KR102264090B1 - Antimicrobial hydrogel with metal organic frameworks - Google Patents

Abstract

The present invention relates to an antibacterial hydrogel comprising a metal-organoframework compound and a hydrogel. The metal-organic framework compound-containing hydrogel of the present invention has excellent antibacterial activity and can be used in various hydrogel products.

Description

Antimicrobial hydrogel with metal organic frameworks

The present invention relates to an antibacterial hydrogel comprising a metal-organoframework compound. The metal-organic framework compound-containing hydrogel of the present invention has excellent antibacterial activity and can be used in various hydrogel products.

A hydrogel is a gel using water as a dispersion medium, and the hydrosol loses fluidity due to cooling, or a hydrophilic polymer having a three-dimensional network structure and microcrystalline structure expands by containing water. Hydrogels of electrolyte polymers exhibit high water absorption properties and have been put to practical use in various fields as water absorbent polymers.

Although hydrogels are not soluble in water, they have the ability to absorb water several times more than their own weight. Using these characteristics, it is possible to minimize scarring or effectively treat wounds without scars by creating a moist environment by absorbing exudate at the wound site. Its uses are diverse, such as being applied to the medical field to prevent adhesions of the intestinal tract during surgery. Do. In particular, recently, it is used in contact lenses and biomedical research on its use in various fields such as artificial discs and artificial cartilage is being conducted.

There are many synthetic or natural polymers such as polyvinyl alcohol (PVA), hyaluronic acid, alginic acid, pectin, chitosan, etc.

In general, wound healing speed is faster in the case of maintaining a moist environment than in the case of treating in a dry state. In this case, it takes a certain period of time until the wound is completely healed, so it is necessary to effectively prevent infection of the affected area during that period. Therefore, the dressing for wound treatment should be able to retain moisture in the wound for a long time and should be able to absorb body fluids such as exudates well. In addition, it should be able to prevent infection of the wound from bacteria, etc., and it should be easy to attach and detach from the wound or skin. Transparent is better for viewing the wound healing process, and oxygen permeability and ease of handling and storage are also required.

Hydrogel (hydrogel) contains more than 70% water, so it can be used in burn treatment or in conditions where a wet state is maintained. In addition, since it has affinity with biological tissues such as body fluids and blood, it can be used for contact lenses, cartilage, etc. in addition to wound dressings. Most of these hydrogels have a three-dimensional network structure to contain moisture, and have hydrophilic functional groups such as carboxyl group (COOH), carboximide group (CONH), sulfonic acid group (SO ₃ H), and osmotic pressure or capillary tube. It contains moisture by development. The reason that hydrogels contain a large amount of water but are not soluble in water is due to the bonding structure between polymer chains as well as electrostatic and lipophilic interactions.

However, the hydrogels as described above have the advantage of creating a wet environment at the wound site due to their water-containing properties, but there are cases in which infection by bacteria is a problem because they do not have antibacterial activity by themselves.

Antibacterial activity is an important factor in wound healing. In particular, purulent bacteria such as Staphylococcus aureus make it difficult to heal wounds, and in many cases, antibiotics must be administered when an infection occurs. The pH of the wound site is also involved in the infection and wound healing process. In a study on the effect of pH on the wound and inflammation, when an acidic environment is created in the wound area during the wound healing process, the proliferation of bacteria is suppressed, and the It has been reported that healing can be accelerated.

In the case of contact lenses, an antibacterial function is also required.

The Metal-Organic Framework (MOF) has been developed over the past few decades for a _{wide range of applications such as energy-related gas storage (H 2} and CH ₄ ), CO ₂ capture/separation, hydrocarbon separation, catalysis and proton conduction. has attracted a lot of attention in the field. Recently, due to their high porosity and regular structural properties, metal-organic frameworks are expanding their applications to the fields of biology and medicine.

Meanwhile, multi-drug-resistant bacteria have emerged, threatening the development of traditional drugs, and transition metal ions and metal nanoparticles including Cu, Zn, Co, and Ag are attracting attention as new antimicrobial substitutes that affect bacterial cells. Metal nanoparticles exhibit excellent antibacterial activity due to their unique properties such as nanometer effect and high surface area/volume ratio. However, it is expected that excessive metal ions arriving in the form of nanoparticles will be harmful not only to bacteria but also to normal tissues.

To solve this problem, many researchers have tried to trap metal ions by coordinating bioactive metal ions to organic ligands. In relation to this, Korean Patent Laid-Open Publication No. 2009-0046888, etc. proposes a method for producing a metal-organic framework material containing copper, but there is no report on the activity potential of the antimicrobial agent in the document.

Korean Patent Publication No. 2003-0045730 Korean Patent Publication No. 2009-0046888

Accordingly, the present invention aims to provide a hydrogel having antibacterial activity including a metal-organic framework (MOF).

The present invention is to provide an antibacterial agent comprising a metal-organic framework (Metal-Organic Framework, MOF) containing hydrogel.

An object of the present invention is to provide a method for preparing a hydrogel having antibacterial properties in a simple and reproducible manner.

An object of the present invention is to provide a product with excellent antibacterial properties, including an antibacterial hydrogel.

In order to achieve the above object, the present invention provides an antibacterial hydrogel comprising a metal-organic framework compound of Formula 1 and a hydrogel.

[Formula 1]

[M ₂ (L1) ₂ (μ-L2)] x(H ₂ O)

Wherein M is Cu, Zn or Co,

L1 is a hydrocarbon group having two carboxylate groups,

L2 is a bis(4-pyridyl) compound or a derivative thereof

x is a number from 1 to 10.

The present invention provides an antimicrobial agent comprising a metal-organic framework compound of Formula 1 and a hydrogel.

[Formula 1]

[M ₂ (L1) ₂ (μ-L2)] x(H ₂ O)

Wherein M is Cu, Zn or Co,

L1 is a hydrocarbon group having two carboxylate groups,

L2 is a bis(4-pyridyl) compound or a derivative thereof

x is a number from 1 to 10.

The present invention is a method for preparing an antibacterial hydrogel by reacting the metal-organic framework compound of Formula 1 and the hydrogel under ultraviolet light.

[Formula 1]

[M ₂ (L1) ₂ (μ-L2)] x(H ₂ O)

Wherein M is Cu, Zn or Co,

L1 is a hydrocarbon group having two carboxylate groups,

L2 is a bis(4-pyridyl) compound or a derivative thereof

x is a number from 1 to 10,

UV light intensity is 1-200mW/cm2,

The concentration of photoinitiator is 0.01~1% (w/v) and

The reaction temperature is 20~70℃,

Reaction pH provides an antibacterial hydrogel preparation method, characterized in that 7.5 ~ 9.

The present invention provides an antimicrobial product comprising the antimicrobial hydrogel.

The present invention has the effect of providing a hydrogel excellent in antibacterial activity. The present invention has the effect of providing a method for preparing a hydrogel having antibacterial properties in a relatively simple manner by mixing the metal-organic framework compound under relatively mild conditions using water as a solvent and mixing them. The metal-organic framework-containing antibacterial hydrogel of the present invention has the advantage that it has excellent antibacterial activity against bacteria such as Escherichia coli, and Staphylococcus aureus, and is very safe. Therefore, the product including the hydrogel has the advantage of excellent antibacterial properties.

1 shows the structural formula of the metal-organic framework compound included in the hydrogel resin of the present invention.
2 is a crystal structure of the metal-organic framework compound of the present invention. _{[Cu 2} (Glu) ₂ (bpy)] (a), [Cu ₂ (Glu) ₂ (bpa)] (b), [Cu ₂ (Glu) ₂ (bpe)] (c) containing water molecules, respectively , and [Cu ₂ (Glu) ₂ (bpp)] (d).
3 shows a schematic diagram of a hydrogel-forming reaction including a metal-organic framework compound.
4 shows the results of the antibacterial effect of the control ((a)) and Cu-Glu-Bpe/hydrogel ((b)) against E. coli.
Figure 5 shows the results of the antibacterial effect of the control ((a)) and Cu-Glu-Bpe/hydrogel ((b)) against Staphylococcus aureus.
6 shows the results of the antibacterial effect of the control ((a)) and Co-Glu-Bpe/hydrogel ((b)) against E. coli.
7 shows the results of the antibacterial effect of the control ((a)) and Co-Glu-Bpe/hydrogel ((b)) against Staphylococcus aureus.
8 shows the results of the antibacterial effect of the control piece ((a)) and the hydrogel ((b)) against E. coli.
Figure 9 shows the results of the antibacterial effect of the control piece ((a)) and the hydrogel ((b)) against Staphylococcus aureus.

The present invention provides an antibacterial hydrogel comprising a metal-organic framework compound of Formula 1 and the hydrogel.

[Formula 1]

[M ₂ (L1) ₂ (μ-L2)] x(H ₂ O)

Wherein M is Cu, Zn or Co,

L1 is a hydrocarbon group having two carboxylate groups,

L2 is a bis(4-pyridyl) compound or a derivative thereof

x is a number from 1 to 10.

The metal-organic framework compound included in the hydrogel of the present invention was designed in consideration of the unique properties of metals and organic ligands, such as oxidation number, counter ion, coordination mode, ligand size, and crosslinking properties.

The metal-organic framework compound has crystallized water molecules and is harmless to the human body.

The metal of the metal-organoframework compound of the present invention is copper, zinc or cobalt. In the present invention, copper, zinc or cobalt may increase the antibacterial effect.

In the present invention, L1 is a hydrocarbon group including two carboxylate groups in the molecule. L1 is preferably the same as the formula (2) below.

[Formula 2]

^- OOC-R-COO ^-

In the above formula, R is a bond, or a straight or branched hydrocarbon group having 1 to 7 carbon atoms, which may have a single bond or a double bond.

L1 is more preferably malonat, succinate, fumarate, glutarate, adipate or muconate.

To the metal of the metal-organoframework compound of the present invention, bis(4-pyridyl) or a derivative thereof is bound as an L2 ligand. The bis(4-pyridyl) or a derivative thereof is preferably represented by the following formula (3).

[Formula 3]

in the above formula

A is a bond, or a linear or branched hydrocarbon group having 1 to 7 carbon atoms, which may have a single bond or a double bond.

Bis(4-pyridyl) is more preferably 4,4...-bipyridine (4,4...-bipyridine, bpy), 1,2-bis(4-pyridyl)ethane (1,2-bis (4-pyridyl)ethane, bpa), 1,2-bis(4-pyridyl)ethene (1,2-bis(4-pyridyl)ethene, bpe) or 1,3-bis(4-pyridyl)propane (1,3-bis(4-pyridyl)propane, bpp).

Hereinafter, the structure of the metal-organic framework compound included in the antibacterial hydrogel of the present invention will be described using the Cu-organic framework compound as an example.

All of the Cu-glutarate metal-organic frameworks of the present invention were crystallized in monoclinic C2/c space groups. Single-crystal X-ray studies show that all of the metal-organic frameworks of the present invention have a two-dimensional (2D) sheet shape including _{paddle-wheel Cu 2 heteronuclear units connected by glutarate.} The two-dimensional sheets are linked by a bipyridyl ligand (L2) to form a three-dimensional (3D) framework (see FIGS. 1 and 2 ). In Figure 2, [Cu ₂ (Glu) ₂ (μ-L2)]x(H ₂ O) In the formula, the 3D framework when L2 is bpy in (a), and the 3D framework in the case of bpa in (b) , the 3D framework in the case of bpe is shown in (c), and the 3D framework in the case of bpp is shown in (d). The number of water molecules as a solvent was calculated from elemental analysis or the like. The coordination structure of each Cu(II) ion in the four metal-organoframework compounds is in the form of a square pyramid composed of four equatorial carboxylate O atoms and axial pyridyl N atoms.

In the metal-organoframework compounds of the present invention, solvate molecules are trapped in one-dimensional (1D) channels. The metal-organic framework of the present invention has a pore volume of 10-40% by volume, preferably 15-35% by volume, respectively, based on PLATON analysis. The metal-organic framework compounds of the present invention all contain well-defined 1D channels and have very similar pore shapes with appropriate pore sizes and pore volumes. It is thought that these pores and pore volumes have the effect of excellent antibacterial activity.

The metal-organoframework compound of Formula 1 is preferably

(a) dissolving a metal (II) salt compound, a hydrocarbon compound having two carboxylate groups, and a pyridyl compound in water after mixing;

(b) reacting for 12 hours to 10 days at 25 to 100° C. in a pressure vessel; and

(c) cooling the reaction solution and then recovering the resulting solid.

The metal (II) salt compound may be a nitrate, sulfate, carbonate, or chloride salt of a metal.

The hydrocarbon compound having two carboxylate groups is preferably HOOCRCOOH (R is a bond, or a linear or branched hydrocarbon group having 1 to 7 carbon atoms that may have a single bond or a double bond) or a sodium salt, calcium salt or It is potassium salt.

When mixing with water, ultrasonic waves can be used to increase solubility, and NaOH aqueous solution can be added if necessary.

As used herein, the term "hydrogel" may refer to a three-dimensional network structure made by cross-linking a hydrophilic polymer through a covalent or non-covalent bond. Due to the hydrophilicity of the constituent materials, it absorbs a large amount of water in an aqueous solution and in an aqueous environment and swells, but does not dissolve due to the cross-linked structure. Therefore, hydrogels having various shapes and properties can be made depending on the components and manufacturing methods, and since they generally contain a large amount of moisture, they may have intermediate properties between liquids and solids.

Polymers used for preparing the hydrogel of the present invention, such as polyethylene glycol, polyvinyl alcohol (PVA), hyaluronic acid, alginic acid, pectin, chitosan, etc. They may be natural polymers, preferably polyethylene glycol.

The hydrogel of the present invention may be produced by a crosslinking reaction between the polymer having an SH, NH2, epoxide group, etc. at the terminal and the polymer having a functional group having a double bond at the terminal. The functional group having a double bond at the terminal may be an acrylic acid group, a methacrylic acid group, glycidyl methacrylate, or the like.

The hydrogel of the present invention may have a degree of polymerization of 100 to 10,000.

The present invention provides a method for preparing an antibacterial hydrogel comprising a metal-organic framework compound of Formula 1 and a hydrogel.

[Formula 1]

[M ₂ (L1) ₂ (μ-L2)] x(H ₂ O)

Wherein M is Cu, Zn or Co,

L1 is a hydrocarbon group having two carboxylate groups,

L2 is a bis(4-pyridyl) compound or a derivative thereof

x is a number from 1 to 10.

A schematic diagram of an example of a hydrogel-forming reaction including a metal-organic framework compound of the present invention is shown in FIG. 3 .

3, from the moment the 4-arm polymer containing SH and the polymer having a straight chain diacrylate functional group are mixed, a Michael type addition reaction also occurs and chemical crosslinking begins to occur. The reaction depends not only on the intensity of UV light, the concentration of the photoinitiator, but also the temperature, the pH of the solvent, and the concentration of the solute. In the present invention, the intensity of UV light ^{can be variously adjusted from 1 to 200 mW/cm 2} , the concentration of the photoinitiator is preferably 0.01 to 1% (w/v), and the temperature is preferably 20 to 70° C. The higher the temperature, the faster the chemical crosslinking. In addition, the higher the pH of the solvent, the better the reaction occurs. In the present invention, the pH is preferably about 7.5 to 9, and the total concentration of the solute (polymer) can be adjusted to 1 to 15 wt%. The higher the concentration of the solute, the stronger the hydrogel is produced.

Hereinafter, polyethylene glycol sulfurhydryl (4-arm PEG-SH) and polyethylene glycol diacrylate (PEG-DA) as an example will be described in detail for a method for preparing an antibacterial hydrogel containing a metal-organic framework compound of the present invention. However, the present invention is not limited to the following manufacturing method.

The metal-organic framework compound of the present invention and the antibacterial hydrogel including the hydrogel are

Put 4-arm polyethylene glycol sulfurhydryl (4-arm PEG-SH) in the first E-tube and dissolve it in phosphate buffer saline (PBS).

Put the linear polyethylene glycol diacrylate (linear PEG-DA) in the second E-tube (E-tube), put PBS here and dissolve.

If necessary, adjust the pH to about 8.2 by adding a small amount of 1N NaOH to each solution.

The MOF is placed in the first tube and dispersed.

Transfer the linear PEG-DA from the second E-tube to the first E-tube with the MOF and mix.

UV photoinitiator (5% w/v) dissolved in ethanol is added so that it becomes 0.1% w/v.

When transferred to a certain mold and irradiated with UV light (200mW/cm ² ) for 5 minutes, a UV light-crosslinked hydrogel in which MOFs are physically captured is formed.

The metal-organic framework compound of the present invention and the antibacterial hydrogel comprising the hydrogel have antibacterial activity. The present invention provides an antimicrobial agent comprising a metal-organoframework compound and a hydrogel.

In the present invention, the metal-organic framework compound may be included in an amount of 0.001 to 5% by weight, preferably 0.05 to 1% by weight, based on the total weight of the antibacterial hydrogel including the metal-organic framework and the hydrogel. When the metal-organic framework is included in the above range, the hydrogel has excellent moisture content and can exhibit an excellent antibacterial effect. In addition, the mixing of the metal-organic framework compound and the hydrogel is performed appropriately and is economical.

The composition of the present invention is particularly excellent in antibacterial activity against bacteria such as Escherichia coli and Staphylococcus aureus.

The present invention provides an antimicrobial product comprising an antimicrobial hydrogel comprising a metal-organoframework compound.

Examples of the antibacterial product include an antibacterial nonwoven fabric, an antibacterial wet band, a dressing, cartilage tissue, and a contact lens.

Hereinafter, the present invention will be described in detail through an embodiment. However, the present invention is not limited to the following examples.

manufacturing example. [M ₂ (Glu) ₂ (L2)] x(H ₂ O) preparation

1. [Cu ₂ (Glu) ₂ (bpy)]·3(H ₂ O)

_{Cu (NO 3) 2 · 3H} 2 O with distilled water 20 mL solution containing (0.193 g, 0.8 mmol), glutaric acid (0.317 g, 2.4 mmol) and 4,4'-bipyridine (0.374 g, 2.4 mmol) were sonicated and placed in a high-pressure vessel lined with Teflon. The vessel was placed in an oven at 80° C. for 48 hours. After cooling to room temperature, the cyan block crystals were recovered by filtration, washed with distilled water and dried in air overnight. The yield was 0.028 g. [Cu ₂ (C ₅ H ₆ O ₄ ) ₂ (C ₁₀ H ₈ N ₂ )] 3(H ₂ O) (MW=597.5)

2. [Cu ₂ (Glu) ₂ (bpa)] 3 (H ₂ O)

_{Cu(NO 3} ) ₂ 3H ₂ O (0.48 g, 2.0 mmol), glutaric acid (0.26 g, 2.0 mmol) and 1,2-bis in distilled water (200 mL) containing 1.0 M NaOH (2 mL) (4-pyridyl)ethane (0.18 g, 1.0 mmol) was added and this was placed in a high pressure vessel lined with Teflon. The vessel was placed in an oven at 80° C. for 48 hours. After cooling to room temperature, cyan crystal needles were obtained. It was recovered by filtration, washed with distilled water and dried in air overnight. The yield was 0.40 g. [Cu ₂ (C ₅ H ₆ O ₄ ) ₂ (C ₁₂ H ₁₂ N ₂ )]·3(H ₂ O) (MW=625.6)

3. [Cu ₂ (Glu) ₂ (bpe)] 6(H ₂ O)

_{Cu(NO 3} ) ₂ 3H ₂ O (0.48 g, 2.0 mmol), glutaric acid (0.26 g, 2.0 mmol) and 1,2-bis in distilled water (200 mL) containing 1.0 M NaOH (2 mL) (4-pyridyl)ethylene (0.18 g, 1.0 mmol) was added and this was placed in a high pressure vessel lined with Teflon. The vessel was placed in an oven at 80° C. for 48 hours. After cooling to room temperature, the cyan crystal needles were recovered by filtration, washed with distilled water and dried in air overnight. The yield was 0.46 g. [Cu ₂ (C ₅ H ₆ O ₄ ) ₂ (C ₁₂ H ₁₀ N ₂ )] 6(H ₂ O) (MW=677.7)

4. [Cu ₂ (Glu) ₂ (bpp)] 6 (H ₂ O)

Cu(NO ₃ ) ₂ 3H ₂ O (0.060 g, 0.25 mmol), glutaric acid (0.033 g, 0.25 mmol), 1,3-bis(4-pyridyl)propane (0.046 g, 0.25 mmol) and urea 0.052 g, 0.87 mmol) was left at room temperature for 7 days. Turquoise crystals were recovered by filtration, washed with distilled water and dried in air overnight. The yield was 0.033 g. [Cu ₂ (C ₅ H ₆ O ₄ ) ₂ (C ₁₃ H ₁₄ N ₂ )] 6(H ₂ O) (MW=693.7)

The structural analysis results of the compounds are shown in Table 1 below.

One 2 3 4 Empirical formula C ₂₀ H ₂₆ Cu ₂ N ₂ O ₁₁ C ₂₂ H ₃₀ Cu ₂ N ₂ O ₁₁ C ₂₂ H ₃₄ Cu ₂ N ₂ O ₁₄ C ₂₃ H ₃₈ Cu ₂ N ₂ O ₁₄ formula weight 597.5 625.6 677.7 693.7 Temperature (K) 296(2) 223(2) 296(2) 296(2) Wavelength (?) 0.71073 Å 0.71073 Å 0.71073 Å 0.71073 Å space group C 2/c C 2/c C 2/c C 2/c

5. [Co ₂ (Glu) ₂ (bpa)]

_{Co(NO 3} ) ₂ 6H ₂ O (0.232 g, 0.8 mmol), glutaric acid (0.317 g, 2.4 mmol) and 1,2-bis(4-pyridyl)ethane (0.442 g, in DMF (20 mL), 2.4 mmol) and placed in a high-pressure vessel lined with Teflon. The vessel was placed in an oven at 130° C. for 48 hours. After cooling to room temperature, the crystals were recovered by filtration, washed with DMF and dried in air overnight. The yield was 0.028 g. [Co ₂ (C ₅ H ₆ O ₄ ) ₂ (C ₁₂ H ₁₂ N ₂ )] (MW=562.3)

6. [Co ₂ (Glu) ₂ (bpe)]

_{Co(NO 3} ) ₂ 6H ₂ O (0.232 g, 0.8 mmol), glutaric acid (0.317 g, 2.4 mmol) and 1,2-bis(4-pyridyl)ethylene (0.437 g) in DMF (20 mL) , 2.4 mmol) and placed in a high pressure vessel lined with Teflon. The vessel was placed in an oven at 130° C. for 48 hours. After cooling to room temperature, the crystals were recovered by filtration, washed with DMF and dried in air overnight. The yield was 0.028 g. [Co ₂ (C ₅ H ₆ O ₄ ) ₂ (C ₁₂ H ₁₀ N ₂ )] (MW=560.3)

7. [Zn ₂ (Glu) ₂ (bpe)] 2 (H ₂ O) preparation

_{Zn (NO 3) 2 · 6H} 2 O (0.0304g, 0.1mmol) and glutaric acid (0.0133g, 0.1mmol) of 1,2-bis (4-pyridyl) above were dissolved in 4mL H ₂ O ethylene (0.0376 g, 0.2 mmol) of 4 mL of acetonitrile solution is carefully added. Crystals can be obtained after standing for two weeks. The yield is 0.0287 g. [Zn ₂ (C ₅ H ₆ O ₄ ) ₂ (C ₁₂ H ₁₀ N ₂ )]·2(H ₂ O) (MW=609.3

Example 1. [Cu ₂ (Glu) ₂ (bpe)] 6(H ₂ O) Preparation of containing hydrogels

Put 20 mg of 4-arm polyethylene glycol sulfurhydryl (4-arm PEG-SH) into the first E-tube. Add 150uL of phosphate buffered saline (PBS) to this and dissolve by stirring (voltexing).

Add 13.6 mg of linear polyethylene glycol diacrylate (linear PEG-AC) to the second E-tube. Add 150uL of PBS and stir to dissolve.

Adjust the pH to about 8.2 by adding a small amount of 1N NaOH to each solution.

The MOF is placed in the first E-tube and dispersed with a pipet.

Transfer the linear PEG-AC from the second E-tube to the first E-tube with the MOF and stir to mix.

When transferred to a certain mold using a pipette, a hydrogel in which MOFs are physically trapped is formed.

As a result of the reaction, the total weight of the polymer was 33.6 mg, the volume of the solvent was 300 uL, and the concentration of the polymer was about 10 wt%.

Thiol:acryl=1:1 molar ratio (1:0.68 weight ratio)

Example 2. Preparation of hydrogel containing Cu-MOF

[Cu ₂ (Glu) ₂ (bpe)] ·6 (H ₂ O) instead of [Cu ₂ (Glu) ₂ (bpa)] · 3 (H ₂ O) was carried out as in Example 1, except that the hydro A gel was prepared.

Example 3. Preparation of Co-MOF containing hydrogel

[Cu ₂ (Glu) ₂ (bpe)] A hydrogel was prepared in the same manner as in Example 1 except that [Co ₂ (Glu) ₂ (bpe)] was used instead of [Cu 2 (Glu) 2 (bpe)]·6(H _{2 O).}

Example 4. Preparation of Zn-MOF containing hydrogel

[Cu ₂ (Glu) ₂ (bpe)] ·6 (H ₂ O) instead of [Zn ₂ (Glu) ₂ (bpe)] · 2 (H ₂ O) was carried out as in Example 1, except that the hydro A gel was prepared.

Example 5. Moisture content of hydrogel containing MOF

Includes [Cu ₂ (Glu) ₂ (bpe)]·6(H ₂ O), [Co ₂ (Glu) ₂ (bpe)] and [Zn ₂ (Glu) ₂ (bpe)]·2(H ₂ O) The water content of the hydrogel was measured and the results are shown in Table 2 below. In the table below, the control is a hydrogel that does not contain MOF.

Sample Control Cu-Glu-BPE Co-Glu-BPE Zn-Glu-BPE swelling ratio 20.1±1.3 21.9±0.5 24.7±0.3 24.9±0.9

Swelling ratio = Ws/Wd

Ws = hydrogel weight as hydrated

Wd = dry hydrogel weight

According to Table 2, it can be seen that the hydrogel containing MOF of the present invention has a higher water content compared to the hydrogel alone, and thus it can be seen that it can be usefully used for products requiring water content.

Test Examples 1 to 2. [Cu ₂ (Glu) ₂ (bpe)] 6(H ₂ O) Including hydrogel antibacterial test

_{[Cu 2} (Glu) ₂ (bpe)] [Cu 2 (Glu) 2 (bpe)] prepared in Example 1 Using the _{6 (H 2} O) containing antibacterial hydrogel was measured by the following procedure as follows. The antibacterial effect was measured in the same manner for the control group.

1) Sample preparation: Prepare a 5cm x 5cm (within 1cm thickness) test piece using a hydrogel.

2) Preparation of control piece: Prepare a control piece using stomacher film 5cm x 5cm.

3) Wipe the entire surface of the test piece and control piece with gauze or cotton wool soaked in ethanol 2 to 3 times, and then dry thoroughly.

4) Use sterilized water to prepare the number of bacteria to be 2.5 ~ 10 × 10 ⁵ CFU/mL, and use it as an inoculum.

5) Put the test piece or control piece in a petri dish and inoculate the test surface so that the initial number of bacteria is 1.1~3.6x10 ⁵ CFU/mL.

6) Incubate stationary at 37°C for 24 hours.

7) Measure the number of viable cells.

Test Example 1. Antibacterial effect on E. coli

An antibacterial test was performed on E. coli, and the results are shown in Table 3 and FIG. 4 below.

Test Example 2. Antibacterial effect on Staphylococcus aureus

An antibacterial test was performed against Staphylococcus aureus, and the results are shown in Table 3 and FIG. 5 below.

Test Examples 3 to 4. [Co ₂ (Glu) ₂ (bpe)] Including hydrogel antibacterial test

[Co ₂ (Glu) ₂ (bpe)] was carried out in the same manner as in Test Example 1 using a containing hydrogel.

Test Example 3. Antibacterial effect on E. coli

An antibacterial test was performed on E. coli, and the results are shown in Table 3 and FIG. 6 below.

Test Example 4. Antibacterial effect on Staphylococcus aureus

An antibacterial test was performed against Staphylococcus aureus, and the results are shown in Table 3 and FIG. 7 below.

Comparative Test Examples 1 to 2. Hydrogel antibacterial test

It was carried out in the same manner as in Test Example 1 using a PEG hydrogel not containing MOF.

Comparative Test Example 1. Antibacterial effect on E. coli

An antibacterial test was performed on E. coli, and the results are shown in Table 3 and FIG. 8 below.

Comparative Test Example 2. Antibacterial effect on Staphylococcus aureus

An antibacterial test was performed against Staphylococcus aureus, and the results are shown in Table 3 and FIG. 9 below.

Test Items
Test result Test Methods test environment initial concentration
(CFU/mL) concentration after 24 hours
(CFU/mL) cell reduction rate
(%) Antibacterial test by E. coli BLANK 1.1x10 ⁵ 5.9x10 ⁶ - KCL-FIR-1003: 2018 (37.0±0.2)℃ Cu-Glu-Bpe/PEG 1.1x10 ⁵ < 10 99.9 Antibacterial test by Staphylococcus aureus BLANK 3.5x10 ⁵ 6.7x10 ⁶ - Cu-Glu-Bpe/PEG 3.5x10 ⁵ < 10 99.9 Antibacterial test by E. coli BLANK 1.1x10 ⁵ 5.9x10 ⁶ - Co-Glu-Bpe/PEG 1.1x10 ⁵ < 10 99.9 Antibacterial test by Staphylococcus aureus BLANK 3.6x10 ⁵ 6.0x10 ⁶ - Co-Glu-Bpe/PEG 3.6x10 ⁵ < 10 99.9 Antibacterial test by E. coli BLANK 1.1x10 ⁵ 5.9x10 ⁶ - PEG 1.1x10 ⁵ 5.7x10 ⁶ 3.3 Antibacterial test by Staphylococcus aureus BLANK 3.6x10 ⁵ 6.0x10 ⁶ - PEG 3.6x10 ⁵ 5.6x10 ⁶ 6.6

CFU : Colony Forming Unit

Strain used: Escherichia coli ATCC 8739

Staphylococcus aureus ATCC 6538P

According to the antibacterial test results, it can be seen that the antibacterial hydrogel resin including the metal-organic framework of the present invention has excellent antibacterial effect against various bacteria. On the other hand, as a result of the antibacterial test of the PEG hydrogel conducted for the comparative test, it can be seen that the PEG hydrogel has almost no antibacterial properties, so it can be seen that the antimicrobial properties of the present invention are not due to the hydrogel itself.

Claims (10)

An antibacterial hydrogel comprising a metal-organic framework compound of Formula 1 and a hydrogel, wherein the metal-organic framework compound is an antibacterial hydrogel comprising 0.001 to 5% by weight relative to the total weight of the antibacterial hydrogel
[Formula 1]
[M ₂ (L1) ₂ (μ-L2)] x(H ₂ O)
Wherein M is Cu or Co,
L1 is a group of Formula 2 below
[Formula 2]
^- OOC-R-COO ^-
In the above formula, R is a linear or branched hydrocarbon group having 1 to 7 carbon atoms, which may have a single bond or a double bond,
L2 is a compound of Formula 3 below
[Formula 3]

in the above formula
A is a straight or branched hydrocarbon group having 2 to 7 carbon atoms having a double bond,
x is a number from 1 to 10,
The hydrogel is produced by a crosslinking reaction between a polymer having an SH group at the terminal and a polymer having a functional group containing a double bond at the terminal, and the degree of polymerization is 100 to 10,000,
The polymer is polyethylene glycol. delete delete The method according to claim 1, L2 is 1,2-bis (4-pyridyl) ethene (1,2-bis (4-pyridyl) ethene, bpe), characterized in that the antibacterial hydrogel delete delete delete An antibacterial agent comprising a metal-organic framework compound of Formula 1 and a hydrogel, wherein the metal-organic framework compound is an antibacterial agent comprising 0.001 to 5% by weight based on the total weight of the antimicrobial agent
[Formula 1]
[M ₂ (L1) ₂ (μ-L2)] x(H ₂ O)
Wherein M is Cu or Co,
L1 is a group of Formula 2 below
[Formula 2]
^- OOC-R-COO ^-
In the above formula, R is a linear or branched hydrocarbon group having 1 to 7 carbon atoms, which may have a single bond or a double bond,
L2 is a compound of Formula 3 below
[Formula 3]

in the above formula
A is a straight or branched hydrocarbon group having 1 to 7 carbon atoms having a double bond,
x is a number from 1 to 10,
The hydrogel is produced by a crosslinking reaction between a polymer having an SH group at the terminal and a polymer having a functional group including a double bond at the terminal, and the degree of polymerization is 100 to 10,000.
The polymer is polyethylene glycol. An antibacterial product comprising the antibacterial hydrogel of claim 1 The antibacterial product according to claim 9, wherein the antibacterial product is an antibacterial nonwoven fabric, an antibacterial wet band, a dressing, cartilage tissue, or a contact lens.

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