KR101139638B1 - Method for forming hydrogel including nanoparticles - Google Patents

Abstract

It provides a method for producing a hydrogel containing nanoparticles. First, nanoparticles containing silica are prepared. A radical polymerization initiator is introduced to the surface of the nanoparticles. Nanoparticles to which the radical polymerization initiator is introduced are mixed with a vinyl monomer represented by the following Chemical Formula 1. The nanoparticles to which the radical polymerization initiator is introduced react with the vinyl monomer to form a hydrogel.

[Formula 1]

R ₁ R ₃ C = CR ₂ R ₄

In Formula 1, R ₁ is a hydroxy group, a carboxyl group, an amide group, a nitro phenyl group or a phenyl group, and R ₂ , R ₃ , and R ₄ are each an alkyl group having 1 to 3 carbon atoms or hydrogen regardless of each other.

Description

Method for producing hydrogel containing nanoparticles {Method for forming hydrogel including nanoparticles}

The present invention relates to a hydrogel, and more particularly to a hydrogel containing nanoparticles.

Hydrogels can be used in stages of ionic or hydrogen bonding, depending on physical factors such as stimulating factors of external environment, temperature, electric field, solvent components, light, pressure, sound, magnetic field, and chemical and biochemical factors such as pH and ionic strength. It refers to a kind that causes a change in volume or a state of gel-sol by suddenly forming and swelling and contracting.

Hydrogels that swell and change actively by appropriate external stimuli are being used for medical applications such as contact lens materials, wound coating agents, adsorbents, and drug delivery agents. In addition, hydrogels have excellent biocompatibility when in contact with blood, body fluids and biological tissues.

Known hydrogels have low mechanical properties, and many studies have been conducted as wound dressing hydrogels or drug carriers, and there are few studies on biocompatible tissues and artificial hip joints.

The problem to be solved by the present invention is to provide a method for producing a hydrogel with improved mechanical strength.

Technical problems of the present invention are not limited to the technical problems mentioned above, and other technical problems not mentioned will be clearly understood by those skilled in the art from the following description.

One aspect of the present invention to achieve the above object provides a hydrogel manufacturing method. First, nanoparticles containing silica are prepared. A radical polymerization initiator is introduced to the surface of the nanoparticles. Nanoparticles to which the radical polymerization initiator is introduced are mixed with a vinyl monomer represented by the following Chemical Formula 1. The nanoparticles to which the radical polymerization initiator is introduced react with the vinyl monomer to form a hydrogel.

R ₁ R ₃ C = CR ₂ R ₄

In Formula 1, R ₁ is a hydroxy group, a carboxyl group, an amide group, a nitro phenyl group or a phenyl group, and R ₂ , R ₃ , and R ₄ are each an alkyl group having 1 to 3 carbon atoms or hydrogen regardless of each other.

The nanoparticles may be silica particles or imogolite.

The radical polymerization initiator may be a peroxide group. In this case, before the radical polymerization initiator is introduced to the surface of the nanoparticles, the nanoparticles may be dispersed in water to form an aqueous nanoparticle solution. Thereafter, the nanoparticle aqueous solution may be irradiated with radiation to introduce a radical polymerization initiator onto the surface of the nanoparticles. The radiation may be Co ⁶⁰ .

Before reacting the nanoparticles to which the radical polymerization initiator is introduced and the vinyl monomer, impurities may be removed from the mixture of the nanoparticles to which the radical polymerization initiator is introduced and the vinyl monomer. Removing the impurities can be carried out using the freezing and thawing method.

The hydrogel generated by reacting the nanoparticles into which the radical polymerization initiator is introduced and the vinyl monomer may be lyophilized.

According to the present invention, such a hydrogel may contain nanoparticles and have high mechanical strength. In addition, the nanoparticles may include silica to introduce a radical polymerization initiator on the surface, thereby polymerizing the vinyl monomer without additional initiator and simultaneously forming a hydrogel. As such, no additional initiator can be added to improve the purity of the hydrogel. In addition, since the nanoparticles and the vinyl polymer are chemically bonded, mechanical strength may be further improved.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings in order to describe the present invention in more detail. However, this is not intended to limit the present invention to specific embodiments, it should be understood to include all modifications, equivalents, and substitutes included in the spirit and scope of the present invention. In the drawings, like reference numerals have been used for like components.

When a component is referred to as being "connected" or "connected" to another component, it may be directly connected to or connected to that other component, but it may be understood that other components may be present in between. Should be. On the other hand, when a component is said to be "directly connected" or "directly connected" to another component, it should be understood that there is no other component in between.

The terminology used herein is for the purpose of describing particular example embodiments only and is not intended to be limiting of the present invention. Singular expressions include plural expressions unless the context clearly indicates otherwise. In this application, the terms "comprise" or "have" are intended to indicate that there is a feature, number, step, operation, component, part, or combination thereof described in the specification, and one or more other features. It is to be understood that the present invention does not exclude the possibility of the presence or the addition of numbers, steps, operations, components, components, or a combination thereof.

Unless defined otherwise, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art. Terms such as those defined in the commonly used dictionaries should be construed as having meanings consistent with the meanings in the context of the related art and shall not be construed in ideal or excessively formal meanings unless expressly defined in this application. Do not.

1 is a flow chart showing a hydrogel manufacturing method according to an embodiment of the present invention. Figure 2 is a schematic diagram showing a hydrogel manufacturing method according to an embodiment of the present invention.

1 and 2, nanoparticles containing silica are prepared (S1). The nanoparticles may be silica particles or imogolite containing silica and having an inorganic nanotube form. The silica particles can be prepared using the Stebber method. Specifically, silica particles may be formed by hydrolyzing and condensing tetraethylorthosilicate (TEOS) under an ammonia catalyst. The average size of the nanoparticles may be about 140nm ~ 500nm.

A radical polymerization initiator is introduced to the surface of the nanoparticles (S2). The radical polymerization initiator may be a peroxide group. Before introducing the peroxide group to the surface of the nanoparticles, the nanoparticles may be dispersed in water to introduce a hydroxyl group to the surface of the nanoparticles. Thereafter, the nanoparticles to which the hydroxy group is introduced may be irradiated to modify the hydroxy group to a peroxide group. Irradiating the radiation may be performed in an oxygen atmosphere. The radiation may be gamma ray, for example Co ⁶⁰ (cobalt-60).

The nanoparticles to which the radical polymerization initiator is introduced are mixed with the vinyl monomer (S3). Specifically, the vinyl monomer is introduced into the aqueous nanoparticle solution into which the radical polymerization initiator is introduced. The vinyl monomer may be represented by the following formula (1).

[Formula 1]

R ₁ R ₃ C = CR ₂ R ₄

In Formula 1, R ₁ is a hydroxy group, a carboxyl group, an amide group, a nitro phenyl group or a phenyl group, and R ₂ , R ₃ , and R ₄ are each an alkyl group having 1 to 3 carbon atoms or hydrogen regardless of each other.

Such vinyl monomers include methacrylic acid, acrylic acid, N-isopropylacrylamide, 1-nitro-4-vinylbenzene, or styrene. (styrene).

Impurities may be removed from the mixture of the nanoparticles and the vinyl monomer to which the radical polymerization initiator is introduced. Specifically, impurities may be removed from the mixture by repeatedly freezing and thawing using the freezing and thawing method in the nitrogen filled state. Thereafter, the resultant may be refrigerated at about 4 ° C. or lower. The nitrogen filling is performed to sequester the nanoparticles and oxygen, and may proceed for about 5 minutes.

The nanoparticles introduced with the radical polymerization initiator are reacted with the vinyl monomer (S4). At this time, a radical polymerization initiator, for example, a peroxide group, introduced on the surface of the nanoparticles may polymerize the vinyl monomer to form a vinyl-based polymer 20 chemically bonded on the surface of the nanoparticles 10. Form. At this time, the radical polymerization initiator introduced on the surface of the nanoparticles may play a role of a crosslinking agent as well as an initiator. The polymerization process may be performed for 6 hours or more at 40 ℃ or more using the ATRP (Atomic Transfer Radical Polymerization) method. In this temperature range, the radical polymerization initiator may form a radical, and thus polymerization may proceed. As one example, the polymerization process may proceed at 40 ~ 50 ℃.

As a result of this polymerization process, the nanoparticles can be connected to each other by vinyl polymer.

The vinyl polymer includes R ₁ of Formula 1 bonded to a side chain thereof. In the polymerization process, the R ₁ is a hydroxy group, a carboxyl group, or a hydrogen bond is produced between the vinyl-based polymer that is, among the R _1, when an amide group, in the case wherein R ₁ is a phenyl group wherein the R ₁ Π-π stacking may occur in between to form a hydrogel. In addition, when R ₁ is a nitro phenyl group, hydrogen bonding and π-π stacking occur to form a hydrogel.

Thereafter, the hydrogel may be lyophilized to remove water and unreacted monomers, thereby obtaining a hydrogel having a 3D-network structure.

Such a hydrogel may contain high nanoparticles and high mechanical strength. In addition, the nanoparticles may include silica to introduce a radical polymerization initiator on the surface, thereby polymerizing the vinyl monomer without additional initiator and simultaneously forming a hydrogel. As such, no additional initiator can be added to improve the purity of the hydrogel. In addition, since the nanoparticles and the vinyl polymer are chemically bonded, mechanical strength may be further improved.

Hereinafter, preferred examples are provided to aid the understanding of the present invention. However, the following experimental examples are only for helping understanding of the present invention, and the present invention is not limited to the following experimental examples.

<Silica Particle Synthesis Example 1 Silica Particles with an Average Radius of 70 nm>

In a round bottom flask, 100 ml of ethanol was stirred for 30 minutes, about 7 ml of NH ₄ OH was added and stirred for 30 minutes. Then, 3 ml of TEOS (Tetraethyl-orthosilicate) was added thereto, stirred for 30 minutes, and 50 ml of ethanol was added thereto for 24 hours. Stirring to synthesize silica particles. Thereafter, an ethanol solution containing silica particles was placed in a centrifuge and centrifuged at 10,000 rpm for 30 minutes to separate silica particles having an average radius of about 70 nm.

<Silica Particle Synthesis Example 2: Silica Particles with an Average Radius of 120 nm>

Silica particles having an average radius of about 120 nm were separated using the same method as in the synthesis example of silica particles except that about 8 ml of NH ₄ OH and 3 ml of TEOS were used.

<Silica Particle Synthesis Example 3: Silica Particles with an Average Radius of 260 nm>

Silica particles having an average radius of about 260 nm were separated using the same method as in the synthesis example of silica particles except that about 9 ml of NH ₄ OH and 3 ml of TEOS were used.

<Silica-hydrogel Production Example 1>

(a) Silica Particles The silica particles obtained in Synthesis Example 1 were mixed with ultrapure water to form an aqueous 2 wt% silica solution.

(b) After irradiating the aqueous silica solution of (a) with Co ⁶⁰ (20 kGy / h) for 2 hours in air, the aqueous silica solution irradiated with gamma rays was filled with liquid gas (N ₂ ) and then cooled to 4 ° C. or less. Refrigerated. Thereafter, 2.5 ml of a 2 wt% silica aqueous solution and 2 ml of acrylic acid as monomers were placed in a glass ampoule to prepare a silica-acrylic acid aqueous solution having a volume ratio of 1.25: 1 between the aqueous silica solution and acrylic acid.

(c) The silica-acrylic acid aqueous solution was frozen for 20 minutes and then vacuumed for 20 minutes using a vacuum pump to remove impurity gases such as water vapor or oxygen, and then dissolved in cold water to form a liquid state.

(d) After repeating the process of (c) three times to remove impurities, the ampoule is cut using a torch in a vacuum state, and the cut ampoule is stirred for 24 hours in an oil bath maintaining about 40 ° C. To obtain silica-hydrogel.

(e) The hydrogel obtained in (d) was lyophilized for 48 hours using a lyophilizer to remove moisture and unreacted monomers contained in the silica-hydrogel, thereby obtaining a silica-hydrogel having a 3D-network structure. .

<Silica-hydrogel Preparation Example 2>

Silica-hydrogel was obtained in the same manner as in the silica-hydrogel preparation example 1 except that the silica particles obtained in the silica particle synthesis example 2 in step (a) were mixed with ultrapure water to form an aqueous 2 wt% silica solution.

<Silica-hydrogel Preparation Example 3>

Silica-hydrogel was obtained in the same manner as in the silica-hydrogel preparation example 1 except that the silica particles obtained in the silica particle synthesis example 3 in step (a) were mixed with ultrapure water to form an aqueous 2 wt% silica solution.

<Silica-hydrogel Production Example 4>

In step (a), the silica particles obtained in Synthesis Example 1 were mixed with ultrapure water to prepare an aqueous 1 wt% silica solution. In step (b), 2 ml of an aqueous 1 wt% silica solution and 2 ml of an acrylic acid acrylic acid monomer were added to a glass ampoule. Silica-hydrogel was obtained in the same manner as in Preparation Example 1, except that silica-acrylic acid aqueous solution having a volume ratio of 1: 1 was prepared.

<Silica-hydrogel Production Example 5>

In step (a), the silica particles obtained in Synthesis Example 1 were mixed with ultrapure water to prepare a 0.5 wt% silica aqueous solution. In step (b), 1 ml of the 0.5 wt% silica aqueous solution and 2 ml of the acrylic acid monomer were added to a glass ampoule. Silica-hydrogel was obtained in the same manner as in Silica-Hydrogel Preparation Example 1, except that a silica-acrylic acid aqueous solution having a volume ratio of aqueous solution and acrylic acid was 0.5: 1.

Experimental Example 1 Silica Particle Size

3A to 3C are scanning electron microscope (SEM) images of silica particles obtained in silica particle synthesis examples 1 to 3, respectively.

3A to 3C, it can be seen that silica particles having a relatively uniform size are formed.

Figure 4 is a graph showing the size distribution of the silica particles obtained in silica particle synthesis examples 1 to 3. The size distribution of silica particles was measured using a DLS (Dynamic Light Scattering) equipment.

4, the average radius of the silica particles obtained through silica particle synthesis example 1 (NH ₄ OH 7ml, TEOS 3ml) is about 70nm, obtained through silica particle synthesis example 2 (NH ₄ OH 8ml, TEOS 3ml). The average radius of the silica particles is about 120nm, it can be seen that the average radius of the silica particles obtained through silica particle synthesis example 3 (NH ₄ OH 9ml, TEOS 3ml) is about 260nm.

Experimental Example 2: Tensile and Compressive Properties of Silica-Hydrogel According to Silica Particle Average Radius

Tensile and compressive properties of silica-hydrogels obtained through silica-hydrogel preparation examples 1 to 3 were measured using a universal testing machine (UTM), and the results related to compression properties are shown in Table 1 below. It was.

[Table 1]

Silica particle average radius Silica-hydrogel Synthesis Compression test Aqueous silica solution / acrylic acid Reaction time
[h] Strain
[%} stress
[MPa] after the test
condition 70 nm 2wt% 2.5ml / 2ml 24 98.2 30.8 recovery 120 nm 2wt% 2.5ml / 2ml 24 96.1 30.8 recovery 260 nm 2wt% 2.5ml / 2ml 24 92.4 22.7 recovery

5 is a graph showing the compression characteristics of silica-hydrogels obtained through silica-hydrogel preparation examples 1 to 3; 6 is a graph showing the tensile properties of silica-hydrogel obtained through silica-hydrogel preparation examples 1 to 3.

Referring to Table 1 and Figure 5, the smaller the average radius of the silica particles, the greater the compressive strength (stress at maximum compressive strain before break) and tensile strength (stress at maximum tensile strain before break) of the silica-hydrogel, It can also be more flexible. This is presumably because the larger the average radius of the silica particles, the more Si-O-C bonds on the surface thereof, thereby making the silica-hydrogel stronger.

From these results, it can be seen that the compression and tensile properties of the silica-hydrogel can be adjusted by controlling the average radius of the silica particles.

Experimental Example 3: Tensile and Compressive Properties of Silica-Hydrogel According to Volume Ratio of Aqueous Silica Particle Solution and Monomer>

The tensile and compressive properties of silica-hydrogels obtained through Silica-Hydrogel Preparation Examples 1, 4, and 5 were measured using a universal testing machine (UTM), and each wt% of silica-hydrogels was measured. The results related to the tensile and compressive properties of 2wt% silica-hydrogel having the strongest viscoelasticity are shown in Table 2 below.

TABLE 2

Silica particle average radius Silica-hydrogel Synthesis Compression test Tensile test Aqueous silica solution / acrylic acid Reaction time
[h] transform
[%} stress
[MPa] transform
[%} stress
[MPa] 70 nm 2wt% 2.5ml / 2ml 24 98.2 30.8 1800 1.8 State of silica-hydrogel after compression test and tensile test: recovery

Referring to Table 2, as the ratio of silica to polymer is increased, it forms a harder and less viscoelastic solid silica-hydrogel, whereas as the ratio of silica to polymer is decreased, the gel is soft and sticky. It can be seen that the hydrogel can be formed.

In addition, it can be seen from these results that by adjusting the volume ratio of the aqueous silica solution and acrylic acid, it is possible to control the compression characteristics, tensile characteristics and shape of the silica-hydrogel.

While the invention has been described above with reference to specific preferred embodiments, it is intended that the specific modifications and variations of the invention fall within the scope of the invention and the specific scope of the invention will be apparent from the appended claims.

1 is a flow chart showing a hydrogel manufacturing method according to an embodiment of the present invention.

Figure 2 is a schematic diagram showing a hydrogel manufacturing method according to an embodiment of the present invention.

3A to 3C are scanning electron microscope (SEM) images of silica particles obtained in silica particle synthesis examples 1 to 3, respectively.

Figure 4 is a graph showing the size distribution of the silica particles obtained in silica particle synthesis examples 1 to 3.

5 is a graph showing the compression characteristics of silica-hydrogels obtained through silica-hydrogel preparation examples 1 to 3;

6 is a graph showing the tensile properties of silica-hydrogel obtained through silica-hydrogel preparation examples 1 to 3.

Claims (9)

Preparing nanoparticles containing silica; Introducing a peroxide group to the surface of the nanoparticles, wherein the peroxide group is in direct contact with the surface of the nanoparticles; Mixing the nanoparticles into which the peroxide group is introduced and the vinyl monomer represented by Formula 1; A method for preparing a hydrogel, comprising: forming a hydrogel by reacting the peroxide-group-introduced nanoparticles with the vinyl monomers: [Formula 1] R ₁ R ₃ C = CR ₂ R ₄ In Formula 1, R ₁ is a hydroxy group, a carboxyl group, an amide group, a nitro phenyl group or a phenyl group, and R ₂ , R ₃ , and R ₄ are each an alkyl group having 1 to 3 carbon atoms or hydrogen regardless of each other. The method of claim 1, The nanoparticles are silica particles or imogolite is a hydrogel manufacturing method. delete The method of claim 1, Before introducing the peroxide group to the surface of the nanoparticles, Dispersing the nanoparticles in water to form a nanoparticle aqueous solution further comprising the step of forming. 5. The method of claim 4, Introducing a peroxide group on the surface of the nanoparticles is a method for producing a hydrogel is performed by irradiating the nanoparticles aqueous solution. The method of claim 5, The radiation is Co ⁶⁰ hydrogel manufacturing method. The method of claim 1, And removing impurities from the mixture of the nanoparticles and the vinyl monomer, into which the peroxide group is introduced, before reacting the nanoparticles into which the peroxide group is introduced, and the vinyl monomer. The method of claim 7, wherein Removing the impurities is a hydrogel manufacturing method performed using a freezing and thawing method (freezing and thawing method). The method of claim 1, A method of producing a hydrogel further comprising lyophilizing a hydrogel produced by reacting the nanoparticles into which the peroxide group is introduced and the vinyl monomer.

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