KR102578739B1 - Novel compound, antibacterial agent, and antibacterial polymer coating composition comprising the same - Google Patents

Abstract

The compound according to the present invention is a photosensitizer and has excellent compatibility with polymers and excellent solubility in aqueous and organic solvents, so it can be usefully used as an antibacterial agent and an antibacterial polymer coating composition containing the same.

Description

Novel compound, antibacterial agent, and antibacterial polymer coating composition comprising the same}

The present invention relates to a novel compound that is a photosensitizer, an antibacterial agent containing the same, and an antibacterial polymer coating composition.

A photosensitizer is a substance that absorbs light and generates reactive oxygen species (ROS). By irradiating light of a specific wavelength from the outside, reactive oxygen species or free radicals are generated from the photosensitizer, which can be used to treat various lesions or cancer cells. Photodynamic therapy (PDT), which destroys cells by inducing their death, is widely used.

Porphyrin-based compounds are known as such photosensitizers, and are known to generate ROS and singlet oxygen by reacting with oxygen. A representative example of this is known as TCPP (4,4',4'',4'''-(porphrin-5,10,15,20-tetrayl)tetrakis(benzoic acid)).

There are various attempts to develop polymer materials with antibacterial properties using this photodynamic reaction. For example, a method of melting a polymer resin and then mixing the melted resin with a photosensitizer, or a method of mixing the polymer resin and light There is a known method of using a coating solution formed by dissolving a sensitizer in a solvent.

However, because photosensitizers such as TCPP have a carboxyl group with good affinity for water as a substituent, they are soluble in a small amount of water, and have poor compatibility with polymer resins and poor solubility in organic solvents for preparing coating solutions. . Accordingly, there is a problem that the dispersibility of the photosensitizer decreases and the antibacterial effect also decreases.

The present invention is intended to provide a novel compound as a photosensitizer that has excellent compatibility with polymers and has excellent solubility in both water and organic solvents.

Additionally, the present invention is to provide an antibacterial agent containing the above compound.

In addition, the present invention is to provide an antibacterial polymer coating composition containing the above compound.

In order to solve the above problems, the present invention provides a compound represented by the following formula (1):

[Formula 1]

In Formula 1,

이고, 나머지는 수소이고,At least one of R

and the remainder is hydrogen,

R ₁ is hydrogen, C _1-5 alkyl, or C _1-5 alkoxy,

k is an integer from 1 to 5,

n is an integer from 3 to 20.

The compound represented by Formula 1 is characterized in that it contains a polymer chain represented by R instead of the terminal carboxyl group in the conventionally used TCPP compound.

Photosensitive agents such as TCPP have the problem of dissolving in a small amount of water because they have a substituent of a carboxyl group that has good affinity for water. In addition, due to the carboxyl group, the solubility in organic solvents is low, so there is a limit to the solvents that can be used when coating TCPP. However, in the present invention, by replacing the carboxyl group with a polymer chain represented by R, not only can the above problem be solved, but also the effect as an antibacterial agent is improved because it has excellent compatibility in water or organic solvents, especially alcohol-based solvents.

이다. 바람직하게는, R 중 2개 이상이

인 경우 이들의 구조는 서로 동일하다. 보다 바람직하게는, 4개의 R 모두

이다.In Formula 1, 1, 2, 3, or 4 of R are

am. Preferably, two or more of R are

In this case, their structures are identical to each other. More preferably, all four R

am.

Preferably, R ₁ is hydrogen, methyl, or methoxy.

Preferably, k is 2 or 3.

Preferably, n is 4 or more, or 5 or more, and is an integer of 19 or less, 18 or less, 17 or less, 16 or less, 15 or less, 14 or less, 13 or less, 12 or less, 11 or less, or 10 or less.

Representative examples of compounds represented by Formula 1 are as follows:

For example, the compound represented by Formula 1 can be prepared by the method shown in Scheme 1 below.

[Scheme 1]

Reaction Scheme 1 is a reaction for substituting a carboxyl group with an ester or ketone, and methods known in the art can be used without limitation. The manufacturing method may be further detailed in examples to be described later.

Additionally, the present invention provides an antibacterial agent containing the compound represented by Formula 1 above. As shown in the experimental examples described later, the compound can inhibit the growth or survival of microorganisms such as bacteria and can be used as an antibacterial agent.

Additionally, the present invention provides an antibacterial polymer coating composition containing the compound represented by Formula 1 above.

As described above, the compound represented by Formula 1 has excellent compatibility with polymers, and therefore, articles requiring antibacterial properties can be coated with a polymer coating composition containing the compound represented by Formula 1 together with a polymer.

Examples of items requiring antibacterial properties include humidifiers, water tanks, refrigerators, air washers, aquariums, air purifiers, etc., which can be applied to items in which harmful bacteria easily grow.

The antibacterial polymer coating composition can be prepared by melting the polymer resin and then mixing the molten resin with the compound according to the invention, or by dissolving the polymer resin and the compound according to the invention together in a solvent. In addition, it can be applied by manufacturing a film using the antibacterial polymer coating composition and applying this film to an article requiring antibacterial properties.

Preferably, an antibacterial polymer coating composition is provided, comprising the compound represented by Formula 1 and a (meth)acrylate-based monomer or oligomer containing an alkylene oxide having 1 to 10 carbon atoms.

In this specification, (meth)acrylate is meant to include both acrylate and methacrylate.

Meanwhile, in the molecular structure of the (meth)acrylate monomer or oligomer containing the alkylene oxide having 1 to 10 carbon atoms, the alkylene oxide having 1 to 10 carbon atoms is at the end of the (meth)acrylate monomer or oligomer or It can be located in the middle of the molecule; In addition, the (meth)acrylate-based monomer or oligomer containing alkylene oxide having 1 to 10 carbon atoms may include a mono(meth)acrylate-based monomer or oligomer containing alkylene oxide having 1 to 10 carbon atoms; Or it may be a di(meth)acrylate-based monomer or oligomer containing alkylene oxide having 1 to 10 carbon atoms. For example, the (meth)acrylate-based monomer or oligomer containing alkylene oxide having 1 to 10 carbon atoms may be a di(meth)acrylate-based monomer or oligomer containing alkylene oxide having 1 to 10 carbon atoms in the middle of the molecule. there is. Monomers or oligomers containing the above (meth)acrylate include pentaerythritol tri(meth)acrylate, pentaerythritol tetra(meth)acrylate, dipentaerythritol penta(meth)acrylate, and dipentaerythritol hexa(meth)acrylate. , tripentaerythritol hepta(meth)acrylate, trilene diisocyanate, xylene diisocyanate, hexamethylene diisocyanate, trimethylolpropane tri(meth)acrylate, trimethylolpropane polyethoxy tri(meth)acrylate, trimethyl These are propane trimethacrylate, ethylene glycol dimethacrylate, butanediol dimethacrylate, hexaethyl methacrylate, or butyl methacrylate.

The (meth)acrylate-based monomer or oligomer containing alkylene oxide having 1 to 10 carbon atoms may have a predetermined molecular weight in consideration of the specific use or physical properties of the antibacterial coating composition, for example, 200 g/mol. It may have a weight average molecular weight of from 10,000 g/mol, more preferably from 300 g/mol to 1,000 g/mol. In this specification, the weight average molecular weight means the weight average molecular weight measured by GPC method.

The antibacterial polymer coating composition may include the compound represented by Formula 1 in a predetermined amount. Specifically, the antibacterial polymer coating composition may include 0.01 to 5 parts by weight of the compound represented by Formula 1 relative to 100 parts by weight of the (meth)acrylate-based monomer or oligomer containing alkylene oxide having 1 to 10 carbon atoms.

Meanwhile, the antibacterial polymer coating composition may include an organic solvent, and the organic solvent is added at the time of mixing each component included in the antibacterial polymer coating composition, or is added while each component is dispersed or mixed in the organic solvent. It may be included in the antibacterial polymer coating composition. For example, the antibacterial polymer coating composition may include an organic solvent so that the total solid concentration of the components included is 1% to 80% by weight, or 2% to 50% by weight. In addition, as described above, the compound represented by Formula 1 includes a polymer chain represented by R instead of the carboxyl group at the terminal of the conventionally used TCPP compound, thereby increasing compatibility with water and organic solvents.

Non-limiting examples of the organic solvent include ketones, alcohols, acetates, and ethers, or mixtures of two or more thereof. Specific examples of such organic solvents include ketones such as methyl ethyl canone, methyl isobutyl ketone, acetylacetone, and isobutyl ketone; Alcohols such as methanol, ethanol, n-propanol, i-propanol, n-butanol, i-butanol, or t-butanol; Acetates such as ethyl acetate, i-propyl acetate, or polyethylene glycol monomethyl ether acetate; ethers such as tetrahydrofuran or propylene glycol monomethyl ether; Or a mixture of two or more types thereof may be mentioned.

Meanwhile, according to another embodiment of the invention, an antibacterial polymer film containing a cured product of the antibacterial polymer coating composition may be provided.

As described above, the antibacterial polymer film manufactured by curing the antibacterial polymer coating composition can be easily applied to various fields and is not only suitable for mass production, but can also achieve high antibacterial properties even when light in the visible light range is applied, In particular, the generated active oxygen remains longer than previously known antibacterial materials, enabling high antibacterial efficiency.

The antibacterial polymer film can be obtained by applying the antibacterial polymer coating composition on a predetermined substrate and photocuring the applied result. The specific type or thickness of the substrate is not greatly limited, and any substrate known to be used in the production of conventional polymer films can be used without major limitations.

Methods and devices commonly used to apply the antibacterial polymer coating composition can be used without any restrictions, for example, bar coating method such as Meyer bar, gravure coating method, 2 roll reverse coating method, vacuum slot die coating method, 2 roll coating method, etc. can be used.

The coating thickness of the antibacterial polymer coating composition may be determined depending on the intended use of the antibacterial polymer film to be finally manufactured. For example, the antibacterial polymer coating composition may be coated (applied) to a thickness of 1 ㎛ to 1,000 ㎛.

In the step of photocuring the antibacterial polymer coating composition, ultraviolet rays or visible light with a wavelength of 200 to 400 nm may be irradiated, and the exposure amount during irradiation is preferably 50 to 2,000 mJ/cm2. The exposure time is also not particularly limited and can be appropriately changed depending on the exposure device used, the wavelength of the irradiation light, or the exposure amount.

Additionally, in the step of photocuring the antibacterial polymer coating composition, nitrogen purging, etc. may be performed to apply nitrogen atmospheric conditions.

The compound according to the present invention is a photosensitizer and has excellent compatibility with polymers and excellent solubility in organic solvents, so it can be usefully used as an antibacterial agent and an antibacterial polymer coating composition containing the same.

Figure 1 shows the results of antibacterial evaluation of the compounds of Examples and Comparative Examples of the present invention.
Figure 2 shows the solubility evaluation results for the compounds of Examples and Comparative Examples of the present invention.

Below, preferred embodiments are presented to aid understanding of the present invention. However, the following examples are provided only to make the present invention easier to understand, and the content of the present invention is not limited thereto.

Example

TCPP (4,4',4'',4'''-(porphrin-5,10,15,20-tetrayl)tetrakis(benzoic acid)) purchased from Sigma-Aldrich; After dissolving 1 eq) in DMF, poly(ethylene glycol) monomethyl ether (weight average molecular weight: 400; 10 eq) was added through a syringe at 0°C. After 10 minutes at 0°C, DMAP (4-(dimethylamino)pyridine; 1 eq) was added. After 30 minutes at 0°C, EDC·HCl (N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride; 10 eq) was added. When the reaction was completed, DMF used as a solvent was removed by drying and extracted with water. The extract was dried using magnesium sulfate and then purified by column chromatography to prepare the compound.

¹ H NMR (500 MHz, CDCl ₃ , ppm): 8.82 (s, 8H), 8.47-8.46 (d, 8H), 8.30-8.29 (d, 8H), 4.68-4.66 (t, 8H), 4.00-3.97 (t, 8H), 3.82-3.80 (m, 8H) 3.76-3.74 (m, 8H), 3.65-3.59 (m, repeating unit), -2.81 (s, 2H)

MS: MALDI TOP-MS: m/z 1882~2851 [M+H] ⁺

2) Preparation of test specimens

36 parts by weight of methyl methacrylate (MMA), 7 parts by weight of dipentaerythrol hexaacrylate (DPHA), 1 part by weight of the compound prepared in the previous example as a photosensitizer, 0.1 parts by weight of surfactant (Product name: F477 DIC) Parts by weight, and 55.6 parts by weight of ethanol were mixed to prepare a coating solution. After coating the above coating solution using #20 bar, curing was carried out at a speed of 2 m/min using a 0.2 J/cm ² UV lamp, and a film with a thickness of 10 ㎛ was manufactured.

Comparative example

A film was manufactured using TCPP, the starting material used in the preparation of the above examples, as a comparative example. Specifically, 36 parts by weight of methyl methacrylate (MMA), 7 parts by weight of dipentaerythrol hexaacrylate (DPHA), 1 part by weight of TCPP compound as a photosensitizer, and 0.1 part by weight of surfactant (Product name: F477 DIC). , and 55.6 parts by weight of dimethylformamide (DMF) were mixed to prepare a coating solution. After coating the above coating solution using #20 bar, curing was carried out at a speed of 2 m/min using a 0.2 J/cm ² UV lamp, and a film with a thickness of 10 ㎛ was manufactured.

Experiment example 1: Antibacterial evaluation

1) Preparation of bacterial suspension

As a test bacterium, E.coli ATCC 8739, a standard E. coli specified in the KS L ISO 27447 standard, was used. The E. coli ATCC 8739 strain was inoculated into LB nutrient medium using a platinum loop, cultured at 37°C for 16 to 24 hours, and then stored in a 5°C refrigerator. The secondary culture was repeated by simulating the above process within 1 month. During secondary culture, the maximum number of CFU (colony forming units) should be 10. LB nutrient medium is prepared by mixing 25 g/L Luria Broth powder and 15 g/L agar powder (available from Sigma-Aldrich) in distilled water, sterilizing it in an autoclave, and then weighing the appropriate amount in a petri dish when the temperature drops to ~40℃. did.

The bacterial culture was centrifuged to separate the bacteria and LB liquid medium, and then the bacteria were transferred to saline solution. Using a spectrophotometer, the suspension was diluted so that the absorption value of the bacterial-saline solution was 0.5 at 600 nm, and the bacterial suspension was used in the test.

The specific dilution method is that each plate is diluted by 1/10, so the number of CFU is reduced by 1/10. The amount of suspension used for plating is 0.1 ml. Since the number of CFU in C ₄ is 299 and the amount of liquid used is 0.1 ml, 299 CFU / 0.1 ml = 2,990 CFU/ml. The number of CFU in C ₁ is ~3.0 × 10 ⁶ CFU/ml multiplied by 1,000, and C ₁ is Since the bacterial stock solution (C ₀ ) is diluted by 1/10, the number of CFU in the bacterial suspension is 3.0 × 10 ⁷ CFU/ml.

2) Bacteria inoculation on test specimen

After quantifying 0.2 mL of bacterial suspension (C ₁ , C ₂ , C ₃ , C ₄ ) on the previously prepared test piece, a polypropylene adhesive film with a transmittance of 80% or more was placed on it to support the photocatalyst sample. It was manufactured as a sandwich structure containing a microbial suspension located between a polymer film and an adhesive film.

3) Antibacterial test (light conditions; light)

Each test piece was placed under a light source and irradiated with light at 34°C for 6 hours. The conditions of 405 nm and 0.35 mW/cm ² were applied to the light used, and the distance between the test piece and the light source was 1 cm.

The results of the above experiment are shown in Figure 1. As shown in Figure 1, the compounds of the Examples exhibited better antibacterial properties compared to the compounds of the Comparative Examples, and although this is not theoretically limited, it is believed that this is due to the improved dispersibility of the compounds of the Examples due to their better compatibility with polymers. It is judged.

Experiment example 2: Solubility evaluation

The solubility of the compound prepared in the above example and the compound of the comparative example (TCPP) was added to water and toluene at 5 wt%, respectively, and the results are shown in Figure 2.

As shown in Figure 2, the compounds prepared in Examples were dissolved in both water and toluene, but the compounds in Comparative Examples were visually observed to be dissolved in water but not in toluene.

Claims (10)

Compound represented by Formula 1:
[Formula 1]

In Formula 1,
At least one of R

and the remainder is hydrogen,
R ₁ is hydrogen, C _1-5 alkyl, or C _1-5 alkoxy,
k is an integer from 1 to 5,
n is an integer from 3 to 20.
According to paragraph 1,
R is all

person,
compound.
According to paragraph 1,
R ₁ is hydrogen, methyl, or methoxy;
compound.
According to paragraph 1,
k is 2 or 3,
compound.
According to paragraph 1,
n is an integer from 5 to 10,
compound.
According to paragraph 1,
The compound represented by Formula 1 is the following compound,
compound:

An antibacterial agent comprising the compound of any one of claims 1 to 6.
The compound of any one of claims 1 to 6, and
Containing a (meth)acrylate-based monomer or oligomer containing alkylene oxide having 1 to 10 carbon atoms,
Antibacterial polymer coating composition.
According to clause 8,
The (meth)acrylate-based monomer or oligomer containing alkylene oxide having 1 to 10 carbon atoms may include a mono(meth)acrylate-based monomer or oligomer containing alkylene oxide having 1 to 10 carbon atoms; or a di(meth)acrylate-based monomer or oligomer containing alkylene oxide having 1 to 10 carbon atoms,
Antibacterial polymer coating composition.
According to clause 8,
Monomers or oligomers containing the above (meth)acrylate include pentaerythritol tri(meth)acrylate, pentaerythritol tetra(meth)acrylate, dipentaerythritol penta(meth)acrylate, and dipentaerythritol hexa(meth)acrylate. , tripentaerythritol hepta(meth)acrylate, trilene diisocyanate, xylene diisocyanate, hexamethylene diisocyanate, trimethylolpropane tri(meth)acrylate, trimethylolpropane polyethoxy tri(meth)acrylate, trimethyl Rolled propane trimethacrylate, ethylene glycol dimethacrylate, butanediol dimethacrylate, hexaethyl methacrylate, or butyl methacrylate,
Antibacterial polymer coating composition.