KR20100027568A - Fabrication method of monodisperse microball-shaped hydrogel particle with saponificated surface - Google Patents

Abstract

PURPOSE: A fabrication method of monodisperse microball-shaped hydrogel particles is provided to prepare polymer particles using relatively inexpensive water-soluble dispersing stabilizers and a large amount of water as a polymerization solvent through a single process. CONSTITUTION: A fabrication method of monodisperse microball-shaped hydrogel particles comprises the steps of: forming monodispersed polyvinyl acetate microspheres using dispersion polymerization of vinyl acetate monomers; and saponifying the polyvinyl acetate microspheres from a dispersing medium in the same arrangement state so that the polyvinyl acetate microspheres have a dual structure of a polyvinyl acetate/polyvinyl alcohol shell.

Description

Fabrication method of monodisperse microball-shaped hydrogel particle with saponificated surface}

The technology disclosed herein relates to a method for producing monodisperse microspherical hydrogel particles with surface saponified, more specifically, having a submicron size by saponifying it in a simple process without separation and drying after polyvinyl acetate polymerization. A method for producing monodisperse microspherical hydrogel particles.

Recently, in order to develop an ideal microspherical hydrogel material, studies have been attempted to produce spherical particles of various polymer materials such as cellulose, gelatin, and collagen, but it is difficult to obtain a uniform size distribution and obtain a submicron size range. Difficult to obtain

First manufactured by German German Hermann and Hanel, polyvinyl alcohol was a hydroxyl group-containing linear crystalline polymer produced by saponifying a vinyl ester-based polymer such as polyvinyl acetate. In addition, it has gained the spotlight as a medical polymer material because of its advantages in that it can be controlled in various ways, technical ease and particle size.

Polymerization methods of vinyl acetate for producing polyvinyl acetate include bulk polymerization, emulsion polymerization and suspension polymerization. It is known that polyvinyl acetate in the form of circular particles cannot be obtained by double bulk polymerization. Emulsion polymerization is widely used as a useful method for producing particles with a very uniform particle size distribution.However, this method is used to impart the stability of the particles to the surface of the particles, resulting in foaming and Physical degradation may occur. Suspension polymerization is a method for producing polymer particles using a monomer insoluble in water in the presence of a dispersion stabilizer of a polymer using water as a dispersion medium. However, this polymerization is a method of polymerization in the state of dispersing monomers in an aqueous phase by mechanical force. Since the obtained polymer particles have a very wide distribution of 0.1 to 1000 microns, an additional mechanism is required to lower the particle size distribution. Shall be. A method for producing particles of a vinyl monomer by suspension polymerization is disclosed in Republic of Korea Patent Publication No. 1986-0001833, Republic of Korea Patent Publication No. 1999-0021562 and the like.

Korean Patent Laid-Open Publication No. 2002-0069054 “Method for saponification of polyvinyl acetate and microspherical particulate polyvinyl alcohol prepared by the same” includes alkali, swelling agent, and polyvinyl acetate prepared by suspension polymerization without undergoing separation and drying process. In addition, a method of preparing polyvinyl alcohol into fine spherical particulates by pouring into an aqueous alkali solution bath containing a dispersant or by adding the above aqueous alkali solution to a polymerization solution to saponify continuously is disclosed. There are many difficulties to follow, and it is difficult to obtain particles having a diameter in the submicron range by suspension polymerization. In addition, the swelling degree of the insoluble polyvinyl acetate particles during the saponification process is low and the particle size is large, it may take several days to fully saponify.

According to one embodiment, the polyvinyl acetate microspheres are formed by forming a monodisperse polyvinyl acetate microspheres by dispersion polymerization of vinyl acetate monomer, and saponifying the polyvinyl acetate microspheres in a batch state without separating them from the dispersion medium. Provided is a method for producing monodisperse microspherical hydrogel particles by having a double structure of polyvinyl acetate core / polyvinyl alcohol shell.

Hereinafter, the technology disclosed herein will be described in detail.

According to one embodiment, a method for producing monodisperse microspherical hydrogel particles having a double structure of a polyvinyl acetate core / polyvinyl alcohol shell is provided. First, monodisperse polyvinyl acetate microspheres are formed by dispersion polymerization of vinyl acetate monomer.

In the dispersion polymerization method, unlike the suspension polymerization method, the monomer may initially be in a single phase dissolved in a solvent, and the polymerization may proceed in such a manner that phase separation occurs as the polymer precipitates according to the polymerization of the monomer.

When dispersion polymerization is carried out using vinyl acetate as the monomer, it is necessary to select an appropriate dispersion medium. For example, a mixed solvent of water and alcohol may be used. The production of polyvinyl acetate by the dispersion polymerization method may be performed by dispersing a vinyl acetate monomer with a dispersion stabilizer in a dispersion medium containing water and alcohol. At this time, it may be carried out by increasing the temperature to an appropriate temperature according to the polymerization initiator to be used.

As an example of a suitable dispersion medium, when using a mixed solvent of water and alcohol, the volume ratio of water: alcohol may be 1: 1 to 1: 4. The ratio of the monomer and the dispersion medium may have a volume ratio of 1: 5 to 1:20. The formation of monodisperse submicron particles may be advantageous when within the volume ratios and ratio ranges.

Dispersion stabilizers are used to increase the stability of the dispersion and to control the shape and distribution of the particles. For example, polyvinyl alcohol, gum arabic, hydroxyethyl cellulose, methylcellulose, starch, polyacrylic acid salts, polymethas Various compounds, such as krylate, gelatin, polyvinylpyrrolidone, can be used alone or in combination. The dispersion stabilizer may be used in an amount of 0.1 to 5 g based on 100 ml of vinyl acetate monomer, and the size of the particles may be excessively increased or microparticles may be increased. After the dispersion stabilizer is mixed with water, it may be stirred by raising the temperature to a temperature of 50 to 90 ℃ to dissolve it in water.

The polymerization initiator may be used alone or in combination with various compounds such as peroxides such as benzoyl peroxide, acetyl peroxide, dilauryl peroxide, di-tert-butyl peroxide, cumyl hydroperoxide, or azo compounds such as azoisobutyronitrile. Can be. The polymerization initiator may be used, for example, from 0.0001 mol to 0.05 mol with respect to 1 mol of vinyl acetate monomer.

Polyvinyl acetate microspheres can be obtained at a conversion rate of 80% or more by heating the mixture of the monomer, the dispersion medium, the polymerization initiator and the dispersion stabilizer at a temperature of 30 to 80 ° C. for several hours.

The average particle diameter of the microspheres obtained by the polymerization in the above manner may be less than 1 μm, and microspheres having monodispersity having a polydispersity index of, for example, 1 to 1.6 may be obtained by selection of an appropriate dispersion medium or polymerization temperature. have.

The polyvinyl acetate microspheres are then saponified. At this time, the polyvinyl acetate microspheres are saponified in a batch state without separating from the dispersion medium so that the polyvinyl acetate microspheres have a double structure of a polyvinyl acetate core / polyvinyl alcohol shell, thereby monodisperse microspherical hydrogel Particles can be prepared.

According to one embodiment of the saponification method of polyvinyl acetate, polyvinyl acetate microspheres prepared by dispersion polymerization are subjected to non-uniform saponification by adding a small amount of sodium hydroxide to the polyvinyl acetate particles without undergoing purification and separation drying processes. You can. In this case, the swelling degree of the fat-soluble polyvinyl acetate particles can be improved by the organic solvent in the dispersion medium. In addition, the increase in the specific surface area of the particles having submicron units can increase the reactivity to saponification. As a result, monodisperse microspherical particles having a double structure of polyvinyl acetate core / polyvinyl alcohol shell can be produced while maintaining a uniform particle size distribution in a few minutes using only a small amount of alkali. have.

Saponification of polyvinyl acetate can be carried out by adding alkali, acid and and amine to the polyvinyl acetate dispersion, for example sodium hydroxide, potassium hydroxide, calcium hydroxide, and hydroxide in the polyvinyl acetate dispersion prepared by the dispersion polymerization. One or more types selected from the group consisting of lithium can be added to the polyvinyl acetate dispersion to advance saponification. For example, adding a small amount of sodium hydroxide (eg, 0.1 to 1 mole with respect to 1 mole of acetic acid vinyl monomer) and performing heterogeneous saponification at room temperature for several hours results in microspherical particles having a core / shell double structure of several hundred nanometers in size. Can be obtained. Depending on the conditions of the saponification reaction, the degree of saponification of the surface of the polyvinyl acetate microspheres may be 20 to 99.9%.

The conventional saponification of polyvinyl acetate is achieved by completely dissolving polyvinyl acetate in methanol and then dropping an alkaline solution. In this case, the produced polyvinyl alcohol exhibits a very irregular surface in appearance and has a very wide size distribution. On the other hand, the saponification method disclosed in this specification proceeds saponification in a non-uniform phase by adding a small amount of sodium hydroxide as it is in solution phase without dispersing polyvinyl acetate as a separate process, and satisfactory saponification while maintaining a uniform size distribution of the microspheres. It is possible to obtain the microspheres of the core / shell structure of the dual structure, that is, monodisperse microsphere hydrogel particles.

Therefore, the polyvinyl alcohol fine monodispersed submicron size can be easily controlled by precisely controlling various dispersion polymerization parameters in the presence of an initiator, a dispersion stabilizer, and a dispersion medium, and dispersing and polymerizing vinyl acetate in a batch saponification without separate separation and purification process. Sphere particles can be obtained.

According to the production method disclosed in the present specification, a large amount of water is used as a polymerization solvent and a polymer particle is manufactured in a single economic process by using a relatively inexpensive water-soluble dispersion stabilizer, thereby reducing the production cost and toxicity of the polymer particle in the existing dispersion polymerization method. It also has the advantage of being smaller in size. The polymer microspheres obtained according to the manufacturing method can be used for various purposes, and in particular, it can be applied in various fields of high value-added through application as a medical material.

Hereinafter, with reference to the accompanying drawings, a specific comparative example and examples for the technology disclosed herein will be described in detail.

<Example 1>

Into a 250 ml three-necked flask equipped with a nitrogen inlet, a condenser and a stirrer, 60 ml of distilled water and 0.5 g / dl of polyvinyl alcohol (degree of soap: 88%, number average molecular weight: 127,000) as a dispersion stabilizer were stirred at 80 ° C. Melted. Next, after cooling to room temperature, oxygen was passed through a pyrogallol-alkali aqueous solution trap to remove oxygen, and the oxygen in the aqueous solution was removed for 1 hour. 10 ml of vinyl acetate (VAc), 30 ml of ethanol, and 0.178 g of azobisisobutyronitrile (1 × 10 ^-3 mol / mol of VAc), a polymerization initiator, were removed for 1 hour, and then oxygen was removed. And then polymerized for 3 hours under a stream of nitrogen. The vinyl acetate was washed with an aqueous sodium sulfite solution, treated with anhydrous calcium chloride, and distilled under reduced pressure.

The results of analyzing the polyvinyl acetate particles obtained by the above method with a scanning electron microscope (SEM) are shown in FIG. 1.

<Examples 2 to 4>

The same procedure as in Example 1 was carried out, but dispersion polymerization was performed while changing the mixing ratio and polymerization temperature of ethanol and water of the dispersion medium as shown in Table 1 below to obtain polyvinyl acetate microspheres.

The results of analyzing the polyvinyl acetate microspheres obtained by the above method with an electron microscope are shown in FIG. 2 (Example 2). 3 shows the results of analyzing the size of the obtained polyvinyl acetate particles and the distribution of the particles.

TABLE 1

division Monomer (ml) Ethanol (ml) Water (ml) Suspension Stabilizer (g / dl) Initiator (mol / mol of VAc) Polymerization temperature (℃) Polymerization time (h) Example 1 10 30 60 0.5 1 × 10 ^-3 60 3 Example 2 10 30 60 0.5 1 × 10 ^-3 70 3 Example 3 10 20 70 0.5 1 × 10 ^-3 60 3 Example 4 10 20 70 0.5 1 × 10 ^-3 70 3

1 and 2 are scanning electron micrographs of polyvinyl acetate microspheres prepared according to Examples 1 and 2 of the present invention, respectively. From the scanning electron micrographs of FIGS. 1 and 2, it can be seen that microspheres having a diameter of submicron size are formed.

Figure 3 is a measurement result of the particle size and distribution of the particle size of the polyvinyl acetate polymer microspheres prepared according to Examples 1, 2, 3, 4 of the present invention. As shown in FIG. 3, when the monomer: ethanol: water ratio was 10:30:60, when the polymerization temperature was polymerized at 60 ° C. for 3 hours (Example 1), the particle distribution was most uniform.

Example 5

50 ml of the polyvinyl acetate dispersion obtained by dispersion polymerization in Example 1 was taken in a two-necked flask, 1 ml of 40% by weight sodium hydroxide solution was added dropwise, and stirred at room temperature for 5 hours to proceed with non-uniform surface saponification. After the surface saponification was carried out, microspherical particles having a double structure of the obtained polyvinyl acetate core / polyvinyl alcohol shell were analyzed by transmission electron microscope (TEM), and the results are shown in FIG. 4. It was.

<Example 6>

50 ml of the polyvinyl acetate dispersion obtained by dispersion polymerization in Example 1 was taken in a two-necked flask, and 3 ml of 40% by weight sodium hydroxide solution was added dropwise, followed by stirring at room temperature for 5 hours, thereby performing non-uniform surface soaping.

<Example 7>

50 ml of the polyvinyl acetate dispersion obtained by dispersion polymerization in Example 1 was taken in a two-necked flask, 5 ml of 40% by weight sodium hydroxide solution was added dropwise, and stirred at room temperature for 5 hours to proceed non-uniform surface soap.

4 is a result of analyzing a microspherical particle having a double structure of a polyvinyl acetate core / polyvinyl alcohol shell prepared according to Example 5 of the present invention with a transmission electron microscope. The bottom scale bar is 500 nm. Referring to FIG. 4, the reaction was performed at room temperature with only a small amount of sodium hydroxide without a separate process or additives. As a result, it was confirmed that submicron-sized polymer microspheres having a double structure were formed.

5 is a measurement result of particle size and particle size distribution of microspherical particles having a double structure of polyvinyl acetate core / polyvinyl alcohol shell prepared according to Examples 5, 6 and 7 of the present invention. . Referring to FIG. 5, it can be seen that when the smallest amount of 1 ml of 40 wt% sodium hydroxide is added (Example 5), the particle size of the most uniform distribution is shown.

1 and 2 are scanning electron micrographs of polyvinyl acetate microspheres prepared according to Examples 1 and 2 of the present invention, respectively.

Figure 3 is a measurement result of the particle size and particle size distribution of the polyvinyl acetate polymer microspheres prepared according to Examples 1, 2, 3, 4 of the present invention.

4 is a result of analyzing a microspherical particle having a double structure of a polyvinyl acetate core / polyvinyl alcohol shell prepared according to Example 5 of the present invention with a transmission electron microscope.

5 is a measurement result of particle size and particle size distribution of microspherical particles having a double structure of polyvinyl acetate core / polyvinyl alcohol shell prepared according to Examples 5, 6 and 7 of the present invention. .

Claims (8)

Forming monodisperse polyvinyl acetate microspheres using dispersion polymerization of vinyl acetate monomer; And Monodisperse microsphere hydrogel comprising the polyvinyl acetate microspheres having a double structure of polyvinyl acetate core / polyvinyl alcohol shell by saponifying in one batch without separating the polyvinyl acetate microspheres from the dispersion medium Method for Producing Particles. According to claim 1, The dispersion polymerization method is a method for producing monodisperse microspherical hydrogel particles, which is carried out by dispersing the vinyl acetate monomer with a dispersion stabilizer in the dispersion medium containing water and alcohol. The method of claim 2, The dispersion medium is a method for producing monodisperse microspherical hydrogel particles, wherein water and alcohol are mixed in a volume ratio of 1: 1 to 1: 4. According to claim 1, The average particle diameter of the polyvinyl alcohol microspheres is a submicron manufacturing method of monodisperse microspheres hydrogel particles. According to claim 1, The saponification is a method for producing monodisperse microspherical hydrogel particles by adding any one of alkali, acid and amine to the dispersion of the polyvinyl acetate microspheres. According to claim 1, Said saponification is a method for producing monodisperse microspherical hydrogel particles, which is carried out by adding 0.1 to 1 mole of the vinyl acetate monomer to at least one selected from the group consisting of sodium hydroxide, potassium hydroxide, calcium hydroxide, and lithium hydroxide. According to claim 1, A method for producing monodisperse microspherical hydrogel particles having a saponification degree of 20 to 99.9% of the surface of the saponified polyvinyl acetate microspheres. Monodisperse microspherical hydrogel particles produced by the method according to any one of claims 1 to 6.

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