The present invention relates to prebiotic cosmetic compositions comprising at least one ingredient with prebiotic activity selected from sugars, oils and extracts for the treatment of signs of aging on the skin, fostering well-balanced skin, nourishing beneficial micro-organisms in the skin microbiota, protecting it from harsh environmental aspects, strengthening it, reducing sensitivity and irritations, and improving its defense system.
Microbiota constitute the set of micro-organisms found in a specific system, such as the skin, for example. Skin microbiota consists mainly of bacteria, but also include viruses, fungi and protozoa.
Micro-organisms found in skin microbiota are defined by environmental conditions such as anatomical location, question, oil and sweat production, oxygen concentration and pH levels, among others, in addition to biological factors such as hormone swings and a person's age.
Microbiota is responsible for several physiological functions, such as the production of nutrients or protective peptides, as well as immunological response modulation.
Micro-organisms can cling to the skin by bonding to skin structures, such as carbohydrates or cell receptors in the skin cells, or may be organized into colonies held together by biofilm.
The biofilm forms a microenvironment with pH, oxygen concentration, nutrients and metabolites that are different from the skin. It also facilitates bacterial communication through quorum sensing and protects microbiota from endogenous and exogenous antimicrobial agents in the person's immunological system.
Human skin has approximately 1000 bacteria for each cell. Genetic sequencing studies show that there are bacteria not only on the skin surface, but also in the sebaceous and sweat glands, follicles and skin folds, as well as at even deeper skin levels such as the dermis.
The most common genera on the surface levels of the skin are Staphylococcus, Propionibacterium, Micrococcus and Corynebacterium.
These bacteria are distributed in different parts of the skin, depending on the microenvironment. For example, Staphylococcus and Corynebacterium are the most abundant genera on the skin, and remain there for life. Propionibacterium, which is anaerobic, is found in the sebaceous glands, while Corynebacterium is found in the armpits, and are related to the production of unpleasant smells. Found on the scalp, Malassezia is related to seborrheic dermatitis and dandruff.
In general, human skin offers a dry and mildly acid environment for microbiota, with only proteins and lipids available.
Keeping skin biota in an even balance involves adhesion mechanisms, interactions with the person's immunological defense system, alterations to the microenvironment, nutrient consumption and the production of antimicrobial agents
The surface layers of the skin are constantly flaking off, removing part of the microbiota. The capacity to adhere viable skin cells ensures that micro-organisms remain in place. Bacteria bond to membrane receptors in the cells, such as those in the toll-like family that recognize patterns associated with the bacteria (TLR 1-10), mannose receptors or NOD-like receptors. These receptors activate immunological pathways that distinguish pathogenic bacteria from their beneficial counterparts, stimulating appropriate responses. The microbiota composition teaches the immune system to distinguish beneficial bacteria more accurately, modulating inflammatory responses and reducing skin sensitivity to external factors such as variations in temperature, moisture and exposure to UV radiation.
Furthermore, microbiota produce lactic acid that, together with free fatty acids (from sebum), acid amino acids (from sweat) and urocanic and pyrrolidone carboxylic acids (from the corneocyte keratinization process), keeps the skin pH more acid and restricts micro-organisms in the biota. Lipids are the main source of carbon used by skin microbiota.
Variations in age, gender and hormone cycles interfere in the availability of nutrients for microbiota, and may result in micro-organism composition swings.
The role played by the skin, serving as a selective barrier against the outside environment, is facilitated considerably by antimicrobial peptides (AMPs) produced by keratinocytes and skin microbiota. More than 200 molecules with antimicrobial activities are described, produced by micro-organisms and cataloged in public and private databases. Among them are a and β-defensins (hBD), cathelicidins, C-type lectins, dermicidins, etc. Most AMPs consist of small peptides measuring approximately 2 to 15 kDa. An imbalance (to many or too few) AMPs on the skin is related to pathologies such as atopical dermatitis, rosacea and psoriasis. Some factors produced by the skin, such as vitamin D and PTH, regulate AMP synthesis. These AMPs are important for protecting the skin against pathogens, controlling the microbiota population and limiting contact between keratinocytes and microbiota. The activity of the AMPs are generally broad-spectrum, encompassing Gram-positive and Gram-negative bacteria, as well as fungi, protozoa and viruses, in some cases.
Microbiota also produce other substances such hyaluronic acid produced by Streptococcus and some Lactobacillus, which is a constituent element of the extracellular matrix that fills the dermis, giving shape to the skin and stimulating the production of β-defensin 2 (hBD2).
Sphingomyelinase is produced by keratinocytes, Streptococcus and Lactobacillus, being an enzyme that participates in the synthesis of ceramides that are vital for skin barrier maintenance.
Lipoteichoic acid (LTA) is the structural component of Gram-positive bacteria such as Staphylococcus, Lactobacillus and Bifidobacteria, stimulating the production of antimicrobial peptides such as β-defensins (hBD) and cathelicidins.
Peptidoglycans are structural components of the cell walls of gram-positive bacteria, which modulate individual immunological responses, stimulating the production of IL-8 by keratinocytes and summoning phagocytes to infected sites.
Lactic acid (alpha hydroxy acid) produced by Lactobacillus and Bifidobacteria stimulates the skin shedding process, weakening cell adhesion and stimulating the production of ceramides by keratinocytes, thus strengthening the skin barrier and constituting a Natural Moisturizing Factor (NMF), which keeps moisture in the skin.
Produced by Lactobacillus and Bifidobacteria, acetic acid offers antibacterial activity against S. aureus and P. aeruginosa.
The main representatives of skin microbiota include Staphylococcus epidermidis, which is a major skin component, halotolerant and able to grow in environments with little water activity. Although generally harmless for the skin, this may cause nosocomial infections through colonizing foreign bodies such as catheters and implants in predisposed and immunocompromised people. Strongly AMP-resistant, they do not damage keratinocytes and produce AMPs (epidermin, Pep5, epilancin K7 and epicidin 280) that control S. aureus and Streptococcus populations.
However, the removal of S. epidermidis from the skin—through the excessive use of topical antibiotics, for example—leaves a person immunocompromised and very susceptible to infection by pathogens.
Furthermore, they synthesize proteases, keratinases, lipases and nucleases that are involved in the physiological turnover of the skin. They synthesize phenol-soluble modulins (PSMs), proteins with surfactant and selective antibacterial properties for S. aureus and Streptococcus through dissolving the biofilm formed by these pathogenic bacteria.
Staphylococcus aureus is found on healthy skins. The main human skin pathogen, it causes folliculitis, boils, subcutaneous abscesses, meningitis, endocarditis and septicemia. Conditions such as atopical dermatitis, virus (Herpes simplex type I or papillomavirus) and opportunistic yeast infections (Trichophyton rubrum) the skin more vulnerable to S. aureus infections.
The steady increase in the number of strains resistant to antibiotics such as metacyclin and vancomycin means that S. aureus has become a serious problem in hospital environments. It synthesizes bacteriocins such as staphylococcin 462 that inhibit other S. aureus strains.
Present on healthy skins, Corynebacterium jeikeium and Corynebacterium striatum are the most common micro-organisms, after S. epidermidis. They are found in the axillary, inguinal and perineal region, due to their high tolerance of salt concentrations. Adhering to keratinocytes at an estimated proportion of 25 bacteria/cell through fibronectin receptors, they produce bacteriocins such as lacticidin Q, which triggers the synthesis of dermicidin and cathelicidin in sweat, constituting a skin defense activity
Found in healthy microbiota on areas such as the face and back, Propionibacteria acnes, is an anaerobic saprophytic micro-organism found mainly in the sebaceous glands and associated with conditions such as folliculitis and acne vulgaris. The main source of its energy consists of lipids and fatty acids in sebum. The presence of porphyrin leaves P. acnes quite sensitive to UV radiation and stimulates the production of IL-8 and IL-12 by keratinocytes, forming a microenvironment that fosters inflammation.
Studies indicate that P. acnes is involved in the hypercornification process of the pilosebaceous duct, exacerbating inflammatory processes. Furthermore, it synthesizes acetic acid and propionic acid, in addition to lipases and proteases. It also synthesizes several bacteriocins such as propionicin PLG-1, jensenin G, propionicin SM1, SM2, T1 and acnein, being active against several lactic and Gram-negative bacteria, fungi and molds.
Malassezia furfur is a fastidious fungus found in healthy microbiota in regions such as the scalp and back, and is the main cause of opportunistic infections such as seborrheic dermatitis, dandruff and Tinea versicolor (or pityriasis). Its main carbon source consists of free fatty acids. Furthermore, it synthesizes an enzyme that can degrade micro-organism cell walls, helping protect the skin against pathogens.
Microbiota imbalance may lead to seborrheic dermatitis, acne vulgaris and atopical dermatitis, among other diseases.
Skin microbiota is constantly improved through natural shedding and renewal of the skin. The capacity of micro-organisms to adhere to viable skin cells—including at deeper layers such as the dermis—is thus a competitive advantage.
The presence of microbiota modulates the inflammatory response of the skin, reducing sensitivity to factors such as temperature variations, moisture and exposure to UV radiation.
Microbiota produce lactic acid, which helps keep the skin pH more acid, antimicrobial peptides (AMPs) that protect the skin from pathogens and whose imbalances related to pathologies such as dermatitis, rosacea and psoriasis, help regulate vitamin D production, and are also involved in the production of extracellular matrix proteins such as hyaluronic acid enzymes that are important for maintaining the cutaneous barrier, such as sphingomyelinase.
Staphyloccocus epidermidis is the main micro-organism in skin microbiota and consequently remains in place, even during aging. Harmless for keratinocytes, S. epidermidis produces AMPs (epidermin, Pep5, epilancin K7, phenol-soluble modulins (PSMs) and epicidin 280) that control S. aureus and Streptococcus populations, protecting the skin.
S. epidermidis synthesizes proteases, keratinases, lipases and nucleases that contribute to the physiological turnover of the skin and play a role in keeping skin healthy, protecting it from harmful opportunistic micro-organisms and fostering physiological mechanisms that renew the skin.
There are countless active ingredients available with suggestive direct or indirect effects on the microbiota, administered either topically or by mouth, such as acetic acid, diacetyl acid, lactic acid and hyaluronic acid, among others. Although microbiota components and their direct and indirect effects on the skin are known, widespread use of antibacterial agents persists, affecting both beneficial and harmful bacteria on the skin. The indiscriminate use thereof weakens the natural defenses of the skin, leaving it more vulnerable to harmful bacteria.
This is why new prebiotic and probiotic ingredients are still being researched.
Prebiotics are ingredients that foster beneficial bacteria, while probiotics are micro-organisms that interact with the natural skin biota and encourage it to produce its own defenses. A probiotic may also act as a selective antibacterial agent, producing substances that control the proliferation of harmful bacteria.
Several prior art publications indicate that prebiotic agents may selectively favor beneficial bacteria and are thus candidates for inclusion in cosmetic compositions intended for this purpose. Nevertheless, despite screening and suggesting possible prebiotic agents, the state of the art is limited in terms of providing effective prebiotic ingredients with proven in vitro efficacy and with mechanisms of action that are clearly explained, particularly for topical administration, which is why investigation is still lacking.
Consequently, the need persists for cosmetic compositions with proven prebiotic effects on the skin, particularly for topical administration.
In an initial aspect, the present invention refers to prebiotic cosmetic compositions comprising at least one ingredient with prebiotic activity selected from sugars, oils and extracts for the treatment of signs of aging on the skin, fostering well-balanced skin, nourishing beneficial micro-organisms in the skin biota, protecting it from harsh environmental aspects, strengthening it, reducing sensitivity and irritations, and improving its defense system, with proven in vitro efficacy.
Particularly, the sugar according to this invention is selected from trehalose and/or babassu palm starch, the oils are selected from crabwood (andiroba), moriche (buriti) palm, Brazilnut and/or micro-algae and wild sage (guaçatonga) extract.
The prebiotic cosmetic compositions addressed by this invention may be presented in different cosmetic forms, including but not limited to, emulsions, gels, powders and sticks, among others, including carriers that are cosmetically suitable for the selected cosmetic form.
The prebiotic cosmetic compositions addressed by this invention are intended for topical administration and foster the proliferation of S. epidermidis, no increase in harmful micro-organisms.
Surprisingly, a prebiotic effect was noted, caused by the active ingredients in the topical prebiotic cosmetic compositions addressed by this invention, whereby not only is it efficient for reducing harmful skin bacteria, fostering beneficial skin bacteria and ensuring evenly-balanced microbiota, it also leads to an even skin balance and the nutrition thereof, stimulating cell turnover, cell renewal, tissue renewal, cutaneous integrity and natural skin defense/protection, resulting in advantageous cosmetic effects such as enhanced skin firmness and elasticity, increase in the skin structuring matrix, strengthening skin architecture and restoring skin density, in addition to providing protection against enzymes that degrade the skin structuring matrix, protection against microinflammation, prevention of microdamage, protection against external aggression, soothing effects and more apparent effects on firmness.
Due to these and other effects noted, the topical cosmetic compositions addressed by this invention are used as anti-aging agents.
In another aspect, the topical prebiotic cosmetic compositions according to this invention present an anti-aging effect, acting directly on cell proliferation, skin protection and sensitivity reduction (through acting on IL-6, IL-8, IL-10 and PGE2 synthesis) together with firmness and elasticity (through acting on collagen and elastin; glycosaminoglycans and metalloproteinase modulation).
The increase in IL-6 and PGE2 reduces the responsiveness of innate immunity cells to external stimuli, such as variations temperature, moisture and UV radiation. The increase in IL-10 modulates the responsiveness of lymphocytes to stimuli such as inorganic particles and other micro-organisms. The reduction in IL-8 lowers the inflammatory cascade activation threshold without adversely affecting skin protection. In turn, increased collagen, elastin and glycosaminoglycans (GAGs) lead to greater firmness and elasticity for the dermis. Metalloproteinase modulation 1 (MMP-1) regulates collagen degradation and ensures skin physiology maintenance.
Particularly, babassu palm starch nourishes the skin, as this is a glucose dimer, protecting it by increasing the S. epidermidis population that produces AMPs and modulates inflammatory cytokines.
In addition to the benefits listed above, trehalose and moriche (buriti) palm oil also renew the skin by increasing the proliferation of fibroblasts and increasing skin hydration through increased absorption and retention of water by the skin, in addition to enhanced skin elasticity through elastin synthesis, together with odor control through not stimulating the proliferation of Corynebacteria.
The topical prebiotic cosmetic compositions addressed by this invention may be presented in any suitable cosmetic for application to the face or body for treatment or cleaning purposes with no constraints, as known to a person skilled in the art, including emulsions, solutions, powders, gels, pastes and toilet soaps, among others.
Cosmetically acceptable carriers may be selected from compounds known at the state of the art. Without imposing any constraints, they may consist of emollient, antioxidant, moisturizing, emulsifying and surfactant agents, texture or viscosity modifiers, preservatives, chelating, stabilizing and solubilizing agents, lubricants, thickeners, dispersants, and other cosmetically acceptable carriers. In another aspect, this invention also encompasses use of the cosmetic compositions addressed by this invention simultaneously as a prebiotic, selective bacteriostatic and skin anti-aging agent, together with the use of the active ingredients described herein, either alone or in combination, for the preparation of cosmetic compositions that are simultaneously pre-biotic, selective bacteriostatic and skin anti-aging agents.
The following examples illustrate this invention, without imposing any constraints thereon.
When a concentration of 10{circumflex over ( )}4 UFC/ml was reached, the micro-organisms were transferred to a minimal carbon support medium that provided the conditions required for micro-organism replication.
Each active ingredient in the compositions addressed by this invention was added to the culture medium and cultivated. Should any increased count be noted, the ingredient would be considered as having prebiotic activity.
The results of each assay were submitted to statistical analysis. The active ingredients used in the prebiotic cosmetic compositions addressed by this invention were tested on different micro-organisms.
The beneficial micro-organisms assayed were: Staphylococcus epidermidis, Staphylococcus xylosus, Staphylococcus warneri, Staphylococcus captis and Corynebacterium xerosis.
The undesirable micro-organisms assayed were: Staphylococcus aureus, Corynebacterium striatum, Corynebacterium jeikeium, Propioniumbacteria acnes and Candida albicans.
It was noted that inulin, which is widely used as a prebiotic in the food industry, did not present selectivity for any of the tested skin-dwelling micro-organisms, as shown in
This Figure also shows that trehalose, which is a cosmetic ingredient used for hydration, selectively favored the growth of S. xylosus and S. epidermidis (0.5%). This difference indicates differences in the microbial mechanism, with S. epidermidis being more sensitive to variations in the concentration of this active ingredient. Used as a texture modifier, babassu palm starch (polisensi) selectively favored S. xylosus, S. warneri and S. captis.
Crabwood (andiroba) oil fostered the growth of S. xylosus at all tested concentrations, and S. epidermidis at a concentration of 1%.
Moriche (buriti) palm oil fostered the growth of S. xylosus at all tested concentrations, and S. epidermidis as from 0.1%. The variation noted for S. xylosus falls within the margin of error for the test (20%).
In order to demonstrate the simultaneous effects described here, the active ingredients listed herein were tested against the anti-age mark parameters under assessment, including cell proliferation, IL-6 synthesis, IL-8, IL-10 and PGE2 synthesis, elastin; GAGs and MMP-1.
The results are presented in Table 1 below.
Tests conducted under the aegis of this invention showed that the extrapolation of the activities of intestinal prebiotics to the skin did not prove true, stressing that each system is endowed with micro-organisms that are closely adapted thereto, with specific needs. Furthermore, it was noted that S. epidermidis and S. xylosus remained the main skin micro-organisms, even in the course of aging.
The literature shows that uncontrolled proliferation of S. epidermidis and S. xylosus leads to infectious conditions that are similar to those caused by S. aureus.
The prebiotic activity noted during the in vitro tests conducted for this invention may be facilitated in vivo, particularly for moriche (buriti) palm oil, due to the permeation facilitating activity of oleic acid (77% of the fatty composition of moriche (buriti) palm oil), which increases its availability to micro-organisms found at all skin levels.
As a positive assay control, human fibroblasts were cultivated in a culture medium supplemented with 2% of fetal bovine serum.
The protective effect of S. epidermidis against S. aureus in keratinocytes (HaCaT) in a culture was also assessed.
To do so, Step I consisted of defining the bacteria concentration through cell feasibility; Step II consisted of prebiotic dilution; Step III consisted of a preventive protocol (S. epidermidis prevents the adhesion of S. aureus); and Step IV consisted of a competition protocol (S. epidermidis prevents the adhesion of S. aureus).
Together, these results show that the prebiotic effect caused by the active ingredients in the topical prebiotic cosmetic compositions according to the present invention is not only efficient for reducing harmful skin bacteria and fostering beneficial skin bacteria, ensuring an evenly-balanced microbiota, but also ensures a well-balanced skin that is nourished, stimulating cell turnover, cell renewal, tissue renewal, cutaneous integrity and natural skin defense/protection, resulting in advantageous cosmetic effects such as enhanced skin firmness and elasticity, increase in the skin structuring matrix, strengthening skin architecture and restoring skin density, in addition to providing protection against enzymes that degrade the skin structuring matrix, protection against microinflammation, prevention of microdamage, protection against external aggression, soothing effects
A person skilled in the art would promptly assess the advantages of the invention through the teachings in the text and the examples presented, proposing equivalent variations and alternative embodiments without extending beyond the scope of the invention, as defined in the Claims appended hereto.
Filing Document | Filing Date | Country | Kind |
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PCT/BR2016/050293 | 11/10/2016 | WO | 00 |
Number | Date | Country | |
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62335381 | May 2016 | US |