KR20220155327A - Cosmetic Use of Leotier Water to Balance Skin Microflora - Google Patents

Abstract

The present invention relates to a cosmetic method for maintaining the balance of skin microflora, which includes applying a cosmetic composition to the skin, wherein the cosmetic composition includes or consists of Reotier water.

Description

Cosmetic Use of Leotier Water to Balance Skin Microflora

The present invention relates to the cosmetic use of rheotier water for maintaining the balance of skin microflora.

Human skin is a balanced system. Thousands of bacteria, viruses, fungi and acarids colonize and make up what is known as the skin microbiota or skin flora. Any alteration of the flora balance, i.e. disruption of bacterial homeostasis, causes skin diseases.

Identification of the composition of the skin microflora has been made possible by metagenomics. Thanks to this sequencing method, it was possible to perform a taxonomic classification of various bacterial species. Thus, in addition to the already known bacteria ( Staphylococcus epidermidis , Staphylococcus hominis , streptococci, propionibacteria and corynebacteria), metaphytes Genomics and other molecular techniques have revealed that skin contains more than 300 subspecies of commensal bacteria.

The distribution and composition of the skin flora varies depending on the area of the skin, mainly due to the water content and sebum content present. Furthermore, there is interindividual variation in the composition of the skin microbiota in terms of number and species of microbes.

The composition of the skin microbiota is the result of a balance between local conditions and the metabolic properties of the microorganisms. In addition to intrinsic factors such as age, gender, genetic background, and immune reactivity, climate (temperature, ambient humidity, UV light), medication (antibiotics, corticosteroids), hospitalization, type of clothing worn, lotions, creams, cleansers, External factors such as use of deodorants or antiperspirants, frequency of washing, presence of trauma, and many other factors can significantly affect the composition of the skin microbiome and affect the delicate balance of the skin microbiome.

Therefore, there is a demand for cosmetics capable of maintaining the balance of skin microflora.

)의 화장품 적용은 피부 장벽의 강화를 통해 피부 보습을 개선하는 것으로 알려져 있다.Leotier Water (

) is known to improve skin moisturization through strengthening of the skin barrier.

Summary of Invention

We have now identified new properties of Reotier water, among which we propose to use it in cosmetic applications to balance the skin microflora.

According to the present invention, the topical application of rhotier water makes it possible to maintain the balance of the skin microflora, in particular avoiding changes due to the environment. The present invention therefore relates to the cosmetic use of rheotier water as an agent intended to stabilize the skin microflora and thus maintain the quality of the skin and/or prevent or reduce skin imperfections.

Topical application of Reotier Water can be used to combat imbalances in skin microflora caused by the use of particularly aggressive skin detergents or cleansers, by exposure to ultraviolet or blue light, or by other increases in body temperature and/or sweating due to physical exercise. make it possible to prevent

Reotier water also makes it possible to limit or reduce the accumulation of squames, thereby maintaining a particularly smooth skin surface and/or contributing to a uniform and smooth appearance.

Reotier water can be used directly in the form of a mist to be sprayed on, or in any form suitable for topical application, preferably to the skin, in particular milks, creams, lotions, gels, masks, shampoos, hair care products, hair masks. , hair lotion, or in the form of a paste. Reotier water can be included in a leave-on composition, in particular a care composition, a make-up composition such as a foundation, or a sunscreen composition.

Figure 1: Shannon diversity index in the case of no treatment, at D0 and D56. Results of statistical tests of studies on taxonomic diversity of untreated skin samples at D0 and D56. The Shannon Diversity Index considers taxonomic diversity (OTU) as well as its relative abundance in a sample.
Figure 2: Diversity index (Operational Taxonomic Unit ( OTU )) with no treatment at D0 and D56. Results of statistical tests of studies on taxonomic diversity of untreated skin samples at D0 and D56.
Figure 3: At D0 and D56, rheotier Shannon Diversity Index with Water Treatment. Statistical test results of a study on the taxonomic diversity of skin samples treated with Reotier water on D0 and D56.
Figure 4: At D0 and D56, rheotier Diversity Index ( OTU ) with water treatment . Statistical test results of a study on the taxonomic diversity of skin samples treated with Reotier water on D0 and D56.
Figure 5: Shannon Diversity Index compared between one individual and two arms of the same individual at D0 and D56.
A. Correlation between areas not yet treated ("pre-active") and control areas at D0. A linear correlation was applied to the sampling at D0 between the area that remained untreated (control area) and the area subsequently treated ("pre-active").
B. Correlation between treated and untreated arms at D56. A linear correlation between treated and untreated areas was applied to sampling at D56.
Figure 6: Distance index by weighted UniFrac analysis. This figure shows the calculated distance or dissimilarity score between samples.
Figure 7: Leotier Limitation of keratin accumulation after water treatment. This figure shows the change in the amount of keratin over time. Statistics: paired student's test * p < 0.05 vs D0.
Figure 8: Absence of effect on transepidermal water loss (TEWL). This figure shows the change of TEWL over time. Statistics: paired student's test *** p < 0.01 vs D0.
Figure 9: This figure shows keratinometric analysis over time comparing subjects treated with Reotier water and untreated control subjects.

skin microflora

The cosmetic composition in particular makes it possible to stabilize the microflora and/or to maintain and/or respect the balance of the skin flora, in particular the commensal flora.

The human microbiome is defined as the group of microorganisms that live symbiotically with the human host. "Symbiotic" microorganisms do not cause disease when living in symbiosis with a host.

The term "skin microbiome", "skin microbiome" or otherwise "skin flora" refers to the bacterial, mycobacterial, fungal, parasitic and viral microorganisms present on the surface of the skin, in the secondary sebaceous and sweat glands, in the deep dermis and in the subcutaneous layer. It is intended to mean an aggregate. This term specifically includes resident flora and transient flora. The skin microflora is in particular bacteria belonging to Actinobacteria (eg Propionibacterium and Corynebacterium ), bacteria belonging to Firmicutes (eg Clostridium ) ), bacteria belonging to the Proteobacteria (such as Pseudomonas ) and Bacteriodetes , and also fungi, mites (Demodex) and viruses, this list is not limited . The relative abundance of bacterial genera varies depending on the skin area (sebaceous, wet or dry areas, the latter often showing more proteobacteria).

For the purposes of the present invention, the expression “maintaining or respecting the balance of the skin flora” means the maintenance or preservation of the existing skin flora prior to application of the cosmetic composition, or the detrimental activity against microbial strains of the commensal flora after application of the cosmetic composition. is intended to mean the absence of It also has a preventive effect against imbalances in the microflora caused, for example, by the environment, particularly high humidity levels, heat, or exposure to ultraviolet light, or exposure to blue light, as well as an increase in body temperature, often accompanied by sweating, after physical exercise. intended to mean Topical application of Reotier Water makes it possible to prevent an imbalance in the skin microflora caused by the use of particularly aggressive skin detergents or cleansers. The expression “aggressive use of a skin detergent or cleanser” is intended to refer to a particular situation in which a personal hygiene routine results in excessive use of a skin detergent or cleanser.

The term "microbiota stabilization" includes preventing an imbalance of the microflora to maintain a normal balance of the skin flora.

Leotier water

Leotier water is a natural water of deep origin with a constant physicochemical composition. The fountain of Leotier is located at an altitude of about 910 m in the municipality of Leotier, Hautes-Alpes, France. Water from a nearby hot spring seeps into the soil and rises again, rich in minerals. The certain composition of Reotier water is listed in the table below.

Table 1

Reotier water is therefore characterized by a high mineral content, especially calcium, sodium, magnesium and strontium.

herbal preparations ( Galenic formulation)

Reotier water can be applied in mist form (which can typically be sprayed via a mist or vaporizer), but can also optionally be used as a cosmetically acceptable excipient and/or as a mixture with active ingredients, suitable for topical or dermal application in herbal medicines. (galenic) form can also be applied.

The cosmetic composition thus formulated may typically contain 1% to 100% by weight of rheotier water. For example, it is a mist containing 100% rheotier water, or 1% to 95%, preferably 1% to 90%, preferably 1% to 80%, more preferably 1% to 70% , 1% to 60%, 1% to 50%, 1% to 40%, 1% to 30%, 1% to 20%, 1% to 10%, or 1% to 5% by weight of Reotier water It may be a composition that In one preferred embodiment, the galenic composition comprises 100% by weight of rheotier water.

Accordingly, solid, liquid or semi-solid formulations such as creams, milks, balms, foams, lotions, serums, gels or cream gels, shampoos, care products, masks or hair lotions may be used. Thus, rheotier water can be formulated in the form of oil-in-water or water-in-oil emulsions, multiple emulsions, aqueous, aqueous-alcoholic or aqueous-glycolic acid solutions or aqueous dispersions. Reotier water is a variety of products for skin care and/or skin makeup, such as moisturizing care products or foundations, or various products for skin cleansing, such as lotions, gels or milks for removing makeup and masks, or else especially shampoos and conditioners. It can be included in hair care and / or hair-washing products such as.

In one specific embodiment, the cosmetic composition is in the form of an aqueous gel or oil-in-water emulsion.

The aqueous phase then contains rheotier water and optionally deionized water and/or at least one component selected from polyols and aqueous gelling agents. Water advantageously comprises between 30% and 95%, preferably between 30% and 90%, of the total weight of the composition. The polyol may be selected especially from glycerol, propylene glycol, butylene glycol, pentylene glycol and mixtures thereof, and may represent between 5% and 30% of the total weight of the composition.

In one specific embodiment, the cosmetic composition is a gel comprising 30% to 95% by weight of rheotier water.

The term “aqueous gelling agent” means a high molecular compound capable of being hydrated to immobilize water molecules and thus increasing the viscosity of the aqueous phase. Such gelling agents may be selected from: polysaccharides such as cellulose and its derivatives, modified starch, carrageenan, agar-agar, xanthan gum and plant gums such as guar gum or locust bean gum; synthetic polymers and in particular copolymers of 2-acrylamido-2-methylpropanesulfonic acid (AMPS) with vinylpyrrolidone, optionally crosslinked sodium acrylate homopolymers, and also acrylic copolymers, especially sodium acrylate and derivatives thereof, and /or copolymers of alkyl (meth)acrylates and/or hydroxylalkyl (meth)acrylates and/or (polyethoxy)alkyl (meth)acrylates, optionally with at least one other monomer, advantageously 2- copolymers with acrylamido-2-methylpropanesulfonic acid (AMPS), these copolymers being optionally crosslinked; and mixtures thereof.

If present, the fatty phase may include one or more volatile and/or non-volatile oils. Examples of volatile oils are branched alkanes, such as isododecane, and linear alkanes, such as C ₁₀ -C ₁₃ . As non-volatile oils, mention may be made in particular of:

- esters of acids with monoalcohols, selected from: mono of saturated linear C ₂ -C ₁₀ (preferably C ₆ -C ₁₀ ) acids and saturated linear C ₁₀ -C ₁₈ (preferably C ₁₀ -C ₁₄ ) monoalcohols esters and polyesters; monoesters and polyesters of saturated linear C ₁₀ -C ₂₀ acids with branched or unsaturated C ₃ -C ₂₀ (preferably C ₃ -C ₁₀ ) monoalcohols; monoesters and polyesters of branched or unsaturated C ₅ -C ₂₀ acids with branched or unsaturated C ₅ -C ₂₀ monoalcohols; monoesters and polyesters of branched or unsaturated C ₅ -C ₂₀ acids with linear C ₂ -C ₄ monoalcohols;

- triglycerides of C ₆ -C ₁₂ fatty acids, such as caprylic and capric triglycerides and triheptanoin;

- branched and/or unsaturated C ₁₀ -C ₂₀ fatty acids (such as linoleic acid, lauric acid and myristic acid);

- branched and/or unsaturated C ₁₀ -C ₂₀ fatty alcohols (eg octyldodecanol and oleyl alcohol);

- hydrocarbons such as squalane (C30), especially vegetable squalane derived from olive oil, and hemisqualane (C15);

- dialkyl carbonates such as dicaprylyl carbonate and diethylhexyl carbonate;

- dialkyl ethers such as dicaprylyl ether; and

- mixtures thereof.

Plant oils containing one or more of the above-mentioned constituents may also be mentioned.

Esters of acids with monoalcohols, in particular monoesters such as coco caprate and mixtures of caprylates, ethyl macadamiaate, shea butter ethyl ester, isostearyl isostearate, isononyl isononanoate, ethylhexyl isono Nanoate, Hexyl Neopentanoate, Ethylhexyl Neopentanoate, Isostearyl Neopentanoate, Isodecyl Neopentanoate, Isopropyl Myristate, Octyldodecyl Myristate, Isopropyl Palmitate, Ethylhexyl Palmyate tate, hexyl laurate, isoamyl laurate, cetostearyl nonanoate, propylheptyl caprylate, and mixtures thereof. Other esters that may be used are diesters of acids with monoalcohols such as diisopropyl adipate, diethylhexyl adipate, diisopropyl sebacate and diisoamyl sebacate.

Examples of plant oils include, among others, wheat germ oil, sunflower oil, argan oil, hibiscus oil, coriander oil, grapeseed oil, sesame oil, corn oil, apricot oil, castor oil, shea oil, avocado oil, olive oil, soybean oil, Sweet Almond Oil, Palm Oil, Rapeseed Oil, Cottonseed Oil, Hazelnut Oil, Macadamia Oil, Jojoba Oil, Alfalfa Oil, Poppy Seed Oil, Pumpkin Seed Oil, Marrow Oil, Blackcurrant Oil, Evening Primrose Oil, Lavender Oil, Borage oil, millet oil, barley oil, quinoa oil, rye oil, safflower oil, candlenut oil, passionflower oil, rose musk oil, echium oil, camelina oil or camellia oil.

The fatty phase may also contain at least one fatty-phase structuring agent. The term "fatty structuring agent" is intended to mean a compound capable of thickening the oil contained in the composition, in particular selected from waxes, fatty gelling agents and pasty fatty substances, and also mixtures thereof.

The composition may also contain various ingredients that can be dispersed in the fatty and/or aqueous phase of the emulsion, provided that the ingredients are compatible with topical application to the skin or any other keratin materials.

It may thus contain at least one oil-in-water or water-in-oil emulsifier, which is generally nonionic, such as polyoxyethylene esters, optionally polyethoxylated sorbitan esters, optionally polyethoxylated fatty acids and glycerol. esters, ethers of fatty alcohols and sugars such as alkyl glucosides, and mixtures thereof. The emulsifier may represent 2% to 10%, preferably 4% to 6%, of the total weight of the composition.

The composition may also include organic and/or inorganic photoprotective agents active in particular in blue light and/or UVA and/or UVB; film-forming polymers based on polysaccharides, capable of forming antifouling protective films, such as those sold by Solabia under the tradenames Pollustop ^® and Solashield ^® ; exfoliants such as α- and β-hydroxy acids; exfoliating particles; perfume; antioxidants; sequestering agent; pH adjusting agent; preservatives; pigment; dyes; and mixtures thereof.

cosmetic application

The composition used according to the invention is applied to the skin, including the scalp (particularly the face but also any part of the body).

The composition can be applied to the target area more than once a day, eg morning and/or evening.

The target site is healthy and the subject does not suffer from a dermatological disorder at least at the target site.

The examples and drawings illustrate the present invention without limiting its scope.

Example

Example 1 (reference): change in bacterial diversity over time (α-diversity)

To confirm that changes in bacterial diversity actually occur in the skin microbiota, an analysis of the bacterial community present in 122 skin samples (from individuals without dermatological disorders) taken from the forearm was performed.

This study is based on 16S profiling of targeted metagenomics and through demonstration of groups of sequences or operational taxonomic units (OTUs).

Seventeen different genus bacteria have been identified ( Actinomyces , Bacillus , Candidatus Koribacter ), Clostridium , Escherichia , Geobacter , Haloferax , Marinobacter , Methanobrevibacter , Novoshingobium , Pedobacter , Propionibacterium , Pseudomonas , Roseaobacter , Staphylococcus , Streptococcus , Sulfurimonas , most represented The genera are Clostridium, Candidaus ringibacter and Marinobacter).

An operational taxonomic unit (OTU) is an operational definition used to group together phylogenetically close individuals.

This study made it possible to obtain a taxonomic profile of the bacterial populations identified within the various samples. These data were used to represent diversity indices as a function of group.

This analysis is based on the study of two indicators that can assess changes in bacterial diversity over time:

- The Shannon index is a quantitative measure that reflects the number of different types (OTUs) present in a cluster and at the same time considers the uniform distribution of the underlying entities among these types.

- The "observed OTU" index corresponds to the count of the various OTUs detected per sample.

Statistical analysis performed with the findings of the taxonomic profile of bacterial populations showed changes in bacterial diversity over time.

On the other hand, the statistical results related to the Shannon index are shown in FIG. This index is based on bacterial richness (number of different bacterial species) and relative abundance of these species. The results shown in Figure 1 show a significant increase in microbial diversity between D0 and D56 in the area not treated with Reotier water (paired Wilcoxon test * p = 0.0414).

On the other hand, analysis of bacterial diversity using the "observed OTUs" index was also performed. Through the graph of FIG. 2, it can be seen that the native microbial diversity (number of OTUs) significantly increased between D0 and D56 in the area not treated with Reotier water (paired Wilcoxon test ** p = 0.0017) ( Fig. 2).

Example 2: Leotier water Changes in bacterial diversity after treatment

To test the effect of Reotier Water on bacterial diversity, the same sample protocol as mentioned in Example 1 was followed, but this time skin samples were treated with Reotier Water. Comparison of microbial diversity between D0 and D56 demonstrates the effectiveness of Reotier water.

Meanwhile, statistical results related to the Shannon index are shown in FIG. 3 . These results show that the difference in diversity at D0 and D56 is not significant when the region is treated with rheotier water (paired Wilcoxon test p = 0.4446). In conclusion, these results show that the increase in microbial diversity observed in the untreated area (FIG. 1) is limited in the area treated with Reotier water (FIG. 3).

Meanwhile, the statistical results related to the "observed OTU" diversity index are shown in FIG. 4 . These results confirm that the Leotier water treatment induces a much smaller increase in microbial diversity between D0 and D56 (paired Wilcoxon test p = 0.0436).

These two results make it possible to argue that rheotier water affects the stabilization of skin microflora by limiting changes in bacterial diversity.

Example 3: Correlation between treated and untreated arms over time

In order to confirm that Reotier Water actually affects the stabilization of skin microflora, a study on the correlation between the arm treated with Reotier Water and the untreated arm of each individual was conducted at D0 and D56 by considering the Shannon Diversity Index. was performed in To this end, between regions left untreated on D0 (control regions) and regions to be subsequently treated (marked as “pre-active”), and between regions treated on D56 (treated arms) ) and a linear correlation between the untreated area (untreated arm) was applied to the sample specimen.

From the results shown in Figure 5A, it can be seen that the bacterial diversity of one volunteer and both arms of the same volunteer is indeed correlated on D0 (between the area to be treated ("pre-active") and the control area). The calculated correlation index corresponds to the value R = 0.72. Nevertheless, after application of Rhetier water to the “pre-active” area for 56 days, the calculated correlation index between the two arms, treated and untreated, is R = 0.39, i.e., that calculated at DO smaller than Thus, the existing correlation between the two arms at D0 decreases at D56 (Fig. 5B).

The inverse correlation between the treated and untreated arms is probably due to the stabilization of the skin microflora by Reotier water. Indeed, alpha diversity (Shannon index) significantly increased at D56 vs. D0 in the control arm, whereas it remained more stable in the arm treated with Reotier water.

Example 4: Dissimilarity between microbial communities (β-diversity)

β-diversity consists of the distance or dissimilarity between the microbial communities of different samples. One method in particular was used to determine this dissimilarity; This is a weighted UniFrac phylogenetic method. This method takes into account species identity and their abundance and accounts for differences in microbial composition between different samples.

Statistical studies based on UniFrac weighted phylogenetic analysis made it possible to demonstrate inter-individual and intra-individual variability.

The results of this analysis, presented in Figure 6, made it possible to show that the interindividual variability always remains greater than the variability between the arms of one individual and the same individual.

Thus, the composition of the microbiota is different for each individual and is relatively similar between two identical regions of an individual and the same individual.

After 56 days of treatment, it is possible to note that the dissimilarity (UniFrac distance index) between the two arms of one individual and the same individual is significantly higher at D56 than at D0 (*p = 0.049), which is significantly higher at D56 than at D0. reflects a larger difference in composition in These results confirm the effect of rheotier water on stabilization of the skin microflora and its composition, while the microbial diversity of the untreated arm increases and its composition varies.

Example 5: Leotier water Limitation of keratin accumulation after treatment

The effect of Reotier Water on the change in the relative surface area of keratin was also studied by comparison between areas not treated with Reotier Water and areas treated with Reotier Water at D28 and D56. The results of this analysis are shown in Figure 7 and Table 2.

Table 2

These results show a 20% reduction in keratin accumulation in areas treated with Reotier Water compared to untreated areas at D28. This reduction becomes more pronounced over time as the increase in the number of dead skin cells is reduced by 51% in areas treated with Reotier Water compared to untreated areas at D56.

The reduction of keratin makes it possible to obtain a better surface uniformity, resulting in less rough and smooth skin. Reotier water thus makes it possible to restore or maintain the quality of the skin thanks to its action on the reduction of keratin accumulation.

Example 6 (Reference): No effect on moisturizing under the same conditions

The effect of Reotier water on skin moisturization was evaluated in parallel with the studies conducted in the above examples. It should be noted that all these studies were conducted in summer conditions with subjects residing in the south of France.

Two moisturizing criteria were evaluated: on the one hand, transepidermal water loss (TEWL) and, on the other hand, keratin measurement.

TEWL proves the condition of the skin barrier. As the barrier is damaged, TEWL increases. As shown in Figure 8, the condition of the skin barrier appeared to be intact throughout the study, and the TEWL values were considered normal.

Keratin measurement measures the degree of moisturization of the superficial layer of the skin. As shown in FIG. 9, the degree of moisturization only slightly changed over time and did not change significantly in the two areas. This change also remains in the same order as the variability in DO between the two domains. Treatment does not induce significant differences from control regions at D28 and D56.

this is Leotier water It shows that the effect on the maintenance of skin microflora and the restriction of keratin is separate from the effect on skin moisturization.

Claims (21)

Leotier Water (

A cosmetic method for maintaining the balance of skin microbiota, comprising applying to the skin a cosmetic composition comprising or consisting of ). The method of claim 1, wherein the cosmetic composition comprises 1% to 100% by weight of Reotier water. The method of claim 2, wherein the cosmetic composition comprises 30% by weight to 100% by weight of Reotier water. 4. The method according to any one of claims 1 to 3, wherein the composition is applied in the form of a mist. 5. The method of claim 4, wherein the composition is a mist composed of 100% rheotier water. 6. The method of claim 5 comprising applying the cosmetic composition to the skin of the face. 7. The method of claim 6 comprising topically applying the cosmetic composition to an area of the body. 8. The method of claim 7 comprising applying the cosmetic composition to the scalp. 9. A method according to any one of claims 1 to 8 for limiting or reducing the accumulation of squames by application to the skin. 10. The method according to any one of claims 1 to 9, for maintaining a smooth skin surface and/or contributing to a smooth and/or uniform appearance of the skin. Cosmetic use of rheotier water as an agent for stabilizing skin microflora. 12. Cosmetic use of rheotier water according to claim 11, for restoring or maintaining the quality of the skin and/or for preventing or reducing skin imperfections. 13. Cosmetic use of rheotier water according to any one of claims 11 and 12, for preventing an imbalance of skin microflora due to the use of aggressive skin detergents or cleansers. 13. The cosmetic use of rheotier water according to claims 11 and 12, for preventing an imbalance of skin microflora caused by the environment. The cosmetic use of Reotier water according to claim 14, which is for preventing an imbalance of skin microflora due to exposure to ultraviolet rays or blue light. Reotier according to any one of claims 11 and 12, or 14 and 15, for preventing an imbalance in skin microflora due to an increase in body temperature and/or sweating due to physical exercise. Water for cosmetic use. Cosmetic use of Reotier Water to limit or reduce the build-up of dead skin cells when applied to the skin. The cosmetic use of rheotier water to maintain a smooth skin surface and/or contribute to a smooth and/or even appearance of the skin. 19. The use according to claim 17 or 18, by applying a cosmetic composition comprising or consisting of rheotier water to the skin of the face. 19. The use according to claim 17 or 18, by applying a cosmetic composition comprising or consisting of rheotier water to a body part. The use according to claim 17 or 18, by applying a cosmetic composition comprising or consisting of rheotier water to the scalp.

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