KR20140148285A - Homo polymer nanoparticles by self-emulsion polymerization and preparation thereof - Google Patents

Abstract

The present invention relates to a method for producing homo-polymer nanoparticles without using a surfactant. The homo-polymer nanoparticles can be used for a semiconductor metal oxide template, a drug delivery system (DDS), an electron transport layer, and a seed in a vertical structure. Moreover, the homo-polymer nanoparticles are expected to be used in a high precision field. For example, the homo-polymer can be used as a substitute for an organic device polystyrene bead film.

Description

[0001] Homo-polymer nanoparticles by self-emulsion polymerization and their preparation [

The present invention relates to a homopolymer nanoparticle by a self-emulsion polymerization reaction and a method for producing the homopolymer nanoparticle. More specifically, the present invention relates to a method for producing homopolymer nanoparticles by a self-emulsion polymerization reaction will be.

The present invention also relates to a drug delivery material comprising the homopolymer nanoparticles, a method for preparing the same, and an electron transport layer comprising the homopolymer nanoparticles.

Polymer fine particles with nanoparticle size, which are excellent in monodispersity, have attracted much research and interest due to various industrial applications in the field of nanomaterials requiring 'smaller', 'smarter', and 'faster'. Applications of these particles can be used for high value added materials that are of great industrial importance, such as organic pigments for paints, color balls, toners, fillers for chromatography, diagnostic reagents, chemical and biological sensors, microelectronics, photonic crystals and drug transport materials. have.

Emulsion polymerization is one of the methods for producing such monodispersed polymer microparticles. Emulsion polymerization is a method in which water-insoluble monomers are emulsified in water together with an emulsifier to make a water-soluble polymerization hydrophilic initiator. Since the reaction takes place in water, the heat of polymerization is easily removed and there is no viscosity. Big. However, it is easily contaminated by the emulsifier, and there is a problem that a lot of cost is required in the step of removing it.

As a conventional technique for overcoming this problem, there has been disclosed a method of polymerizing without using an emulsifier. Soap-free emulsion polymerization is a method in which an emulsifier, that is, an ionic hydrophilic initiator or an ionic hydrophilic initiator As a method of using a monomer, particularly excellent in a short dispersibility. The mechanism is that the polymer adsorbs to the particle nuclei. In this mechanism, the growth process of the particles depends on the deposition rate of the polymeric materials in the bulk, and when the concentration of the hydrophilic initiator is high, the polymeric materials in the bulk are increased, leading to the synthesis of larger particles. However, the reaction rate is slow and there is a limit to use only hydrophobic monomers.

Accordingly, a first object of the present invention is to provide a method for preparing homopolymer nanoparticles capable of forming micelles without using a surfactant through self-emulsion polymerization, and a method for preparing homopolymer nanoparticles Polymer nanoparticles.

It is another object of the present invention to provide a drug delivery material comprising the homopolymer nanoparticles and a method for producing the same.

The present invention also provides an electron transport layer comprising the homopolymer nanoparticles.

The present invention relates to a process for preparing homopolymer nanoparticles and provides the following steps:

(a) obtaining a surfactant-free emulsion comprising an amphiphilic monomer, a hydrophilic initiator, and water; And

(b) performing a self-emulsion polymerization reaction in the surfactant-free emulsion.

The homopolymer may be represented by the following formula.

(Wherein A represents a substituted aryl group, a substituted or unsubstituted aromatic heterocyclic group, an alkyl halide group, a cyano group, a carboxy group, an ester group, an amide group, a cyanate group, a thiocyanate group, , Pyrrolidone group.)

The amphiphilic monomer may be represented by the following formula.

(Wherein A is a substituted aryl group, a substituted or unsubstituted aromatic heterocyclic group, an alkyl halide group, a cyano group, a carboxy group, an ester group, an amide group or a pyrrolidone group)

According to one embodiment of the present invention, the hydrophilic initiator is selected from the group consisting of 2,2'-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride, 4,4- 1-azobis (1-methylbutyronitrile-3-sodium sulfonate), ammonium persulfate, potassium persulfate, sodium persulfate, ammonium bisulfate, sodium bisulfate and 1,1-azobis Or more.

The present invention also provides a homopolymer nanoparticle composed of a homopolymer represented by the following general formulas (1) to (8) (wherein n is an integer of 10-10,000)

[Chemical Formula 1] < EMI ID =

[Chemical Formula 6] [Chemical Formula 7] [Chemical Formula 8]

The homopolymer nanoparticles are spherical with a diameter of 1-800 nm;

Wherein the homopolymer nanoparticles are composed of 2 to 1,000 homopolymers;

Wherein an outer portion of the homopolymer nanoparticle is composed of a hydrophobic main chain constituting the homopolymer and a hydrophilic side chain of a hydrophilic side chain and the inner layer of the homopolymer nanoparticle comprises a hydrophobic main chain of 70-95% By volume of hydrophilic side chains.

The present invention also provides a drug delivery material comprising the homopolymer nanoparticles and the pharmaceutically active material trapped in the inner layer of the homopolymer nanoparticles.

The present invention provides a method for preparing a drug delivery material comprising the steps of:

(a) obtaining a surfactant-free emulsion comprising an amphipathic monomer, a hydrophilic initiator, water, and a pharmaceutically active substance; And

(b) performing a self emulsion polymerization reaction in the surfactant-free emulsion;

Wherein the drug delivery material comprises homopolymer nanoparticles and a pharmaceutically active material trapped in an inner layer of the homopolymer nanoparticles;

The homopolymer nanoparticles are composed of homopolymers represented by the following general formulas (1) to (8) (wherein n is an integer of 10-10,000)

[Chemical Formula 1] < EMI ID =

[Chemical Formula 6] [Chemical Formula 7] [Chemical Formula 8]

The homopolymer nanoparticles are spherical with a diameter of 1-800 nm;

Wherein the homopolymer nanoparticles are composed of 2 to 1,000 homopolymers;

Wherein an outer portion of the homopolymer nanoparticle is composed of a hydrophobic main chain constituting the homopolymer and a hydrophilic side chain of a hydrophilic side chain and the inner layer of the homopolymer nanoparticle comprises a hydrophobic main chain of 70-95% % Hydrophilic side chains;

The amphiphilic monomer may be selected from the group consisting of vinylpyridine, 4-vinylpyridine, acrylic acid, methacrylic acid, styrene sulfonic acid, 4-styrenesulfonic acid, methyl methacrylate, 2-hydroxyethyl methacrylate, Vinylpyridine-3-carbonitrile, hydroxybutyl methacrylate, methacrylamide, N-vinylpyrrolidone, acrylonitrile, 4- (4-vinylphenyl) pyridine and 6-vinylpyridine-3-carbonitrile;

The hydrophilic initiator may be at least one selected from the group consisting of 2,2'-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride, 4,4- azobis (4-cyanovaleric acid) , At least one selected from the group consisting of potassium persulfate, sodium persulfate, ammonium bisulfate, sodium bisulfate, and 1,1-azobis (1-methylbutyronitrile-3-sodium sulfonate);

Wherein the self-emulsion polymerization reaction is carried out at 55-95 DEG C for 50-160 minutes.

The present invention also provides a method for preparing a drug delivery material comprising the steps of:

(a) obtaining a surfactant-free emulsion comprising an amphiphilic monomer, a hydrophilic initiator, and water;

(b) performing self-emulsion polymerization in the surfactant-free emulsion to prepare homopolymer nanoparticles;

(c) swelling the homopolymer nanoparticles and collecting the pharmaceutical active material in an inner layer of the homopolymer nanoparticles;

The homopolymer nanoparticles are composed of a homopolymer selected from the following general formulas (1) to (6), wherein n is an integer of 10 to 10,000:

[Chemical Formula 1] < EMI ID =

[Chemical Formula 6] [Chemical Formula 7] [Chemical Formula 8]

The homopolymer nanoparticles are spherical with a diameter of 1-800 nm;

Wherein the homopolymer nanoparticles are composed of 2 to 1,000 homopolymers;

Wherein an outer portion of the homopolymer nanoparticle is composed of a hydrophobic main chain constituting the homopolymer and a hydrophilic side chain of a hydrophilic side chain and the inner layer of the homopolymer nanoparticle comprises a hydrophobic main chain of 70-95% % Hydrophilic side chains;

The amphiphilic monomer may be selected from the group consisting of vinylpyridine, 4-vinylpyridine, acrylic acid, methacrylic acid, styrene sulfonic acid, 4-styrenesulfonic acid, methyl methacrylate, 2-hydroxyethyl methacrylate, Vinylpyridine-3-carbonitrile, hydroxybutyl methacrylate, methacrylamide, N-vinylpyrrolidone, acrylonitrile, 4- (4-vinylphenyl) pyridine and 6-vinylpyridine-3-carbonitrile;

The hydrophilic initiator may be at least one selected from the group consisting of 2,2'-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride, 4,4- azobis (4-cyanovaleric acid) , At least one selected from the group consisting of potassium persulfate, sodium persulfate, ammonium bisulfate, sodium bisulfate, and 1,1-azobis (1-methylbutyronitrile-3-sodium sulfonate);

Wherein the self-emulsion polymerization reaction is carried out at 55-95 DEG C for 50-160 minutes.

The present invention also provides an electron transport layer comprising the homopolymer nanoparticles.

The present invention relates to a method for producing homopolymer nanoparticles through self-emulsion polymerization using only water, an amphiphilic monomer and a hydrophilic initiator, and homopolymer nanoparticles produced thereby, wherein the amphiphilic monomer or the homopolymer itself forms an interface Act as an activator to form micelles. Since a surfactant is not used, the nanoparticles can be safely manufactured because of a simple manufacturing process, environmentally friendly, and the homopolymer nanoparticles thus prepared can be used in various fields such as a drug delivery material or an electron transport layer.

FIG. 1 is a mechanism showing a self-emulsion polymerization process.
FIG. 2 is a graph and photographs showing the sizes of the poly-4-vinylpyridine homopolymer nanoparticles according to the self-emulsion polymerization reaction time.
3 (a) to 3 (d) are TEM (Transmission Electron Microscope) photographs of the nanoparticles prepared in Example 1, and (e) and (f) Microscope) is a photograph.
FIG. 4 is a graph showing the ¹ H-NMR (nuclear magnetic resonance) spectrum of the nanoparticles prepared in Example 1. FIG.
5 is a graph showing a DSC (differential scanning calorimetry) thermal curve of the nanoparticles prepared in Example 1. Fig.
6 is a graph showing DLS (Dynamic Light Scattering) measurement values of the nanoparticles prepared in Example 2. FIG.
FIG. 7A is a DLS photograph of the nanoparticles prepared in Example 3, and FIG. 7B is a TEM photograph.
FIG. 8A is a graph showing DLS measurement values of the nanoparticles prepared in Example 4, FIG. 8B is an SEM, and FIG. 8C is a TEM photograph.
FIG. 9A is a graph showing DLS measurement values of nanoparticles prepared in Example 5, and FIG. 9B is a TEM photograph.
10 is a graph showing the particle size according to the hydrophilic initiator concentration of the nanoparticles prepared in Example 6. FIG.
11 is a graph illustrating the conversion of homopolymer nanoparticles according to an embodiment of the present invention.
12 is a graph showing DLS (Dynamic Light Scattering) measurement values of the nanoparticles prepared in Example 7. FIG.
13 is a graph (a) showing DLS measurement values of the nanoparticles prepared in Example 8, and is an SEM photograph (b) and a TEM photograph (c).

Hereinafter, the present invention will be described in detail.

As used herein, unless otherwise defined, "amphiphilic" means having both hydrophilic and hydrophobic properties in a molecule, "hydrophobic" means a property that is not easily combined with a water molecule, and "hydrophilic" It means a property that binds well with water molecules.

The present invention relates to a method for preparing homopolymer nanoparticles using a self-emulsion polymerization reaction. Self-emulsion polymerization (SEP) does not use a surfactant, a crosslinking agent or an emulsifier used in emulsion polymerization by using a monomer having both a hydrophilic group and a hydrophobic group. Therefore, washing and purification thereof, And the homopolymer nanoparticles produced by this method have no impurities.

The present invention provides a method for producing homopolymer nanoparticles comprising the following steps.

(a) obtaining a surfactant-free emulsion comprising an amphiphilic monomer, a hydrophilic initiator, and water; And

(b) performing a self emulsion polymerization reaction in the surfactant-free emulsion.

To make a homopolymer by self-emulsion polymerization, only water, a hydrophilic initiator, and an amphiphilic monomer are used. FIG. 1 shows the mechanism of the self-emulsion polymerization process. When a hydrophilic initiator is added to water at a certain temperature, the hydrophilic initiator undergoes addition polymerization with the amphiphilic monomer to form a polymer. The polymer forms micelles in water by arranging the hydrophilic and hydrophobic moieties together. The use of surfactants does not require the use of surfactants as in emulsion polymerization by the addition of amphiphilic monomers or polymers. As the polymer is polymerized in the micelle, the micelle grows and forms nanoparticles. FIGS. 3A to 3D) are TEM (projection electron microscopic) photographs of poly (4-vinylpyridine homopolymer nanoparticles) by self-emulsion polymerization over time. 3a), the homopolymer chain begins to make micelles with hollow interior. 3b), some dark areas indicate that the polymer chains enter the micelle. 3C) and FIG. 3D), nanoparticles were formed while growing the polymer in the micelles and the micelles, and it was confirmed that no further growth was observed after 60 minutes of reaction.

The homopolymer nanoparticles prepared by the above method do not contain a surfactant and can be used for a drug delivery material or an electron transporting layer which does not contain impurities and requires a high-purity water.

The homopolymer may be represented by the following formula.

(Wherein A represents a substituted aryl group, a substituted or unsubstituted aromatic heterocyclic group, an alkyl halide group, a cyano group, a carboxy group, an ester group, an amide group, a cyanate group, a thiocyanate group, , Pyrrolidone group, and n is an integer of 10 to 10,000).

In one embodiment, the homopolymer may be one selected from the following formulas (1) to (8).

[Chemical Formula 1] < EMI ID =

[Chemical Formula 6] [Chemical Formula 7] [Chemical Formula 8]

In the above formula, n is an integer of 10-10,000.

In one embodiment, the amphiphilic monomer has both a hydrophilic group and a hydrophobic group, and may be represented by the following formula.

(Wherein A is a substituted aryl group, a substituted or unsubstituted aromatic heterocyclic group, an alkyl halide group, a cyano group, a carboxy group, an ester group, an amide group or a pyrrolidone group)

Examples thereof include vinylpyridine, 4-vinylpyridine, acrylic acid, methacrylic acid, styrene sulfonic acid, 4-styrenesulfonic acid, methyl methacrylate, 2-hydroxyethyl methacrylate, hydroxypropyl methacrylate, Acrylonitrile, 4- (4-vinylphenyl) pyridine, and 6-vinylpyridine-3-carbonitrile may be used.

In another embodiment, the hydrophilic initiator is dissolved in water to initiate a polymerization reaction with an amphiphilic monomer such as, for example, 2,2'-azobis [2- (2-imidazolin-2-yl) propane ] Dihydrochloride, 4,4-azobis (4-cyanovaleric acid), ammonium persulfate, potassium persulfate, sodium persulfate, ammonium bisulfate, sodium bisulfate, Methylbutyronitrile-3-sodium sulfonate), but are not limited thereto. Specifically, 2,2'-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride.

In another embodiment, the autolymopolymerization reaction may be conducted at 55-95 < 0 > C. Below the lower limit, the reaction rate is slow and the reaction takes a long time. In the case where the upper limit is above the upper limit, water may evaporate and the reaction may be difficult.

In another embodiment, the autolymopolymerization reaction may be performed for 50-160 minutes. Below the lower limit, the polymerization reaction is not terminated, and the nanoparticles are growing. When the upper limit is exceeded, the reaction is terminated and there is no further growth of the particle size. As can be seen from Fig. 2, after 60 minutes from the start of the self emulsion polymerization reaction, the particle size does not grow any further.

The present invention also provides homopolymer nanoparticles prepared by the above method. The homopolymer nanoparticles are spherical with a diameter of 1-800 nm; 2 to 1,000 homopolymers;

Wherein an outer portion of the homopolymer nanoparticle is composed of a hydrophobic main chain constituting the homopolymer and a hydrophilic side chain of a hydrophilic side chain and the inner layer of the homopolymer nanoparticle comprises a hydrophobic main chain of 70-95% % Hydrophilic side chain.

The size of the homopolymer nanoparticles can be controlled by changing the conditions of the self emulsion polymerization reaction. The size of nanoparticles by self - emulsion polymerization tends to increase as the hydrophilic initiator concentration increases, as the concentration of amphiphilic monomer increases, and as the reaction temperature increases, the size decreases.

The more hydrophilic initiators and amphiphilic monomers are, the more short-length polymers that can act as a surfactant, and the more micelles are formed, the larger the number of polymers that can grow, and the larger the nanoparticle size.

As can be seen in Table 3, the nanoparticle size tends to decrease with increasing temperature in the self-emulsion polymerization reaction because the propagation rate of the amphiphilic monomer which improves the initiation efficiency is increased by reducing the radical termination at high temperature to be. As a result, more ionic groups are involved in the stability of the nanoparticles and the particle size becomes smaller.

The present invention also provides a drug delivery material comprising the homopolymer nanoparticles and the pharmaceutically active material trapped in the inner layer of the homopolymer nanoparticles.

In addition, as a method for producing the drug delivery material, the present invention can provide the following steps:

(a) obtaining a surfactant-free emulsion comprising an amphipathic monomer, a hydrophilic initiator, water, and a pharmaceutically active substance; And

(b) performing a self emulsion polymerization reaction in the surfactant-free emulsion; The drug delivery material includes homopolymer nanoparticles according to the present invention and a pharmaceutically active material trapped in the inner layer of the homopolymer nanoparticles.

Further, as another method for producing the drug delivery material, a step of swelling the homopolymer nanoparticles produced by the above-mentioned preparation method may be provided.

In addition, the present invention can provide an electron transport layer comprising the homopolymer nanoparticles. When the electron transport layer is formed using the homopolymer nanoparticles according to the present invention, the morphology of the active layer on the electron transport layer is improved, and the overall device performance can be improved.

Hereinafter, the present invention will be described in more detail with reference to the drawings, examples and experimental examples. It will be apparent to those skilled in the art, however, that these examples and experiments are intended to further illustrate the present invention and that the scope of the present invention is thereby not limited thereby.

Example  One: Poly 4 - Vinylpyridine Homopolymer  Manufacture of nanoparticles

4-vinylpyridine (4-VP) and water were added to a 500 mL flask, oxygen was removed by purging with argon for 30 minutes, and the mixture was stirred at 400 rpm for 5 minutes at 65 ° C. To the stirring solution was added a hydrophilic initiator (VA-044). Followed by stirring at 65 DEG C for 60 minutes to prepare poly-4-vinylpyridine homopolymer nanoparticles.

The self-emulsion polymerization of 4-vinylpyridine (4-VP) homopolymer is formed by the following Reaction Scheme 1.

[Reaction Scheme 1]

Experimental results according to hydrophilic initiator concentration, solvent concentration and temperature are summarized in Tables 1-3 below.

Monomer
4VP
(mmol) Initiator
VA-044
(mmol) menstruum
H ₂ O
(ml) Time / Temperature
(Minutes / C) Particle size
(by DLS in nm) 4.75 0.475 60 60/65 290 4.75 0.237 60 60/65 230 4.75 0.158 60 60/65 192 4.75 0.118 60 60/65 183 4.75 0.016 60 60/65 80

Monomer
4VP
(mmol) Initiator
VA-044
(mmol) menstruum
H ₂ O
(ml) Time / Temperature
(min / DEG C) Particle size
(by DLS in nm) 4.75 0.475 30 60/65 316 4.75 0.475 60 60/65 200 4.75 0.475 90 60/65 180 4.75 0.475 120 60/65 140 4.75 0.475 150 60/65 90

Temperature (℃) Particle size (by DLS in nm) 65 190 75 180 85 160

3a) to 3d) are TEM photographs of the nanoparticles prepared in Example 1 with time, and Figs. 3e) and 3f) are SEM photographs. FIG. 4 is a graph showing ¹ H NMR spectra of the nanoparticles prepared in Example 1, and FIG. 5 is a graph showing a thermal curve obtained by differential scanning calorimetry (DSC). Since the glass transition temperature was observed at 145 캜, it can be confirmed that the poly-4-vinylpyridine nanoparticles according to Example 1 were prepared. FIG. 2 is a graph and photographs showing the sizes of the poly-4-vinylpyridine homopolymer nanoparticles according to the self-emulsion polymerization reaction time.

Example  2: Polymethacrylic acid Homopolymer  Manufacture of nanoparticles

Methacrylic acid (MAA) and 60 mL of water were added to a 500 mL flask, oxygen was removed by purging with argon for 30 minutes, and the mixture was stirred at 400 rpm for 5 minutes at 60 ° C. A hydrophilic initiator (VA-044) was added to the stirring solution and stirred at 65 ° C for 60 minutes under an argon atmosphere to prepare poly-4-vinylpyridine homopolymer nanoparticles.

The self-emulsion polymerization of polymethacrylic acid (poly-MAA) homopolymer is formed by the following reaction formula (2).

[Reaction Scheme 2]

Experimental results according to the concentration of methacrylic acid (MAA) and the hydrophilic initiator are summarized in Table 4, and the DLS measurement values are shown in FIG.

Monomer
MAA
(mmol) Initiator
VA-044
(mmol) menstruum
H2O
(ml) Time / Temperature
(min / DEG C) Particle size
(by DLS in nm) 1.2 0.15 70 120/75 66 1.2 0.24 70 120/75 78 1.2 0.08 125 120/90 52

Example  3: Polyacrylonitrile Homopolymer  Manufacture of nanoparticles

Polyacrylonitrile was prepared in the same manner as in Example 1 except that acrylonitrile (AN) was used instead of 4-vinylpyridine (4-VP).

The self-emulsion polymerization of acrylonitrile (AN) homopolymer is formed by the following reaction formula (3).

[Reaction Scheme 3]

FIG. 7A is a DLS photograph of the nanoparticles prepared in Example 3, and FIG. 7B is a TEM photograph.

Example  4: Poly 4 -(4- Vinylphenyl ) Pyridine Homopolymer  Manufacture of nanoparticles

4- (4-vinylphenyl) pyridine (P4VPPy) was used instead of 4-vinylpyridine (4-VP) in the same manner as in Example 1 to prepare poly 4- (4-vinylphenyl) pyridine.

The self-emulsion polymerization of 4- (4-vinylphenyl) pyridine (P4VPPy) homopolymer is formed by the following reaction formula (4).

[Reaction Scheme 4]

Experimental results according to hydrophilic initiator, solvent concentration and temperature are summarized in Table 5 below.

Monomer
P4VPPy
(mmol) Initiator
VA-044
(mmol) menstruum
(H ₂ O, in ml) Time / Temperature
(min / ° C) Particle size
(by DLS in nm) 1.2 0.15 70 120/75 66 1.2 0.24 70 120/75 78 1.2 0.08 125 120/90 52

FIG. 8A is a graph showing DLS measurement values of the nanoparticles prepared in Example 4, FIG. 8B is an SEM, and FIG. 8C is a TEM photograph.

Example  5: Poly N- Vinylpyrrolidone Homopolymer  Manufacture of nanoparticles

N-vinylpyrrolidine (N-VP) was used instead of 4-vinylpyridine (4-VP) as in Example 1 to prepare poly-N-vinylpyrrolidone.

The self-emulsion polymerization of N-vinylpyrrolidine (N-VP) homopolymer is formed by the following reaction formula (5).

[Reaction Scheme 5]

FIG. 9A is a graph showing DLS measurement values of nanoparticles prepared in Example 5, and FIG. 9B is a TEM photograph.

Example  6: Poly 2 - Hydroxyethyl Methacrylate Homopolymer  Manufacture of nanoparticles

The procedure of Example 1 was repeated except that 2-hydroxyethyl methacrylate (HEMA) was used instead of 4-vinylpyridine (4-VP) to prepare poly-2-hydroxyethyl methacrylate.

The self-emulsion polymerization reaction of the 2-hydroxyethyl methacrylate (HEMA) homopolymer is formed by the following reaction formula (6).

[Reaction Scheme 6]

Experimental results according to the concentration of the hydrophilic initiator are summarized in Table 6 and graphically shown in FIG.

Monomer
HEMA
(mmol) Initiator
VA-044
(mmol) menstruum
H ² O
(ml) Time / Temperature
(min / DEG C) Particle size
(by DLS in nm) 1.53 0.001 60 120/65 143 1.53 0.004 60 120/65 212 1.53 0.015 60 120/65 420 1.53 0.030 60 120/65 525 1.53 0.060 60 120/65 534

Example  7: Polymethyl methacrylate Homopolymer  Manufacture of nanoparticles

Polymethylmethacrylate was prepared in the same manner as in Example 1 except that methyl methacrylate was used in place of 4-vinylpyridine (4-VP). 12 is a graph showing DLS (Dynamic Light Scattering) measurement values of the nanoparticles prepared in Example 7. FIG.

The self-emulsion polymerization reaction of the methyl methacrylate homopolymer is formed by the following reaction formula (7).

[Reaction Scheme 7]

Reaction materials, reaction conditions and sizes of the homopolymer nanoparticles produced are summarized in Table 7 below.

Monomer
MMA
(mmol) Initiator
VA-044
(mmol) menstruum
(H ₂ O, in ml) Time / Temperature
(min / DEG C) Particle size
(by DLS in nm) 4.9 0.049 60 120/65 160

Example  8: Poly 6 - Vinylpyridine -3- Carbonitrile Homopolymer  Manufacture of nanoparticles

6-vinylpyridine-3-carbonitrile was prepared in the same manner as in Example 1 except that 6-vinylpyridine-3-carbonitrile (VPyCN) was used instead of 4-vinylpyridine (4-VP). 13 is a graph (a) showing DLS measurement values of the homopolymer nanoparticles prepared in Example 8, and is a SEM photograph (b) and a TEM photograph (c).

The self-emulsion polymerization of 6-vinylpyridine-3-carbonitrile (VPyCN) homopolymer is formed by the following reaction formula (8).

[Reaction Scheme 8]

Reaction materials, reaction conditions and sizes of the homopolymer nanoparticles produced are summarized in Table 8 below.

Monomer
VPyCN
(mmol) Initiator
VA-044
(mmol) menstruum
(H ₂ O, in ml) Time / Temperature
(min / DEG C) Particle size
(by DLS in nm) 1.53 0.076 30 120/65 121

Initiator  Relationship with concentration.

As can be seen in Tables 1, 4 and 5, the size of the nanoparticles is almost linearly related to the concentration of the initiator. As the initiator concentration decreases, long homopolymer chains have low concentrations. This means that less polymeric nuclei are formed, resulting in a smaller number of nanoparticles.

Relationship with solvent.

Increasing the volume of water as a solvent increases the amount of monomer dissolved in water and therefore homogeneous nucleation sites become larger as small size particles are produced, which can be seen in Table 2.

Relation with temperature.

The effect of temperature on nanoparticle size was studied. As the temperature increases, the size of the homopolymer nanoparticles of the present invention tends to decrease. This seems to be due to the decomposition of the initiator at high temperatures, thus reducing the number of monomers per growth chain. As a result, more ion groups are involved in stabilization while forming smaller sized particles.

Evaluation example  1. Measurement of Shape Coefficient

To further observe the growth mechanism, the shape factor ρ (R _g / R _h) useful for analyzing nanoscale particle structures such as micelles ; R _g is the turning radius, and R _h is the hydrodynamic radius). When R _g / R _h is close to 1, a hollow structure is formed, and when it is close to 0.7, it shows a solid sphere. Poly (4-vinylpyridine) homopolymer nanoparticles The shape factor ρ values at polymerization times of 2, 20 and 60 minutes were 0.97, 0.76 and 0.73, respectively.

Evaluation example  2. The monomer conversion rate and SEP  analysis

To calculate the percent conversion of the monomer, an additional polymerization reaction was performed and the monomer conversion was calculated by an abbreviated measurement. A sample of poly 4-vinylpyridine homopolymer nanoparticles at various reaction polymerization times was transferred to an aluminum cup in a reaction flask, dried and weighed. The solvent in the cups evaporated at room temperature and the remaining product was dried at 80 < 0 > C until a constant weight was reached.

The synthesis rate from the sample to the homopolymer nanoparticles at the reaction time of 60 minutes was 92%, and most of the monomers were polymerized into nanoparticles having a size of 200 ± 5 nm.

SEC (size exclusion chromatography) was performed using a sample at a reaction time of 60 minutes. The high number average molecular weight M _n was 209418 g / mol and the unimodal but broad molecular weight M _w / M _n was 1.52 though it was a single-rod type. These values show that the SEP method also behaves like a free radical polymerization in an aqueous medium.

Claims (15)

(a) obtaining a surfactant-free emulsion comprising an amphiphilic monomer, a hydrophilic initiator, and water; And
(b) performing a self-emulsion polymerization reaction in the surfactant-free emulsion. The method of claim 1, wherein the homopolymer is represented by the following formula:

(Wherein A represents a substituted aryl group, a substituted or unsubstituted aromatic heterocyclic group, an alkyl halide group, a cyano group, a carboxy group, an ester group, an amide group, a cyanate group, a thiocyanate group, , Pyrrolidone group, and n is an integer of 10 to 10,000). 3. The method of claim 2, wherein the homopolymer is represented by the following general formulas (1) to (8):
[Chemical Formula 1] < EMI ID =

[Chemical Formula 6] [Chemical Formula 7] [Chemical Formula 8]

In the above formula, n is an integer of 10-10,000. 2. The method of claim 1, wherein the amphiphilic monomer is represented by the following formula.

(Wherein A represents a substituted aryl group, a substituted or unsubstituted aromatic heterocyclic group, an alkyl halide group, a cyano group, a carboxy group, an ester group, an amide group, a cyanate group, a thiocyanate group, , Pyrrolidone group.) 5. The composition of claim 4 wherein said amphiphilic monomer is selected from the group consisting of vinylpyridine, 4-vinylpyridine, acrylic acid, methacrylic acid, styrene sulfonic acid, 4-styrenesulfonic acid, methyl methacrylate, 2-hydroxyethyl methacrylate, Selected from the group consisting of hydroxypropyl methacrylate, hydroxybutyl methacrylate, methacrylamide, N-vinylpyrrolidone, acrylonitrile, 4- (4-vinylphenyl) pyridine and 6-vinylpyridine-3-carbonitrile Wherein the homopolymer nanoparticle is a homopolymer nanoparticle. The method of claim 1, wherein the hydrophilic initiator is selected from the group consisting of 2,2'-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride, 4,4- (1-methylbutyronitrile-3-sodium sulfonate), ammonium persulfate, potassium persulfate, sodium persulfate, ammonium bisulfate, sodium bisulfate, and 1,1-azobis By weight based on the total weight of the homopolymer nanoparticles. The method of claim 1, wherein the self-emulsion polymerization is performed at 55-95 ° C. The method of claim 1, wherein the self-emulsion polymerization is performed for 50-160 minutes. Homopolymer nanoparticles composed of homopolymers represented by the following general formulas (1) to (8) (wherein n is an integer of 10 to 10,000):
[Chemical Formula 1] < EMI ID =

[Chemical Formula 6] [Chemical Formula 7] [Chemical Formula 8]

The homopolymer nanoparticles are spherical with a diameter of 1-800 nm;
Wherein the homopolymer nanoparticles are composed of 2 to 1,000 homopolymers;
Wherein an outer portion of the homopolymer nanoparticle is composed of a hydrophobic main chain constituting the homopolymer and a hydrophilic side chain of a hydrophilic side chain and the inner layer of the homopolymer nanoparticle comprises a hydrophobic main chain of 70-95% By volume of hydrophilic side chains. The homopolymer nanoparticle according to claim 9, wherein the homopolymer nanoparticle is produced by the method of any one of claims 1 to 7. A drug delivery material comprising the homopolymer nanoparticles of claim 9 and a pharmaceutically active material trapped in the inner layer of the homopolymer nanoparticle. A method for preparing a drug delivery material comprising the steps of:
(a) obtaining a surfactant-free emulsion comprising an amphipathic monomer, a hydrophilic initiator, water, and a pharmaceutically active substance; And
(b) performing a self emulsion polymerization reaction in the surfactant-free emulsion;
Wherein the drug delivery material comprises homopolymer nanoparticles and a pharmaceutically active material trapped in an inner layer of the homopolymer nanoparticles;
The homopolymer nanoparticles are composed of homopolymers represented by the following general formulas (1) to (8) (wherein n is an integer of 10-10,000)
[Chemical Formula 1] < EMI ID =

[Chemical Formula 6] [Chemical Formula 7] [Chemical Formula 8]

The homopolymer nanoparticles are spherical with a diameter of 1-800 nm;
Wherein the homopolymer nanoparticles are composed of 2 to 1,000 homopolymers;
Wherein an outer portion of the homopolymer nanoparticle is composed of a hydrophobic main chain constituting the homopolymer and a hydrophilic side chain of a hydrophilic side chain and the inner layer of the homopolymer nanoparticle comprises a hydrophobic main chain of 70-95% % Hydrophilic side chains;
The amphiphilic monomer may be selected from the group consisting of vinylpyridine, 4-vinylpyridine, acrylic acid, methacrylic acid, styrene sulfonic acid, 4-styrenesulfonic acid, methyl methacrylate, 2-hydroxyethyl methacrylate, Vinylpyridine-3-carbonitrile, hydroxybutyl methacrylate, methacrylamide, N-vinylpyrrolidone, acrylonitrile, 4- (4-vinylphenyl) pyridine and 6-vinylpyridine-3-carbonitrile;
The hydrophilic initiator may be at least one selected from the group consisting of 2,2'-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride, 4,4- azobis (4-cyanovaleric acid) , At least one selected from the group consisting of potassium persulfate, sodium persulfate, ammonium bisulfate, sodium bisulfate, and 1,1-azobis (1-methylbutyronitrile-3-sodium sulfonate);
Wherein the self-emulsion polymerization reaction is carried out at 55-95 < 0 > C for 50-160 minutes. A method for preparing a drug delivery material comprising the steps of:
(a) obtaining a surfactant-free emulsion comprising an amphiphilic monomer, a hydrophilic initiator, and water;
(b) performing self-emulsion polymerization in the surfactant-free emulsion to prepare homopolymer nanoparticles; And
(c) swelling the homopolymer nanoparticles and collecting the pharmaceutical active material in an inner layer of the homopolymer nanoparticles;
The homopolymer nanoparticles are composed of a homopolymer selected from the following general formulas (1) to (6), wherein n is an integer of 10 to 10,000:
[Chemical Formula 1] < EMI ID =

[Chemical Formula 6] [Chemical Formula 7] [Chemical Formula 8]

The homopolymer nanoparticles are spherical with a diameter of 1-800 nm;
Wherein the homopolymer nanoparticles are composed of 2 to 1,000 homopolymers;
Wherein an outer portion of the homopolymer nanoparticle is composed of a hydrophobic main chain constituting the homopolymer and a hydrophilic side chain of a hydrophilic side chain and the inner layer of the homopolymer nanoparticle comprises a hydrophobic main chain of 70-95% % Hydrophilic side chains;
The amphiphilic monomer may be selected from the group consisting of vinylpyridine, 4-vinylpyridine, acrylic acid, methacrylic acid, styrene sulfonic acid, 4-styrenesulfonic acid, methyl methacrylate, 2-hydroxyethyl methacrylate, Vinylpyridine-3-carbonitrile, hydroxybutyl methacrylate, methacrylamide, N-vinylpyrrolidone, acrylonitrile, 4- (4-vinylphenyl) pyridine and 6-vinylpyridine-3-carbonitrile;
The hydrophilic initiator may be at least one selected from the group consisting of 2,2'-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride, 4,4- azobis (4-cyanovaleric acid) , At least one selected from the group consisting of potassium persulfate, sodium persulfate, ammonium bisulfate, sodium bisulfate, and 1,1-azobis (1-methylbutyronitrile-3-sodium sulfonate);
Wherein the self-emulsion polymerization reaction is carried out at 55-95 < 0 > C for 50-160 minutes. An electron transport layer comprising the homopolymer nanoparticles of claim 9. An electron transport layer comprising the homopolymer nanoparticles of claim 10.

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