KR102093827B1 - Cosmetic compositions containing poly(butyl cyanoacrylate) - Google Patents

Abstract

The present invention relates to an antiseptic cosmetic composition having excellent antimicrobial and antiseptic activity by mixing polybutyl cyanoacrylate, alkylglycerin ether and 1,2-alkanediol in a certain ratio, and having less skin irritation than chemical preservatives. will be. The cosmetic composition of the present invention exhibits excellent antimicrobial and preservative effects without adding a chemical preservative, and a preservative effect and a safe cosmetic composition for the skin can be obtained.

Description

Cosmetic preservative composition comprising poly (butyl cyanoacrylate) {COSMETIC COMPOSITIONS CONTAINING POLY (BUTYL CYANOACRYLATE)}

The present invention relates to a cosmetic preservative composition containing poly (butyl cyano acrylate), poly (butyl cyano acrylate), alkyl glycerin ether and 1,2-alkanediol mixed in a suitable amount to have a very good antibacterial activity The present invention relates to a cosmetic preservative composition having a broad antibacterial spectrum, having excellent antiseptic ability for cosmetics, and also having very little physicochemical stability and an effect on cosmetic formulations, and not adding a chemical preservative to cause skin irritation. .

When the existing cosmetic composition is manufactured or distributed without adding a chemical preservative (labeled ingredients), microbial contamination may easily occur during the manufacturing process, distribution process, or consumer use, thereby causing a problem in skin safety. Labeled ingredients refer to ingredients that must be labeled by the Ministry of Food and Drug Safety and legally designated as permitted when used for fear of harm to the human body, and include tar color, antiseptic, antiseptic, antihistamine, sunscreen, gold leaf, hair Phosphate is a product of all phosphates.

Preservative among the designated ingredients refers to a drug that prevents decay of substances, and it is an antiseptic that prevents animal and vegetable organic matters from decaying by the action of microorganisms, and a drug that is added for preservation for preservation purposes is a preservative. In products such as food, pharmaceuticals, and cosmetics, preservatives that prevent spoilage by microorganisms are essential to maintain quality for a long time. In particular, in the case of cosmetics, which has a relatively long shelf life, a high probability of contact with microorganisms in the process of use and storage, and a combination of various carbon and nitrogen sources, and a high moisture content essential for microbial growth, preservative treatment is more important than food. Has more needs and problems for.

If an appropriate preservative system is not established in cosmetics, microbes multiply during the manufacturing process, distribution process, and consumer use process, causing odor and odor due to metabolism of microorganisms, or causing changes in product properties due to discoloration and product pH changes. In addition, it has a harmful effect on the human body, such as inducing stimulation to the human body due to the metabolites and microorganism itself generated during the microbial metabolism process. In particular, pathogenic microorganisms cause disease.

Therefore, in cosmetics, preservatives are not simply additives added to prevent product spoilage, but irreversibly or accidentally applied to products from the time the cosmetics are manufactured at the factory to the end of the use of the product by the consumer. It can be said to be a generic term for additives added for the purpose of preventing the deterioration, deodorization, and deterioration of cosmetics caused by the growth of microorganisms by inhibiting the growth of contained or contaminated microorganisms.

When preservatives are properly added to cosmetics, it not only prevents microbial contamination of products due to microbial contamination during raw materials and manufacturing processes, but also prevents microbial contamination during consumer use and storage to maintain product properties and ensure product safety. And safety, minimizing the health risks to consumers.

The types of preservatives used in cosmetics are very diverse, and as the production of cosmetics is increased, preservatives are becoming more diverse and the amount of use is also increasing. On the other hand, preservatives, on the other hand, can affect the public health, so in Korea, the type and formulation limit is designated as a labeling ingredient by the Ministry of Food and Drug Safety Notification. Cosmetic preservatives mainly consist of artificially synthesized materials that are easy to manufacture, low in cost, and easy to mass-produce. Representative cosmetic preservatives are paraoxybenzoic acid esters such as methyl paraben, ethyl paraben, propyl paraben, butyl paraben and quaternium-15, imida Chemicals such as Imidazolidinyl Urea Diazolidinyl Urea, Phenooxyethanol, Benzalkonium Chloride, Gluconic Acid Chlorohexidine gluconic acid and Triclosan And preservatives.

However, these chemical preservatives inhibit the growth of microorganisms to give safety and stability to cosmetics, but they also cause irritation to the skin of users. A typical example is formalin glass-type preservatives. Formalin-type preservatives, including diazolidinyl urea and imidazolidinyl urea, have recently been reviewed for safety worldwide, and their use has been decreasing. Its use is limited to some wash-off products, and in some countries, including Japan, its use is prohibited or its use is strictly limited. Formalin-free preservatives are known to slowly release the formalin groups contained in the structure over time, and it is known that free formalin not only causes skin irritation but also has the potential to cause cancer.

In addition, even the most preservatives as chemical preservatives and even parabens preservatives used universally in cosmetics and pharmaceuticals are skin allergies (Andrea Counti et al., Contact Dermatitis, 1997, 37, 35-36) and the potential as environmental hormones (Edwin, etc.). , Toxicology and Applied Pharmacology, 1998, 153, 12-19) and inducing resistant bacteria. In addition, the use within the permitted standards has been distrusted, and new problems such as acute and chronic toxicity and mutagenesis due to continuous accumulation in the body are emerging (Shin Dong-hwa, food science and industry, 1990, 23 (4) 68-72). .

As described above, the side effects of the chemical preservatives degrade the user's confidence in the product, ultimately acting as a consumer complaint factor for cosmetics and beauty products.

Therefore, research on anti-preservative systems that reduce the amount of preservatives in cosmetics or use no preservatives is actively being conducted, and also, it solves side effects of existing chemical preservatives and has less irritation to the skin for product safety. The need for natural preservatives that are not toxic and resistant is emerging.

To date, studies on natural antimicrobial substances have been reported, including alkaloids, flavonoids, phytoalexin, antimicrobial peptides and antimicrobial properties such as organic acids and fatty acids. And chelate (EI-shenawy, MA et al., J. Food Protec., 1989, 52 (11), 771-778) (Bizri, JN et al., J. Food Science , 1994, 59 (1), 130-135).

However, some of these natural antimicrobial ingredients, such as spices and herbal medicines, are too dark in color and have strong characteristics of raw materials, so their use is limited or unsuitable for cosmetics that require beautiful product properties. It is not suitable as a cosmetic raw material because it affects the formulation stability, such as affecting the emulsification system. In addition, the characteristics of natural antibacterial materials as antibacterial materials have a narrower antimicrobial spectrum than chemical preservatives, and the antimicrobial active ingredients contained in plant extracts often have very low physicochemical stability against heat, light, oxygen, etc. , Due to the limitation as a natural material, such as the problem that the antimicrobial active ingredient is decomposed during the distribution period and cannot provide sufficient antiseptic activity in actual use by consumers, it has not been commercialized. Commercially available natural antibacterial agents include hinokiitiol, a cypress extract, magnool, a magnolia extract, and grapefruit seed extract (DF-100), but most have economical efficiency, narrow antimicrobial spectrum, and limited use. Due to problems, a more advanced natural antibacterial agent is required. Antibacterial peptides have also been studied as an alternative for the combined effect (Giacometti A et al., J. Antimicrob. Chemother 2000, 46 (5), 807-811), but these are peptides due to their physicochemical properties and are relatively weak to heat. It is very vulnerable to existing proteolytic enzymes, and thus has limitations in general use. Moreover, they lack the selectivity for bacteria, fungi, and animal cells due to their mechanism of action, so they are also limited to use as pharmaceuticals. It is relatively expensive (Lee JH et al., Protein. Expr. Purif, 1998 Feb; 12 (1), 53-60).

In Patent No. 10-0481637, tetraacetyl phytosphingosine, pentylene glycol, polyglyceryl-2 laurate / glyceryl caprate / polyglyceryl-10 laurate, grapefruit seed extract, cordyceps extract added according to each prescription Although it discloses a preservative-free cosmetic composition characterized by having one, it is a preservative-free cosmetic composition using a chemical synthetic raw material except for grapefruit seed extract and cordyceps extract. It has the potential to cause skin irritation and solubility in the case of tetraacetylphytosphingosine. There are problems such as low application to cosmetics requiring various types of formulations. Patent Publication No. 10-2002-0066118 discloses a technique for a natural antibacterial agent comprising a chito-oligosaccharide complex and a golden extract. However, the natural antibacterial agent has a low stability like the existing natural antibacterial agent, is more effective against gram-positive bacteria than gram-negative bacteria, shows relatively weak antimicrobial activity against fungi, and has a narrow antibacterial spectrum, such as insignificant antibacterial activity against the genera containing chitosan in the cell wall As it indicates, there are many difficulties in commercialization due to limitations in the range of use as well as problems in the formulation (Riccardo M et al., Antimicrobial Society and Chemotheraphy, 1990, 34, 2019-2023). In addition, Patent Publication No. 10-2004-0080717 discloses a cosmetic composition containing chitosan and grapefruit seed extracts having antiseptic and antibacterial activity, but in the case of grapefruit seed extracts and chitosan, Pseudomonas aeroginosa It has a weak antibacterial activity against Gram-negative bacteria such as, and it is difficult to apply to various types of cosmetics due to problems such as limited application to cosmetics due to strong positive charge of chitosan.

Thus, the present inventors have been researching various antibacterial substances in order to solve the side effects of the existing chemical preservatives and to overcome the problems of existing natural antibacterial agents such as cosmetic raw materials. Representatively, the antibacterial agent for Gram-negative bacteria using the basic structure and antibacterial activity of polybutyl acrylate (Japanese Patent 5618284; September 26, 2014), is an antibacterial cosmetic containing a staining countermeasure, and is a Gram-positive bacterial antibacterial agent and antibacterial activity enhancer (Japan Patent 5397881; 2013.11.1.) Cyanoacrylate-based polymer particles and manufacturing method thereof (Japanese Patent 49632221; 2012.4.6.), Antibacterial agent (Japanese Patent Publication 2016-50194; 2016.4.11.), Contains amino acids Cyanoacrylate polymer particles (Japanese Patent 5663741; 2014.12.19.), Gram-positive bacteria antibacterial agent (Japanese Patent 5907515; 2016.4.1.), Anti-cell effect and new adjustment method showing higher order structure (Japanese patent) 6108371; 2017.3.17.), Plant hospital bacteria antibacterial agent (Japanese Patent 6192543; 2017.8.18.), Etc. were invented.

The present invention is intended to solve the problems of the prior art, and more specifically, in order to solve the side effects of the existing chemical preservatives, such as the possibility of skin irritation, and to overcome the problems of the existing natural antibacterial agents as cosmetic raw materials, the antibacterial spectrum is very wide and cosmetic It is intended to provide an excellent cosmetic preservative composition having excellent antiseptic ability, and very little effect on physical and chemical stability and cosmetic formulation.

While studying the antibacterial and preservative properties as cosmetic raw materials, the present inventors used Gram-negative bacteria, Gram-positive bacteria, and fungi when used in an appropriate combination of poly (butyl cyanoacrylate) aqueous solution, alkyl glycerin ether, and 1,2-alkanediol. It has a very good antibacterial activity against fungi including yeast and yeast, it has been found that the antibacterial spectrum is very wide, and it has excellent antiseptic ability against cosmetics, and also has very little impact on physical and chemical stability and cosmetic formulation, and existing chemical preservatives. Compared to the fact that the possibility of skin irritation is very low, the preservative composition for cosmetics was invented.

The composition according to the present invention contains a poly (butyl cyanoacrylate) aqueous solution, which has antimicrobial action in an innovative manner different from the existing preservatives or preservatives, and has the advantage of being capable of antibacterial action in a small amount. However, it was found that this material has excellent antimicrobial activity and is not effective in the spectrum of a wide range of microorganisms because it is limited to bacteria, and has a disadvantage in terms of formulations in which turbidity occurs and separation occurs when mixed with other materials. In order to compensate for these shortcomings, the present invention was completed by preparing a mixture by adding 1,2-alkanediol, which acts as an excellent preservative and an alkylglycerin ether having excellent antibacterial activity to various bacteria, and helps in stability.

The cosmetic preservative composition according to the present invention contains a poly (butyl cyanoacrylate) aqueous solution, an alkylglycerin ether and 1,2-alkanediol in appropriate proportions to gram-negative bacteria and gram-positive bacteria, fungi including mold and yeast. It has a very good antibacterial activity, and has a wide antibacterial spectrum, so it has excellent antiseptic ability for cosmetics, very little physicochemical stability and an effect on cosmetic formulations, and does not add a separate chemical preservative. It is characterized by low. In addition, the composition of the present invention is characterized in that it is a cosmetic that minimizes the possibility of skin irritation by antibacterial action even in a smaller amount than the existing materials by combining with substances that exhibit synergistic effects.

The present invention will be described in more detail as follows.

The cosmetic preservative composition according to the present invention contains a poly (butyl cyanoacrylate) aqueous solution, and this material has an advantage of antimicrobial action and a small amount of antimicrobial action in an innovative manner different from a preservative or preservative. However, this material has an excellent antibacterial action limited to bacteria, and it is difficult to exhibit a relatively excellent antibacterial effect in fungi, yeast, etc., and there is a disadvantage in terms of a formulation in which separation occurs or the formulation becomes cloudy when mixed with other substances. To compensate for these shortcomings, a cosmetic preservative was prepared by adding alkylglycerin ether, which exhibits excellent antibacterial activity against various bacteria, and 1,2-alkanediol, which serves as an excellent preservative and stability.

The cosmetic preservative composition according to the present invention is a cosmetic preservative containing one or two selected from alkylglycerin ether and 1,2-alkanediol and poly (butyl cyanoacrylate) in aqueous solution. The cosmetic preservative composition according to the present invention contains one or two selected from alkyl glycerin ether and 1,2-alkanediol in a certain ratio in a poly (butyl cyanoacrylate) aqueous solution, and gram-negative bacteria and gram-positive bacteria , Shows very good antibacterial activity against fungi including mold and yeast, has a wide antibacterial spectrum, has excellent antiseptic ability against cosmetics, is also physically and chemically stable, has very little effect on cosmetic formulations, and adds chemical preservatives It is characterized by low probability of causing skin irritation. In addition, the cosmetic preservative composition according to the present invention is characterized by minimizing the possibility of skin irritation by antibacterial action even in a smaller amount than conventional materials by combining with substances that exhibit a synergistic effect.

Look at the components constituting the cosmetic preservative composition of the present invention.

Poly (butylcyanoacrylate) {Poly (butylcyanoacrylate)} is an antimicrobial agent for Gram-positive bacteria, which is a polymer particle having a structure represented by Formula 1 below, as mentioned in Japanese Patent JP 5618284.

<Formula 1>

(However, Z is a cyano group, R is a butyl group.)

Briefly summarized, poly (butylcyanoacrylate) binds to the cell wall of Gram-positive bacteria, adheres to the cell membrane of mammals, has a particle size of 5 μm or less, and effectively contains particles that do not contain any antibacterial active ingredients against Gram-positive bacteria. As a gram-positive bacterial antibacterial agent contained as a component, the particles contain the above formula (1) in a repeating unit.

Alkyl glycerin ether is an organic compound of glyceryl ether and is a type of glycerin, and this material is mainly used as a skin conditioning agent. A typical alkyl glycerin ether is ethylhexyl glycerin, and the name of IUPAC is 3-[(2-Ethylhexyl) oxy] -1,2-propanediol, and the structure is as shown in Chemical Formula 2. It is insoluble in water, so only a small amount can be dissolved.

<Formula 2>

1,2-Alkanediol is a structure in which one alcohol group is attached to the first and the second of a linear alkyl chain, and various compounds exist depending on the length of the alkyl chain, and it is a surfactant structure having both hydrophobic and hydrophilic groups. This material acts as an antimicrobial and antioxidant effect, as a preservative for cosmetics, and also blocks moisture by evaporating the skin. It is a substance that mixes well with water and has emulsifying properties for oil. Representative 1,2-alkane diols include 1,2-pentylene glycol, 1,2-hexanediol, 1,2-octanediol, and the like.

The cosmetic preservative composition of the present invention is a substance that enhances the antibacterial spectrum by mixing an aqueous poly (butyl cyanoacrylate) solution with an alkylglycerin ether and 1,2-alkane diol. The existing antibacterial method of the poly (butyl cyanoacrylate) aqueous solution is innovative and has excellent antimicrobial properties, but has the disadvantage of weak microbial antibacterial activity against fungi, such as bacteria. Accordingly, the antimicrobial action against microorganisms other than bacteria, which was insufficient with only a poly (butyl cyanoacrylate) aqueous solution, was complemented by mixing with alkylglycerin ether and 1,2-alkanediol, and thus the cosmetic preservative composition of the present invention The present invention has been completed by showing a broad antibacterial spectrum.

The cosmetic preservative composition of the present invention is a substance that enhances antibacterial activity by mixing alkyl glycerin ether and 1,2-alkanediol in a poly (butyl cyanoacrylate) aqueous solution. As a result of conducting FIC synergistic test with poly (butyl cyanoacrylate) aqueous solution with each of alkylglycerin ether and 1,2-hexane diol, the FIC index has a synergistic effect with a value of 1 or less in bacteria with antibacterial activity. It showed an additive effect in yeast and fungi, which had no antibacterial activity. As a result, even when each substance is used in a lower concentration, it may exhibit sufficient antibacterial activity. Thus, skin irritation could be minimized by reducing the concentration required for the antibacterial action.

The poly (butylcyanoacrylate) mixture is an aqueous solution in which poly (butylcyanoacrylate) is dispersed in a small size in water, and thus does not mix well with alkylglycerin ethers such as ethylhexylglycerin. To this end, 1,2-hexanediol was added so that the two substances could be mixed well, solubility was increased, and at the same time, an effect of increasing antibacterial activity could be obtained.

The present invention is 0.05 to 5.0% by weight, based on 0.5% aqueous solution of poly (butylcyanoacrylate) in aqueous solution as a cosmetic preservative, 0.05 to 5.0% by weight of alkylglycerin ether, and 0.01 to 5.0% by weight of 1,2-alkanediol 2 It relates to a cosmetic composition containing a component of more than one species, without a separate chemical preservative. The poly (butyl cyanoacrylate) component dissolves well in the range of 0.1 to 10.0% by weight aqueous solution. The poly (butyl cyanoacrylate) aqueous solution is preferably 0.05 to 5.0% by weight in the entire cosmetic composition on the basis of 0.5% aqueous solution. If the content is less than 0.05% by weight, the preservative function decreases, and when it exceeds 5.0% by weight, it is uneconomical. In terms of this, poly (butyl cyanoacrylate) contains 0.0025 to 2.5% by weight of the entire cosmetic composition. Alkyl glycerin ether and 1,2-alkanediol also decrease the preservative function when the concentration is lower than the minimum concentration, and are uneconomical when the concentration exceeds the maximum concentration.

The cosmetic composition containing the cosmetic preservative composition according to the present invention, in addition to the materials constituting the cosmetic preservative composition, preferably within the scope of not impairing the main effect intended by the present invention, other main effects It may also contain ingredients and the like. The cosmetic preservative composition may preferably be present in 0.11 to 15.0% by weight relative to the entire cosmetic composition.

Cosmetic compositions comprising the cosmetic preservative compositions of the present invention are aqueous, aqueous-alcoholic, oily solutions, oil-in-water, water-in-oil, multiple emulsions, aqueous gels, oily gels, liquid anhydrous products, pasty anhydrous products, solid anhydrous products, Oil dispersion in aqueous phase with globules, ionic lipid vesicles and nonionic lipid vesicles, and more preferably ionic and / or nonionic lipid vesicles.

The cosmetic composition comprising the cosmetic preservative composition of the present invention may be somewhat fluid, and may have the appearance of a white or colored cream, ointment, milk lotion, serum, essence, paste or mousse. It may optionally be applied to the skin in the form of an aerosol, or it may be in the form of a solid, for example a stick. It can also be used as a skin care product and / or makeup product.

Cosmetic compositions comprising the cosmetic preservative composition of the present invention in a known manner are also customary auxiliaries in the cosmetic field, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic actives, preservatives, antioxidants, solvents, fragrances, fillers, blockers, Pigments, odorants and dyes. The amount of these various adjuvants is an amount conventionally used in the art, for example, 0.01 to 20% by weight based on the total weight of the composition. Depending on their nature, these adjuvants can be introduced into the fatty phase, aqueous phase, lipid vesicles and / or particles. In any case, the adjuvant and its proportions will be selected so as not to adversely affect the desirable properties of the cosmetic composition according to the invention.

The cosmetic composition of the present invention may include an excipient. The excipient is typically used in cosmetics, and typical examples thereof are water, physiological saline, and glycerol.

The cosmetic composition of the present invention is manufactured in the form of basic cosmetic products such as flexible lotion, milk lotion, nourishing cream, massage cream, essence, cleansing foam, cleansing water, pack or vodioyl, and color cosmetics such as foundation, lipstick, mascara or makeup base can do. When the cosmetic composition of the present invention is used as a cleaning agent, it can be prepared as a face wash and a bath agent.

As described above, the cosmetic composition containing the cosmetic preservative composition according to the present invention and without a chemical preservative contains poly (butylcyanoacrylate) and alkylglycerin ether, 1,2-alkanediol in appropriate proportions, It exhibits very good antibacterial activity, has a broad antibacterial spectrum, has excellent antiseptic ability for cosmetics, has very little effect on physicochemical stability and cosmetic formulations, and is not likely to cause skin irritation by not adding chemical preservatives.

Hereinafter, the configuration of the present invention will be described in detail through the following examples and experimental examples, which are presented to help the understanding of the present invention, but the present invention is not limited thereto.

< Comparative example  1>

50 g of poly (butyl cyanoacrylate) 0.5% aqueous solution and 50 g of 1,3-butylene glycol are stirred for 10 minutes at a 1: 1 weight ratio to prepare 100 g of a mixture.

< Example  1>

100 g of the mixture is prepared by stirring 50 g of a poly (butyl cyanoacrylate) 0.5% aqueous solution and 50 g of 1,2-hexanediol for 10 minutes at a 1: 1 weight ratio.

< Example  2>

50 g of a poly (butyl cyanoacrylate) 0.5% aqueous solution and 50 g of ethylhexylglycerin in a 1: 1 weight ratio were added and stirred for about 10 minutes to prepare 100 g of a mixture.

< Experimental example  1>

In order to measure the antibacterial activity of the materials, the minimum inhibitory concentration was measured using a solid culture dilution method. The strains used were Staphylococcus aureus ATCC 6538P, Gram-negative Escherichia coli (Escherichia coli ATCC 8739), Pseudomonas aeruginosa ATCC 9027), as yeast, Candida albicans ATCC 10231, and as bacteria, Aspergillus niger ATCC 22343.

Bacterium was used tryptic soy broth, and the cells were inoculated with the medium and pre-incubated for 24 hours in a 37 ° C shake incubator. Potato dextrose broth was used for cultivation of yeast, and bacteria were inoculated into the medium and pre-incubated for 2 days in a 25 ° C shake incubator. Potato dextrose agar was used for the culture of filamentous fungi, and the bacteria were inoculated into the medium and pre-cultured for 7 days in a 25 ° C incubator.

For a more specific antimicrobial test, in the case of bacteria, tryptic soy broth is inoculated with bacteria and prepared by pre-incubation at 37 ° C for 24 hours, and in the case of yeast, bacteria in Potato dextrose broth After inoculation and pre-incubation at 25 ° C for 2 days, the filamentous fungus was inoculated into Potato dextrose agar and pre-incubated for 7 days in a 25 ° C incubator, and then formed on the surface of the medium using sterilized cotton swabs. The spores of filamentous bacteria were collected and diluted in sterile saline.

On the other hand, 200 μl of each substance diluted to the appropriate concentration in tryptic soy agar medium and potato dextrose agar medium for each test species in a sterile 96-well plate, and the control group are tryptic soy agar medium and potato dextrose agar medium Add 200 μl.

Thereafter, each pre-cultured test bacterium is inoculated to each plate at a final concentration of about 1 × 10 ⁶ CFU for bacteria, and inoculated to each plate at a yeast concentration of about 1 × 10 ⁵ CFU for yeast. , In the case of filamentous fungi, each plate is inoculated with a fungal concentration of about 1 × 10 ⁴ CFU. In each well plate, bacteria are cultured for 24 hours at 37 ° C, and yeast and filamentous fungi are cultured for 3 days in a 25 ° C incubator, and then observed for colony formation in each plate to minimize the minimum concentration of antibacterial agent in the plate compartment where growth is not recognized. Let the concentration be (MIC, Minimum inhibitory concentration).

microbe Minimum inhibitory concentration (MIC) (% by weight) Poly (butyl cyanoacrylate) 0.5% aqueous solution alone Ethylhexyl glycerin (alone) 1,2-hexanediol (alone) 1,3-butylene glycol (alone) Comparative Example 1 Example 1 Example 2 Remark S. aureus 10.0 0.1 2.0 20.5 15.0 1.26 1.88 E. coli 10.0 0.4 1.0 25.0 20.0 5.1 5.5 P. aeruginosa 20.0 0.4 1.0 20.5 15.0 2.7 5.5 C. albicans > 40.0 0.2 2.0 25.0 25.0 0.83 2.7 A. niger > 40.0 0.1 1.0 25.0 25.0 0.73 1.7

As shown in Table 1, in the case of a poly (butyl cyanoacrylate) aqueous solution, it exhibited excellent antibacterial activity even at a concentration of 10% by weight or less with respect to Staphylococcus aureus, which is a gram-positive bacterium, and is also relatively superior to E. coli and Pseudomonas aeruginosa, which are Gram-negative bacteria. Although it showed antibacterial activity, it showed very weak antibacterial activity against Candida yeast and black yeast.

In the case of alkyl glycerin ethers such as ethylhexyl glycerin, it showed excellent antibacterial activity even at concentrations of 0.2% by weight or less for Candida yeast and Bukgukgyun. Showed.

In the case of 1,2-hexane diol, it showed excellent antibacterial activity even at a concentration of 1.0% by weight or less for Candida yeast and Bukgukgyun, and also had relatively sufficient antibacterial activity against Staphylococcus aureus and Gram-negative bacteria, and E. coli and Pseudomonas aeruginosa. Showed.

The use of 1,3-butylene glycol alone and the mixture of 1,3-butylene glycol and poly (butylcyanoacrylate) (Comparative Example 1) showed no antibacterial activity at all.

On the other hand, alkyl glycerin ether (Example 1) and hexanediol (Example 2) mixed with poly (butyl cyanoacrylate) all showed broad antibacterial efficacy.

< Experimental example  2>

The FIC (Fractional Inhibitory Concentration) index was measured using the Agar Serial Dilution Method and the Checker Board Method to measure the synergy and the degree of synergy between the substances. The strains used were Staphylococcus aureus ATCC 6538P, Gram-negative E. coli ( Escherichia coli ATCC 8739), Pseudomonas aeruginosa ATCC 9027), as yeast, Candida albicans ATCC 10231, and as bacteria, Aspergillus niger ATCC 22343.

Bacterium was used tryptic soy broth, and the cells were inoculated with the medium and pre-incubated for 24 hours in a 37 ° C shake incubator. Yeast was inoculated with bacteria in Potato dextrose broth and pre-incubated for 2 days in a 25 ° C shake incubator. The filamentous fungus was inoculated into a potato dextrose agar, and pre-cultured for 7 days in a 25 ° C incubator.

For a more specific antimicrobial test, in case of bacteria, tryptic soy broth is inoculated with bacteria, and prepared by pre-incubation at 37 ° C for 24 hours. In the case of yeast, bacteria are inoculated into Potato dextrose broth. Pre-incubation at 25 ° C for 2 days, and the filamentous fungus was inoculated into Potato dextrose agar and pre-incubated for 7 days in a 25 ° C incubator. The spores were collected and diluted with sterile saline.

After that, 100 μl of a solution diluted with tryptic soy agar medium and potato dextrose agar medium with 100 μl of poly (butyl cyanoacrylate) aqueous solution was added to 7 lines of the 96-well plate on the vertical axis, and one line was a pure tryptic as a comparison group. Soy agar and potato dextrose agar were added. At this time, twice the MIC of each bacterium of the substance was filled with a double dilution method with the highest concentration. On the horizontal axis of the 96-well plate, dilute ethylhexylglycerin and 1,2-hexanediol on tryptic soy agar and potato dextrose agar, respectively, in 7 rows, and fill 100 μl each. Tryptic soy agar and potato dextrose agar were added. At this time, twice the MIC of each fungus of the two substances was filled with a double dilution method with the highest concentration.

Thereafter, each pre-cultured test bacterium is inoculated to each plate at a final concentration of about 1 × 10 ⁶ CFU for bacteria, and inoculated to each plate at a yeast concentration of about 1 × 10 ⁵ CFU for yeast, In the case of filamentous fungi, each plate was inoculated at a fungal concentration of about 1 × 10 ⁴ CFU. Each well plate was cultured at 37 ° C for 24 hours, and yeast and filamentous fungi were cultured for 3 days in a 25 ° C incubator. After observing the colony formation in each plate, the concentration of the cells in which growth was not recognized was determined as the bacteria inhibitory concentration. Confirmed.

The synergistic effects between substances were determined by calculating the value of ΣFIC (Fractional inhibitary concentration). The ΣFIC value is obtained by adding the FIC value of each substance, and the FIC value of each substance is obtained by (concentration of substance in mixture) / (MIC of pure substance). Among the concentrations in which bacteria were inhibited, the lowest value of ΣFIC was set as the FIC index of synergy. At this time, when the FIC index value was less than 0.5, it was judged to show strong synergy when it was less than 0.5, weak synergy when it was 0.5 or more and less than 1.0, subadditive when it was 1.0 or more and less than 2.0, and hostile when it was 2.0 or more.

microbe FIC index (MIC%) Poly (butyl cyanoacrylate) 0.5% aqueous solution alone Ethylhexyl glycerin (alone) 1,2-hexanediol (alone) 1,3-butylene glycol
(Exclusive) Comparative Example 1 Example 1 Example 2 Remark S. aureus 10.0 0.1 2.0 20.5 > 1.50
(15.0%)
Additive effect 0.25
(1.26%)
Strong synergy 0.28
(1.88%)
Strong synergy E. coli 20.0 0.4 1.0 25.0 1.20
(20.0%)
Additive effect 0.5
(5.1%)
Strong synergy 0.75
(5.5%)
Weak synergy P. aeruginosa 20.0 0.4 1.0 20.5 1.05
(15.0%)
Additive effect 0.62
(2.7%)
Weak synergy 0.75
(5.5%)
Weak synergy C. albicans > 40.0 0.2 2.0 25.0 > 1.8
(25.0%)
Additive effect > 1
(0.83%)
Additive effect > 1
(2.7%)
Additive effect A. niger > 40.0 0.1 1.0 25.0 > 1.8
(25.0%)
Additive effect > 1
(0.73%)
Additive effect > 1
(1.7%)
Additive effect

* FIC notation; <0.5 Strong Synergy (Marked Synergy), Weak Synergy (0.5 ~ 1.0), Subadditive (1.0 ~ 2.0), Hostile Effect (2.0).

Synergistic effect of both substances and Gram-negative and Gram-positive bacteria as a result of the checker board synergy test of each of the poly (butyl cyanoacrylate) aqueous solution, alkylglycerin ether, and 1,2-hexanediol, which are components of the mixture. And showed an additive effect on mold and yeast. Since the poly (butyl cyanoacrylate) aqueous solution shows a synergistic effect with both substances, it was confirmed that an appropriate antimicrobial effect can be exhibited even in a smaller amount than a conventional preservative in an appropriate ratio.

< Experimental example  3>

Although the substances in the mixture each had a synergistic effect with each other, when the two were mixed with each other, the formulation stability was not good, and the mixing ratio of each compound was mixed in an appropriate ratio to increase the stability in the emulsion state.

< Example  3-6>

A poly (butyl cyanoacrylate) 0.5% aqueous solution and 1,2-hexanediol were stirred for 5 minutes at each weight ratio, and then ethylhexylglycerin was added for each content in Table 3 and stirred for 5 minutes to prepare a cosmetic preservative composition 100g To prepare.

ingredient Comparative Example 1 Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Poly (butyl cyanoacrylate) aqueous solution (0.5%) 50% 50% 50% 50% 50% 70% 30% 1,3 butylene glycol 50% - - - - - - Ethylhexylglycerin - - 50% 30% 20% 15% 35% 1,2-hexanediol - 50% - 20% 30% 15% 35%

In order to confirm the properties and stability as a preservative of the composition, the stability of the compositions prepared in Examples 1 to 6 was stored and observed for one week, and the results are shown in Table 4.

division Comparative Example 1 Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Low temperature stability
(5 ℃) stability Instability
(Precipitation) Instability
(detach) stability stability stability Instability
(detach) Room temperature stability
(25 ℃) stability stability Instability
(detach) stability stability stability Instability
(detach) High temperature stability
(40 ℃) stability Instability
(Precipitation) Instability
(detach) stability stability stability Instability
(detach)

< Experimental example  4>

In order to measure the antibacterial activity of the material by adopting only the high stability among the above materials, the minimum inhibitory concentration was measured using the Agar Serial Dilution Method. The strains used were Staphylococcus aureus ATCC 6538P and Escherichia as Gram-negative bacteria. coli ATCC 8739), Pseudomonas aeruginosa ATCC 9027, and Candida yeast ( Candida albicans ATCC 10231), a black bacterium ( Aspergillus niger ATCC 22343) was used as a filamentous fungus.

Bacterium was used tryptic soy broth, and the cells were inoculated with the medium and pre-incubated for 24 hours in a 37 ° C shake incubator. Potato dextrose broth was used for cultivation of yeast, and bacteria were inoculated into the medium and pre-incubated for 2 days in a 25 ° C shake incubator. Potato dextrose agar was used for the culture of filamentous fungi, and the bacteria were inoculated into the medium and pre-cultured for 7 days in a 25 ° C incubator.

For a more specific antibacterial test, in case of bacteria, tryptic soy broth is inoculated with bacteria, and prepared by pre-incubation at 37 ° C for 24 hours. In the case of yeast, bacteria are inoculated into Potato dextrose broth. Pre-incubation at 25 ° C for 2 days, and the filamentous fungus is inoculated into a potato dextrose agar and pre-cultured for 7 days in a 25 ° C incubator, after which the fungus is formed on the surface of the medium using a sterile swab. Spores were collected and diluted in sterile saline.

On the other hand, 200 μl of each substance diluted to the appropriate concentration in tryptic soy agar medium and potato dextrose agar medium for each material and test species in a sterile 96-well plate is added, and the control group is tryptic soy agar medium and potato dextrose Add 200 μl to agar medium.

Thereafter, each pre-cultured test bacterium is inoculated to each plate at a final concentration of about 1 × 10 ⁶ CFU for bacteria, and inoculated to each plate at a yeast concentration of about 1 × 10 ⁵ CFU for yeast, In the case of filamentous fungi, each plate is inoculated at a fungal concentration of about 1 × 10 ⁴ CFU. Each well plate is cultured at 37 ° C for 24 hours, and yeast and filamentous fungi are cultured for 3 days in a 25 ° C incubator, and then observed for colonization in each plate to minimize the minimum concentration of antibacterial agent in the plate compartment where growth is not recognized. Let the concentration be (MIC, Minimum inhibitory concentration).

division Minimum inhibitory concentration (% by weight) S. aureus E. coli P. aeruginosa C. albicans A. niger Comparative Example 1 10% 20% 20% 40% or more 40% or more Example 3 0.4% 0.8% 0.8% 0.4% 0.4% Example 4 0.4% 0.8% 0.8% 0.5% 0.4% Example 5 0.2% 0.5% 0.5% 0.8% 1.2%

As a result of testing the antibacterial activity of those having high formulation stability among the above substances, the antibacterial activity of the poly (butyl cyanoacrylate) aqueous solution of Comparative Example 1 is suitable for alkylglycerin ethers such as ethylhexylglycerin and 1,2-hexanediol. By adding at a ratio, the antibacterial activity increased significantly, and it showed antibacterial activity against Candida yeast and filamentous fungi, which showed no antibacterial activity. Especially, when the three compounds were mixed at the same time, the minimum inhibitory concentration was the lowest and the physicochemical stability increased.

< Experimental example  5>

A emulsion containing the compound and an existing chemical preservative was prepared.

Cosmetics used in the experiment are in the form of emulsion, the composition is shown in Table 6. First, the a) phase recorded in Table 6 is heated and stored at 70 ° C. To this, b) phase is added, and after pre-emulsification, it is uniformly emulsified with a homomixer, and c) phase is added thereto, and then cooled slowly. After the cooling was completed, the compound (D) or a chemical preservative was added and stirred uniformly to prepare emulsions (Examples 7 to 14, Comparative Examples 2 and 3).

division ingredient weight% end Purified water 70.0 Disodium LED 0.01 Panthenol 0.2 Betaine 3.0 Butylene Glycol 4.0 glycerin 3.0 I Butylated Hydroxy Toluene 0.02 Stearic acid 0.5 Cetearyl alcohol 0.5 Glycerylcetearate 0.3 Polysorbate 60 0.6 Methylglucose sesquistearate 1.3 Polyethylene glycol monostearate 1.0 Butyrodpermium PARKII 2.0 Tocopheryl Acetate 0.1 Mineral oil 10.0 Dimethicone 0.3 Acrylate / sodium acrylamide copolymer 0.9 Cyclomethicone 1.0 All Triethanolamine 0.1 Purified water 1.0 la Antibacterial compound or preservative 1.0 Purified water Balance

< Example  7 to 10>

According to the composition of Table 7, the emulsions of Examples 7 to 10 containing the compound were prepared by the method of <Experimental Example 5>.

ingredient Example 7 Example 8 Example 9 Comparative Example 2 Comparative Example 3 Poly (butyl cyanoacrylate) 0.5 0.5 0.7 - - Ethylhexylglycerin 0.2 0.3 0.15 - - 1,2-hexanediol 0.3 0.2 0.15 - - Methyl paraben - - - 0.2 - Propyl paraben - - - 0.1 - Phenoxyethanol - - - 0.7 - Purified water - - - - 1.0

(Unit:% by weight)

< Comparative example  2 to 3>

According to the composition of Table 7, emulsions of Comparative Example 2 containing chemical preservatives and Comparative Example 3 containing no chemical preservatives and the above compounds were prepared by the method of <Experimental Example 5>.

< Experimental example  6>

In order to confirm the antiseptic activity of the cosmetic composition containing the mixture, a test for confirming the antiseptic activity of the mixture in a material prepared as a skin formulation was performed. The antiseptic activity test is a method of confirming the death after inoculating microorganisms into cosmetics (Challenge test, Inoculum test), and the cosmetics have an appropriate antiseptic system to prevent microbial contamination in the process of use and storage by consumers, and property of the product It is a test to check whether it is possible to minimize the health hazards to consumers by maintaining and maintaining product safety and stability. As the test method, the 11930 Preservative Challenge Test method of the International Organization for Standardization (ISO) was used.

The strains used were Gram-positive bacteria, Staphylococcus aureus ATCC 6538P, and Gram-negative bacteria, Escherichia coli ATCC 8739), Pseudomonas aeruginosa ATCC 9027, and Candida yeast ( Candida albicans ATCC 10231), a black bacterium ( Aspergillus niger ATCC 22343) was used as a filamentous fungus.

Bacterium was used tryptic soy broth, and the cells were inoculated with the medium and pre-incubated for 24 hours in a 37 ° C shake incubator. Potato dextrose broth was used for cultivation of yeast, and bacteria were inoculated into the medium and pre-incubated for 2 days in a 25 ° C shake incubator. Potato dextrose agar was used for the culture of filamentous fungi, and the bacteria were inoculated into the medium and pre-cultured for 7 days in a 25 ° C incubator.

For a more specific antiseptic activity test, in the case of bacteria, tryptic soy broth is inoculated with bacteria and prepared by pre-incubation at 37 ° C. for 24 hours, and in the case of yeast, bacteria in potato dextrose broth. After inoculation, the cells are pre-cultured for 2 days in a 25 ° C shake incubator, and the filamentous fungus is inoculated into a potato dextrose agar and pre-cultured for 7 days in a 25 ° C incubator, using a sterile cotton swab, the surface of the medium. The spores of the filamentous fungi formed on the cells were collected and diluted in sterile saline.

On the other hand, the test bacteria prepared by pre-incubation in 50 g of the cosmetic material to be tested in a sterilized container are inoculated at a final concentration of about 1 × 10 ⁶ CFU for bacteria, and a yeast concentration of about 1 × 10 ⁵ CFU for yeast. Inoculate with and, in the case of filamentous bacteria, inoculate each sample with a bacteria concentration of about 1 × 10 ⁴ CFU. Immediately after inoculation, each sample was taken to perform a total aerobic viable cell test. Bacteria are cultured at 37 ° C. for 24 hours, yeast is cultured at 25 ° C. for 3 days, and filamentous bacteria are cultured at 25 ° C. for 3 days, and then the initial number of bacteria inoculated in each sample is checked. Each inoculated sample is then stored at room temperature, and after 1 day, 2 days, 3 days, 7 days, 14 days, and 28 days, the total number of aerobic viable cells is tested to confirm the number of bacteria and the degree of death, The antiseptic activity of the cosmetic was measured.

division Experiment period
(Days) Experimental strain name S. aureus E. coli P. aeruginosa C. albicans A. niger Example 7 T = 0 3 × 10 ⁶ 4 × 10 ⁶ 3 × 10 ⁶ 2 × 10 ⁵ 2 × 10 ⁵ T = 1 4 × 10 ³ 2 × 10 ⁴ 6 × 10 ³ 2 × 10 ³ 6 × 10 ³ T = 2 <1 × 10 <1 × 10 <1 × 10 5 × 10 2 × 10 T = 7 <1 × 10 <1 × 10 <1 × 10 <1 × 10 <1 × 10 T = 14 <1 × 10 <1 × 10 <1 × 10 <1 × 10 <1 × 10 Example 8 T = 0 3 × 10 ⁶ 4 × 10 ⁶ 3 × 10 ⁶ 2 × 10 ⁵ 2 × 10 ⁵ T = 1 1 × 10 ⁴ 9 × 10 ³ 3 × 10 ³ 9 × 10 ² 8 × 10 ² T = 2 <1 × 10 <1 × 10 <1 × 10 1 × 10 3 × 10 T = 7 <1 × 10 <1 × 10 <1 × 10 <1 × 10 <1 × 10 T = 14 <1 × 10 <1 × 10 <1 × 10 <1 × 10 <1 × 10 Example 9 T = 0 3 × 10 ⁶ 4 × 10 ⁶ 3 × 10 ⁶ 2 × 10 ⁵ 2 × 10 ⁵ T = 1 6 × 10 ³ 4 × 10 ⁴ 1 × 10 ⁴ 8 × 10 ³ 7 × 10 ³ T = 2 <1 × 10 <1 × 10 <1 × 10 5 × 10 ³ 2 × 10 ² T = 7 <1 × 10 <1 × 10 <1 × 10 2x10 1x10 T = 14 <1 × 10 <1 × 10 <1 × 10 <1 × 10 <1 × 10 Comparative Example 2 T = 0 3 × 10 ⁶ 4 × 10 ⁶ 3 × 10 ⁶ 2 × 10 ⁵ 2 × 10 ⁵ T = 1 5 × 10 ³ 1 × 10 ⁵ 1 × 10 ⁴ 6 × 10 ³ 6 × 10 ³ T = 2 <1 × 10 <1 × 10 <1 × 10 3 × 10 ² 1 × 10 ³ T = 7 <1 × 10 <1 × 10 <1 × 10 <1 × 10 <1 × 10 T = 14 <1 × 10 <1 × 10 <1 × 10 <1 × 10 <1 × 10 Comparative Example 3 T = 0 3 × 10 ⁶ 4 × 10 ⁶ 3 × 10 ⁶ 2 × 10 ⁵ 2 × 10 ⁵ T = 1 3 × 10 ⁶ 4 × 10 ⁶ 3 × 10 ⁶ 2 × 10 ⁵ 2 × 10 ⁵ T = 2 3 × 10 ⁶ 4 × 10 ⁶ 3 × 10 ⁶ 2 × 10 ⁵ 2 × 10 ⁵ T = 7 3 × 10 ⁶ 4 × 10 ⁶ 3 × 10 ⁶ 2 × 10 ⁵ 2 × 10 ⁵ T = 14 3 × 10 ⁶ 4 × 10 ⁶ 3 × 10 ⁶ 2 × 10 ⁵ 2 × 10 ⁵

In the case of emulsions containing 0.5% poly (butyl cyanoacrylate), 0.2% alkylglycerin ether, and 0.2% 1,2-hexanediol, Gram-positive bacteria and Gram-negative bacteria were mostly killed after 7 days of inoculation. , It was also confirmed that the fungus had a very good antiseptic activity compared to Comparative Example 2 in which 1.0% of the chemical preservatives in Table 8 were added by killing most test bacteria after 7 days. In addition, the emulsion containing 0.5% of poly (butyl cyanoacrylate), 0.2% of alkyl glycerin ether, and 0.2% of 1,2-hexanediol has very little effect on emulsion stability, and thus has excellent cosmetic raw material properties. It has been found to be a suitable antiseptic cosmetic composition with excellent antibacterial activity and broad antibacterial spectrum. In Comparative Example 2, which contained 0.2% of the chemical preservative, methyl paraben, 0.1% of propyl paraben, and 0.7% of phenoxyethanol, it showed adequate antiseptic activity against both bacteria and fungi, and also had little effect on emulsion stability. In addition, in Comparative Example 3, which did not contain a chemical preservative and a polybutylisocyanate mixture, it was confirmed that most of all test bacteria were detected even after 28 days or rather showed an increasing pattern.

< Experimental example  7>

The possibility of skin irritation was confirmed by a closed patch test. A certain amount of the emulsions of Examples 7 to 9 and the chemical preservatives of Comparative Example 2 were added to the inside of the upper arm of both arms of 30 healthy males and females aged 20 to 40 with no abnormality on the skin, and closed for 48 hours. After applying the patch test, it was removed to confirm the degree of erythema formation and the degree of irritation to the tester through the question.

Skin irritation determination was made according to the skin irritation index criteria of Table 9 made by itself using sodium lauryl sulfate, no irritation of the irritation of the skin irritation index 0 to 1, mild irritation of the irritation of 2-3, mild irritation of 4 or more Was judged as a strong stimulus. Table 10 shows the experimental results.

division Stimulus index Criteria stimulus
none 0 Erythema was not formed, and the tester did not complain of irritation or itching. One Erythema was not formed, but the tester complained of minor itching. light
stimulus 2 There are minor skin changes, or the tester complains of mild irritation. 3 Mild erythema formed, tester complained of irritation strong
stimulus 4 A clear erythema was formed, and the tester complained of irritation. 5 A vivid erythema of red color was formed, and the tester complained of strong stimulation.

division Stimulation Stimulation incidence Average stimulation index No irritation Slight irritation Strong stimulation Example 7 29 One 0 3.3% 0.50 Example 8 28 2 0 6.7% 0.70 Example 9 28 2 0 6.7% 0.70 Comparative Example 2 21 9 0 30.0% 1.23

As can be seen from the results in Table 10, in the case of Comparative Example 2 containing 0.2% of methyl preservatives methyl paraben, propyl paraben 0.1%, 0.7% phenoxyethanol, the incidence incidence of irritation index 2 or higher was 30% and the average irritation index was 1.23. It was shown that the possibility of generating a stimulus over a slight stimulus is very high, but the emulsions of Examples 7 to 9 in which poly (butyl cyanoacrylate), alkylglycerin ether, and 1,2-hexanediol were mixed in an appropriate ratio are shown. All of them showed very low irritation with a stimulation incidence rate of 10% or less, and an average stimulation index of 0.9 or less, confirming that it is a safe cosmetic composition with a very low probability of irritation.

Claims (6)

Cosmetic composition containing one or two selected from alkyl glycerin ether and 1,2-alkanediol as a cosmetic preservative and poly (butyl cyanoacrylate) in aqueous solution
The method according to claim 1,
The cosmetic composition is a cosmetic composition without a separate chemical preservative
The method according to claim 1,
The alkyl glycerin ether is 0.05 to 5.0% by weight, the 1,2-alkanediol 0.01 to 5.0% by weight and the poly (butyl cyanoacrylate) is a cosmetic composition containing 0.0025 to 2.5% by weight.
The method according to claim 1,
The 1,2-alkanediol is a 1,2-pentylene glycol, 1,2-hexanediol or 1,2-octanediol cosmetic composition
The method according to claim 1,
The cosmetic composition is aqueous, aqueous-alcoholic, oily solution, oil-in-water, water-in-oil, multiple emulsion, aqueous gel, oily gel, liquid anhydrous product, pasty anhydrous product, solid anhydrous product, oil in aqueous phase using globules Cosmetic composition as a form of dispersion, ionic lipid vesicle and nonionic lipid vesicle
The method according to claim 1,
The cosmetic composition is a flexible cosmetic lotion, milk lotion, nourishing cream, massage cream, essence, cleansing foam, cleansing water, pack, body oil, foundation, lipstick, mascara or makeup base cosmetic composition