WO2024085570A1 - Fluorine-based polymer and method for preparing same - Google Patents

Abstract

The present invention relates to a method for preparing a fluorine-based polymer and a fluorine-based polymer prepared thereby, the method comprising modifying at least a portion of a hydroxy group contained in a main chain copolymer comprising a repeating unit derived from a temperature-sensitive monomer and a repeating unit derived from a hydroxy group-containing monomer with an oxygennucleophilic perfluorinated hydrocarbon-based compound.

Description

Fluorine-based polymer and method for producing the same

[Cross-citation with related applications]

This application claims the benefit of priority based on Korean Patent Application No. 10-2022-0133371, dated October 17, 2022, and all contents disclosed in the document of the Korean Patent Application are included as part of this specification.

[Technology field]

The present invention relates to fluorine-based polymers and methods for producing the same.

Fluorine-based polymers have excellent hydrophobicity, water repellency, oil repellency, and biostability due to high electrical conductivity, low polarizability, small atomic radius, and strong C-F bond. Additionally, fluorine-based polymers are optically transparent and have low surface energy.

Meanwhile, fluorine-based polymers are compounds that can be used in the medical field, as they are known to have anti-inflammatory effects when injected into the lungs. However, among fluorine-based polymers, long-chain perfluorinated chemicals (PFCs) accumulate in the natural environment, animals, plants, and the human body. According to research until recently, it has not been demonstrated that the long-chain perfluorinated compounds accumulate in humans and cause harmful effects, but it has been reported that harmful effects appear in animal experiments. Considering that the long-chain perfluorinated compounds generally have a long half-life in the human body, exposure to the long-chain perfluorinated compounds is expected to have adverse effects in the human body.

A temperature-responsive polymer is a compound that has chemically and physically reversible properties in response to changes in temperature. A representative temperature-sensitive polymer is poly(N-isopropylacrylamide). The material undergoes a phase transition (phase change) rapidly or gradually around the lower critical solution temperature (LCST) due to changes in the hydrophilic/hydrophobic balance of the polymer chain as the temperature rises/decrease. If the temperature is higher than LCST, the hydrogen bonds between the polymer and water are broken, and the polymers clump together to form an opaque state. If the temperature is lower than LCST, the hydrogen bonds are maintained and the polymer becomes transparent.

In conventional heat-sensitive polymer compositions, LCST almost always appears at a predetermined temperature of about 30 to 45°C, but the LCST cannot be further adjusted (increased or decreased) or thermal hysteresis occurs, thereby reducing its usability and energy savings. There was a problem of insufficient efficiency. To solve this problem, the LCST temperature can be adjusted when using a general monomer, but the problem is that transparency is lost at room temperature or the LCST changes along the heating/cooling route due to the deepening of the thermal hysteresis, which limits its application. There was this.

The present invention is intended to solve the above problems. By introducing a functional fluorine compound with a perfluorinated tertiary carbon structure into a temperature-sensitive polymer, the LCST of the temperature-sensitive polymer can be controlled more freely, while its thermal hysteresis is also reduced, making it easier to heat. /The purpose is to provide a fluorine-based polymer that can provide a relatively constant LCST regardless of the cooling route and has better biocompatibility such as cell viability.

As a result of repeated research, the inventors of the present invention have found that at least part of the hydroxyl group contained in the main chain copolymer containing a repeating unit derived from a temperature-sensitive monomer and a repeating unit derived from a hydroxyl group-containing monomer is oxygen-nucleophilic. ) The present invention was completed by discovering that the above-described technical problems could be solved through a method for producing fluorine-based polymers that includes modification with perfluorinated hydrocarbon-based compounds.

According to another embodiment of the present invention, it includes a repeating unit derived from a temperature-sensitive monomer and a repeating unit derived from a hydroxy group-containing monomer, and at least some of the hydroxy groups included in the repeating unit derived from the hydroxy group-containing monomer It provides a fluorine-based polymer in which is substituted with an oxygen-nucleophilic perfluorinated hydrocarbon-based ether group.

The fluorine-based polymer of the present invention can have its LCST more freely adjusted through modification of the perfluorinated hydrocarbon-based compound, and thermal hysteresis is reduced to provide a relatively constant LCST regardless of the heating and cooling route, while maintaining cell viability. It has better biocompatibility effects.

Figures 1 (a) and (b) show the results of nuclear magnetic resonance spectroscopy (NMR) and Fourier transform infrared spectroscopy (FTIR) of the polymers of Example 1 and Preparation Example 1.

2 (a) to (d) are the temperatures obtained through an ultraviolet-visible spectrophotometer for each aqueous solution (1 wt%) of the polymers of Examples 1 to 3 and Comparative Examples 1 to 3. -Permeability curve) and a graph of the LCST variation (△LCST: difference between the temperature of the cloud point and the temperature of the clear point) according to the ratio of the NIPAm repeat unit in the copolymerization repeat unit.

Figure 3 is a thermal hysteresis graph obtained for an aqueous solution (1 wt%) of the polymer of Example 1, the polymer of Comparative Example 1, and the polymer of Comparative Example 4 {poly(N-isopropylacrylamide) (PNIPAm)}.

Figure 4 is a graph showing the temperature-permeability curve and the start and end temperatures of the permeability according to the concentration (wt%) of the aqueous solution containing the polymer of Example 1 at different weight%.

Figure 5 is a graph showing the change in LCST according to the incident wavelength for each of the polymer of Example 1, the polymer of Comparative Example 1, and the polymer (PNIPAm) of Comparative Example 4.

Figure 6 is a dynamic light scattering (DLS) spectrum of each polymer aqueous solution containing the polymers of Examples 1 and 2 and the polymers of Comparative Examples 1, 2, and 4 at a concentration of 10 mg/ml.

Figure 7 is a graph showing the high temperature nuclear magnetic resonance spectroscopy spectrum for the polymer in Example 1 and the normalized integration ratio of each peak according to temperature change.

Figure 8 is a graph and image showing the results of cell viability experiments for the polymer of Example 1 and the polymers of Comparative Examples 1 and 4, respectively.

Hereinafter, the present invention will be described in more detail to facilitate understanding of the present invention.

In the present invention, the "Lower Critical Solution Temperature (LCST)" refers to the temperature by irradiating light of a specific wavelength (for example, may be 550 nm, but is not limited thereto) to an aqueous solution containing a temperature-sensitive polymer. When the transmittance is measured, it refers to the temperature at which the transmittance is 50%.

1. Method for producing fluorine-based polymers

The present invention provides a method for producing fluorine-based polymers.

In one embodiment of the present invention, the method for producing a fluorine-based polymer is to oxygenate at least a portion of the hydroxy groups included in the main chain copolymer comprising a repeating unit derived from a temperature-sensitive monomer and a repeating unit derived from a hydroxy group-containing monomer. It may include modification with an oxygennucleophilic perfluorinated hydrocarbon-based compound.

The repeating unit or temperature-sensitive polymer or polymer derived from the temperature-sensitive monomer of the present invention is a polymer whose physical properties change depending on the external temperature. The polymer of the present invention is predominantly hydrophilic at temperatures below LCST, and exists in the form of a coil through hydrogen bonding with the hydrophilic portion of the polymer and the solvent. However, at temperatures above LCST, hydrophobicity within the polymer is dominant, and the hydrophilicity of the polymer is reduced. It can exist in the form of a globule due to hydrophobic bonds within the polymer rather than hydrogen bonds between parts and the solvent. At this time, polymers in the form of coils have low permeability, but polymers in the form of globules may have relatively high permeability.

In one embodiment of the present invention, the repeating unit derived from the temperature-sensitive monomer may be a repeating unit derived from a (meth)acrylamide-based monomer. For example, the (meth)acrylamide-based monomer is N-alkyl (meth) ) It may be an acrylamide-based monomer. The N-alkyl (meth)acrylamide monomer may have a C ₂ to C ₁₈ alkyl group, a C ₂ to C ₁₅ alkyl group, or a C ₂ to C ₁₂ alkyl group bonded to the nitrogen atom of the amide group. Since the number of carbon atoms of the alkyl group bonded to the nitrogen atom of the amide group is within the above-mentioned range, the temperature-sensitive characteristics of the copolymer can be sufficiently expressed.

In one embodiment of the present invention, the (meth)acrylamide-based monomer is (meth)acrylamide, N-methyl (meth)acrylamide, N-ethyl (meth)acrylamide, and N-propyl (meth)acrylamide. , N-(n-butyl)methacrylamide, N-(sec-butyl)methacrylamide, N-( tert -butyl)methacrylamide, N-(n-pentyl)(meth)acrylamide, N-( n-hexyl)(meth)acrylamide, N-(n-heptyl)(meth)acrylamide, N-(n-octyl)(meth)acrylamide, N-( tert -octyl)(meth)acrylamide, N -(1,1,3,3-Tetramethylbutyl)(meth)acrylamide, N-ethylhexyl(meth)acrylamide, N-(n-nonyl)(meth)acrylamide, N-(n-decyl) (meth)acrylamide, N-(n-undecyl)(meth)acrylamide, N-tridecyl(meth)acrylamide, N-myristyl(meth)acrylamide, N-pentadecyl(meth)acrylamide, N-Palmityl (meth)acrylamide, N-heptadecyl (meth)acrylamide, N-nonadecyl (meth)acrylamide, N-arakinyl (meth)acrylamide, N-behenyl (meth)acrylamide, N-lignoserenyl (meth)acrylamide, N-serotinyl (meth)acrylamide, N-melicinyl (meth)acrylamide, N-palmitoleinyl (meth)acrylamide, N-oleyl ( Meta)acrylamide, N-linolyl (meth)acrylamide, N-linolenyl (meth)acrylamide, N-stearyl (meth)acrylamide, N-lauryl (meth)acrylamide, N, N-dimethyl It may include at least one selected from the group consisting of (meth)acrylamide, N,N-diethyl (meth)acrylamide, piperidinyl (meth)acrylamide, and morpholinyl (meth)acrylamide.

Furthermore, in one embodiment of the present invention, the repeating unit derived from the temperature-sensitive monomer is N-isopropylacrylamide, N,N-diethylacrylamide, 2-(dimethylamino)ethyl methacrylate, N,N- Dimethylacrylamide, acrylamide, 2-(diethylamino)ethyl acrylate, 2-(acryloxyethyl)trimethylammonium chloride, vinyl methyl ether, hydroxyethylmethyl acrylate, 4-hydroxybutyl acrylate, 2- Hydroxyethyl methacrylate, 3-hydroxypropyl methacrylate, 2-carboxyethyl acrylate, 2-carboxyethyl acrylate oligomer, ethylene glycol methacrylate, 2-(dimethylamino)ethyl methacrylate hydroxypropyl It may be at least one selected from the group consisting of cellulose, vinyl caprolactam, and 2-isopropyl-2-oxazoline.

In one embodiment of the present invention, the repeating unit derived from the hydroxy group-containing monomer may be a repeating unit derived from a hydroxy group-containing (meth)acrylamide-based monomer, preferably, a hydroxy group-containing (meth)acrylamide-based monomer. The amide-based monomer may be an N-hydroxyalkyl (meth)acrylamide monomer, and more preferably, the N-hydroxyalkyl (meth)acrylamide monomer has an alkyl group of C ₂ to C ₁₈ on the nitrogen atom of the amide group, It may be a C ₂ to C ₁₅ alkyl group, or N-hydroxyalkyl (meth)acrylamide to which a C ₂ to C ₁₂ alkyl group is bonded. Since the carbon number of the alkyl to which the hydroxy group is connected is within the above-mentioned range, the hydroxy group can be efficiently converted to a perfluorinated hydrocarbon system.

In one embodiment of the present invention, the hydroxyl group-containing (meth)acrylamide monomer is N-hydroxymethylacrylamide, N-hydroxymethylmethacrylamide, N-hydroxyethylacrylamide, N-hydroxy Ethyl methacrylamide, N-hydroxypropylacrylamide, N-hydroxypropyl methacrylamide, N-hydroxyisopropyl acrylamide, N-hydroxyisopropyl methacrylamide, N-hydroxybutylacrylamide, N -Hydroxybutyl methacrylamide, N-hydroxyisobutylacrylamide, N-hydroxyisobutyl methacrylamide, N-hydroxyisopentyl acrylamide, N-hydroxyisopentyl methacrylamide, N-hydroxy It may include at least one selected from the group consisting of neopentylacrylamide and N-hydroxyneopentyl methacrylamide.

In one embodiment of the present invention, the oxygen-nucleophilic perfluorinated hydrocarbon-based compound may include a compound represented by Formula 1 below. Oxygen-nucleophilicity may mean that the lone pair of electrons of the oxygen atom contained in the perfluorinated hydrocarbon-based compound acts as a nucleophile. Specifically, the oxygen-nucleophilic perfluorinated hydrocarbon compound may contain at least one hydroxy group in the molecule, and the lone pair of electrons of the oxygen atom of the hydroxy group may act as a nucleophile.

[Formula 1]

In Formula 1, n, m, and p are the number of repetitions of the unit within the parentheses, and are each integers from 0 to 3.

The n, m and p may be the same or different from each other.

When n, m, and p are 0, it may mean direct bonding.

The oxygen-nucleophilic perfluorinated hydrocarbon compound may be a symmetrical compound (n, m, and p are the same).

Alternatively, the oxygen-nucleophilic perfluorinated hydrocarbon compound may be a compound with an asymmetric structure.

The compound represented by Formula 1 may include a compound represented by at least one selected from the following Formulas 1-1 to 1-4.

[Formula 1-1]

[Formula 1-2]

[Formula 1-3]

[Formula 1-4]

Preferably, the oxygen-nucleophilic perfluorinated hydrocarbon-based compound may include perfluorinated tert -butyl alcohol.

In one embodiment of the present invention, at least a portion of the hydroxy groups contained in the main chain copolymer including a repeating unit derived from a temperature-sensitive monomer and a repeating unit derived from a hydroxy group-containing monomer are reacted with an oxygen nucleophilic perfluorinated hydrocarbon-based compound. By modifying, a hydrophobic moiety can be introduced into the polymer, and through this, hydrophobicity can dominate over hydrophilicity within the polymer. Accordingly, the polymer aggregates to minimize the surface energy of the polymer, and also As interference with hydrogen bonds increases, LCST may decrease.

Additionally, in one embodiment of the present invention, as the content of the oxygen-nucleophilic perfluorinated hydrocarbon compound in the polymer increases, hydrophobicity increases, which may affect intermolecular attraction. As the intermolecular attraction increases, the polymer chains become more aggregated, and phase transitions may also occur gradually, forming clusters, rather than occurring all at once. In other words, as the content of oxygen-nucleophilic perfluorinated hydrocarbon compounds in the polymer increases, the permeability of the polymer may decrease over a wider temperature range. As a result, in the temperature-permeability curve described later, the difference between the start temperature (onset point) and the end temperature (off set point) of the permeability change (phase transition) can be adjusted to be 5 to 30 ℃, preferably 10 to 20 ℃. There will be.

In one embodiment of the present invention, the repeating unit derived from the (B) hydroxy group-containing monomer in the main chain copolymer has a content of more than 0 and 30 mol% or less, more than 3 and 27 mol% or less, or more than 5 and 25 mol% or less. may be included. Since the repeating unit derived from the hydroxyl group-containing monomer is within the above-mentioned range, water solubility can be maintained and sufficient hydroxyl groups can be provided for modification into a fluorine-based polymer.

In one embodiment of the present invention, the repeating unit derived from a (meth)acrylamide-based monomer modified (substituted) with an oxygen-nucleophilic perfluorinated hydrocarbon-based ether group is greater than 0 and 30 mol% or less, greater than 5 and 25 mol% or less, Alternatively, it may be more than 10 and less than or equal to 20 mol%. Because the repeating unit derived from a (meth)acrylamide-based monomer modified (substituted) with an oxygen-nucleophilic perfluorinated hydrocarbon-based ether group exists in the above-mentioned range, the LCST of the copolymer can be sufficiently adjusted, and the thermal hysteresis is It can be reduced more sufficiently. In addition, the higher the content of repeating units derived from (meth)acrylamide-based monomers modified (substituted) with oxygen-nucleophilic perfluorinated hydrocarbon-based ether groups, the LCST variation (△LCST: cloud point temperature and clear point temperature) difference) increases, and the change in permeability due to heating occurs gently, that is, a phase transition may occur gradually.

In one embodiment of the present invention, a method for producing a fluorine-based polymer includes a repeating unit derived from a temperature-sensitive monomer; In order to prepare a main chain copolymer comprising a repeating unit derived from a hydroxy group-containing monomer, the step of heating a mixture of the temperature-sensitive monomer and the first solvent in which the hydroxy group-containing monomer is mixed to a temperature of 30° C. or higher. It can be included. Specifically, it may include heating to a temperature of 30 to 90°C, 40 to 80°C, 50 to 70°C, or 50 to 60°C.

In one embodiment of the present invention, the method for producing a fluorine-based polymer may include adding a polymerization initiator to prepare a main chain copolymer comprising a repeating unit derived from a temperature-sensitive monomer and a repeating unit derived from a hydroxy group-containing monomer. You can. The polymerization initiator is not limited as long as it is for performing radical polymerization. For example, the polymerization initiator may include benzoyl peroxide, acetyl peroxide, dilauryl peroxide, di- tert -butyl peroxide, cumyl hydroperoxide, and potassium persulfate. , azobisisobutyronitrile (AIBN), tert -butyl peroxypivalate, or diisopropyl peroxydicarbonate, etc. can be used.

In one embodiment of the present invention, after mixing a main chain copolymer containing a repeating unit derived from a temperature-sensitive monomer and a repeating unit derived from a hydroxy group-containing monomer with a second solvent, the oxygen-nucleophilic perfluorinated hydrocarbon system It may include adding a compound. At this time, the second solvent is not limited as long as it is a solvent that can dissolve the hydroxy group-containing copolymer (main chain copolymer). For example, the second solvent may be triphenylphosphine (PPh ₃ ), tetrahydro Furan, dimethylformamide, etc. can be used.

In one embodiment of the present invention, at least a portion of the hydroxy groups included in the copolymer may be modified with an oxygen-nucleophilic perfluorinated hydrocarbon-based compound, and the modification is performed using the oxygen-nucleophilic (oxygen-nucleophilic) perfluorinated hydrocarbon-based compound. ) The perfluorinated hydrocarbon-based compound may be added in an amount of 1.5 to 6 equivalents relative to the equivalent of the hydroxyl group of the main chain copolymer. Since the content of the oxygen-nucleophilic perfluorinated hydrocarbon compound is within the above-mentioned range compared to the equivalent weight of the hydroxyl group of the main chain copolymer, the conversion rate may be sufficient and most of the hydroxyl groups in the polymer may be converted.

In one embodiment of the present invention, a catalyst may be further included in order to modify at least a portion of the hydroxy groups included in the hydroxy group-containing copolymer into the oxygen-nucleophilic perfluorinated hydrocarbon-based compound. The catalyst may include diisopropyl azodicarboxylate or diethyl azodicarboxylate.

In one embodiment of the present invention, the step of modifying at least a portion of the hydroxy groups included in the hydroxy group-containing copolymer may be performed through a Mitsunobu reaction.

In one embodiment of the present invention, a step of heating may be included to modify at least a portion of the hydroxy groups included in the hydroxy group-containing copolymer into an oxygen-nucleophilic perfluorinated hydrocarbon-based compound, for example It may include heating a mixture of the hydroxy group-containing copolymer and the second solvent in which the oxygen-nucleophilic perfluorinated hydrocarbon-based compound is mixed to a temperature of 30° C. or higher. Specifically, it may include heating to a temperature of 30 to 90°C, 40 to 80°C, 50 to 70°C, and 50 to 60°C.

In one embodiment of the present invention, the repeating unit derived from the hydroxy group-containing monomer may be 0 to 25 mol%, 3 to 22 mol%, or 5 to 20 mol% of the total content of monomers constituting the copolymer. Since the content of the hydroxy group-containing monomer is within the above-mentioned range, the physical properties of the temperature-sensitive polymer can be maintained and sufficient hydroxy groups for introduction of fluorine groups can be contained.

2. Fluorine-based polymer

The present invention provides a fluorine-based polymer.

In the description of the fluorine-based polymer of the present invention, parts that are the same as the manufacturing method of the fluorine-based polymer are the same as those described above.

The fluorine-based polymer of the present invention generates thermal hysteresis when measuring permeability according to temperature during heating and cooling. Thermal hysteresis can result from the aggregation and dissociation of temperature-sensitive polymers, which can be reversible phase transitions. Specifically, in fluorine-based polymers, the arrangement of the surrounding solvent is not stable at temperatures exceeding LCST, and hydrophobic bonds may become dominant. In addition, hydrogen bonds are formed between amides within the molecule, which can serve as a cross-link. Due to the hydrophobic bonds and hydrogen bonds between amides, the polymer swells like a gel, causing chain dissociation. By delaying, the temperature of the cloud point corresponding to the LCST during heating and the temperature of the clearing point corresponding to the LCST during cooling are mismatched, resulting in the LCST variation (△LCST: the temperature of the clouding point and the clearing point) Differences in point temperature) may occur.

In one embodiment of the present invention, the LCST of the fluorine-based polymer can be adjusted by the wavelength of irradiated light. Scattering of fluorine-based polymers may vary depending on the wavelength of incident light. The shorter the wavelength of incident light, the more scattering occurs, so a solution containing a fluorine-based polymer can exhibit higher transmittance at a longer wavelength.

The present invention provides an aqueous solution or fluorine-based composition (including water-soluble compositions, etc.) containing a fluorine-based polymer.

In one embodiment of the present invention, the fluorine-based polymer may be included in an amount of 0.01 to 3.0 parts by weight, 0.05 to 2.8 parts by weight, 0.1 to 2.5 parts by weight, and 0.15 to 2.0 parts by weight based on 100 parts by weight of the aqueous solution or fluorine-based composition. By including the fluorine-based polymer in the aqueous solution or fluorine-based composition at the above-mentioned concentration, LCST can be adjusted depending on the concentration of the aqueous solution or fluorine-based composition.

The fluorine-based polymer of the present invention can be used as a material for smart windows by utilizing the change in permeability in an aqueous solution or fluorine-based composition due to phase transition. In particular, the fluorine-based polymer of the present invention is capable of a more gradual phase transition near LCST, making it possible to observe changes in the permeability of materials such as smart window films according to the increase or decrease in temperature at various levels, making it possible to improve the existing smart window The application may be more comprehensive than that of the fluorine-based polymers used.

The fluorine-based polymer and the aqueous solution or fluorine-based composition containing the fluorine-based polymer of the present invention have a small amount of variation in LCST due to heating and cooling in thermal hysteresis, and the change in physical properties due to changes in temperature is minimized, so the precision of sensing can be improved.

In addition, the fluorine-based polymer of the present invention reduces biotoxicity resulting from long-chain perfluorinated compounds of existing biocompatible polymers, helps cell growth, and can significantly increase cell viability. .

The fluorine-based polymer of the present invention changes into a coil and globule form around the LCST temperature, thereby changing its solubility, so it can be used as a drug delivery system (DDS) by taking advantage of the fact that the temperature varies depending on the body's organs. ) can be used as a drug carrier.

Hereinafter, the present invention will be described in more detail through examples. However, these examples are only intended to aid understanding of the present invention, and the scope of the present invention is not limited to these examples in any way.

<Examples 1 to 3>

N-isopropylacrylamide (NIPAm) monomer and 2-hydroxyethyl (meth)acrylamide monomer (HEAAm) monomer were mixed in 50 mL of solvent (N-methyl 2-pyrrolidone (NMP)). Next, azobisisobutyronitrile (AIBN) was polymerized as an initiator at 60°C under a nitrogen atmosphere to prepare a hydroxy group-containing copolymer.

Next, 0.7 g of a hydroxy group-containing copolymer, triphenylphosphine (1.6 equivalents compared to the hydroxy group), and diisopropyl azodicar were added to 30 mL of solvent (tetrahydrofuran (THF)/dimethylformamide (DMF)). Modify the hydroxy group-containing copolymer by mixing boxylic acid (diisopropyl azodicarboxylate, 1.6 equivalents compared to the hydroxy group) and perfluoro-t-butyl alcohol (2.0 equivalents compared to the hydroxy group) through Mitsunobu reaction in a nitrogen atmosphere at 50°C. A fluorine-based polymer having the composition shown in Table 1 below was prepared.

	NIPAm	NHEAAM-F
Example 1	80	20
Example 2	90	10
Example 3	95	5

<Comparative Examples 1 to 4>

N-isopropylacrylamide (NIPAm) monomer and, if necessary, 2-hydroxyethyl (meth)acrylamide monomer (HEAAm) monomer were mixed in 50 mL of solvent (N-methyl 2-pyrrolidone (NMP)). Next, azobisisobutyronitrile (AIBN) was polymerized as an initiator at 60°C under a nitrogen atmosphere to prepare a hydroxyl group-containing copolymer and N-isopropylacrylamide (NIPAm) homopolymer having the compositions shown in Table 2 below. .

	NIPAm	NHEAAM
Comparative Example 1	80	20
Comparative Example 2	90	10
Comparative Example 3	95	5
Comparative Example 4	100	0

<Experimental Example 1: Confirmation of copolymer production> Nuclear magnetic resonance spectroscopy (NMR) on the fluorine-based polymer of Example 1 and the hydroxyl group-containing copolymer of Comparative Example 1 using deuterium-substituted acetone and dimethyl sulfoxide as solvents. The results are shown in (a) of FIG. 1, and the results of Fourier transform infrared spectroscopy (FT-IR) are shown in (b) of FIG. According to (a) of FIG. 1, (b) 3.1 ppm and (c) 3.4 ppm corresponding to the methylene group of Comparative Example 1 moved from the fluorine-based polymer of Example 1 to (b') and (c'). It was confirmed that the (f) 4.7 ppm peak corresponding to the -OH group in Comparative Example 1 also mostly disappeared with the introduction of NFtB (nonafluoro- tert -butanol) in Example 1.

According to (b) of FIG. 1, it was confirmed that the 3300 cm ^-1 peak corresponding to the NH bond of the amide group was strong and wide in the spectra of Example 1 and Comparative Example 1. Meanwhile, in the spectrum of Example 1, the CO stretch of 1060 cm ^-1 that existed in the spectrum of Comparative Example 1 disappears, and the peaks corresponding to the CF bond in Example 1 are 950, 990, and 1250 cm ^-1 , it was confirmed that the reforming reaction with the NFtB group had occurred successfully.

<Experimental Example 2: Confirmation of composition, molecular weight, Tg, and PDI of Examples 1 to 3 and Comparative Examples 1 to 4>

It was calculated from the intensity (integration ratio) of the peak (a) of the isopropyl group of NIPAm and the peak (b) of the methylene group of HEAAM-F in the NMR spectrum of Figure 1 (a) according to Experimental Example 1. In addition, the molecular weight, polydispersity index (PDI), and glass transition temperature (Tg) of the experimental examples and comparative examples were measured by differential scanning calorimetry (DSC; Q1000, TA Instruments) and gel permeation chromatography (GPC). Measured using Waters 2690, Waters Corporation) and shown in Table 3 below.

[Table 3]

<Experimental Example 3: Confirmation of LCST of fluorine-based polymer>

In order to determine the phase transition characteristics of the fluorine-based polymers of Examples 1 to 3 and Comparative Examples 1 to 3, the polymers of the Experimental Examples and Comparative Examples were each prepared in an aqueous solution with a concentration of 1 wt%, and then measured using an ultraviolet-visible spectrophotometer (UV). After adding the polymer aqueous solution to a -vis spectrometer, 550 nm light was irradiated to measure the temperature dependent transmittance curve, and the results are shown in Figure 2. PNIPAm, a temperature-sensitive polymer, is known to have an LCST in the range of 30 to 45°C, and the transmittance of each aqueous solution decreased to less than 50% at temperatures above LCST. When comparing the polymer aqueous solutions of Comparative Examples 1 to 3 with those of Examples 1 to 3, it was confirmed that when the NFtB group was introduced into the polymer, the LCST of the polymer was lowered. According to (a) of Figure 2, the phase transition occurred at 43.3°C in the polymer aqueous solution of Comparative Example 1 (i.e., LCST was 43.3°C), but the phase transition occurred at 32.7°C in the polymer aqueous solution of Example 1 (i.e., LCST is 32.7℃). It was confirmed that as the NFtB group was introduced, the LCST was lowered by 10.6°C. Meanwhile, when comparing Example 2 and Comparative Example 2 and Example 3 and Comparative Example 3, the smaller the amount of NFtB was introduced, the smaller the reduction rate of LCST.

Meanwhile, the LCST variation (△LCST: difference between the temperature of the cloud point and the temperature of the clear point) according to the ratio of the NIPAm repeat unit in the copolymer repeat unit, that is, the content of the NFtB group, was calculated and shown in Figure 2 (d). . According to Figure 2 (d), it was confirmed that the amount of variation in LCST was relatively constant depending on the content of the introduced NFtB group.

Meanwhile, in the case of Examples 2 and 3 in (b) and (c) of Figure 2, the transmittance showed a sharp decrease as the temperature increased (heating), but in the example of Figure 2 (a) In case 1, it was confirmed that the permeability gradually decreased as the temperature increased.

<Experimental Example 4: Confirmation of thermal hysteresis curve according to polymer type>

After adding the polymers of Example 1, Comparative Example 1, and Comparative Example 4 to an ultraviolet-vis spectrometer, the temperature was changed while irradiating 550 nm light to change the transmittance according to the heating-cooling route. The thermal hysteresis curve was measured by measuring/observation, and the results are shown in FIG. 3. Figure 3 (a) is a thermal hysteresis curve of the polymer corresponding to Example 1, showing an LCST variation (ΔLCST) of 0.5°C. Figure 3 (b) is a thermal hysteresis curve of the polymer corresponding to Comparative Example 1. There was no temperature difference, so the amount of LCST variation (ΔLCST) was hardly confirmed. In other words, the cloud point and clearing point coincided. Meanwhile, Figure 3 (c) is a thermal hysteresis curve of the polymer corresponding to Comparative Example 4, and it was confirmed that an LCST variation (ΔLCST) of about 1°C appeared. Through Figure 3, the polymers of Example 1 and Comparative Example 1 dissociate at a relatively higher temperature than the polymer of Comparative Example 4 as the hydrogen bonds formed by the amide group within the molecule formed during the heating process are cooled, and the temperature at which phase transition occurs is I was able to confirm that it was high. In addition, it was confirmed that the polymer of Example 1 had a gradual change in transmittance compared to the polymers of Comparative Examples 1 and 4.

<Experimental Example 5: Confirmation of hysteresis curve according to difference in concentration>

Each polymer of Example 1 was dissolved in water to obtain 0.1 wt%. After preparing aqueous solutions with concentrations of 0.2 wt%, 0.5 wt%, 1.0 wt%, and 2.0 wt%, LCST was measured as in Experimental Example 3 and is shown in FIG. 4. At 0.1 wt%, LCST was observed at 36.2°C. In addition, compared to an aqueous solution with a concentration of 1 wt%, it was confirmed that the hysteresis curve of 0.1 wt% decreased the permeability over a wider temperature range (i.e., phase transition occurred more gradually). In order to calculate the range in which the phase transition characteristics of aqueous solutions of different concentrations change, the start temperature (onset point) and end temperature (off set point) of the permeability change (phase transition) were measured and shown in (b) of FIG. 4. In an aqueous solution with a concentration of 2.0 wt%, the phase transition occurred over a temperature range of 6.1°C, but in an aqueous solution with a concentration of 0.1 wt%, the transition occurred over a temperature range of 12°C. In other words, it was confirmed that even in an aqueous solution with a concentration of 0.1 to 0.2 wt%, the permeability decreases close to 0 and that the range of phase transition change can be controlled over a wide range by changing the concentration.

<Experimental Example 6: Confirmation of LCST change according to incident wavelength>

The change in LCST according to the incident wavelength was measured for each of the polymers of Example 1, Comparative Example 1, and Comparative Example 4, and is shown in Figure 5. For the polymers of Comparative Examples 1 and 4, as the incident wavelength became longer, the transmission-temperature curve shifted to a higher temperature value. As a result, a change in LCST occurred, but the extent of the change was small. Meanwhile, in the case of the polymer of Example 1, the transmission-temperature curve shifted to a higher temperature value as the incident wavelength became longer, and the LCST, which was 34.1°C at a wavelength of 900 nm, was 300. In nm, it was shown as 29.8℃, confirming that there was a difference of about 4.3℃. Through this, it was confirmed that compared to the polymer of Comparative Example 1, the polymer of Example 1 gradually aggregated and increased in size before reaching LCST, and the scattering intensity changed depending on the wavelength, resulting in a change in LCST value. In other words, it was confirmed that LCST can be adjusted depending on the wavelength.

<Experimental Example 7: Confirmation of aggregation by dynamic light scattering (DLS) spectroscopy>

After preparing a polymer aqueous solution containing the polymers of Examples 1 to 2 and Comparative Examples 1 to 2 and Comparative Example 4 at a concentration of 10 mg/ml, Dynamic Light Scattering (DLS) spectroscopy was performed at various temperatures. did. Examples 1 to 2 and Comparative Examples 1 to 2 and Comparative Example 4 all showed strong hydrogen bonding with water molecules at a temperature below LCST and a hydrodynamic radius (R _h ) of 25 nm or less. The polymers of Examples 1 to 2 and Comparative Examples 1 to 2 and Comparative Example 4 aggregated as the temperature increased, and when the temperature reached LCST or higher, R _h increased significantly. It was confirmed that the polymers of Examples 1 to 2, Comparative Examples 1 to 2, and Comparative Example 4 agglomerated at a temperature similar to the transmittance reduction section observed in an ultraviolet-vis spectrometer (UV-vis spectrometer).

Figure 6(a) is the dynamic light scattering spectrum of Example 1, and in the case of Figure 6(a), it was confirmed that R _h gradually increased from 29°C before reaching 32.7°C, which is the LCST. Through this, it was confirmed that when the hydrophobicity within the polymer increases, it begins to aggregate and form clusters.

Figure 6c is a dynamic light scattering spectrum of Comparative Example 4, in which R _h with a size of 342 ± 23 (nm) was formed at a temperature above LCST. In Figures 6 (a) and (b), Examples 1 and 2 in which the NFtB group was introduced showed R _h of 242 ± 18 and 320 ± 17 (nm), respectively, above LCST, similar to that of PNIPAm. On the other hand, Comparative Example 1 in Figure 6(a) showed an unstable tendency in which R _h continued to increase above LCST. Therefore, through comparison of Examples 1 to 2 and Comparative Examples 1 to 2, as the content of hydroxy groups increases, the behavior of R _h becomes unstable, but as the content of NFtB groups increases, R _h becomes stable as in Comparative Example 4. It was confirmed that appeared.

<Experimental Example 8: Confirmation of functional groups that affect dehydration>

High-temperature nuclear magnetic resonance spectroscopic analysis was performed to observe which functional group among the polymers of Example 1 affects dehydration, and is shown in FIG. 7. Specifically, the polymer of Example 1 was added to D ₂ O to prepare a 1.0 wt% D ₂ O solution, and then ¹ H NMR was measured at 25 to 45°C, and the results were shown. The characteristic signal was normalized to the D ₂ O peak δ = 4.70 ppm. According to (a) of Figure 7, as the temperature increased, the intensity of the peak began to decrease at a temperature near LCST, and as the temperature continued to increase, some peaks disappeared. Through this, it was confirmed that at temperatures above LCST, the hydrogen bond between the polymer chain and D ₂ O is weakened and dehydration occurs.

Meanwhile, Figure 7(b) shows the normalized integral (%) of each peak according to temperature change. It was confirmed that the peaks of CH(CH ₃ ) ₂ (a), CH ₃ CHCONH (d+e), CONHCN ₂ CH ₃ (b'), and CONHCH (g) were near LCST, and the normalized integration ratio began to decrease. The CONHCH ₂ CH (c') peak began to decrease at a higher temperature than the other peaks, but decreased most rapidly. Through Figure 7, it was confirmed that the hydrogen bond between the polymer and water is broken and the polymer chain is dehydrated, and that the protons around the NFtB group affect dehydration more than the protons around the main chain and the isopropyl group.

<Experimental Example 9: Confirmation of cell viability>

In order to confirm the cell viability of the polymers of Example 1, Comparative Example 1, and Comparative Example 4, the cell viability in MRC5 (human lung infant cells) was measured using the MTT assay. Figure 8 (a) shows the cytotoxicity measured by dissolving each polymer in MEM at a concentration of 0.1 to 10 mg/ml. The cell viability of the polymers of Example 1, Comparative Example 1, and Comparative Example 4 increased as the concentration of the polymer increased, but decreased at 10 mg/ml. When compared to Comparative Example 4, Example 1 and Comparative Example 1 had significantly higher cell survival rates. In particular, in Example 1, the cell viability reached about 278±39 (%) at a concentration of 5 mg/ml. Through this, it was confirmed that the polymer of Example 1 was not toxic to cells but rather played a role in growing cells.

Figure 8 (b) is an image after a cell viability test of the polymers of Example 1, Comparative Example 1, and Comparative Example 4 at a concentration of 5 mg/ml. The left column of Figure 8 (b) is an image of Example 1, Comparative Example 1, and Comparative Example 4 at 37°C, and the right column is an image after dissolving the polymer of Example 1 by leaving the sample at 25°C for 30 minutes. It is an image. In Example 1 at 37°C, the polymer was aggregated because the temperature was higher than LCST, and cells were confirmed to have grown around it. Afterwards, even after the sample was left at 25°C for 30 minutes to dissolve the aggregates, it was confirmed that the grown cells remained intact. Meanwhile, when Comparative Example 1 and Example 1 were compared, the cell survival rate of Example 1 was much better, confirming the bioinert properties of perfluorinated hydrocarbons and the anti-inflammatory effect in the lung.

Claims (22)

1. (A) Repeating units derived from temperature-sensitive monomers; and (B) a repeating unit derived from a hydroxy group-containing monomer; modifying at least a portion of the hydroxy groups included in the main chain copolymer with an oxygen-nucleophilic perfluorinated hydrocarbon-based compound. Method for producing polymers.
2. In claim 1,

   The repeating unit derived from the (A) temperature-sensitive monomer is a repeating unit derived from a (meth)acrylamide-based monomer, and the repeating unit derived from the hydroxyl group-containing monomer (B) is a hydroxyl group-containing (meth)acrylamide-based monomer. A method for producing a fluorine-based polymer, including a repeating unit derived from a fluorine-based polymer.
3. In claim 2,

   A method for producing a fluorine-based polymer, wherein the (meth)acrylamide-based monomer includes an N-alkyl (meth)acrylamide-based monomer.
4. In claim 3,

   The N-alkyl (meth)acrylamide monomer includes N-alkyl (meth)acrylamide in which an alkyl group of C ₂ to C ₁₈ is bonded to the nitrogen atom of the amide group.
5. In claim 2,

   A method for producing a fluorine-based polymer, wherein the hydroxy group-containing (meth)acrylamide-based monomer includes an N-hydroxyalkyl (meth)acrylamide-based monomer.
6. In claim 5,

   The N-hydroxyalkyl (meth)acrylamide monomer is a fluorine-based polymer comprising N-hydroxyalkyl (meth)acrylamide in which an alkyl group of C ₂ to C ₁₈ is bonded to the nitrogen atom of the amide group. Manufacturing method.
7. In claim 1,

   A method for producing a fluorine-based polymer, wherein the oxygen-nucleophilic perfluorinated hydrocarbon-based compound includes a perfluorinated tertiary alcohol.
8. In claim 1,

   A method for producing a fluorine-based polymer, wherein the oxygen-nucleophilic perfluorinated hydrocarbon-based compound includes a compound represented by the following formula (1):

   [Formula 1]

   

   (In Formula 1, n, m, and p are the repeating numbers of the units in parentheses, and are each integers from 0 to 3.)
9. In claim 1,

   A method for producing a fluorine-based polymer, wherein the repeating unit derived from the (B) hydroxy group-containing monomer in the main chain copolymer is contained in an amount of more than 0 and 30 mol% or less.
10. In claim 1,

    The modification includes adding the oxygen-nucleophilic perfluorinated hydrocarbon compound in an amount of 1.5 to 6 equivalents relative to the equivalent weight of the hydroxyl group of the main chain copolymer.
11. (C) a repeating unit derived from a temperature-sensitive monomer and (D) a repeating unit derived from a hydroxy group-containing monomer,

    (D) A fluorine-based polymer in which at least a portion of the hydroxy groups contained in the repeating unit derived from the hydroxy group-containing monomer is substituted with an oxygen-nucleophilic perfluorinated hydrocarbon-based ether group.
12. In claim 11,

    The repeating unit derived from the (C) temperature-sensitive monomer is a repeating unit derived from a (meth)acrylamide-based monomer, or the repeating unit derived from the (D) hydroxy group-containing monomer is a hydroxy group-containing (meth)acrylamide-based monomer. A fluorine-based polymer containing a repeating unit derived from a fluorine-based polymer.
13. In claim 12,

    The (meth)acrylamide-based monomer is a fluorine-based polymer that includes an N-alkyl (meth)acrylamide-based monomer.
14. In claim 13,

    The N-alkyl (meth)acrylamide monomer is a fluorine-based polymer that includes N-alkyl (meth)acrylamide in which an alkyl group of C ₂ to C ₁₈ is bonded to the nitrogen atom of the amide group.
15. In claim 12,

    A fluorine-based polymer wherein the hydroxyl group-containing (meth)acrylamide-based monomer includes an N-hydroxyalkyl (meth)acrylamide-based monomer.
16. In claim 15,

    The N-hydroxyalkyl (meth)acrylamide monomer is a fluorine-based polymer that includes N-hydroxyalkyl (meth)acrylamide in which an alkyl group of C ₂ to C ₁₈ is bonded to the nitrogen atom of the amide group.
17. In claim 11,

    A fluorine-based polymer wherein the oxygen-nucleophilic perfluorinated hydrocarbon-based compound includes a perfluorinated tertiary alcohol.
18. In claim 11,

    A fluorine-based polymer wherein the oxygen-nucleophilic perfluorinated hydrocarbon-based compound includes a compound represented by the following formula (1):

    [Formula 1]

    

    (In Formula 1, n, m, and p are the repeating numbers of the units in parentheses, and are each integers from 0 to 3.)
19. In claim 11,

    The fluorine-based polymer is a fluorine-based polymer in which the difference between the start temperature (onset point) and the end temperature (off set point) of the phase transition in the temperature-permeability curve is 5 to 30 ° C.
20. A fluorine-based composition comprising the fluorine-based polymer according to any one of claims 11 to 19.
21. In claim 20,

    The fluorine-based polymer is contained in an amount of 0.1 to 2.5 parts by weight based on 100 parts by weight of the fluorine-based composition.
22. A polymer film containing the fluorine-based polymer of any one of claims 11 to 19,

    The polymer film is a film for smart window covers, a temperature-sensitive packaging film, or a film for attaching a drug delivery device (DDS).

Images