KR102262467B1 - Preservative system with enhanced anti-microbial activity - Google Patents

Abstract

The present invention relates to an antiseptic system comprising a preservative and a chelating agent and having improved antibacterial activity compared to the preservative alone, and a cosmetic composition comprising the same.

Description

Preservative system with enhanced anti-microbial activity

The present invention relates to an antiseptic system comprising a preservative and a chelating agent and having improved antibacterial activity compared to the preservative alone, and a cosmetic composition comprising the same.

Cosmetics mainly contain oil or water, and in particular, contain glycerin or sorbitol, which are carbon sources for microorganisms, and amino acid derivatives and proteins as nitrogen sources. Therefore, like foods with similar ingredients, microorganisms such as molds and bacteria easily penetrate and are advantageous for propagation. In addition, compared with food, cosmetics have a relatively long period of use, so the risk of changes due to microorganisms is higher than that of food. Therefore, it is necessary to use preservatives because cosmetics are easily contaminated from fingers and need to be protected for a long period of time from discoloration and odor caused by microorganisms.

Preservatives are formulated in cosmetics to inhibit the growth of microorganisms that contaminate cosmetics from the outside, and prevent product changes by killing microorganisms over time. However, there is controversy over safety enough to regulate the compounding limit of preservatives in the US FDA, the Japanese Ministry of Health, and the Korea Food and Drug Administration, and there is a problem to the extent that the news and other media also report the harm of preservatives. is being aggravated Despite these problems, when preservatives are not used, even bigger problems such as product deterioration, contamination of microorganisms, and contamination of pathogens harmful to humans may occur, so it is a reality that has no choice but to use preservatives even after recognizing the harmfulness.

Currently, the most used preservatives are synthetic preservatives, for example, parabens, imidazolidinyl urea, diazolidinyl urea, phenoxy ethanol, and the like. The cytotoxic mechanism of parabens binds to the cell membrane, destroys the lipid bilayer, and leaks intracellular components, resulting in cell death. The antibacterial mechanism of benzalkonium chloride, which is also widely used in pharmaceuticals, is also adsorbed to the cell surface of microorganisms, and then the antibacterial material diffuses through the cell wall and the cell membrane is destroyed, ^{releasing K +} ions and cytoplasmic components such as DNA and RNA. This will inactivate microorganisms. However, such a preservative that destroys cell membranes can affect not only microorganisms but also human cells. Parabens are classified as safe chemicals because of their small amount of penetrating into the skin and have been used as preservatives, but problems of allergic reactions, potential as environmental hormones, and induction of resistant bacteria have been revealed. It was also confirmed that parabens are absorbed into the blood through the skin and accumulate in the internal organs, fat, and muscles. In this situation, efficacy and safety studies on various types of preservatives currently available should be conducted simultaneously so that safe preservatives can be used in cosmetics.

In addition, for the purpose of preventing product deterioration in some products, the problem of ignoring consumer safety and excessively using preservatives more than necessary is also emerging.

As such, the possibility of contact dermatitis of existing preservatives and the risk of endocrine system disturbance due to accumulation in the body are reported through the mass media every day, and in order to meet the well-being trend of domestic and foreign consumers who pursue safety harmless to the environment and human body, the cosmetics industry Many studies are currently underway to use natural antibacterial substances as preservatives to replace chemical preservatives. Furthermore, in order to reduce the amount of the unavoidably added preservative, efforts are being made to discover additives that can promote its activity.

Under this background, the present inventors have made intensive research efforts to discover additives that can promote the antimicrobial activity of preservatives used in the past. As a result, when a chelating agent is used in a predetermined amount, the antibacterial activity of the preservative is synergistically improved. was confirmed, and the present invention was completed.

One object of the present invention is to provide an antiseptic system comprising a preservative and a chelating agent, which has improved antimicrobial activity compared to the preservative alone.

Another object of the present invention is to provide a cosmetic composition comprising the antiseptic system.

As a first aspect, the present invention provides an antiseptic system comprising a preservative and a chelating agent, the antiseptic system having improved antimicrobial activity compared to the preservative alone.

In one embodiment, the preservative system may be characterized in that it contains a preservative in an amount of 0.1 to 10% based on the total mass of the preservative system.

In another embodiment, the preservative system may be characterized by including at least one selected from the group consisting of phenoxyethanol, 1,2-hexanediol, and hydroxyacetophenone as a preservative.

In another embodiment, the preservative system may be characterized in that it contains a chelating agent in an amount of 0.1 to 1% based on the total mass of the preservative system.

In another embodiment, the preservative system is a chelating agent EDTA (ethylenediaminetetraacetic acid), derivatives or salts thereof, phytic acid, and sodium citrate (sodium citrate) at least one selected from the group consisting of It may be characterized by including.

In another embodiment, the antiseptic system is Escherichia coli (Escherichia coli), Pseudomonas aeruginosa (Pseudomonas aeruginosa), Staphylococcus aureus (Staphylococcus aureus), Candida albicans ( Candida albicans), and Aspergillus brasiliensis (Aspergillus brasiliensis) may be characterized by exhibiting antibacterial activity against one or more strains selected from the group consisting of.

As a second aspect, the present invention provides a cosmetic composition comprising the antiseptic system of the first aspect.

In another embodiment, the cosmetic composition is Escherichia coli (Escherichia coli), Pseudomonas aeruginosa (Pseudomonas aeruginosa), Staphylococcus aureus ( Staphylococcus aureus, Staphylococcus aureus), Candida albicans (Candida albicans), and Aspergillus brasiliensis (Aspergillus brasiliensis) characterized by reducing the growth, proliferation, or both of one or more strains selected from the group consisting of can

The antiseptic system of the present invention can boost the antibacterial activity of the preservative by including a predetermined chelating agent together with the preservative, so it can effectively block the growth and/or proliferation of microorganisms even with a small amount of preservative, thereby preventing contamination by microorganisms. It can be usefully used in cosmetic compositions that may cause side effects.

1 is a diagram showing the antibacterial effect of an antiseptic system including phenoxyethanol and a chelating agent as preservatives.
2 is a diagram showing the antibacterial effect of a preservative system including 1,2-hexanediol and a chelating agent as preservatives.
3 is a diagram showing the antibacterial effect of a preservative system including hydroxyacetophenone and a chelating agent as preservatives.

Each description and embodiment disclosed herein is also applicable to each other description and embodiment. That is, all combinations of the various elements disclosed herein are within the scope of the present invention. In addition, it cannot be said that the scope of the present invention is limited by the specific descriptions described below.

In addition, those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Also, such equivalents are intended to be encompassed by the present invention.

In addition, in the entire specification of the present application, when a part "includes" a certain component, it means that other components may be further included, rather than excluding other components unless otherwise stated. do.

Hereinafter, the present invention will be described in more detail.

The present invention is based on the discovery that by further including a chelating agent in the preservative, the antibacterial activity of the preservative can be significantly improved synergistically, so that the same effect can be exhibited even when the use of the preservative is reduced.

A first aspect of the present invention provides an antiseptic system comprising a preservative and a chelating agent, the antiseptic system having improved antimicrobial activity compared to the preservative alone.

The preservative system may include a preservative in an amount of 0.1 to 10% based on the total mass of the preservative system. For example, if the content of the preservative is less than 0.1%, it may be difficult to achieve a desired activity, and if it is more than 10%, an additional increase in activity according to the increase in the amount of the preservative may not appear.

The preservative system may include at least one selected from the group consisting of phenoxyethanol, 1,2-hexanediol, and hydroxyacetophenone as a preservative.

As used herein, the term "phenoxyethanol" is a phenol ether combined with phenol and ethylene glycol. It is one of the natural ingredients contained in green tea, but it is also used chemically and is one of the indirect food additives approved by the US FDA. As the toxicity of parabens, which were previously used as preservatives, is known, it has emerged as an ingredient to replace them. It is added to almost all cosmetics and acts as a preservative and a fixative, but it can also cause allergies. it is known that there is Currently, in cosmetics and personal care products, use up to 1% is considered safe.

As used herein, the term "1,2-hexanediol" is a colorless liquid with hygroscopic nature, and is widely used as an emollient, humectant, and wetting agent in cosmetics and skin care products. It is known to have antibacterial and anti-inflammatory activity.

As used herein, the term "hydroxyacetophenone" is a synthetic antioxidant and is also used in cosmetics as a skin conditioning ingredient. Furthermore, hydroxyacetophenone is used in a preservative system in cosmetics, and since it can exhibit a preservative effect in a smaller amount than phenoxyethanol, it is a substance expected to reduce the risk of allergic reactions while maintaining the effect. In addition, hydroxyacetophenone is known to have a soothing effect as it can inhibit enzymes that can cause signs of irritation on the skin surface, such as COX-2.

The preservative system may include a chelating agent in an amount of 0.1 to 1% based on the total mass of the preservative system. For example, if the content of the chelating agent is less than 0.1%, it may be difficult to achieve the desired level of antibacterial activity boosting effect of the preservative, and if it is more than 1%, it may be an unnecessary supersaturation state that does not show an additional increase in activity according to the increase in usage. have.

The preservative system may include an amine-based or natural-based chelating agent alone or in combination as a chelating agent. Specifically, the chelating agent may be at least one selected from the group consisting of ethylenediaminetetraacetic acid (EDTA), for example, the disodium salt of EDTA, phytic acid, and sodium citrate.

As used herein, the term “EDTA” is a synthetic organic compound having a chemical formula of C ₁₀ H ₁₆ N ₂ O ₈ , and acts as a hexadentate ligand as a single molecule to form a chelate compound by binding with a metal ion. EDTA can coordinate simultaneously to the six vertices of the octahedron centered on the metal ion, so that the central metal is surrounded by ligands. EDTA exists as white crystals or powder and decomposes at 245°C. The molecular weight is 292.24 and the density is 0.86 g/cm ³ . It can act as a tetraprotic acid and can form various salts. The EDTA is EDTA as such, or dipotassium EDTA, disodium EDTA, tetrasodium EDTA, diammonium EDTA, calcium disodium EDTA, TEA (triethanolamine)-EDTA, tripotassium EDTA, trisodium EDTA, HEDTA (hydroxyethylethylenediaminetriacetic acid) , trisodium HEDTA, and the like, and thus, EDTA or a salt thereof may be used alone or in combination of two or more thereof. The EDTA is known as a safe material with a risk of 1, and is used in various fields. In particular, in cosmetics, it is added as a sequestering agent and chelates with metal ions that may be mixed in the manufacturing process or oxidizing substances that can be generated when air enters the product over time to generate harmful substances or catalyze it It is known to act as a deterrent. Preferably, the antiseptic system of the present invention may use EDTA in the form of a disodium salt as a chelating agent, but is not limited thereto. For example, the preservative system of the present invention may contain EDTA as a chelating agent in an amount of 0.1 to 1%, or 0.1 to 0.2%, but is not limited thereto.

As used herein, the term "phytic acid" is a 6-fold dihydrogenphosphate ester of inositol, also called inositol hexakisphosphate (IP6) or inositol polyphosphate, (1R,2S,3r) ,4R,5S,6s)-cyclohexane-1,2,3,4,5,6-hexaylhexakis[dihydrogen (phosphate)]((1R,2S,3r,4R,5S,6s)-cyclohexane It is a compound with the IUPAC name of -1,2,3,4,5,6-hexayl hexakis[dihydrogen (phosphate)]), and at physiological pH, phosphate groups can be partially ionized to form phytate anions. Phytic acid, widely known as phytate, is a naturally occurring antioxidant alpha-hydroxy acid (AHA) extracted from cereal seeds, fruit seeds and bran of natural plants. The scope of application extends to chemical peeling. It works by inducing exfoliation of the skin and accelerating the natural skin cell renewal cycle. Specifically, it promotes the excretion of cells in the outer layer of the epidermis and restores moisture to improve skin texture and reduce signs of aging. Although the mechanism of action is not fully elucidated, it is believed that it is destroyed by reducing the calcium ion concentration in the epidermis and removing ions from the cell adhesion through chelation, resulting in exfoliation.

The peeling action of phytic acid is similar to that of glycolic acid, which is widely used, but does not require neutralization after application. It is a slow release agent, works gradually and sequentially and is not as aggressive as glycolic acid. Phytic acid has been shown to be particularly effective as a chemical exfoliant for the treatment of melasma and acne. It is used with glycolic acid, lactic acid and mandelic acid, and the typical burning sensation seen with glycolic acid is not observed.

Such phytic acid is a low-risk ingredient for use in skin care, is safe for skin use, and is a substance whose safety is secured enough to be used as a food additive approved by the FDA. For example, the antiseptic system of the present invention may contain phytic acid as a chelating agent in an amount of 0.1 to 1%, or 0.2 to 0.7%, but is not limited thereto.

As used herein, the term "sodium citrate" is a substance assigned the E number of E331, present in the form of 1-3 sodium salts of citric acid. Monosodium citrate as an anticoagulant of the blood, disodium citrate as an antioxidant or as a food additive to enhance the effect of other antioxidants, or as an acid regulator and sequestering agent, and trisodium citrate as a flavoring agent ) or as a food additive as a preservative. As a cosmetic additive, sodium citrate is used as a buffering agent for pH adjustment, or is also used as a preservative. Applicable items range from baby products to makeup, bath products, hair dyes and skin care products. For example, the antiseptic system of the present invention may include sodium citrate as a chelating agent in an amount of 0.5 to 1%, or 0.8 to 1%, but is not limited thereto.

The antiseptic system is Escherichia coli (Escherichia coli), Pseudomonas aeruginosa (Pseudomonas aeruginosa), Staphylococcus aureus (Staphylococcus aureus), Candida albicans (Candida albicans), and It may exhibit antibacterial activity against one or more strains selected from the group consisting of Pergillus brasiliensis. The strains in which the antiseptic system of the present invention exhibits antibacterial activity are strains known to be particularly harmful to cosmetics.

Among them, Escherichia coli (Escherichia coli ), Pseudomonas aeruginosa ( Pseudomonas aeruginosa ), and Staphylococcus aureus ( Staphylococcus aureus ) are bacteria, Candida albicans ( Candida albicans ) yeast ( Candida albicans ) Fungi), Aspergillus brasiliensis ( Aspergillus brasiliensis ) is a strain of fungi.

As used herein, the term "Escherichia coli" is also called Escherichia coli, and is an intestinal bacterium that uses the intestinal tract of mammals, including humans, as a parasitic place.

As used herein, the term "Pseudomonas aeruginosa" is also called Pseudomonas aeruginosa, and is a pathogenic bacterium that causes intractable infections in patients with sepsis, systemic infections, chronic airway infections and pancreatic cystic fibrosis. Recently, P. aeruginosa has been detected in urethral infections and corneal ulcers of contact lens users. Although it is rare that P. aeruginosa causes corneal ulcers, once infected, it is dangerous enough to cause blindness.

As used herein, the term "Staphylococcus aureus" is the most representative suppurative bacteria also called staphylococcus, and staphylococcal food poisoning caused by enterotoxin producing strains is the most frequent among bacterial food poisoning along with enteritis vibrio food poisoning. It is a bacterium that can lead to the risk of blindness due to bacterial keratitis when infected with the eye.

As used herein, the term "Candida albicans" is a bacterium that mainly causes Candida vaginitis. As used herein, the term "Aspergillus brassiliensis" is a causative agent of pneumonia transmitted through the respiratory tract.

A second aspect of the present invention provides a cosmetic composition comprising the preservative system of the first aspect.

The antiseptic system of the first aspect is as described above.

Specifically, the cosmetic composition of the present invention is Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Aspergillus brasiliensis, compared to a composition containing the same amount of preservatives of the same type. It can exert the effect of reducing the growth, proliferation, or both of one or more strains selected from the group consisting of.

For example, the cosmetic composition of the present invention is preferably harmless to the human body while ensuring stability for long-term storage due to the nature of being directly applied to human skin. In this context, the cosmetic composition of the present invention may contain phenoxyethanol in an amount of 0.19 to 1%, or 0.38 to 0.75% as a preservative in the antiseptic system, but is not limited thereto. In addition, the cosmetic composition may contain hexanediol as a preservative in an amount of 0.31 to 5%, or 1.25 to 2.5%, but is not limited thereto. Furthermore, the cosmetic composition may contain hydroxyacetophenone in an amount of 0.1 to 1%, or 0.13 to 0.5%, as a preservative, but is not limited thereto.

The cosmetic composition according to the present invention includes solutions, external ointments, creams, foams, nourishing lotions, softening lotions, packs, soft water, emulsions, makeup bases, essences, soaps, liquid detergents, bathing agents, sunscreen creams, sun oils, suspensions, Emulsions, pastes, gels, lotions, powders, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, wax foundations, patches and sprays can be prepared in a formulation selected from the group consisting of, but not limited to does not

In addition, the cosmetic composition of the present invention may further include one or more cosmetically acceptable carriers to be formulated in general skin cosmetics, and conventional ingredients include, for example, oil, water, surfactant, humectant, lower alcohol, Thickeners, chelating agents, colorants, preservatives, fragrances and the like may be appropriately mixed, but the present invention is not limited thereto.

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

Example 1: Preparation of antiseptic system by combination of various preservatives and chelating agents

As a preservative, 3% phenoxyethanol, 5% 1,2-hexanediol, and 1% hydroxyacetophenone were each added to 0.16% disodium EDTA (2- Na EDTA), 0.5% phytic acid, and 0.83% sodium citrate in combination with a total of 9 types of preservative systems were prepared.

Example 2: Minimum inhibitory concentration (MIC) test

Using the nine antiseptic systems prepared in Example 1, the antimicrobial activity against the strains was measured by five MIC tests, and the results are shown in Table 1 and FIGS. 1 to 3 below. As the strain, representative strains that can be a source of contamination of cosmetics were selected, and bacterial Escherichia coli (E. coli, Escherichia coli, ATCC NO. 8739), Pseudomonas aeruginosa ( Pseudomonas aeruginosa , ATCC NO. 9027) , Staphylococcus aureus (Staphylococcus aureus, ATCC NO. 6538), yeast (fungi) Candida albicans (Candida albicans, ATCC NO. 10231), and mold Aspergillus brassiliensis ( Aspergillus brasiliensis , ATCC NO. 16404) was used. As a control, a preservative system containing no chelating agent and only each preservative was used.

Specifically, among the strains, bacteria were cultured at 32.5° C. for 1 to 2 days using TSB (tryptic soy broth) as a culture medium, and fungi were cultured at 22.5° C. for 2 to 3 days using SDB (sabourd dextrose broth). cultured. The proliferation of the strain was confirmed by measuring OD (optical density) at a wavelength of 570 nm using a spectrophotometer. The strain was diluted with 0.85% NaCl ^{and inoculated at 1×10 5} to 1×10 ⁶ CFU/mL.

Furthermore, the minimum inhibitory concentration was calculated by measuring the OD while adding an amount of the chelating agent to the solution prepared while diluting the concentration of the preservative by 1/2.

antiseptic chelating agent strain S. aureus P. aeruginosa E. coli C. albicans A. brasiliensis Phenoxyethanol 2-Na EDTA ◎ ◎ ◎ ◎ ◎ phytic acid × ○ ○ × ◎ sodium
citrate ◎ ○ ○ × ◎ 1,2-Hexanediol 2-Na EDTA ◎ ◎ ◎ ◎ ◎ phytic acid × ○ ○ ○ ◎ sodium
citrate ◎ ○ ○ ○ ◎ hydroxy
acetophenone 2-Na EDTA ◎ ◎ ◎ ◎ ◎ phytic acid × × × × ◎ sodium
citrate ○ ○ ○ × ◎

◎: synergistic significant improvement, ○; enhancement, ×; equal or negligible improvement

From the above description, those skilled in the art to which the present invention pertains will understand that the present invention may be embodied in other specific forms without changing the technical spirit or essential characteristics thereof. In this regard, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. The scope of the present invention should be construed as being included in the scope of the present invention, rather than the above detailed description, all changes or modifications derived from the meaning and scope of the claims described below and their equivalents.

Claims (8)

An antiseptic system comprising a preservative and sodium citrate as active ingredients, which has improved antibacterial activity compared to a preservative alone,
The preservative is at least one selected from the group consisting of phenoxyethanol, 1,2-hexanediol and hydroxyacetophenone.
According to claim 1,
Wherein the preservative is included in an amount of 0.1 to 10% based on the total mass of the preservative system.
delete According to claim 1,
The sodium citrate will be included in an amount of 0.1 to 1% based on the total mass of the preservative system.
delete According to claim 1,
Escherichia coli (Escherichia coli ), Pseudomonas aeruginosa ( Pseudomonas aeruginosa ), Staphylococcus aureus ( Staphylococcus aureus ), Candida albicans ( Candida albicans ), and Aspergillus bra Siliensis ( Aspergillus brasiliensis ) The antiseptic system that exhibits antibacterial activity against one or more strains selected from the group consisting of.
A cosmetic composition comprising the preservative system of any one of claims 1, 2, 4 and 6.
8. The method of claim 7,
The cosmetic composition is Escherichia coli (Escherichia coli), Pseudomonas aeruginosa ( Pseudomonas aeruginosa ), Staphylococcus aureus (Staphylococcus aureus) compared to the composition containing the same amount of the same type of preservative. ), Candida albicans (Candida albicans), and Aspergillus brasiliensis ( Aspergillus brasiliensis ) Growth inhibition of one or more strains selected from the group consisting of, growth inhibition, or inhibiting both growth inhibition, a cosmetic composition.

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