WO2024049114A1 - Topical skin composition containing 1,3-propanediol as active ingredient for maintaining microbiome balance in skin - Google Patents

Abstract

The present disclosure relates to a topical skin composition containing 1,3-propanediol as an active ingredient and optionally a boosting ingredient for maintaining microbiome balance in the skin. The composition can be formulated as a cosmetic composition or a pharmaceutical composition for application to the skin. The topical skin composition according to this disclosure promotes the growth of beneficial skin microbes and inhibits the growth of harmful skin microbes to maintain the balance of the skin microbiome, whereby the composition can improve and strengthen the barrier function of the skin against external irritants, tighten skin tissues, improve skin texture, and help maintain overall skin health.

Description

A skin external composition for maintaining the skin's microbiome balance containing 1,3-propanediol as an active ingredient

Cross-reference to related applications

This disclosure claims priority to Patent Application No. 10-2022-0110525 filed on September 1, 2022 and Patent Application No. 10-2023-0111037 filed on August 24, 2023. The entire contents of each are incorporated herein by reference into this disclosure.

Technology field

The present disclosure relates to an external skin composition, preferably a cosmetic composition, for maintaining the microbiome balance of the skin, containing 1,3-propanediol as an active ingredient.

Microbiome is a compound word of microbiota and genome. It can be said to be a microbial community that includes microorganisms that live or coexist in all environments, including humans, animals and plants, soil, sea, lakes, rocks, and the atmosphere, and their entire genetic information. , Recently, it also refers to microbial communities in various environments. In addition, research is being conducted on various microbiomes, including plant microbiome, animal microbiome, environmental microbiome, human microbiome, intestinal microbiome, and skin microbiome, and among these, human microbiome. The most research is in progress.

The human body is a complex and active ecosystem, and various microorganisms exist in the human stomach and skin. In the stomach and skin, 500 to more than 1,000 different types of microorganisms coexist, forming a microbial flora.

Microorganisms present on the skin surface affect physiological functions such as human growth, nutrition, immunity, and resistance to pathogens, and play a role in blocking the invasion of external microorganisms, especially pathogenic microorganisms.

However, the microorganisms present on the skin include not only beneficial skin bacteria but also harmful bacteria, so for skin health, it is necessary to maintain the balance of the skin microbiome by promoting the growth of beneficial bacteria while suppressing the growth of harmful bacteria.

The problem that the present disclosure seeks to solve is to provide a cosmetic composition that can maintain the microbiome balance of the skin by increasing beneficial bacteria in the skin and reducing harmful bacteria.

In one aspect, the present disclosure provides a skin external composition and a cosmetic composition for maintaining the microbiome balance of the skin, including 1,3-propanediol as an active ingredient.

In the present disclosure, maintaining microbiome balance may mean increasing beneficial bacteria in the skin and reducing harmful bacteria.

In the present disclosure, the beneficial bacteria include Staphylococcus epidermidis , Streptococcus pneumoniae, Lactobacillus acidophilus , Lactobacillus rhamnosus , and Bifidobacterium. One or more species selected from the group consisting of Bifidobacterium bifidum , and the harmful bacteria may be one or more species selected from the group consisting of Staphylococcus aureus and Cutibacterium acnes .

The effective concentration of 1,3-propanediol in the cosmetic composition according to the present disclosure may be 0.1 to 20% by weight, preferably 0.2 to 10% by weight, based on the total weight of the cosmetic composition.

In another aspect, the present disclosure provides a cosmetic composition for maintaining microbiome balance in the skin comprising 1,3-propanediol and optionally a boosting ingredient.

In the present disclosure, the boosting ingredient may be at least one selected from fructan and yeast extract.

In the present disclosure, the effective concentration of the boosting ingredient may be 0.06 to 0.25% by weight, preferably 0.09 to 0.12% by weight, based on the total weight of the cosmetic composition.

In the present disclosure, the combination ratio of 1,3-propanediol and boosting component may be 6 to 25:1, preferably 12.5 to 16.7:1, by weight.

In the present disclosure, the cosmetic composition includes a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing agent, oil, microcapsule, microgranule, ionic vesicle dispersant, non-ionic vesicle dispersant, It may be formulated in a form selected from the group consisting of powder foundation, emulsion foundation, wax foundation, stick, mask pack, and spray.

In another aspect, the present disclosure provides topical application of a skin external composition, particularly a cosmetic composition, comprising 1,3-propanediol or a combination of 1,3-propanediol and a boosting ingredient as an active ingredient to the skin. This provides a way to maintain or restore the skin's microbiome balance.

In another aspect, the present disclosure is an active ingredient for use in maintaining the microbiome balance of the skin in an external skin composition, especially a cosmetic composition, comprising 1,3-propanediol or 1,3-propanediol and a boosting ingredient. Provides the use of the combination.

The present disclosure can provide a skin external composition that is beneficial to skin health by maintaining and/or restoring the microbiome balance of the skin by increasing beneficial bacteria on the skin while suppressing the proliferation and/or activity of harmful bacteria on the skin.

In addition, the skin external composition according to the present disclosure includes 1,3-propanediol as an active ingredient, thereby promoting the growth of beneficial skin bacteria and inhibiting the growth of harmful skin bacteria to maintain the balance of the skin microbiome, thereby maintaining the skin's health. It has high utility value as it can improve and strengthen the barrier function against external irritants. It can help tighten skin tissue, improve skin texture, maintain overall skin health, and improve the user's confidence in their skin. It has the advantage of contributing to quality of life.

Figures 1A to 1J show the results of analyzing the effect of 1,3-propanediol on the growth of the skin-beneficial bacterium Staphylococcus epidermidis ATCC 12228. Figures 1A to 1J show the growth trend through the change in absorbance (OD) value according to the incubation time of beneficial skin bacteria compared to the control group at each treatment concentration of 1,3-propanediol: Figure 1A: 1,3-propanediol treatment concentration 0.05 %; Figure 1B: 1,3-propanediol treatment concentration 0.1%; Figure 1c 1,3-propanediol treatment concentration 0.2%; Figure 1D: 1,3-propanediol treatment concentration 0.5%; Figure 1E: 1,3-propanediol treatment concentration 1.0%; Figure 1f: 1,3-propanediol treatment concentration 3.0%; Figure 1g: 1,3-propanediol treatment concentration 5.0%; Figure 1h: 1,3-propanediol treatment concentration 10.0%; Figure 1I: 1,3-propanediol treatment concentration 20.0%; Figure 1j: 1,3-propanediol treatment concentration 25.0%.

Figures 2a to 2j show the results of analyzing the effect of 1,3-propanediol on the growth of Staphylococcus aureus ATCC 6538, a skin-harmful bacterium. Figures 2a to 2j show the growth trend through the change in absorbance (OD) value according to the incubation time of harmful skin bacteria compared to the control group at each treatment concentration of 1,3-propanediol: Figure 2a: 1,3-propanediol treatment concentration 0.05 %; Figure 2b: 1,3-propanediol treatment concentration 0.1%; Figure 2c 1,3-propanediol treatment concentration 0.2%; Figure 2d: 1,3-propanediol treatment concentration 0.5%; Figure 2e: 1,3-propanediol treatment concentration 1.0%; Figure 2f: 1,3-propanediol treatment concentration 3.0%; Figure 2g: 1,3-propanediol treatment concentration 5.0%; Figure 2h: 1,3-propanediol treatment concentration 10.0%; Figure 2I: 1,3-propanediol treatment concentration 20.0%; Figure 2j: 1,3-propanediol treatment concentration 25.0%.

Figure 3 shows the results of analyzing the effect of 1,3-propanediol on the growth of beneficial and harmful bacteria during co-culture. Figure 3a is a graph showing the CFU/g value of microorganisms converted to a log value according to the 1,3-propanediol treatment concentration of the skin-beneficial bacteria Staphylococcus epidermidis ATCC 12228, and Figure 3b is a graph showing the 1,3- of the skin-harmful bacteria Staphylococcus aureus ATCC 6538. This is a graph showing the CFU/g value of microorganisms according to propanediol treatment concentration converted to log value.

Figure 4 shows harmful bacteria of diol-based compounds, specifically 1,3-Propanediol, 2-Methyl-1,3-propanediol, 1,3-Butanediol, 2,3-Butanediol, 1,2-Pentanediol, and 1,2-Hexanediol. It shows the results of a comparative analysis of the effect on the growth of (top graph of the figure) and beneficial bacteria (bottom graph of the figure). Figure 4a: 1,3-Propanediol, Figure 4b: 2-Methyl-1,3-propanediol; Figure 4c: 1,3-Butanediol; Figure 4d: 2,3-Butanediol; Figure 4e: 1,2-Pentanediol; Figure 4f: 1,2-Hexanediol.

Figure 5 is a graph showing the effect on the growth of beneficial and harmful bacteria on the skin when combined treatment with 1,3-propanediol and fructan compared to treatment with fructan alone. Left: Change in OD value according to incubation time of Staphylococcus aureus after treatment of each sample; right: Change in OD value according to incubation time of Staphylococcus epidermidis after treatment of each sample.

Figure 6 is a graph showing the effect on the growth of beneficial and harmful bacteria on the skin when combined treatment with 1,3-propanediol and yeast extract compared to treatment with yeast extract alone. Left: Change in OD value according to incubation time of Staphylococcus aureus after treatment of each sample; right: Change in OD value according to incubation time of Staphylococcus epidermidis after treatment of each sample.

Hereinafter, embodiments of the present disclosure will be described in detail with reference to the attached drawings so that those skilled in the art can easily practice the present disclosure. However, the present disclosure may be implemented in many different embodiments and is not limited to the embodiments described herein. Throughout the specification, similar parts are given the same reference numerals.

In addition, when similar expressions such as "about", "approximately", or at least are used in relation to a numerical value in the present disclosure, ±10%, ±7% based on the numerical value. %, ±5%, ±3%, ±2%, or ±1% theoretical, experimental, statistical, or rule of thumb error is intended to be permitted.

In one aspect, the present disclosure provides a composition for topical skin application for maintaining the microbiome balance of the skin, including 1,3-propanediol as an active ingredient.

In the present disclosure, the term 'propanediol' refers to a C3 compound in which two hydroxyl groups (-OH) are linked to a saturated hydrocarbon that forms a chain with a single bond between carbons, and is either 1,2- or 1,3- depending on the position of the hydroxyl group. It has two isomers.

1,3-propanediol used in the present disclosure is used as a moisturizing ingredient in cosmetics and pharmaceuticals, and is also used to a limited extent as a food additive. It contains a hydrophilic hydroxyl group and a hydrophobic carbon chain, making it amphipathic, and easily destroys the cell membrane of microorganisms. It can penetrate and has excellent antibacterial properties.

The term “microbiome” used in this disclosure refers to a community of various microorganisms, such as bacteria and viruses, living in the human body. Additionally, in the present disclosure, “microbiome” may be “skin microbiome,” and the skin microbiome refers to microorganisms that typically live on human skin.

In the present disclosure, “maintaining the microbiome balance of the skin” refers to relatively increasing (or enhancing) the proliferation and/or activity of beneficial bacteria on the skin in order to maintain a healthy skin condition in an individual, while the proliferation and/or enhancement of harmful bacteria on the skin /or means maintaining the appropriate balance of the skin's microbial community by relatively reducing (or suppressing) its activity.

In the present disclosure, “increasing beneficial skin bacteria” means relatively promoting engraftment and/or proliferation of beneficial bacteria that reside on the skin or can be introduced from outside and/or relatively activating the growth of beneficial bacteria.

In the present disclosure, “reducing harmful bacteria on the skin” means maintaining the microbial balance of the skin by relatively suppressing the engraftment and/or proliferation of harmful bacteria that reside on the skin or can be introduced from outside and/or relatively inhibiting the growth of harmful bacteria. do.

In the present disclosure, the term “relatively” refers to any environment or condition (e.g., temperature, humidity, light, ultraviolet rays, etc.), skin condition (e.g., skin condition) involved in maintaining the overall balance of the skin microbiome. A healthy state without skin problems, a state in which skin problems occur or are at risk of occurring, a state in which the balance of beneficial and/or harmful bacteria is stable or broken (e.g., due to excessive proliferation and/or death of beneficial and/or harmful bacteria, etc.), This means that the interaction between skin microorganisms and/or introduced bacteria, the substance(s) applied to the skin, and the results caused by the above(s) act favorably on skin beneficial bacteria and unfavorable on skin harmful bacteria. .

In the present disclosure, the beneficial bacteria may be one or more selected from the group consisting of Staphylococcus epidermidis, Streptococcus pneumoniae, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Bifidobacterium bifidum, and specifically, may be Staphylococcus epidermidis, and more specifically may be Staphylococcus epidermidis ATCC 12228.

For example, Staphylococcus epidermidis is a Gram-positive bacterium that is generally present on the skin and mucous membranes of humans and livestock. It produces glycerin to maintain the skin's moisturizing effect, synthesizes organic acids to keep the skin acidic, and contains antibiotics. It can suppress the growth of harmful bacteria such as Staphylococcus aureus.

In the present disclosure, the harmful bacteria may be one or more species selected from the group consisting of Staphylococcus aureus and Cutibacterium acnes, and may specifically be Staphylococcus aureus, and more specifically, Staphylococcus aureus. It could be Us ATCC 6538.

For example, Staphylococcus aureus is a Gram-positive facultative anaerobic bacterium that exists on the skin and nasal surfaces of healthy humans and livestock and is known to cause not only food poisoning but also purulent diseases such as skin suppuration, otitis media, and cystitis.

In the present disclosure, the cosmetic composition may contain 0.1 to 20% by weight of 1,3-propanediol, specifically 1 to 20% by weight, and more specifically 5 to 20% by weight.

If the content of 1,3-propanediol is less than 0.1% by weight, it cannot promote the growth of beneficial bacteria, cannot maintain the skin's microbiome balance, and ultimately does not show the effect of improving skin condition. 20% by weight If it exceeds %, there is a problem that the microbiome balance of the skin is broken by suppressing the activity of both harmful and beneficial bacteria.

In the present disclosure, the composition for external application for skin is 0.5 to 10% by weight to relatively increase the growth of skin beneficial bacteria and relatively inhibit the growth of skin beneficial bacteria without drastically changing the engraftment, proliferation, death, etc. of beneficial skin bacteria and harmful bacteria. It may contain 1,3-propanediol.

In another aspect, the present disclosure provides a composition for topical skin application for maintaining the microbiome balance of the skin, including 1,3-propanediol as an active ingredient and optionally a boosting ingredient.

In the present disclosure, the boosting ingredient may be at least one selected from fructan and yeast extract.

Fructan is a polymer composed of fructose (fructose), and fructan with a short chain is known as fructooligosaccharide. Fructans can be found in angiosperms, including monocots and dicots such as agave, artichoke, asparagus, chives, garlic, onions (including green onions), yacon, soybean potatoes, barley, and wheat. It is known to help moisturize the skin and enhance skin elasticity, and is registered as CAS No.9046-37-1 or 639001-44-8.

In the present disclosure, the fructan may be extracted and isolated from natural raw materials such as plants known to contain fructan, or may be used as a commercially available material.

In the present disclosure, the yeast extract refers to an extract obtained by extracting yeast with a solvent, a fraction obtainable by hydrolyzing yeast cells, a culture medium of yeast in which yeast and a culture coexist, an extract extracted from the above-mentioned fraction or culture medium, and the above-mentioned fraction. Alternatively, it may encompass a filtrate obtained by filtering yeast from a culture medium, a diluted solution or dried product of the above-mentioned fraction or extract, etc. For example, yeast extract may be a fraction obtained by extracting yeast with a pharmaceutically acceptable organic solvent, or by hydrolyzing yeast cells using an enzyme and then separating them with a solvent.

In the present disclosure, the yeast extract may be a beer-derived yeast extract. Beer-derived yeast extract has CAS No. The one listed as 84604-16-0 can be used.

In the present disclosure, the effective concentration of the boosting ingredient may be 0.06 to 0.25% by weight, preferably 0.09 to 0.12% by weight, based on the total weight of the cosmetic composition.

If the content of the boosting ingredient is less than 0.06% by weight, it cannot promote the growth of beneficial bacteria, cannot maintain the skin's microbiome balance, and ultimately does not show the effect of improving skin condition, and if it exceeds 0.25% by weight, it cannot maintain the skin's microbiome balance. , there is a problem that the microbiome balance of the skin is broken by suppressing the activity of both harmful and beneficial bacteria.

In particular, when used in combination with 1,3-propanediol, using a boosting ingredient in an amount of 0.09 to 0.12% by weight can relatively increase the growth of beneficial skin bacteria without drastically changing the engraftment, proliferation, and death of skin beneficial and harmful bacteria. This can be advantageous because it can relatively reduce the growth of skin beneficial bacteria by increasing it.

In the skin external composition according to the present disclosure, the combination ratio of 1,3-propanediol and boosting component may be 6 to 25:1, preferably 12.5 to 16.7:1, based on weight.

In the present disclosure, the composition for topical skin application may be formulated as a cosmetic composition or pharmaceutical composition in a form applicable to the skin.

In the present disclosure, the cosmetic composition can be prepared in liquid or solid form using bases, auxiliaries, and additives commonly used in the cosmetics field. Cosmetics in liquid or solid form may include, for example, lotions, creams, lotions, bath additives, etc., but are not limited thereto. Bases, auxiliaries and additives commonly used in the cosmetics field are not particularly limited and include, for example, water, alcohol, propylene glycol, stearic acid, glycerol, cetyl alcohol, liquid paraffin, etc.

The cosmetic composition of the present disclosure may include ingredients commonly used in cosmetic compositions, such as antioxidants, stabilizers, solubilizers, vitamins, conventional auxiliaries such as pigments and fragrances, and carriers.

The cosmetic composition in the present disclosure can be prepared in any formulation commonly prepared in the art, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing, It can be formulated as oil, microcapsule, microgranule, ionic vesicle dispersant, non-ionic vesicle dispersant, powder foundation, emulsion foundation, wax foundation, stick, mask pack, and spray, but is not limited thereto. More specifically, it can be manufactured in the form of softening lotion, nourishing lotion, nourishing cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray, or powder.

In the present disclosure, when the formulation of the cosmetic composition is a paste, cream, or gel, the carrier ingredient may include animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, or zinc oxide. This can be used.

In the present disclosure, when the formulation of the cosmetic composition is powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder can be used as the carrier ingredient. In particular, in the case of spray, chlorofluorohydride may be additionally used. May contain propellants such as carbon, propane/butane or dimethyl ether.

In the present disclosure, when the formulation of the cosmetic composition is a solution or emulsion, a solvent, solubilizing agent, or emulsifying agent may be used as a carrier component, for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, and benzyl. Benzoate, glycerol aliphatic ester, polyethylene glycol, or sorbitan fatty acid ester may be used.

In the present disclosure, when the formulation of the cosmetic composition is a suspension, the carrier ingredients include water, a liquid diluent such as ethanol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, and microcrystals. Cellulose, aluminum metahydroxide, bentonite, agar, or tracant may be used.

In the present disclosure, when the formulation of the cosmetic composition is a surfactant-containing cleansing agent, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, imidazolinium derivative, methyl taurate, sarcosinate, and fatty acid amide ether are used as carrier ingredients. Sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, or ethoxylated glycerol fatty acid esters may be used.

The cosmetic composition in the present disclosure may be used alone or in multiple applications, or may be used in multiple applications with other cosmetic compositions other than the present disclosure. Additionally, the cosmetic composition of the present disclosure can be used according to conventional usage methods, and the number of uses can vary depending on the user's skin condition or preference.

In the present disclosure, when the cosmetic composition is a soap, a surfactant-containing cleansing formulation, or a surfactant-free cleansing formulation, it may be applied to the skin and then wiped off, removed, or washed with water. For example, soaps include liquid soap, powdered soap, solid soap, and oil soap; cleansing formulations containing surfactants include cleansing foam, cleansing water, cleansing towels, and cleansing packs; cleansing formulations that do not contain surfactants include cleansing cream, cleansing lotion, These include cleansing water and cleansing gel, but are not limited thereto.

In the present disclosure, the pharmaceutical composition applicable to the skin may further include a pharmaceutically acceptable carrier, excipient, or diluent, if necessary, in addition to the above-mentioned active ingredient and boosting ingredient. The pharmaceutically acceptable carrier, excipient or diluent is not limited as long as it can achieve the effect of the composition according to the present disclosure, and includes, for example, fillers, extenders, binders, wetting agents, disintegrants, surfactants, lubricants, sweeteners. , fragrances, preservatives, etc.

Representative examples of the pharmaceutically acceptable carriers, excipients or diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, maltitol, starch, gelatin, glycerin, gum acacia, alginate, calcium phosphate, calcium carbonate. , calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, propylene glycol, polyethylene glycol, vegetable oil. , injectable esters, Wethepsol, Macrogol, Tween 61, Cacao, Lauridge, etc., but are not particularly limited thereto.

The pharmaceutical composition of the present invention can be manufactured as a normal quasi-drug. Examples of such quasi-drugs include, but are not limited to, solutions, powders, ointments, lotions, wet tissues, sprays, bands or patches, and the formulation method, dosage, usage method, and components of the quasi-drugs are as per It can be appropriately selected by a person skilled in the art from conventional techniques known in the technical field.

The pharmaceutical composition of the present disclosure may additionally include one or more active ingredients that may exhibit the same or similar functions as the above-mentioned active ingredients. The added active ingredient can be selected taking into account synergy effect due to combined use, skin safety, ease of formulation, etc. The additional active ingredient may be included in an amount of 0.0001 to 10% by weight (w/w) based on the total weight of the quasi-drug composition, and the content range can be appropriately adjusted by a person skilled in the art in consideration of skin safety, ease of formulation, etc.

In addition, the pharmaceutical composition according to the present disclosure adds other ingredients or substances to provide secondary effects such as skin whitening, trouble improvement, anti-inflammatory, moisturizing, skin wrinkle improvement, and antioxidant activity enhancement in addition to the main effects shown by the active ingredients. It can be included as .

Hereinafter, the configuration and effects of the present disclosure will be described in more detail through examples. These examples are only for illustrating the present disclosure, and the scope of the present disclosure is not limited by these examples.

<Preparation of strains and samples>

1) Staphylococcus epidermidis ATCC 12228 and Staphylococcus aureus ATCC 6538 strains were obtained through ThermoFisher scientific, cultured in tryptic soy medium (culture conditions: 32°C for 18 hours), and then 0.85 It was prepared by diluting with % NaCl and adjusting the absorbance (600 nm) to 0.5~0.6.

2) 1,3-propanediol was obtained through Sigma-Aldrich.

3) 2-Methyl-1,3-propanediol was obtained through Sigma-Aldrich, 1,3-Butanediol was obtained through Sigma-Aldrich, 2,3-Butanediol was obtained through Sigma-Aldrich, 1, 2-Pentanediol was obtained through Sigma-Aldrich, and 1,2-Hexanediol was obtained through Sigma-Aldrich.

4) Fructan was obtained through Sigma-aldrich.

5) Yeast extract was obtained through Sigma-aldrich.

<Experimental Example 1> Analysis of the effect (growth rate) of 1,3-propanediol on beneficial skin bacteria

The effect of 1,3-propanediol on the growth of Staphylococcus epidermidis ATCC 12228 was analyzed.

For this purpose, 1,3-propanediol was diluted with 10% tryptic soy medium to prepare concentrations of 0.05, 0.1, 0.2, 0.5, 1.0, 3.0, 5.0, 10, 20, and 25% by weight, respectively.

1,3-Propanediol prepared at each concentration was added to 10% tryptic soy medium and then inoculated with S. epidermidis at 1% (v/v).

Afterwards, the cells were cultured at a temperature of 32°C for 24 hours and the absorbance (600 nm) was measured every 2 hours to analyze the growth of beneficial skin bacteria.

At this time, 10% tryptic soy medium without addition of 1,3-propanediol was set as the control.

Table 1 below shows the results of analyzing the degree of S. epidermidis growth according to the concentration of 1,3-propanediol.

Concentration of 1,3-propanediol	Effect on the growth of beneficial bacteria ( S. epidermidis )
0.05% by weight	No influence
0.1% by weight	Promotion
0.2% by weight	Promotion
0.5% by weight	Promotion
1.0% by weight	Promotion
3.0% by weight	Promotion
5.0% by weight		Promotion
10% by weight		Promotion
20% by weight	No influence
25% by weight	control

The standard for determining the effect on the growth of beneficial bacteria is 10% tryptic soy medium without 1,3-propanediol (control) when culturing for 2 to 16 hours after inoculation with S. epidermidis and measuring absorbance (600㎚). If the absorbance was higher than that, it was judged that the growth of S. epidermidis was promoted. If there was no difference, it was judged to be no effect, and if the absorbance was low, it was judged to be inhibited. Referring to Figure 1 and Table 1, it can be seen that 1,3-propanediol at a concentration of 0.05% by weight or less did not promote the growth of S. epidermidis , and that it promoted the growth of S. epidermidis when the concentration was 0.1% by weight or more. You can. In addition, when the concentration was 20% by weight, it did not promote the growth of S. epidermidis , and when it exceeded 25%, it was confirmed that the growth of S. epidermidis was inhibited. As a result, the concentration of 1,3-propanediol It can be confirmed that the growth of S. epidermidis is promoted when it exceeds a specific range of 0.05% by weight and is less than 20% by weight.

<Experimental Example 2> Analysis of the effect (growth rate) of 1,3-propanediol on harmful skin bacteria

The effect of 1,3-propanediol on the growth of Staphylococcus aureus ATCC 6538 was analyzed.

For this purpose, 1,3-propanediol was diluted with 10% tryptic soy medium to prepare concentrations of 0.05, 0.1, 0.2, 0.5, 1.0, 3.0, 5.0, 10, 20, and 25% by weight.

1,3-Propanediol prepared at each concentration was added to 10% tryptic soy medium and then inoculated with S. aureus at 1% (v/v).

Afterwards, the cells were cultured at a temperature of 32°C for 24 hours and the absorbance (600 nm) was measured every 2 hours to analyze the growth of beneficial skin bacteria.

At this time, 10% tryptic soy medium without addition of 1,3-propanediol was set as the control.

Concentration of 1,3-propanediol	Effect on the growth of harmful bacteria ( S. aureus )
0.05% by weight	No influence
0.1% by weight	No influence
0.2% by weight	No influence
0.5% by weight	No influence
1.0% by weight	No influence
3.0% by weight	control
5.0% by weight		control
10% by weight		control
20% by weight		control
25% by weight	control

The standard for determining the effect on the growth of harmful bacteria is 10% tryptic soy medium without 1,3-propanediol (control) when culturing for 2 to 16 hours after inoculation with S. aureus and measuring absorbance (600 nm). If the absorbance was lower than that, it was determined that S. aureus growth was inhibited, and if there was no difference in absorbance, it was judged to have no effect. Referring to Figure 2 and Table 2, the concentration of 1,3-propanediol was 1.0% by weight or less. , it did not inhibit the growth of S. aureus , and it was confirmed that the growth of S. aureus was inhibited when the concentration of 1,3-propanediol was 3.0% by weight or more.

As a result, it can be confirmed that when the concentration of 1,3-propanediol is 3.0% by weight or more, the growth of S. aureus is inhibited.

<Experimental Example 3> Analysis of growth of beneficial and harmful bacteria during co-culture

The effect of 1,3-propanediol on skin beneficial and harmful bacteria during co-culture was analyzed.

For this purpose, 1,3-propanediol was diluted with 10% tryptic soy medium to prepare concentrations of 0.05, 0.1, 0.2, 0.5, 1.0, 3.0, 5.0, 10, 20, and 25% by weight.

After adding 1,3-propanediol prepared at each concentration to 10% tryptic soy medium, S. epidermidis and S. aureus were inoculated at 1% (v/v) each.

Afterwards, a 0.4㎛ insert was used in a 12-well plate to create a condition in which beneficial and harmful bacteria were cultured independently while sharing metabolites.

After culturing at 32°C for 6 hours, the number of viable bacteria was measured to analyze the effect of 1,3-propanediol on beneficial and harmful bacteria on the skin.

At this time, 10% tryptic soy medium without addition of 1,3-propanediol was used as a control.

Referring to Figure 3, the concentration of 1,3-propanediol, which promotes the growth of beneficial bacteria, ranges from 0.1% by weight to 20% by weight, and the concentration of 1,3-propanediol, which inhibits the growth of harmful bacteria, ranges from 0.05% by weight. It was confirmed that it was up to 25% by weight.

Therefore, when the concentration of 1,3-propanediol is 0.1 to 20% by weight, the balance of the skin microbiome can be maintained by promoting the growth of beneficial bacteria and suppressing the growth of harmful bacteria. In particular, the preferred concentration of 1,3-propanediol to increase the growth rate of beneficial bacteria relative to the growth rate of harmful bacteria without drastic changes in beneficial and harmful bacteria is 0.2 to 10% by weight.

<Experimental Example 4> Comparison of the effects of various diol-based compounds on maintaining microbiome balance

The effect of 1,3-propanediol in maintaining microbiome balance is shown in Tables 3 and 4 below, compared with other diol-based compounds.

division	Diol-based compound concentration
	Effect on growth of harmful bacteria ( S. aureus )
	0.1% by weight	1% by weight	5% by weight	10% by weight	20% by weight
1,3-Propanediol	++	++	+++	+++	+++
2-Methyl-1,3-propanediol	+	+	++	+++	+++
1,3-Butanediol	+	+	++	++	+++
2,3-Butanediol	+	+	++	+++	+++
1,2-Pentanediol	+	+	+++	+++	+++
1,2-Hexanediol	+	++	+++	+++	+++

* Criteria for evaluating the impact on the growth of S. aureus - No impact: +; Growth inhibition: ++; Suppression greater than 50%: +++

division	Diol-based compound concentration
	Effect on beneficial bacteria growth ( S. epidermidis )
	0.1% by weight	1% by weight	5% by weight	10% by weight	20% by weight
1,3-Propanediol	++	++	+	+	+
2-Methyl-1,3-propanediol	+	+	-	- -	- -
1,3-Butanediol	++	-	-	- -	- -
2,3-Butanediol	++	-	- -	- -	- -
1,2-Pentanediol	++	-	- -	- -	- -
1,2-Hexanediol	++	-	- -	- -	- -

* Criteria for evaluating the impact on the growth of S. epidermidis - Growth promotion: ++; No effect: +; Growth inhibition: -; Growth inhibition of more than 50%: - -

Referring to Figure 4 and Tables 3 and 4, as a result of comparing the effects of inhibiting the growth of harmful bacteria, it can be confirmed that all diol-based compounds including 1,3-propanediol of the present disclosure inhibit the growth of harmful bacteria at similar concentrations. there is.

However, as a result of comparing the growth effects of beneficial bacteria, it was confirmed that diol-based compounds other than 1,2-propanediol inhibit the growth of beneficial bacteria when the concentration exceeds 0.1% by weight.

That is, in the case of ordinary diol-based chemicals, when the concentration increases, the growth of both beneficial and harmful bacteria is suppressed, whereas in the case of 1,3-propanediol, the growth of beneficial bacteria is promoted and the growth of harmful bacteria is suppressed. .

As a result, it can be confirmed that 1,3-propanediol can promote the growth of beneficial bacteria and suppress the activity of harmful bacteria at a specific concentration, and can be applied as a composition for maintaining the microbiome balance of the skin.

<Experimental Example 5> Evaluation of the effect on the skin microbiome according to the combined use of 1,3-propanediol and fructan

To evaluate the effect of 1,3-propanediol and fructan on the skin microbiome, the effect on the growth rate of Staphylococcus epidermidis ATCC 12228, a representative skin beneficial bacteria, and Staphylococcus aureus ATCC 6538, a harmful skin bacteria, was confirmed. Staphylococcus epidermidis ATCC 12228 and Staphylococcus aureus ATCC 6538 were cultured in tryptic soy medium at 32°C for more than 18 hours, then diluted with 0.85% NaCl and adjusted to an absorbance (600 nm) of 0.5 to 0.6.

1,3-Propanediol was fixed at 1.5% by weight, and 10% tryptic soy medium containing fructan was added at each concentration shown in the table below, and S. epidermidis and S. aureus prepared above were added at 1% each (v/ v) was inoculated. The culture was incubated at 32°C for 12 hours, and the absorbance (600 nm) was measured at 2-hour intervals to compare the growth levels of skin beneficial bacteria and skin harmful bacteria.

The results are shown in Table 5 and Table 6.

division		Fructan concentration (% by weight)
		Effect on growth of harmful bacteria ( S. aureus )
		0.00	0.04	0.06	0.09	0.10	0.12	0.25	0.30
1,3- propanediol	0 weight%	*	*	*	*	*	*	*	*
	1.5 weight%	++	++	++	++	++	++	++	++

* (Standards for evaluating the impact on the growth of S. aureus ) No noticeable effect (within 1% change in absorbance): *; Mild growth inhibition (absorbance change (decrease) 3%): +; Significant growth inhibition (absorbance change (reduction) 5%): ++; Significant growth inhibition (absorbance change (reduction) greater than 10%): +++

division		Fructan concentration (% by weight)
		Effect on beneficial bacteria growth ( S. epidermis )
		0.00	0.04	0.06	0.09	0.10	0.12	0.25	0.30
1,3- propanediol	0 weight%	*	*	+	+	+	+	++	++
	1.5 weight%	+	+	++	+++	+++	+++	+++	+++

* (Standards for evaluating the impact on the growth of S. aureus ) No noticeable effect (within 1% change in absorbance): *; Mild growth stimulation (absorbance change (increase) 3%): +; Significant growth promotion and growth inhibition (absorbance change (increase) 5%): ++; Significant growth stimulation (absorbance change (increase) of 10% or more): +++; Mild growth inhibition (change (decrease) in absorbance 3% or more): -; Significant growth inhibition (absorbance change (reduction) of 5% or more): - -

From Tables 5 and 6 above, if the fructan content is less than 0.06% by weight, the growth of beneficial bacteria cannot be promoted, and if it exceeds 0.25% by weight, the activity of both harmful and beneficial bacteria is suppressed, thereby maintaining the skin's microbiome balance. There was this problem of breaking.

In addition, when treating 0.1% by weight of fructan and 1.5% by weight of 1,3-propanediol compared to 0.3% by weight of fructan, there was no significant effect on inhibiting the growth of harmful bacteria as the incubation time increased, but the effect of promoting the growth of beneficial bacteria was relatively high. It was confirmed that there was an increase (see Figure 5).

This result is believed to be due to the fact that fructan boosted the beneficial bacteria growth promoting effect of 3-propanediol.

<Experimental Example 6> Evaluation of the effect on the skin microbiome according to the combined use of 1,3-propanediol and yeast extract

To evaluate the effect of 1,3-propanediol and yeast extract on the skin microbiome, the growth levels of beneficial skin bacteria and harmful skin bacteria were compared in the same manner as <Experimental Example 5>.

The results are shown in Tables 7 and 8.

division		Yeast extract concentration (% by weight)
		Effect on growth of harmful bacteria ( S. aureus )
		0.00	0.04	0.06	0.09	0.10	0.12	0.25	0.30
1,3- propanediol	0 weight%	*	*	*	*	*	*	*	*
	1.5 weight%	++	++	++	++	++	++	++	++

* (Standards for evaluating the impact on the growth of S. aureus ) No noticeable effect (within 1% change in absorbance): *; Mild growth inhibition (absorbance change (decrease) 3%): +; Significant growth inhibition (absorbance change (reduction) 5%): ++; Significant growth inhibition (absorbance change (reduction) greater than 10%): +++

division		Yeast extract concentration (% by weight)
		Effect on beneficial bacteria growth ( S. epidermis )
		0.00	0.04	0.06	0.09	0.10	0.12	0.25	0.30
1,3- propanediol	0 weight%	*	*	+	+	+	+	++	++
	1.5 weight%	+	+	++	+++	+++	+++	+++	+++

* (Standards for evaluating the impact on the growth of S. aureus ) No noticeable effect (within 1% change in absorbance): *; Mild growth stimulation (absorbance change (increase) 3%): +; Significant growth promotion and growth inhibition (absorbance change (increase) 5%): ++; Significant growth stimulation (absorbance change (increase) of 10% or more): +++; Mild growth inhibition (change (decrease) in absorbance 3% or more): -; Significant growth inhibition (absorbance change (reduction) of 5% or more): - -

From Tables 7 and 8 above, if the yeast extract content is less than 0.06% by weight, it cannot promote the growth of beneficial bacteria, and if it exceeds 0.25% by weight, the activity of both harmful and beneficial bacteria is suppressed, thereby maintaining the skin's microbiome balance. This breaking problem appeared.

In addition, when treating 0.1% by weight of yeast extract and 1.5% by weight of 1,3-propanediol compared to 0.3% by weight of yeast extract, the effect of promoting the growth of beneficial bacteria was found to increase along with the inhibition of growth of harmful bacteria as the incubation time increased. It was confirmed that the effect of promoting the growth of beneficial bacteria was relatively greater (see Figure 6).

This is believed to be a result of the yeast extract boosting the beneficial bacteria growth-promoting effect of 3-propanediol.

The present disclosure confirms that only 1,3-propanediol exhibits the effect of maintaining skin microbiome balance compared to other diol-based compounds commonly used industrially, and surprisingly, the effect is significant when the concentration is 0.1 to 20% by weight. It has been confirmed that it can be effective, and there are no special problems in formulating it into pharmaceutical compositions such as cosmetic compositions and external skin products, so it has high industrial value.

The composition for external use for skin according to the present disclosure has high industrial value because it can help maintain the skin health of an individual by being formulated into a pharmaceutical composition such as a cosmetic composition or a quasi-drug for external use on the skin.

The skin external composition according to the present disclosure includes 1,3-propanediol as an active ingredient, thereby promoting the growth of beneficial skin bacteria and inhibiting the growth of harmful skin bacteria, thereby maintaining the balance of the skin microbiome and thereby reducing external irritation of the skin. It has high utility value as it can improve and strengthen the barrier function against skin. It can help to tighten skin tissue, improve skin texture, and maintain overall skin health, and it can improve the user's confidence in their skin and improve their life. There are advantages that can contribute to the quality of the product.

Claims (18)

1. A skin external composition for maintaining the skin's microbiome balance, comprising 1,3-propanediol as an active ingredient and optionally a boosting ingredient.
2. According to paragraph 1,

   An external skin composition that maintains microbiome balance by increasing beneficial bacteria on the skin and reducing harmful bacteria.
3. According to paragraph 2,

   Beneficial bacteria include Staphylococcus epidermidis , Streptococcus pneumoniae, Lactobacillus acidophilus , Lactobacillus rhamnosus , and Bifidobacterium bifidum. Contains one or more species selected from the group consisting of ( Bifidobacterium bifidum ),

   A composition for external application for skin, wherein the harmful bacteria include one or more species selected from the group consisting of Staphylococcus aureus and Cutibacterium acnes .
4. According to paragraph 1,

   A cosmetic composition wherein the effective concentration of 1,3-propanediol in the external skin composition is 0.1 to 20% by weight.
5. According to paragraph 1,

   A composition for external use on the skin, wherein the boosting ingredient is at least one selected from fructan and yeast extract.
6. According to paragraph 1,

   A composition for external application for skin, wherein the effective concentration of the boosting ingredient in the composition is 0.06 to 0.25% by weight, or 0.09 to 0.12% by weight.
7. According to paragraph 1,

   A composition for external application for skin, wherein the combination ratio of 1,3-propanediol and boosting component is 6 to 25:1, or 12.5 to 16.7:1, based on weight.
8. According to paragraph 1,

   A composition for external application to the skin, which is formulated as a cosmetic composition or pharmaceutical composition that can be applied topically to the skin.
9. According to clause 8,

   The cosmetic composition includes a cosmetically acceptable carrier, excipient, diluent, or mixtures thereof,

   Solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing, oils, microcapsules, microgranules, ionic vesicular dispersants, non-ionic vesicular dispersants, powder foundation, emulsion foundation. , a composition for external application to the skin, which is formulated in a form selected from the group consisting of wax foundation, stick, mask pack, and spray.
10. According to clause 8,

    Pharmaceutical compositions include pharmaceutically acceptable carriers, excipients, diluents, or mixtures thereof,

    A composition for external application to the skin, which is formulated in a form selected from the group consisting of liquid, powder, ointment, lotion, wet tissue, spray, band, and patch.
11. Maintaining or restoring the microbiome balance of the skin by topically applying to the skin an external skin composition containing 1,3-propanediol or a combination of 1,3-propanediol and a boosting ingredient as an active ingredient. method.
12. According to clause 11,

    The method wherein the boosting ingredient is at least one selected from Fructan and Yeast Extract.
13. According to clause 11,

    The method wherein the effective concentration of the boosting ingredient in the skin external application composition is 0.06 to 0.25% by weight, or 0.09 to 0.12% by weight.
14. According to clause 11,

    The method wherein the combination ratio of 1,3-propanediol and boosting component is 6 to 25:1, or 12.5 to 16.7:1 by weight.
15. Use of 1,3-propanediol or a combination of 1,3-propanediol and a boosting component as an active ingredient for use in maintaining the microbiome balance of the skin in a composition for external application to the skin.
16. According to clause 15,

    Use wherein the boosting ingredient is at least one selected from Fructan and Yeast Extract.
17. According to clause 15,

    Use wherein the effective concentration of the boosting ingredient in the external skin composition is 0.06 to 0.25% by weight, or 0.09 to 0.12% by weight.
18. According to clause 15,

    Use wherein the combination ratio of 1,3-propanediol and boosting component is 6 to 25:1, or 12.5 to 16.7:1 by weight.

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