physiological function of the epithelium. Its main function is related to promoting skin hydration due to its ability to retain and attract moisture, thus maintaining skin softness and elasticity. It also decreases transepidermal water loss from the stratum corneum, improving skin barrier function and stratum corneum hydration, and has anti-inflammatory properties, providing a soothing effect to irritated skin. Dexpanthenol also stimulates the epithelialization process, increasing epidermal differentiation and aiding in the healing of small wounds. (Gorski J, Proksch E, Baron JM, Schmid D, Zhang L. Dexpanthenol in Wound Healing after Medical and Cosmetic Interventions (Postprocedure Wound Healing). Pharmaceuticals. 2020; 13(7):138)

[0045] . Dexpanthenol improves and helps maintain skin hydration; it has an anti-inflammatory and calming effect on irritated skin, keeps the skin softer and more elastic, stimulates re-epithelialization and helps heal small wounds (such as scratches and blisters) and acts as an adjuvant in the treatment of skin lesions, mucous membranes and healing of wounds

[0046] . Dexpanthenol is present in this composition in an amount ranging from 0.05% wt to 2% wt, and preferably 1% wt, based on the total weight of the composition.

[0047] . Hyaluronic acid has anti-inflammatory (Fraser JR, Laurent TC, Laurent UB. Hyaluronan: its nature, distribution, functions and turnover. J Intern Med. 1997 Jul;242(1):27-33), healing and skin regenerating actions (Fraser JR, Laurent TC, Laurent UB. tissues (Price RD, Berry ΜG, Navsaria HA. Hyaluronic acid: The scientific and clinical evidence. J. Plast. Reconstr. Aesthet. Surg. 2007; 60:1110-1119; Hussain SN, Goodman GJ, Rahman E. Treatment of a traumatic atrophic depressed scar with hyaluronic acid fillers: a case report. Clin Cosmet Investig Dermatol. 2017 Aug 3;10:285-287), immunomodulatory (Litwiniuk, M. et al. Hyaluronic Acid in Inflammation and Tissue Regeneration. Wounds. 2016; 28(3):78-88), anti-aging (Papakonstantinou E, Roth M, Karakiulakis G. Hyaluronic acid: A key molecule in skin aging. Dermatoendocrinol. 2012; 4(3):253-258) and helps the skin maintain elasticity and hydration (Pavicic T, Gauglitz GG, Lersch P, Schwach-Abdellaoui K, Malle B, Korting HC, Farwick M. Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment. J Drugs Dermatol. 2011 Sep;10(9):990-1000). The cosmetic composition contains hyaluronic acid of different molecular weights; 250-1300 kDa (Due to its size range, it can act both in retaining water molecules in the dermis and positioning itself around collagen fibers, thus improving the quality of the epidermis, and in film formation, reducing transepidermal water loss and maintaining hydration) and 2000 kDa (acts in the formation of a film on the skin, which maintains molecular hydration).

[0048] . Low molecular weight hyaluronic acid allows it to penetrate the lower layers of the stratum corneum in a few hours, repairs the barrier function, protects phospholipids from oxidation while stimulating the activity of the beta-glucocerebrosidase enzyme, retains a large amount of water in its structure, providing hydration of the outer and inner layer of the skin, this process has an indirect positive effect on the cells in deeper layers, because the increased water content in the skin normalizes the metabolic activity of the cells, which then produce less free radicals.

[0049] . High molecular weight hyaluronic acid functions as a tissue lubricant and plays an important role in modulating interactions between adjacent tissues; it is a natural moisturizing factor of the skin, involved in tissue repair and collagen synthesis; helps with film formation to prevent water loss from the skin; nourishes repair, increases metabolism and skin elasticity, and makes the skin feel smooth

[0050] . The association of low molecular weight and high molecular weight hyaluronic acid helps in the formation of a firmer and more consistent film on the skin, preventing the loss of natural moisture from the skin and providing a feeling of smoothness.

[0051] . Hyaluronic acid with a molecular weight of 250 to 1300 kDa is found in an amount that varies from 0.01% p.p to 0.1% p.p and with a molecular weight of 2000 kDa is found in an amount that varies from in the range from 0.01% p.p to 0.1% p.p, and preferably hyaluronic acid with a molecular weight of 250 to 1300 kDa is found in an amount of 0.05% p.p and hyaluronic acid with a molecular weight of 2000 kDa is found in an amount of 0.05% p.p., based on the total weight of the composition.

[0052] . Vitamin E is a well-known antioxidant used in cosmetic compositions. It scavenges peroxyl radicals, which protects polyunsaturated fatty acids and lipoproteins from the degradation process by peroxidation (Niki E, Traber ΜG. A history of vitamin E. Ann Nutr Metab. 2012;61(3):207-12 ); it has a photoprotective and anti-photoaging action (Nachbar F, Korting HC. The role of vitamin E in normal and damaged skin. J Mol Med (Berl). 1995 Jan;73(l):7-17). In addition to its antioxidant power, the vitamin is said to be important for maintaining the structural integrity of virtually every cell in the human body, influencing cell signaling. Vitamin E also modulates connective tissue growth factor expression and regulates gene expression and transcription, thereby facilitating wound protection against infection (Ehterami A, Salehi M, Farzamfar S, et al. Chitosan/alginate hydrogels containing Alpha -tocopherol for wound healing in rat model. Journal of Drug Delivery Science and Technology. 2019; 51:204-213).

[0053] . Vitamin E is present in the formulation in amounts ranging from 0.5% p.p. to 1.5% p.p., and preferably 1.2% p.p., depending on the total composition.

[0054] . Furthermore, the cosmetic composition comprises cosmetically acceptable carriers which include, but are not limited to, emollients, emulsifiers, sequestering agents, thickeners, absorbent opacifiers, conditioners and cosmetically acceptable mixtures thereof.

[0055] . The emollients of the present cosmetic composition are cyclopentasiloxane, dimethicone crosspolymer, cyclomethicone, isononyl isononanoate and mixtures thereof.

[0056] . The emulsifiers of the present cosmetic composition are cetyl alcohol, polyglyceryl-2 stearate, glyceryl monostearate, stearyl alcohol and mixtures thereof.

[0057] . The scavenger of the present cosmetic composition is edetate disodium dihydrate.

[0058] . The thickeners of the present cosmetic composition are cyclopentasiloxane, dimethicone, dimethicone vinyl crosspolymer and mixtures thereof.

[0059] . The opacifier of the present cosmetic composition is polymethylisylsesquioxane.

[0060] . The absorbent of the present cosmetic composition is disiloxane.

[0061] . The conditioner of the present cosmetic composition is ethylhexylglycerin.

[0062] . The vehicle of the present cosmetic composition is water.

PRECLINICAL STUDY

[0063] . The stratum corneum is located in the most external part of the epidermis, being an impermeable layer formed by keratinocytes, which have a very important function of protecting the underlying tissues against injuries and infections. (I de Souza, R Spagolla Napoleão Tavares, ΜG Landim Bravo, L Rigo Gaspar. Biology, Histology and Physiology of the Skin. USP Ribeirão Preto.)

[0064] . Keratinocytes, when they differentiate and become old and functionless cells, are identified as corneocytes, forming the stratum corneum. Corneodesmosomes, composed of a glycoprotein called corneodesmosin, are found between corneocytes, promoting cohesion Together with the intercellular lipid matrix, keeping the stratum corneum intact (I de Souza, R Spagolla Napoleão Tavares, ΜG Landim Bravo, L Rigo Gaspar. Biology , Skin Histology and Physiology. USP Ribeirão Preto). This protein confers adhesive property and plays a key role in providing resistance through primary cohesive strength and preventing cell desquamation, maintaining skin hydration.

[0065] . When the stratum corneum is out of balance, either due to environmental factors or skin sensitization processes (Vincenz Oji; Katja-Martina Eckl; Karen Aufenvenne. Loss of Corneodesmosin leads to severe skin barrier defect, pruritus, and Atopy: unraveling the peeling skin desease.Am J Hum Genet.2010 Aug 13;87(2):274-281), the corneodesmosomes break and detach from the corneocytes, initiating the desquamation process and opening this stratum corneum, causing the loss of skin protection. The damage starts with the loss of transepidermal water, making the skin dry and can be prolonged, initiating an inflammatory process due to the imperfections that the corneocytes left because they were not united and keeping the layer impenetrable.

EVALUATION OF THE EFFECTS OF THE ACTIVE INGREDIENTS OF THE REPAIRING COSMETIC COMPOSITION OF THE PRESENT INVENTION ON THE REGENERATION OF THE CUTANEOUS BARRIER IN A MODEL OF RECONSTRUCTED HUMAN EPIDERMIS STIMULATED BY LACTIC ACID Goals

[0066] . Evaluate the expression of the corneodesmosin protein.

Methodology

[0067] . The 8-day reconstituted human epidermis was stimulated with 0.6% lactic acid to demonstrate skin aggression (topical application). The reconstituted epidermis was incubated in culture containing the restorative cosmetic composition of the present invention (systemic application). The reconstituted epidermis was then incubated for 48 hours with a new treatment after 24 hours (lactic acid and the repairing cosmetic composition of the present invention). RHE (Reconstructed Human Epidermis) was used for control, where there was no lactic acid stimulation for comparison.

[0068] . The concentration of the active ingredients was previously tested on NHEK (Normal Human Keratinocytes). The technique used for corneodesmosin expression was in situ immunofluorescence and semiquantitative image analysis.

Results

[0069] . Corneodesmosin was mainly detected on the surface of cells allocated within the granular layer. In response to lactic acid stress, corneodesmosin expression decreased considerably (-72%). Within the concentration of restorative cosmetic composition of the present invention, a limited decrease in corneodesmosin expression in response to lactic acid (-38% vs. -72% in untreated RHE) was observed (See Figures 1, 2, 3 and 4) .

Conclusion

[0070] . As expected, lactic acid stress resulted in skin barrier aggression and in this study the restorative cosmetic composition of the present invention was shown to limit skin barrier damage caused by topical application of lactic acid.

CLINICAL STUDIES

[0071] . The product of the present invention underwent several safety and efficacy studies, evaluating its performance both in instrumental evaluations and clinical and subjective evaluations. In all, more than 220 research participants were considered.

[0072] . How to use the product was determined by the following instruction: apply 2 times a day (morning and afternoon) on clean, dry skin.

[0073] . All participants who agreed to participate in the studies previously signed the TCLE (Term of Free and Informed Consent) and were advised to suspend the use of any cosmetic product on the face up to 48 hours before the start of the study.

EVALUATION OF THE POTENTIAL OF PRIMARY DERMAL IRRITATION, ACCUMULATED DERMAL IRRITABILITY, SKIN SENSITIZATION AND THE POTENTIAL OF CUTANEOUS PHOTOSENSITIZATION AND PHOTOTOXICITY SUPERVISED BY A DERMATOLOGIST goal I. Primary and cumulative sensitization

[0074] . The objective of the study was to prove the absence of both irritating and allergenic potential, confirming the safety of the product in a controlled amount applied, keeping the research participant's skin in contact with maximized doses of the product.

II. Photosensitivity and Phototoxicity:

[0075] . The objective of the study was to prove the absence of allergenic potential of a product applied to the skin when exposed to ultraviolet radiation, also using maximized doses of the product, controlling the amount applied.

Methodology I. Primary and cumulative sensitization:

[0076] . The product under investigation is applied in semi-occlusive pads of 1cm2 and inserted in the dorsal region of the research participant. One deposit contains the product under investigation (50μL/cm2 - maximized dose) and another deposit contains only saline solution, representing the control. These dressings cause a certain cutaneous occlusion that favors the contact of the product's components with the skin. The back region is preferably chosen because it is a more homogeneous area, facilitating the evaluation of the product under investigation and better adhesion of the dressings in the region. Several readings are performed over 3 weeks, evaluating the possibility of skin reactions at the sites of contact with the product under investigation.

II. Photosensitivity and Phototoxicity

[0077] . In the Phototest study, irradiation of the site of the patches on the skin was carried out to investigate dermal photosensitization and dermal phototoxicity, where there was an increase in skin reactivity to ultraviolet light. A solar simulator containing two ultraviolet radiation lamps with irradiation time control and a transparent glass to separate the radiation was used. Available ultraviolet radiation corresponds to sun exposure at peak sun time for one hour.

Results I. Primary and cumulative sensitization:

[0078] . The study was completed by 55 research participants, 78% female and 22% male, aged between 18 and 60 years (mean age 45 years) and phototype (Fitzpatrick) from I to IV.

[0079] . During the study, no participant had a significant skin reaction (erythema, edema, papules or vesicles).

[0080] . The product did not induce primary and accumulated dermal irritability and skin sensitization.

[0081] . Therefore, the following claim can be proven: "Dermatologically tested".

II. Photosensitivity and Phototoxicity

[0082] . The study was completed by 30 female and male participants, aged between 18 and 60 years (mean age 45 years) and phototype (Fitzpatrick) from I to IV.

[0083] . During the study, no participant had a significant skin reaction (erythema, edema, papules or vesicles) in the areas of application and irradiation of the investigational product.

[0084] . The product did not induce irritating phenomena or skin sensitization, and did not cause significant photosensitivity and phototoxicity effects during the study period, thus being considered safe for topical use.

[0085] . Therefore, the following claims could be supported: “Hypoallergenic” and “Dermatologically Tested”.

EVALUATION OF THE ABSENCE OF ACNEGENIC AND COMEDOGENIC POTENTIAL AND OF THE CUTANEOUS AND OCULAR ACCEPTABILITY OF A LOTION UNDER NORMAL CONDITIONS OF USE goal

[0086] . The objective of the study was to evaluate the absence of acnegenic (count of inflammatory lesions) and comedogenic (count of non-inflammatory lesions) potential and to verify the acceptability of the product by not observing the non-occurrence of adverse events and sensations of cutaneous and ocular discomfort, when applied under recommended conditions of use, through use accompanied by a Dermatologist and Ophthalmologist, respectively.

Methodology

[0087] . The study was carried out for 21 days, in which the participants were instructed to use the product daily on their face, at home, during this period. They were submitted to dermatological and ophthalmological clinical evaluation before using the product (TO) and after 21 days of using the product (T21). In these evaluations, the counting of acne lesions (open and closed comedones, papules and pustules) on the face (chin, cheekbones and forehead) of the participants was also performed, before using the product (TO) and after 21 days of using the product. product (T21).

Results

[0088] . The study ended with 35 female participants, aged between 18 and 45 years (mean age 33 years), with combination to oily skin with a tendency to acne.

[0089] . During the study, none of the participants showed clinical signs of the skin, nor did they feel discomfort with the use of the product.

[0090] . None of the participants also did not present feelings of ocular discomfort related to the use of the product.

[0091] . After 21 days of using the product, no significant increase was observed in the total number of non-inflammatory lesions (p-value of 0.164) and in the total number of lesions on the participants' faces (p-value of 0.222).

[0092] . With this, it was proven that the product did not present acnegenic and comedogenic potential, confirming its safety in use under the evaluated conditions.

[0093] . The following claims were supported: “Non-comedogenic/acnegenic”, “Dermatologically Tested” and “Ophthalmologically Tested”.

CLINICAL STUDY TO EVALUATE THE EFFECTIVENESS AND SAFETY OF THE COSMETIC COMPOSITION THROUGH OBJECTIVE INSTRUMENTAL ANALYSIS, SUBJECTIVE ANALYSIS BY CLINICAL AND PERCEIVED EFFECTIVENESS AND CUTANEOUS ACCEPTABILITY IN USE Goals

[0094] . Evaluate the effectiveness of the investigational product in providing improvement in hydration and general aspects of sensitive skin.

[0095] . Evaluate skin hydration through objective instrumental analyzes using the biometric technique of corneometry and evaporimetry (TEWL) to prove the appeal of immediate and prolonged hydration.

• · Maciez;
• · Suavidade e hidratação;
• · Textura;
• · Aparência Geral da pele.

[0096] . To verify the cutaneous acceptability in daily use of the investigational product for 21 days, through subjective techniques by clinical evaluation of the Dermatologist and perceived evaluation of the research participants, evaluating the following appeals:

• · Softness;
• · Softness and hydration;
• · Texture;
• · General appearance of the skin.

[0097] . Perform representative images of hydration and prevention of transepidermal water loss from the facial skin through the water map.

[0098] . Evaluate the clinical safety by application of the investigational product and its continuous use for 21 consecutive days according to the indicated mode of use, in order to verify the occurrence of discomfort or irritative or allergenic skin reactions and confirming the indication of the product for sensitive skin.

Methodology

[0099] . 33 participants, aged between 30 and 65 years, all female and with sensitive facial skin diagnosed at the Research Center by the Sting Test, participated in the research. Phototypes (Fitzpatrick): type II to IV.

[00100] . The effectiveness of the product for skin hydration was verified using the Corneometer® 825 equipment and the integrity of the skin barrier performed using the Tewameter TM® 300 equipment, evaluated at 15 minutes (immediate), 2 hours, 4 hours, 6 hours and 8 hours after application of the product on the facial region and forearm of each participant.

[00101] . The clinical and perceived efficacy was evaluated during the daily use of the product for 21 days by the Dermatologist and by each participant, respectively, recording their perceptions in the clinical form and answering the previously approved questionnaire, with a six-point rating scale. The clinical evaluation was performed in the face region.

[00102] . The clinical safety assessment of the product was performed through cutaneous acceptability in use.

[00103] . The water map was performed using an algorithm that creates a color map based on capacitance values and transepidermal skin loss. A digital image was captured in the frontal position of the participant's face, and capacitance measurements obtained were recorded in the times: at the beginning of the study (OD) and after 21 days (21) of using the investigational product.

Results Evaluation of skin hydration by Corneometry and Evaporimetry Forearms (Corneometry)

[00104] . The product increased the skin hydration level by 37.9% after 15 minutes, 25.0% after 2 hours, 19.5% after 6 hours and 9.3% after 8 hours of application, in relation to the basal condition of the skin.

[00105] . 100% of research participants showed improvement in skin hydration after 15 minutes, 2 and 4 hours of application and 96% of research participants showed improvement in skin hydration after 6 and 8 hours of application of the investigational product. (See Figure 5)

Forearms (TEWL)

[00106] . The product reduced the skin TEWL rate by 12.2% after 15 minutes, 10.3% after 2 hours, 9.3% after 4 hours, 8.4% after 6 hours and 6.6% after 8 hours of application, in relation to the baseline condition of the skin.

[00107] . 100% of research participants showed improvement in skin barrier/barrier integrity and skin hydration, as evidenced by reduced TEWL rate, after 15 minutes, 2, 4, 6, and 8 hours of application of the investigational product (See Figure 6 ).

Face (Corneometry)

[00108] . The product increased the skin's moisture level by 27% after 21 days of home use of the investigational product, relative to baseline skin condition (See figure 7).

[00109] . 95% of research participants showed improvement in skin hydration after 21 days of home use of the investigational product.

Face (TEWL)

[00110] . The product reduced the skin TEWL rate by 4.0% after 21 days of home use of the investigational product, relative to baseline skin condition.

[00111] . After checking the analyses, the following claims can be verified: “Maintains skin hydration for up to 8 hours”; “Immediate and prolonged hydration”, “Increases and maintains skin hydration”; “Maintains the integrity of the skin barrier”; “Improves the skin barrier”; "Improves skin barrier integrity and hydration."

[00112] . Check figure 8 which demonstrates the improvement in hydration after continuous use of the product for 21 days.

Evaluation of cutaneous acceptability in use

[00113] . 97% of the research participants did not experience adverse reactions or any signs or symptoms of discomfort and did not report irritating or allergenic reactions and/or feelings of discomfort resulting from the use of the investigational product. With this, it was considered that the skin tolerance to the product could be considered good.

[00114] . With that, the following claims were proven: “Clinically and Dermatologically tested”; “Suitable for sensitive skin”.

Subjective evaluation by clinical efficacy

[00115] . After 21 days of home use, it was observed: 91.0% improvement in skin hydration; 89.7% improvement in skin smoothness; 88.5% improvement in skin texture and 88.5% improvement in overall skin appearance. 100% of survey participants showed improvement after 21 days of use (See Figure 8).

CLINICAL STUDY TO EVALUATE THE EFFECTIVENESS AND SAFETY OF THE REPAIRING COSMETIC COMPOSITION IN REDUCING FACIAL ERYTHEMA, POST-PROCEDURE SOOTHING EFFECT AND IMPROVEMENT OF GENERAL ASPECTS OF THE SKIN THROUGH INSTRUMENTAL, SUBJECTIVE EVALUATIONS AND DERMATOLOGICAL AND OPHTHALMOLOGICAL ACCEPTABILITY Goals

[00116] . Evaluate the effectiveness of the cosmetic composition in providing a calming action, neutralizing the occasional redness of sensitized skin (post-procedure).

[00117] . Evaluate the improvement of the general aspects of the skin and verify the occurrence of discomfort or irritative and/or allergenic skin and ocular reactions during the study period.

[00118] . Evaluate, through an objective instrumental technique and subjective analysis by clinical and perceived efficacy, the appeals related to the calming, healing, renewal and hydration effect.

[00119] . Evaluate the sensory and visible benefits of the investigational product through the research participant's perception.

Methodology

[00120] . 33 participants participated in the research, aged between 37 and 59 years, average age of 49 years, all female and Phototypes (Fitzpatrick) III and IV. They used the investigational product for 14 days continuously.

[00121] . On the day of the beginning of the study, the participants were divided into two groups and underwent the Facial Skin Sensitization Insults that were performed in two ways: application of Jessner's chemical peel or procedure of intense pulsed light of light intensity.

[00122] . Instrumental, clinical and subjective evaluations were performed before the start of the study (baseline period) prior to sensitization and application of the investigational product, immediately after the insult, 30 minutes after application of the investigational product, after 24 and 48 hours and after 7 and 14 days of continuous use of the product.

[00123] . The effectiveness of the investigational product in the evaluation of the maintenance of the physiological pH of the skin was evaluated through the biometric technique of pHmetry by the Skin-pHmeter® equipment. The evaluations were performed in the malar region (right or left) of the research participant.

[00124] . The evaluation of the improvement in the general aspects of the skin was performed using subjective techniques based on clinical and perceived efficacy.

[00125] . The clinical safety of the investigational product was carried out through the cutaneous and ophthalmological acceptability in use by the Dermatologist and Ophthalmologist.

Results Evaluation of balance and restoration of skin pH

[00126] . No significant variation was observed in skin pH values after 30 minutes of application, after 24 and 48 hours of application and after 7 and 14 days of treatment with the investigational product in relation to the initial condition (pre-insult).

[00127] . The investigational product restored the cutaneous pH after 30 minutes, 24 and 48 hours after product application, and cutaneous pH balance after 7 and 14 days of treatment.

[00128] . As a result, the claims obtained were: “the product restores and balances the cutaneous pH of the skin”; “maintains the physiological pH of the skin” (See Figure 9).

Evaluation of cutaneous acceptability in use

[00129] . 91% of the research participants had no adverse reactions or any signs or symptoms of skin discomfort and did not report irritating or allergenic reactions and/or feelings of discomfort resulting from the use of the investigational product.

[00130] . The skin tolerance of the product can be considered good.

[00131] . The following claims could be proven: "Clinically and Dermatologically tested"; "Indicated for sensitive skin".

Evaluation of ocular acceptability in use

[00132] . 100% of the research participants had no adverse reactions or any signs or symptoms of ocular discomfort and did not report irritating or allergenic reactions and/or feelings of discomfort resulting from the use of the investigational product.

[00133] . Ocular tolerance to the product can be considered very good.

[00134] . The following claim can be proven: "Ophthalmologically tested".

Subjective analysis by clinical efficacy

[00135] . After 30 minutes of product application, a significant increase in facial skin erythema was observed, compared to the initial skin condition (pre-insult).

[00136] . The skin sensitization procedures used in the study maintained erythema on the skin for up to 30 minutes after application.

[00137] . Erythema: After 24 and 48 hours of application and after 7 and 14 days of treatment with the investigational product, there was no significant difference in the erythema attribute, in relation to the baseline condition (pre-insult), indicating that the product provides a calming effect and restores the skin barrier integrity.

[00138] . Dryness: A significant improvement of 12.5% after 48 hours and 14.3% after 14 days of treatment with the product was observed in relation to the initial condition (pre-insult).

[00139] . Hydration: A significant improvement of 18.3% was observed after 48 hours of application, 25.6% after 7 days and 40.2% after 14 days of treatment with the product in relation to the initial condition (pre-insult).

[00140] . Tenderness: An improvement of 31.8% after 7 days and 36.5% after 14 days of treatment with the product was observed in relation to the initial condition.

[00141] . General appearance of the skin: An improvement of 22.5% after 7 days and 32.5% after 14 days of treatment with the product was observed in relation to the initial condition.

• · 100% consideraram que o produto possui textura leve e suave
• · 97% consideraram que o produto possui textura não oleosa
• · 88% consideraram que o produto apresenta toque seco após a aplicação
• · 91% consideraram que o produto possui cheiro agradável
• · 97% consideraram que o produto espalha com facilidade.

[00142] . Regarding the pleasantness of the investigational product, the research participants:

• · 100% considered that the product has a light and smooth texture
• · 97% considered that the product has a non-greasy texture
• · 88% considered that the product had a dry feel after application
• · 91% considered that the product has a pleasant smell
• · 97% thought the product spreads easily.

EVALUATION OF THE CUTANEOUS ACCEPTABILITY AND EVALUATION OF THE CLINICAL, INSTRUMENTAL AND PERCEIVED EFFECTIVENESS BY RESEARCH PARTICIPANTS OF THE REPAIRING COSMETIC COMPOSITION AFTER A DERMATOLOGICAL PROCEDURE UNDER NORMAL CONDITIONS OF USE Goals

[00143] . Evaluate the benefits of restorative cosmetic composition after dermatological procedure with Jessner peeling:

[00144] . Assessment of perceived efficacy and clinical efficacy;

[00145] . Instrumental techniques of Corneometry (hydration), Tewametry (transepidermal water loss), shine and oiliness (Visia) and cell regeneration (Confocal Laser Reflectance Microscope).

[00146] . Evaluation of the maintenance of the skin microbiota.

Methodology

[00147] . 36 participants completed the survey, aged between 33 and 59 years old, mean age 47 years old, all female and phototypes (Fitzpatrick) from I to IV, presenting facial spots, photoaging, melasma (mild or moderate) or some other condition skin whose performance has been recommended by the Dermatologist. The cosmetic composition was used daily by the participants for 14 days.

[00148] . The cosmetic composition was applied on half the face, in a random way. The other face was used as a control to compare the results.

[00149] . Instrumental and clinical evaluations were performed before the beginning of the study (baseline period) prior to sensitization and application of the investigational product, 30 minutes after the peeling procedure, 15 minutes after application of the cosmetic composition, after 24 and 48 hours and after 7 and 14 days of continuous use of the product.

[00150] . The Visia CR® equipment was used to evaluate shine and oiliness through frontal images of the face of selected participants (10 participants).

[00151] . The instrumental evaluation to verify skin regeneration used the Laser Reflectance Confocal Microscope (Vivascope®) equipment, capturing cellular images of the participants' faces where the cosmetic composition was applied. The images obtained evaluate the cutaneous characteristics, among others, the thickness of the layers of the epidermis and organization of the keratinocytes. Captures were performed before the start of the study (TO) and 14 days after continuous use of the product (T14) (See figure 24).

[00152] . The function of microbiological collections was to study the metagenomics of the microbiota. Collections were performed on the surface of the skin by means of a sterile swab before the beginning of the study (TO) and 14 days after continuous use of the product (T14) in the selected participants (10 participants).

[00153] . The metagenomic study of microbial communities, where their characteristics can function as biomarkers, is an effective approach to identify the microorganisms or microbial metabolic characteristics of any non-culturable sample and seeks to identify the specific organisms, genera, operational taxonomic units or relative abundance that differs between two or more sample groups. The main steps of the methodology were DNA analysis and sequencing and Bioinformatics Analysis.

[00154] . Microbiota analysis is performed both quantitatively (abundance) and qualitatively (diversity). The microbiota readings generated from each sample are compared against existing public databases to classify the species present.

Results Clinical Efficacy Assessment

[00155] . Improvement in the general appearance, softness, and erythema of the skin was observed 7 days after the peeling procedure associated with the use of the product (See Figure 10: T7-T0: <0.0001 (significant at the 5% level - Test t of Student). Participants with improvement: 93.1%; Figure 11: T7-T0: <0.001 (significant at the 5% level - Student's t test). Participants with improvement: 86.2%; Figure 12: T7-T0: <0.036 (significant at the 5% level - Student's t test) Participants with improvement: 24.1%).

Instrumental Measurement of Electrical Capacitance (Corneometry)

[00156] . Improvement in skin hydration was observed immediately, 24 and 48 hours after application of the product after the peeling procedure and 7 and 14 days after the peeling procedure and product use (See Figure 13: <0.001 (significant at level 5% - Student's t test). level 5% - Student's t test) Participants with improvement: T7: 71.4%; T14: 78.6%).

Instrumental measurement of transepidermal water loss (TEWL)

[00157] . Improvement in the skin barrier was observed immediately, 24 and 48 hours after application of the product after the peeling procedure and 7 and 14 days after the peeling procedure associated with the use of the product (See Figure 15: <0.018 in Timap, < 0.012 at T24h and <0.001 at T48h (significant at the 5% level - Student's t test). Participants with improvement: Timap: 53.6%; T24h: 60.7%; T48h: 75.0%; Figure 16: < 0.001 (significant at the 5% level - Student's t test) Participants with improvement: T7: 71.4%; T14: 89.3%).

Obtaining images with the Visia CR® Equipment

[00158] . An improvement in skin oiliness was observed after 7 and 14 days of the peeling procedure associated with the use of the product (See Figure 17: <0.002 at T7 and <0.043 at T14 (significant at the 5% level - Student's t test ) Participants with improvement: T7: 81.4%; T14: 72.7%).

Analysis of Confocal Reflectance Microscopy (MOR)

[00159] . Recovery of the stratum corneum was observed, restoring its initial thickness 14 days after the peeling procedure associated with the use of the investigational product (See Figure 19: <0.040 (significant at the 5% level - Student's t test). Participants with improvement: 71, 4%).

[00160] . An increase in the thickness of the epidermis was observed, indicating cell proliferation that, together with the increase in the size of the papillae and the better organization of the keratinocytes (honeycomb pattern), indicate better structuring of the basal layer and cell renewal (See Figure 20: <0.022 (significant at 5% level - Student's t test) Participants with improvement: 71.4% Figure 22: <0.027 (significant at 5% level - Student's t test) Participants with improvement: 71.4% and Figure 24).

[00161] . An increase in the reflectance of the granular layer was observed, indicating deep hydration and greater nutrition in the region (See Figure 23: <0.014 (significant at the 5% level - Student's t test). Participants with improvement: 71.4%).

[00162] . A significant reduction in the surface irregularity parameter was observed after fourteen days of product use compared to the TO time, indicating a more cohesive and therefore more uniform stratum corneum (See Figure 25: <0.018 (significant at the 5% level - Student's t test) Participants with improvement: 85.7%) (See Figure 26).

Microbiological Analysis of the Skin Surface

[00163] . Maintenance of proportions between the main phyla of the resident microbiota of human skin, as well as the main species belonging to them, was observed after the peeling procedure and after 14 days of product use, indicating maintenance of the microbiome. (See Figure 30)

[00164] . An increase in alpha diversity in the microbiome was observed after the peeling procedure and after 14 days of product use, suggesting skin recovery, since greater diversity of species denotes an increase in beneficial metabolites and a balanced skin.

• - Clinicamente Testado;
• - Alívio imediato de sinais e/ou sintomas da pele irritada/sensibilizada (vermelhidão, coceira, queimação, pinicação e descamação);
• - Efeito Calmante (alívio imediato).
• - Restabelece a integridade da barreira da pele e mantém a integridade da barreira da pele;
• - Aumenta a hidratação (imediata) e mantém a hidratação;
• - Para pele sensibilizada;
• - Não arde;
• - Efeito mate imediato;
• - Controle do brilho de oleosidade;
• - Manutenção da microbiota da pele;
• - Auxilia na renovação celular, efeito cicatrizante;
• - Hidratação profunda;
• - Nutrição celular.

[00165] . After analyzing all these parameters reported in this study, the following claims could be proven:

• - Clinically Tested;
• - Immediate relief of signs and/or symptoms of irritated/sensitized skin (redness, itching, burning, itching and flaking);
• - Soothing Effect (immediate relief).
• - Restores skin barrier integrity and maintains skin barrier integrity;
• - Increases hydration (immediate) and maintains hydration;
• - For sensitive skin;
• - Does not burn;
• - Immediate matte effect;
• - Control of oiliness shine;
• - Maintenance of the skin microbiota;
• - Assists in cell renewal, healing effect;
• - Deep hydration;
• - Cell nutrition.

Claims (11)

COSMETIC COMPOSITION to restore the skin barrier, maintaining skin hydration and restoring and maintaining the skin microbiota, in addition to calming sensitized, irritated and/or sensitive skin, characterized by the fact that it comprises (i) a regenerating complex and (ii) a pharmaceutically acceptable vehicle, considering that: (i) the regenerating complex is composed of alpha-glucan oligosaccharide in the range of 2% p.p. at 4% p.p.; niacinamide in the range of 3% p.p. at 7% p.p.; alpha-bisabolol in the range of 0.05% p.p. at 2% p.p.; dexpanthenol in the range of 0.05% p.p. at 2% p.p.; low molecular weight hyaluronic acid in the range of 0.01% p.p to 1% p.p; high molecular weight hyaluronic acid in the range of 0.01% p.p to 1% p.p; and vitamin E (racealfatocopherol acetate) in the range of 0.5% p.p. to 2% p.p. COSMETIC COMPOSITION, according to claim 1, characterized in that it comprises 3% p.p. of alpha-glucan oligosaccharide; 5% w.w. niacinamide; 1% p.p. of bisabolol; 1% p.p. dexpanthenol; 0.05% p.p. of low weight hyaluronic acid with 250-1300 kDa; 0.05% p.p. 2000 kDa high molecular weight hyaluronic acid; 1.2% p.w. vitamin E (racealfatocopherol acetate); and cosmetically acceptable vehicles, where the range is based on 100% of the total composition weight. COSMETIC COMPOSITION, according to claim 1 and 2, characterized in that it comprises cosmetically acceptable vehicles including, but not limited to emollients, emulsifiers, sequestrant, thickener, absorbent opacifier, conditioner and cosmetically acceptable mixtures thereof. COSMETIC COMPOSITION, according to claims 1 to 3, characterized in that suitable emollients are cyclopentasiloxane, dimethicone crosspolymer, cyclomethicone, isononyl isononanoate and mixtures thereof. COSMETIC COMPOSITION, according to claims 1 to 4, characterized in that suitable emulsifiers are cetyl alcohol, polyglyceryl-2 stearate, glyceryl monostearate, stearyl alcohol and mixtures thereof. COSMETIC COMPOSITION, according to claims 1 to 5, characterized in that the suitable sequestrant is edetate disodium dihydrate. COSMETIC COMPOSITION, according to claims 1 to 6, characterized in that the suitable thickener is cyclopentasiloxane, dimethicone, dimethicone vinyl cross-polymer and mixtures thereof. COSMETIC COMPOSITION, according to claims 1 to 7, characterized in that the opacifier is polymethylisylsesquioxane. COSMETIC COMPOSITION, according to claims 1 to 8, characterized in that the absorbent is disiloxane. COSMETIC COMPOSITION, according to claims 1 to 9, characterized in that the conditioner is ethylhexylglycerin. COSMETIC COMPOSITION, according to claims 1 to 10, characterized in that the vehicle is water.

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