KR20190088171A - 1,2-Diol type polyol derivative compound and preparation method thereof and anti-microbial composition containing it - Google Patents

Abstract

The present invention relates to a polyol derivative compound having a 1,2-diol structure represented by chemical formula 1, a method of preparing the same, and an anti-microbial composition containing the compound as an active ingredient. In the chemical formula: R1 is nitrogen (N) or sulfur (S); and R2 is OH or C2 alkyl. According to the present invention, the polyol derivative compound having a 1,2-diol structure represented by the chemical formula 1 exhibits excellent anti-microbial activities better than 1,2-hexanediol, which is known to have the best anti-microbial activity among polyols, thereby being effectively used as a preservative for a food product, a medicine, a cosmetic, and the like to prevent spoilage caused by microorganisms.

Description

TECHNICAL FIELD The present invention relates to a polyol derivative compound having a 1,2-diol structure, a process for producing the same, and an antimicrobial composition containing the 1,2-diol structure and an antimicrobial composition containing the 1,2-

The present invention relates to a novel antimicrobial compound, specifically to a polyol derivative compound having a 1,2-diol structure represented by the general formula (1), a process for producing the same, and an antimicrobial composition containing the compound as an active ingredient.

Many products such as foods, medicines, and cosmetics require preservatives that prevent microbial decay. Especially, cosmetics have a relatively long distribution period and contain a large amount of substances that can be used as a nutrient source of microorganisms in cosmetics. It is also an optimal condition for microbes to reproduce easily due to the presence of water. To solve these problems, parabens such as methylparaben, ethylparaben, propylparaben, butylparaben and preservatives such as phenoxyethanol have been used (registered patent 10-1567299). Recently, however, there have been reports that when these preservatives are applied to cosmetics, they cause skin allergies and accumulate in the human body, causing various problems such as the possibility of environmental hormones.

There are various antimicrobial substances in nature. Research on natural antimicrobial substances has been studied by many researchers and has been reported to have antibacterial activity such as alkaloids, flavonoids, phytoalexins, antimicrobial peptides and chitosan isolated from various natural products. However, these natural-derived antimicrobials do not have antimicrobial activity compared to conventional synthetic preservatives and thus are not used as preservatives in actual products.

Another approach is polyols such as glycerin, 1,3-butanediol, and propylene glycol. Recently, 1,2-hexanediol has been widely used as a preservative to replace parabens and phenoxyethanol (Registered Patent No. 10-1567299). However, it has a limitation of using a high content of 2.0% or more in order to exhibit preservative efficacy Have.

For this reason, there is a strong need for the development of novel antimicrobial compounds that can ameliorate the problems of polyols including 1,2-hexanediol, which must use the above-mentioned high contents.

The inventors of the present invention have conducted intensive researches to overcome the problems of the prior art. As a result, the inventors of the present invention have found that a polyol derivative compound having a 1,2-diol structure represented by Formula 1 exhibits superior antibacterial activity to 1,2- The present invention has been completed.

KR 10-1567299 B

Accordingly, a main object of the present invention is to provide a polyol compound having a 1,2-diol structure represented by the general formula (1) and a process for producing the same.

Another object of the present invention is to provide an antimicrobial composition containing the polyol compound having the 1,2-diol structure as an active ingredient.

As a result of analyzing the structure of various polyol compounds exhibiting antibacterial activity, the present inventors have found that the neighboring diol structure (1,2-diol) plays an important role in exhibiting antibacterial activity. Based on the results of the analysis, a diol compound having a 1,2-diol structure was prepared, and the antibacterial activity was measured in comparison with 1,2-hexanediol which exhibited the best effect among the conventional polyols. 3-Butylamino-propane-1,2-diol and 3-Butylsulfanyl-propane-1,2-diol were prepared as follows. As a result of a comparative study of the antibacterial activity against 2-hexanediol, all of the three compounds showed superior antibacterial activity to 1,2-hexanediol and completed the present invention.

Although there are examples of 3- (2-Hydroxy-ethylamino) -propane-1,2-diol used as intermediates for the preparation of polymers, there is no measured example of antibacterial activity (Reactive & Functional Polymers, 2007, 67, 936). 3-Butylamino-propane-1,2-diol compound is known, but there is no example of this compound (CN 101161632 A). The 3-Butylsulfanyl-propane-1,2-diol compound has been used as a composition of a lubricant but has not been used as a compound showing antibacterial activity (US 4384967 A).

According to one aspect of the present invention, there is provided a polyol derivative compound having a 1,2-diol structure represented by the following formula (1): < EMI ID =

[Chemical Formula 1]

Wherein R ₁ is Nitrogen (N) or Sulfur (S) and R ₂ is OH or C ₂ alkyl.

According to another aspect of the present invention, there is provided a process for preparing a polyol derivative compound of the 1,2-diol structure represented by the above formula (1), which comprises the following first step reaction:

1) Glycidol or 3-Chloro-propane-1,2-diol with an epoxy structure and excess ethanolamine, butylamine, or butanethiol Lt; / RTI >

That is, the compound according to the present invention can be obtained through a one-step reaction as shown in the following reaction formula (1).

[Reaction Scheme 1]

In the production process of the present invention, it is preferable to use ethanolamine, butylamine, butane (3-chloro-propane-1,2-diol), which reacts with glycidol or 3-chloro- The ratio of thiol can be from 1: 1.5 to 1:10, preferably 1: 3 in the case of ethanolamine, 1: 1.1 in the case of vanillamine, and 1: 1 in the case of butanethiol.

Specific examples of the polyol compound having a 1,2-diol structure of the formula (1) obtained by the above-mentioned production method include the following compounds 1 to 3,

Compound 1: 3- (2-Hydroxy-ethylamino) -propane-1,2-diol,

Compound 2: 3-Butylamino-propane-1,2-diol,

Compound 3: 3-Butylsulfanyl-propane-1,2-diol,

According to another aspect of the present invention, there is provided an antimicrobial composition comprising, as an active ingredient, a polyol derivative compound having a 1,2-diol structure represented by the general formula (1).

The polyol compound having the 1,2-diol structure represented by the above formula (1) exhibits an excellent antibacterial activity as compared with 1,2-hexanediol, and thus can be used as an antimicrobial agent or preservative in cosmetics, medicines and foods. In the present invention, "antibacterial" means resistance to contaminated microorganisms such as bacteria, fungi and yeast, and "preservative " means prevention of corruption caused by contaminated microorganisms such as bacteria, fungi and yeast.

According to a test example of the present invention, the polyol compound according to the present invention is used in combination with Escherichia coli (ATCC 8739), Pseudomonas aeruginosa (ATCC 9027), Staphylococcus aureus (ATCC 6538) , Yeast and molds such as Candida albicans (ATCC 10231) and Aspergillus niger (ATCC 16404).

According to another aspect of the present invention, there is provided an external preparation for skin comprising a polyol derivative compound having a 1,2-diol structure represented by Formula 1 as a preservative.

In the present invention, the blending amount of the polyol derivative compound having the 1,2-diol structure represented by the above-mentioned formula (1) can be suitably determined by a person skilled in the art depending on the antimicrobial activity or the degree of the antifungal force required for the product for external application, . Preferably, the present invention provides a composition for external application comprising a polyol derivative compound having a 1,2-diol structure represented by Formula 1 as a preservative in an amount of 0.01 to 20% by weight based on the total weight of the composition.

In the present invention, the external preparation for skin may be in the form of any one of a softening agent, a convergent lotion, a nutritional lotion, an eye cream, a nutritional cream, a massage cream, a cleansing cream, a cleansing foam, a cleansing water, a powder, And the formulation is not particularly limited. Further, in the respective formulations, other ingredients may be selected and mixed without difficulty by those skilled in the art depending on the kind of the other cosmetic composition or the purpose of use.

In addition, the polyol compound of the present invention may be formulated into a composition for external application such as a skin softener (emollient), a humectant or a wetting agent in an external preparation such as a cosmetic.

INDUSTRIAL APPLICABILITY As described above, according to the present invention, the polyol derivative compound having a 1,2-diol structure represented by the formula (1) exhibits superior antibacterial activity to 1,2-hexanediol known to exhibit the best antimicrobial activity among conventional polyols , Foods, medicines, and cosmetics can be effectively used as a preservative to prevent microbial decay.

Hereinafter, the present invention will be described in more detail with reference to Examples. These embodiments are only for illustrating the present invention, and thus the scope of the present invention is not construed as being limited by these embodiments.

[Example 1] Preparation of 3- (2-Hydroxy-ethylamino) -propane-1,2-diol

Glycidol (3.65 g, 49.2 mmol) was slowly added dropwise to ethanolamine (9.15 g, 149.8 mmol) while maintaining the reaction temperature below 10 ° C. After the dropwise addition, the reaction mixture was stirred at room temperature for 10 hours. The excess amount of ethanolamine is 75 < 0 > C to 80 The desired final product (6.20 g, yield 93%) was obtained in an oil phase after removal under reduced pressure at 1 (1 torr). The product was allowed to stand at room temperature to become a viscous syrup.

¹ H NMR (500 MHz, D ₂ O)? 3.86-3.83 (m, 1H), 3.72-3.52 (m, 4H), 2.80-2.61 (m, 4H).

[Example 2] Preparation of 3-Butylamino-propane-1,2-diol

N-Butylamine (4.5 g, 61.5 mmol) was dissolved in ethanol (20 mL) and glycidol (4.1 g, 55.3 mmol) was slowly added. The reaction mixture was stirred at room temperature for 5 hours and then the ethanol was removed under reduced pressure. The reaction mixture was distilled at 130-135 ° C (4 torr) to give the final product (5.3 g, 65% yield) as a colorless liquid.

_{^{1 H NMR (500MHz, CDCl 3}} ) δ 3.73 ~ 3.66 (m, 2H), 3.58 ~ 3.55 (m, 1H), 2.90 ~ 2.75 (brs, 3H), 2.75 ~ 2.70 (m, 1H), 2.67 ~ 2.53 ( m, 3H), 1.45-1.42 (m, 2H), 1.33-1.29 (m, 2H), 0.88 (t, 3H, J = 6.5Hz).

[Example 3] Preparation of 3-Butylsulfanyl-propane-1,2-diol

A solution of sodium hydroxide (0.4 g, 1.0 mmol) dissolved in ethanol (10 mL) was added dropwise at room temperature while dissolving glycidol (0.74 g, 1.0 mmol) and 1-butanethiol (0.90 g, 1.0 mmol) Slowly added and stirred for 12 hours. The reaction mixture was diluted with water (100 ml) and extracted with ethyl acetate (50 ml). The organic layer was washed with 0.1N hydrochloric acid solution, saturated sodium hydrogencarbonate solution and saturated sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by column chromatography to obtain the product (0.98 g, yield 59%) as a pale yellow liquid phase.

_{^{1 H NMR (500MHz, CDCl 3}} ) δ 3.80 ~ 3.74 (m, 2H), 3.60 ~ 3.55 (m, 1H), 2.82 (brs, 1H), 2.72 ~ 2.52 (m, 4H), 2.07 (brs, 1H) , 1.60-1.57 (m, 2H), 1.42-1.39 (m, 2H), 0.91 (t, 3H, J = 7.5 Hz).

[Test Example 1]

The antibacterial activity of the polyol compound of the 1,2-diol structure obtained in Example 1-3 was compared with that of 1,2-hexanediol. The test for the measurement of the antimicrobial activity can be carried out in the following order: Escherichia coli (ATCC 8739), Pseudomonas aeruginosa (ATCC 9027), Staphylococcus aureus (ATCC 6538), Candida albicans 10231) and Aspergillus niger (ATCC 16404). Each substance was added to a Tryptic Soy broth medium and a Sabouraud dextrose (SD) medium at a concentration of 0.01 to 10%, and then the culture broth was prepared as a liquid, and the bacteria, yeast and fungus were inoculated The cells were cultured at 25 ° C - 32 ° C for 24 - 72 hours. The antimicrobial activity was measured using the minimum growth inhibitory concentration (MIC) at a concentration that significantly decreased the initial number of bacteria inoculated. The results are shown in Table 1 (antibacterial activity of polyol compound).

1,2-hexanediol Example 1 Example 2 Example 3 Escherichia coli (E. coli) 0.90% 0.23% 0.22% 0.24% Pseudomonus aeruginosa 0.94% 0.23% 0.25% 0.30% Staphylococcus aureus 0.86% 0.33% 0.24% 0.21% Candida albicans 0.90% 0.24% 0.26% 0.21% Aspergillus niger 0.92% 0.24% 0.30% 0.23%

As shown in Table 1, all of the three compounds of Examples 1 to 3 were found to exhibit high antimicrobial activity in all five bacteria measured from 1,2-hexanediol used as a positive control.

[Formulation Example 1] Production of nutritional lotion (milk lotion)

A nutritional lotion containing the polyol compound of the 1,2-diol structure prepared in Example 1-3 was prepared.

ingredient Content (% by weight) One. Purified water Balance 2. glycerin 8.0 3. Butylene glycol 4.0 4. Hyaluronic acid extract 5.0 5. Beta Glucan 7.0 6. Carbomer 0.1 7. A polyol having a 1,2-diol structure Suitable amount 8. Caprylic / capric triglyceride 8.0 9. Squalene 5.0 10. Cetearyl glucoside 1.5 11. Sorbitan stearate 0.4 12. Cetearyl alcohol 1.0 13. incense Suitable amount 14. Pigment Suitable amount 15. Triethanolamine 0.1

[Formulation Example 2] Preparation of nutritional cream

A nutritional cream containing the polyol compound of the 1,2-diol structure prepared in Example 1-3 was prepared.

ingredient Content (% by weight) One. Purified water Balance 2. glycerin 3.0 3. Butylene glycol 3.0 4. Liquid paraffin 7.0 5. Beta Glucan 7.0 6. Carbomer 0.1 7. A polyol having a 1,2-diol structure Suitable amount 8. Caprylic / capric triglyceride 3.0 9. Squalene 5.0 10. Cetearyl glucoside 1.5 11. Sorbitan stearate 0.4 12. Polysorbate 1.2 13. incense Suitable amount 14. Pigment Suitable amount 15. Triethanolamine 0.1

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it will be understood by those of ordinary skill in the art that various modifications and equivalent arrangements may be made therein without departing from the scope of the present invention . Accordingly, the true scope of the present invention should be determined by the technical scope of the appended claims.

Claims (5)

A polyol derivative compound having a 1,2-diol structure represented by the following formula
[Chemical Formula 1]

Wherein R ₁ is Nitrogen (N) or Sulfur (S) and R ₂ is OH or C ₂ alkyl
A process for producing a polyol derivative compound having a 1,2-diol structure according to claim 1, comprising the following first step reaction:
1) Glycidol or 3-Chloro-propane-1,2-diol with an epoxy structure and excess ethanolamine, butylamine, or butanethiol Lt; / RTI >
An antimicrobial composition comprising the polyol derivative compound of the 1,2-diol structure according to claim 1 as an active ingredient.
A composition for external application for skin comprising a polyol derivative compound having a 1,2-diol structure according to claim 1 as a preservative.
The composition according to claim 4, wherein the external preparation for skin is at least one selected from the group consisting of a softening agent, a convergent lotion, a nutritional lotion, an eye cream, a nutritional cream, a massage cream, a cleansing cream, a cleansing foam, a cleansing water, a powder, Wherein the external preparation for skin is a composition for external application for skin.