KR20210007736A - Catecholamine-grafted substrate and preparing method thereof - Google Patents

Abstract

The present invention relates to a method for introducing a catecholamine, such as dopamine, into a substrate and, more specifically, to a catecholamine-grafted substrate with catecholamine grafted, and to a production method thereof. The production method of a catecholamine-grafted substrate of the present invention includes a step of grafting catecholamine to the substrate in a solution in the presence of radiation. In addition, according to the production method, the catecholamine is introduced in a form of a catecholamine monomer without changing a structure of the catecholamine in the substrate.

Description

Catecholamine-grafted substrate and preparing method thereof

The present invention relates to a method for introducing catecholamines into a substrate. Specifically, the present invention relates to a catecholamine grafted substrate, and a method for preparing the same.

Since mussels produce and secrete a special water-insoluble adhesive, they are being studied as a potential raw material for an effective water-resistant bio-adhesive, and a coating technology using dopamine as a surface treatment technology using a polymer derived from mussels is being actively studied.

Dopamine is a monomolecular substance with a molecular weight of 153 Da having catechol and amine functional groups. In 2007, it was reported that a polydopamine coating layer was formed by oxidation of catechols on the surface of the material when a material to be modified on the surface was put in and taken out in an aqueous dopamine solution under the same conditions as the underwater environment (pH 8.5).

Polydopamine shows excellent surface adhesion to various surfaces regardless of the chemical properties of the surface, just as mussels have adhesion on various surfaces through their adhesive proteins in an aquatic environment. Surface modification using dopamine, specifically poly-dopamine, as well as specific surface adhesion ability, is capable of modifying the car surface by its own chemical properties, and thus studies are being conducted in various fields of application.

The polydopamine coating film formed on the surface still has a catechol functional group, but the catechol functional group has the ability to oxidize, reduce, and form covalent bonds with an amine functional group, thereby forming metal nanoparticles on the desired surface or various molecules having amine functional groups. Can also be introduced to the surface as a secondary surface modification. In addition, it has been reported that bioactive molecules such as gelatin or basic fibroblast growth factor (BFGF) can be successfully bound to the surface by controlling the degree of hydrophilicity of the surface. Accordingly, the surface modification method using dopamine has the potential to act as a very important technology in the field of developing various adhesive biomaterials and tissue engineering as a biocompatible coating technique that is an important factor of biomaterials as well as adhesion.

However, despite the usefulness of the catecholamine dopamine coating technology as described above, the dopamine coating technology known to date dissolves dopamine in an alkaline solvent (pH 8.5) to prepare a polydopamine solution, and the substrate is immersed in the polydopamine solution to obtain dopamine. This is a method of introducing a functional group.At this time, when the reaction is to proceed in the alkaline region for polydopamine coating, or when the reaction is to proceed in the neutral or acidic region, an oxidizing agent is added to proceed with polymerization through redox reaction with polydopamine. There is a problem that must be added as. In addition, there is also a problem of treating a large amount of polydopamine waste liquid generated after coating, and a problem in that the surface shape of the coating with polydopamine is not homogeneous has been reported. In addition, since the coating is in the form of polydopamine rather than dopamine, the amount to be introduced must be adjusted according to the coating time, so it is difficult to accurately measure the amount of introduction, and if it is introduced in an excessive amount, it is difficult to measure pores in materials with pores such as fibers. This clogging can also occur.

An object of the present invention is to provide a method of introducing catecholamine into a substrate in a short time without structural change.

Specifically, it is intended to provide a method of coating a catecholamine on a substrate without the use of a chemical additive such as an oxidizing agent to induce polymerization of the catecholamine.

In order to achieve the above object, the present invention provides a method for preparing a catecholamine grafted substrate comprising the step of grafting a catecholamine onto a substrate in a solution in the presence of radiation.

In addition, the present invention provides a radiation-induced catecholamine grafting substrate.

When the method for preparing a catecholamine grafted substrate of the present invention is used, the catecholamine can be introduced into the substrate in the form of, for example, a catecholamine monomer without changing the structure of the catecholamine. For example, dopamine may be introduced into the substrate in the form of a dopamine monomer.

In addition, compared to the conventional coating technology of catecholamine such as dopamine using a polydopamine solution, it is possible to reduce the time required to introduce the catecholamine to the substrate, and there is an effect of reducing the amount of catecholamine waste liquid.

In addition, it is possible to quantitatively measure the degree to which catecholamines are grafted, and there is an effect of being able to control the amount of catecholamines to be grafted.

1 is a graph showing a result of measuring a graft rate according to an irradiation amount of an electron beam when an electron beam irradiation sequence is different.
2 is a graph showing the measurement result of the graft rate according to the dopamine concentration.
3 is a graph showing the result of measuring the pH of the solution according to the concentration of dopamine.
4 is a graph showing the graphs of FIGS. 2 and 3 at the same time.

In the present invention, catecholamine includes a hydroxy group (-OH) at the ortho position of the benzene ring, and represents a single molecule having various alkylamines at the para position. In the present invention, the catecholamine may represent various compounds derived from the above structure together, but is not limited thereto, for example, dopamine, dopamine quinone, alpha-methyldopamine, norepinephrine, epinephrine, alpha-methylopa , May include at least one selected from the group consisting of droxydopa and 5-hydroxydopamine.

For example, dopamine represents a catecholamine represented by the following formula (1).

[Formula 1]

Hereinafter, a method for preparing the catecholamine grafted substrate of the present invention will be described in detail.

In the present invention, the'substrate' may be a material capable of generating radicals by radiation, and specifically, may be a crosslinked stable polymer. Such material may be, for example, at least one selected from the group consisting of polymer fibers, films, hydrogels, pipes, electric wires and tires, or a woven or nonwoven fabric thereof. The polymer fiber is preferably a material containing a double bond such as carbon-carbon, carbon-oxygen, etc., but is not limited thereto, for example, polypropylene, polyethylene, polypropylene-polyethylene copolymer, nylon, polyester synthesis It may be at least one selected from the group consisting of fiber, polycarbonate, ethylene vinyl acetate, and fluororesin.

In one example, polypropylene fibers grafted with dopamine as catecholamine were prepared.

The method for preparing a catecholamine grafted substrate of the present invention includes grafting a catecholamine to the substrate in solution in the presence of radiation.

The radiation may be present by mixing a substrate with a catecholamine-containing solution and then irradiating the radiation. Alternatively, before adding catecholamine to the solution containing the substrate, it may be present by irradiating the solution containing the substrate with radiation.

First, the method for preparing a catecholamine grafted substrate of the present invention may include mixing the substrate with a catecholamine-containing solution and then irradiating radiation. When irradiating a solution containing a catecholamine and a substrate with radiation, the irradiated radiation induces the generation of radicals in the substrate, and the catecholamine is introduced into the substrate due to the combination of the generated radical with the hydroxy group and/or amine group of the catecholamine. Although it can be inferred that the catecholamine grafting mechanism of the present invention is not limited thereto.

Next, the method for preparing a catecholamine grafted substrate of the present invention may include the step of adding a catecholamine after irradiating the substrate-containing solution with radiation. When radiation is irradiated to a solution containing both a substrate and a coating material, radicals are generated not only in the substrate but also in the coating material itself, so that there may be a problem that the graft rate is lowered due to a crosslinking reaction between the coating materials. When irradiated, the catecholamine monomer is activated, and the reaction with the substrate of the activated catecholamine monomer is more dominant than the binding reaction between the activated monomers, so that even when the solution containing the substrate and catecholamine is irradiated with radiation, the substrate and catecholamine are in high yield. Can be grafted.

In terms of the grafting yield (GY) of the catecholamine, it may be more preferable to irradiate the substrate with radiation after mixing the substrate with the catecholamine-containing solution than to add the catecholamine after irradiating the substrate-containing solution with radiation.

In the present invention, "geurapeuteuyul 'is due to a graft reaction, relative to the weight of the substrate before the reaction (Wo) weight increment (△ W) the will as a percentage (△ W / Wo X 100 ( %)), of the present invention When the method for preparing a catecholamine grafted substrate is used, a graft rate of 5% or more, for example, a graft rate of 10% or more can be exhibited.

In addition, the solution in which the catecholamine grafting is performed, the concentration of catecholamine is, for example, 0.1 to 10% by weight, specifically 0.5 to 6% by weight, 0.5 to 5% by weight, 0.5 to 4% by weight, 0.5 to 3% by weight, 0.5 It may be to 2% by weight or 1 to 2% by weight. The graft rate of catecholamines can be best when the concentration of catecholamines is 1 to 2% by weight.For example, when the concentration of catecholamines is less than the above range, the number of catecholamine monomers participating in the reaction is small in terms of the probability of reaction with the substrate. Therefore, the graft rate may be low. In addition, when the concentration of the catecholamine exceeds the above range and is excessive, the pH of the solution increases with the increase of the catecholamine monomer, so that the grafting rate of the catecholamine rapidly decreases. At this time, the concentration of the catecholamine represents the concentration in the state of excluding the substrate in the solution.

In addition, the reaction in which catecholamine is grafted onto the substrate may exhibit strong reactivity in a weakly acidic or weakly basic solution, and the reactivity may be significantly reduced in a strongly acidic solution. Accordingly, the pH of the solution in which the catecholamine grafting is performed is not limited thereto, but may be, for example, 4 to 7, for example, 4.4 to 6.5, 5 to 6, or 5.4 to 6.

In order to adjust the pH of the solution, the solution may further contain an alkali salt, and the method of preparing the catecholamine grafting substrate of the present invention may include adding an alkali salt to the solution prior to the grafting reaction. have. The alkali salt is added, depending on the pH of the target solution, or that can be selected appropriately for the type and amount, for example, ^{Na +, Li +, K +} , NH 4 +, Ca 2+, Cl - and NH ₃ ^- At least one selected from the group consisting of may be used.

In addition, the method for preparing a catecholamine grafted substrate of the present invention may further include purging the solution with nitrogen prior to the step of grafting the catecholamine onto the substrate in the presence of radiation. By removing dissolved oxygen in the solution by purging with nitrogen, oxygen radicals are generated by radiation and a side reaction to the grafting reaction of catecholamines is prevented, thereby shortening the grafting reaction time of catecholamines and improving the reaction rate. have. The nitrogen purging step may be performed by a conventional method, and is not limited to the means or method.

In addition, even if the dissolved oxygen is removed by purging with nitrogen, since some peroxides may be generated in the sample by contacting the reaction vessel with oxygen in the air, metal salts such as Ag ⁺ , Fe ²⁺ , Cu ²⁺ , Zn ²⁺ , At least one metal salt selected from the group consisting of Ni ²⁺ , Co ^+, and Pb ²⁺ may be added to the reaction solution to perform grafting of catecholamine. The added metal salt may suppress polymerization between catecholamines by providing electrons to OH radicals generated by peroxide decomposition through a mechanism as shown in Equation 1 below, thereby improving the grafting rate.

[Equation 1]

^{ROOH + Fe 2+ -> RO ·} + OH - + Fe 3+

The radiation inducing the grafting of the catecholamine may be at least one selected from the group consisting of, for example, electron beam, gamma ray, alpha ray, beta ray, neutron ray, and X-ray, and the energy of radiation and the efficiency of grafting reaction of catecholamine In terms of the radiation, it may be preferable to use an electron beam.

The amount of radiation to be irradiated can be appropriately selected depending on the amount of the substrate and/or catecholamine in the solution, the desired grafting rate, and the like. For example, the radiation may be irradiated with an irradiation amount of 1 to 500 kGy. More specifically, the radiation may be irradiated at an irradiation dose of 10 to 500 kGy, 50 to 300 kGy, 50 to 200 kGy, 80 to 150 kGy, for example 100 kGy.

In addition to water as a solvent, the solution may contain at least one selected from the group consisting of hydrocarbons, alcohols, aldehydes, ethers, esters, ketones, and glycol derivatives .

Examples of the hydrocarbons include aliphatic hydrocarbons such as gasoline, kerosene, and normal hexane, alicyclic hydrocarbons such as cyclohexane and methylcyclohexane, and aromatic hydrocarbons such as benzene, toluene, and xylene. In addition, aliphatic chlorinated hydrocarbons such as dichloromethane, chloroform, dichloroethane, trichloroethane, tetrachloroethane, dichloroethylene, trichloroethylene, tetrachloroethylene, etc., aromatic chlorinated hydrocarbons such as chlorobenzene, ortho-dichlorobenzene, dimethylsulfoxide Organic sulfur compounds such as, and the like, formic acid amide such as dimethylformamide, and the like are exemplified.

Examples of the alcohols include 1-butanol, 2-butanol, isobutyl alcohol, isopentyl alcohol, and isopropyl alcohol. The ethers may include ethyl ether, dioxane, tetrahydrobutane, and the like, and the esters are methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, pentyl acetate, acetic acid Isopentyl, etc., and the ketones include acetone, methyl ethyl ketone, methyl butyl ketone, and methyl isobutyl ketone, and the glycol derivative is ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol mono Ethyl ether acetate, ethylene glycol monobutyl ether, and the like.

In one embodiment, dimethyl sulfoxide, dimethylformamide, or the like may be used as the solvent.

Through the above method, the present invention provides a radiation-induced catecholamine grafting substrate.

The radiation may be, for example, at least one selected from the group consisting of electron rays, gamma rays, alpha rays, beta rays, neutron rays, and X-rays.In terms of the energy of the radiation and the efficiency of the grafting reaction of the catecholamine, the radiation It may be desirable to use.

In addition, the substrate may be a material capable of generating radicals by radiation, and for example, may be at least one selected from the group consisting of polymer fibers, films, hydrogels, pipes, wires, and tires. The polymer fiber is preferably a material containing a double bond such as carbon-carbon, carbon-oxygen, etc., but is not limited thereto, for example, polypropylene, polyethylene, polypropylene-polyethylene copolymer, nylon, polyester synthesis It may be at least one selected from the group consisting of fiber, polycarbonate, ethylene vinyl acetate, and fluororesin.

Hereinafter, the present invention will be described in more detail by way of examples.

[Manufacture of dopamine grafted polypropylene nonwoven fabric]

Experimental Example 1. Measurement of grafting rate according to the irradiation sequence of radiation

Polypropylene nonwoven fabric (Abspil, Inc.) and dopamine (SIGMA, Dopamine hydrochloride) were prepared.

First, a polypropylene nonwoven fabric was put into a container in an A4 size (210*297 mm), followed by purging with nitrogen, followed by irradiation with electron beams. The electron beam irradiated a total of 100 kGy under the conditions of 1.2 MeV*36.9 mA*8 m/min. After irradiation with an electron beam, dopamine was grafted onto a polypropylene nonwoven fabric by adding an aqueous dopamine solution (Fig. 1, pre).

In addition, after the polypropylene nonwoven fabric was added to the container as described above, dopamine aqueous solution was added to purify with nitrogen, and then dopamine was grafted onto the polypropylene nonwoven fabric by irradiation with electron beams (Fig. 1, simultaneous). Electron beam irradiation conditions were the same as in the pre-experiment above.

When dopamine was grafted in the same manner as described above, the grafting rate according to the amount of electron beam irradiation was measured, and the results are shown in Table 1 and FIG. 1 below. Grafting rate is measured by measuring the weight before and after the graft reaction, and the weight increase ( △W ) by the graft reaction relative to the weight ( Wo ) of the substrate before the reaction, and the percentage ( ΔW/Wo X 100 (%)). It was carried out by the method to obtain.

Dose (kGy) Simultaneous G.Y (%) Pre G.Y (%) 50 8.14 3.02 100 12.31 3.28 150 11.94 4.56

As shown in the results of Table 1 and Fig. 1, when the dopamine and the substrate were irradiated with an electron beam, the dopamine graft showed a much higher graft rate than when the dopamine was added after the substrate was irradiated with an electron beam. It was inferred that the dopamine monomer is activated and the activated monomer participates in the graft reaction.

Experimental Example 2. Measurement of the grafting rate according to the concentration of dopamine

After the polypropylene nonwoven fabric was put into a container in A4 size (210*297 mm), the dopamine solution was mixed, purged with nitrogen, and then dopamine was grafted onto the polypropylene nonwoven fabric by irradiation with electron beams. Electron beam irradiation conditions were performed in the same manner as in the above experiment.

When dopamine was grafted in the same manner as described above, the grafting rate according to the concentration of dopamine in the dopamine solution was measured, and the results are shown in Table 2 and FIG. 2 below. The measurement of the grafting rate was performed in the same manner as above.

In addition, the pH of the reaction solution before electron beam irradiation according to the dopamine concentration was measured with a pH meter (HM-25R, DKK-TOA corporation), and the results are shown in Table 3 and FIG. 3, and the pH of the reaction solution according to the dopamine concentration The change and the change of the graft rate are shown in FIG. 4.

Dopamine concentration (wt%) G.Y (%) 0.2 0.19 0.5 0.37 One 12.31 3 5.52 5 1.51 7 0.16

Dopamine concentration (wt%) pH 0.2 6.25 0.5 5.81 One 5.43 3 5.01 5 4.73 7 4.46

From the above results, when the dopamine concentration is low, specifically, when the concentration is less than 1 wt%, the graft rate is low because the number of monomers participating in the reaction is low in terms of the reaction probability, and as the concentration of dopamine increases, specifically in 0.2 to 1 wt% It was confirmed that the graft rate was improved due to the increase of the monomer concentration.

However, at a concentration exceeding 1 wt%, it was confirmed that the pH of the solution decreased as the monomer increased and the graft rate of dopamine was rapidly reduced. Through this, it was inferred that dopamine has a strong reactivity in the weakly acidic to neutral region, and it was confirmed that the concentration of dopamine can exhibit the highest graft rate between 1 wt% and 2 wt% for the same reason.

Claims (25)

A method for preparing a catecholamine grafted substrate comprising the step of grafting a catecholamine onto a substrate in a solution in the presence of radiation. The method according to claim 1,
After mixing the substrate in the catecholamine-containing solution, the method for producing a catecholamine grafted substrate comprising the step of irradiating radiation. The method according to claim 1,
After irradiating the substrate-containing solution with radiation, the method for producing a catecholamine grafted substrate comprising the step of adding a catecholamine. The method according to claim 1,
The method for producing a catecholamine grafted substrate in which the concentration of catecholamine in the solution is 0.5 to 6% by weight. The method of claim 4,
The method for producing a catecholamine grafted substrate in which the concentration of catecholamine in the solution is 1 to 2% by weight. The method according to claim 1,
The method for preparing a catecholamine grafted substrate in which the pH of the solution is 4 to 7. The method of claim 6,
The method for preparing a catecholamine grafted substrate in which the pH of the solution is 5.4 to 6. The method according to claim 1,
The method of producing a catecholamine grafting substrate further comprising the step of purging with nitrogen prior to the grafting step. The method according to claim 1,
The substrate is at least one selected from the group consisting of polymer fibers, films, hydrogels, pipes, wires, and tires, or fabrics or nonwovens thereof. The method of claim 9,
The polymer fiber is at least one selected from the group consisting of polypropylene, polyethylene, polypropylene-polyethylene copolymer, nylon, polyester synthetic fiber, polycarbonate, ethylene vinyl acetate, and fluororesin. Method for producing a catecholamine grafted substrate . The method according to claim 1,
The radiation is a method for producing a catecholamine grafted substrate that is irradiated with an irradiation amount of 1 to 500 kGy. The method according to claim 1,
The radiation is at least one selected from the group consisting of electron rays, gamma rays, alpha rays, beta rays, neutron rays, and X-rays. The method of manufacturing a catecholamine grafted substrate. The method of claim 12,
The method of manufacturing a catecholamine grafted substrate, wherein the radiation is an electron beam. The method according to claim 1,
The method for producing a catecholamine grafted substrate that the solution further comprises an alkali salt. The method of claim 14,
The catecholamines process for producing a grafted substrate that is at least one selected from the group consisting of: ^- the alkaline salts are ^{Na +, Li +, K +} , NH 4 +, Ca 2+, Cl - and NH _3. The method according to claim 1,
The solution is a method for producing a catecholamine grafted substrate comprising at least one selected from the group consisting of water, hydrocarbons, alcohols, aldehydes, ethers, esters, ketones, and glycol derivatives as a solvent. The method of claim 16,
The solvent is a method of producing a catecholamine grafted substrate comprising at least one selected from the group consisting of water, dimethyl sulfoxide, and dimethylformic acid amide. The method according to claim 1,
The catecholamine is dopamine, dopamine quinone, alpha-methyldopamine, norepinephrine, epinephrine, alpha-methylopa, droxydopa, and 5-hydroxydopamine. Method of manufacturing. The method of claim 18,
The catecholamine is a method for producing a substrate for grafting catecholamine containing dopamine. Radiation-induced catecholamine grafting substrate. The method of claim 20,
The radiation is at least one selected from the group consisting of electron rays, gamma rays, alpha rays, beta rays, neutron rays, and X-rays. The method of claim 20,
The substrate is a catecholamine grafted substrate that is at least one selected from the group consisting of polymer fibers, films, hydrogels, pipes, electric wires and tires. The method of claim 20,
A catecholamine grafted substrate having a grafting rate of 5% or more. The method of claim 20,
The catecholamine is a catecholamine grafted substrate comprising at least one selected from the group consisting of dopamine, dopaminequinone, alpha-methyldopamine, norepinephrine, epinephrine, alpha-methylopa, droxydopa, and 5-hydroxydopamine. The method of claim 20,
The catecholamine is a catecholamine grafted substrate containing dopamine.

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