KR20220046900A - Oxidation-Responsive Emulsion Stabilized With Amphiphilic Copolymer - Google Patents

Abstract

The present invention relates to oxidation-responsive emulsion which uses as an emulsifier a copolymer which maintains amphiphilicity in a reducing environment, but decreases amphiphilicity by oxidation. The emulsion specifically responds to an oxidizing environment and promotes the release of the loaded active ingredient, and thus the active ingredient is released slowly through constant simple diffusion regardless of the surrounding environment, thereby providing an advantage of compensating for the disadvantages of emulsions, which are difficult to express the efficacy of active ingredients to the maximum. The oxidation-responsive emulsion of the present invention specifically responds to oxidation of the loaded active ingredient and shows a release rate beyond simple diffusion, and thus can be used as a drug delivery system and a cosmetic raw material which delivers active ingredients in response to an oxidizing environment.

Description

Oxidation-Responsive Emulsion Stabilized With Amphiphilic Copolymer

The present invention relates to oxidation responsive emulsions stabilized with amphiphilic copolymers. Specifically, an oxidation-responsive emulsion that uses poly(vinylpyrrolidone-co-allylphenylsulfide) as an emulsifier to stabilize the aqueous phase and oil phase, but fusion of droplets and phase separation are induced in an oxidizing environment to promote release of active ingredients is about

A drug delivery system refers to a formulation designed to efficiently deliver the required amount of an active ingredient in order to minimize the side effects of existing drugs and maximize the efficacy and effect of the active ingredient. The drug delivery system includes solid dispersions, gels, nanoparticles, liposomes, emulsions, pellets, matrix tablets, and osmotic agents. (Osmotic pumps) technology, etc. can be used, and a sustained drug release system, controlled release system, or target-directed drug delivery that improves bioavailability, controls the amount and time of delivery of an active ingredient, and allows the active ingredient to be delivered specific to a target site available as a system.

The emulsion is composed of a continuous phase, a dispersion phase and an emulsifier. The continuous phase is also referred to as a dispersion medium and the dispersed phase is also referred to as a discontinuous phase. For example, in the case of an oil-in-water type (or O/W type) emulsion, the continuous phase is water, the disperse phase is oil, and a water-in-oil type (or W/O type) emulsion. The continuous phase is oil and the disperse phase is water. Surface-active molecules are used as emulsifiers to reduce the interfacial energy between oil and water. Therefore, when the surface active molecule is used in the emulsion, oil droplets and water droplets of a continuous phase are stabilized.

Emulsifiers can change their molecular structure in response to stimuli such as light, changes in temperature, and changes in pH values. When the emulsifier as described above is used, oil droplets and water droplets are fused (coalescence) and phase separated by a specific stimulus, so that the droplets are released. The fusion means that the interface is collapsed, the particles contact each other and are united, and the phase separation means that the continuous phase and the dispersed phase are separated from each other.

If the stimulus-responsive emulsifier is used, it is possible to prepare an emulsion that is easily demulsified if necessary. As an example of an emulsion that responds to stimulation, the copolymer poly(N-isopropylacrylamide-co-methacrylic acid-co-octadecylacrylate)) There are temperature and pH responsive emulsions containing as emulsifiers. The copolymer has a property of changing the contracted form when the temperature and pH value are changed. Therefore, when the temperature and pH of the emulsion are changed, the copolymer is contracted and thus the O/W interface is not completely covered, so fusion and phase separation occur.

As an example of another emulsion that responds to stimulation, the copolymer poly(2-hydroxyethyl acrylate-co-coumaryl acrylate) (poly(2-hydroxyethyl acrylate- co -coumaryl acrylate) - Emulsions containing co -2-ethylhexyl acrylate)) as emulsifiers include temperature and light (UV) responsive emulsions. Since the copolymer has a lower critical solution temperature (LCST) in the aqueous phase, when the temperature of the medium rises above the phase change temperature, it has a contracted form. In addition, the copolymer has a coumaryl group, and the coumaryl residue forms a photo-dimer when irradiated with UV to connect the copolymer chains to each other, so it has a contracted form. Therefore, when the emulsifier is heated to a temperature higher than LCST or exposed to UV, the copolymer shrinks and does not have a large area to stabilize the O/W interface, so coalescence and phase separation occur.

Another example of an emulsion that responds to stimulation is a reduction-responsive emulsion containing proteinoid sulfide as an emulsifier. When the protenoid sulfide is placed in a reducing environment, the disulfide bond is removed to become a thiol proteinoid. Since the thiol pretonoid has a low emulsification performance compared to the protenoid sulfide, when the emulsifier is placed in a reducing environment, fusion and phase separation of oil droplets occur.

As another example of an emulsion responsive to stimulation, poly(2-hydroxyethyl acrylate- co -propyl methacryate), a thermosensitive amphipathic copolymer There is a near InfraRed (NIR) responsive emulsion prepared by using as an emulsifier and emulsifying oil in a gold nanoparticle (GNP) solution. When the emulsion is irradiated with near-infrared rays, heat is generated by surface plasmon resonance of the gold nanoparticles, and the copolymer is contracted by the heat to achieve fusion and phase separation.

Since the emulsion slowly releases the active ingredient loaded as a drug delivery system by simple diffusion, there is a problem in that it is difficult to maximize the efficacy of the active ingredient. Therefore, if an emulsion having the characteristic of specifically releasing an active ingredient by a specific stimulus as described above is developed, it is expected that the efficacy of the active ingredient can be improved through the release of the target site.

The patents and references mentioned in this specification are hereby incorporated by reference to the same extent as if each publication were individually and expressly specified by reference.

Wessln, B., Kober, M., Freij-Larsson, C., Ljungh, Å. And Paulsson, M. Biomaterials. 1994, 15, 278-284. Maltesh, C., Xu, Q., Somasundaran, P., Benton, W. J. and Hung, N. Langmuir. 1992, 8, 1511-1513. Brugger, B. and Richtering, W. Adv. Mater. 2007, 19, 2973-2978. Tang, J., Quinlan, PJ and Tam, KC Soft Matter. 2015, 11, 3512-3529. Brugger, B., Rosen, BA and Richtering, W. Langmuir. 2008, 24, 12202-12208. Besnard, L., Marchal, F., Paredes, JF, Daillant, J., Pantoustier, N., Perrin, P. and Guenoun, P. Adv. Mater. 2013, 25, 2844-2848. Khoukh, S., Perrin, P., Bes de Berc, F., Tribet, C. Chem. Phys. Chem. 2005, 6, 2009-2012. Li, Z. and Ngai, T. Colloid. Polym. Sci. 2011, 289, 489-496. Seo, SR, Lee, HY and Kim, JCJ Disper. Sci. Technol. 2013, 34, 1280-1285. Seo, SR and Kim, JCJ Macromol. Sci. A. 2013, 50, 855-860. Kwon, K. and Kim, JCJ Disper. Sci. Technol. 2018, 39, 333-340. Park, SH and Kim, JCJ Disper. Sci. Technol. 2018, 39, 961-969. Chung, SL and Ferrier, LKJ Food. Sci. 1992, 57, 40-42. Zorba, O. Food hydrocolloids. 2006, 20, 698-702. Liu, Y., Bhatnagar, A., Ji, Q., Riffle, JS, McGrath, JE, Geibel, JF and Kashiwagi, T. Polymer. 2000, 41, 5137-5146. Zhunuspayev, DE, Mun, GA and Khutoryanskiy, VV Langmuir. 2010, 26, 7590-7597. Israelachvili, JN and Wennerstroem, HJ Phys. Chem. 1992, 96, 520-531. Zilman, A., Tlusty, T. and Safran, SAJ Phys. Condens. Mat. 2002, 15, S57. Nie, Z., Fava, D., Kumacheva, E., Zou, S., Walker, GC and Rubinstein, M. Nat. Mater. 2007, 6, 609. Busico, V., Ferraro, A. and Vacatello, M. Mol. Crystal. Liq. Crystal. 1985, 128, 243-261. Mondal, J. and Yethiraj, AJ Phys. Chem. Lett. 2011, 2, 2391-2395.

Wessln, B., Kober, M., Freij-Larsson, C., Ljungh, Å. And Paulsson, M. Biomaterials. 1994, 15, 278-284. Maltesh, C., Xu, Q., Somasundaran, P., Benton, WJ and Hung, N. Langmuir. 1992, 8, 1511-1513.

The present invention is to solve the above problem, and it contains a copolymer as an emulsifier, characterized in that the amphiphilicity is maintained in a reducing environment to stabilize the aqueous phase and the oil phase, and the residue is oxidized in an oxidizing environment to reduce the amphiphilicity. , an object of the present invention is to provide an oxidation-responsive emulsion in which droplets are fused in response to an oxidizing environment and phase separation proceeds to promote release of loaded active ingredients.

Other objects and technical features of the present invention are more specifically set forth by the following detailed description of the invention, claims and drawings.

The present invention provides an oxidation-responsive emulsion containing poly(vinyl pyrrolidone-co-allyl phenyl sulfide) as an emulsifier.

The poly (vinyl pyrrolidone-co-allyl phenyl sulfide) (poly (vinyl pyrrolidone-co-allyl phenyl sulfide) is amphiphilic as an emulsifier, and the allylphenyl sulfide residue is oxidized to an allylphenyl sulfone residue in an oxidizing environment to become amphiphilic. As this decreases, fusion and phase separation of the droplets are induced.

The poly(vinylpyrrolidone-co-allylphenylsulfide) is characterized in that the vinylpyrrolidone monomer and the allylphenylsulfide monomer are composed of a molar ratio of 100: 3 to 10, and the interfacial tension of the stabilized group in the aqueous solution is 55 to 66 dyne/ It is characterized in that it is cm.

The oxidation-responsive emulsion contains a hydrophilic solution containing 0.5% poly(vinylpyrrolidone-co-allylphenylsulfide) emulsifier as a water phase and oil in water containing oil as an oil phase As an (O/W) type emulsion, the diameter of the oil droplets was at a level of 3 to 4 µm in a reducing environment and increased to 30 to 15 to 35 µm after 300 hours, and the diameter of the oil droplets was 3 to 4 µm in an oxidizing environment It is characterized in that it increases to 30 to 40 to 100 μm after 300 hours. In addition, the oxidation-responsive emulsion is characterized in that the phase separation stability (stability, 50%) in the oxidizing environment is reduced to a level of 55 to 80% of the phase separation stability (stability, 50%) in the reducing environment.

The present invention relates to an emulsion using, as an emulsifier, a copolymer whose amphiphilic properties are reduced by oxidation while maintaining amphiphilic properties in an oxidation-responsive emulsion in a reducing environment. Therefore, regardless of the surrounding environment, the active ingredient is gradually released through a constant simple diffusion, so it has the advantage of compensating for the disadvantages of the emulsion, which is difficult to maximize the efficacy of the active ingredient.

The oxidation-responsive emulsion of the present invention responds specifically to oxidation of the loaded active ingredient and exhibits a release rate above simple diffusion, so it can be used as a drug delivery system and cosmetic raw material that specifically responds to an oxidizing environment to deliver the active ingredient There is this.

1 shows a process in which droplets are fused and phase separation is induced by oxidation of the oxidation-responsive emulsion of the present invention.
2 shows the results of nuclear magnetic resonance analysis of poly(vinylpyrrolidone-co-allylphenylsulfide) (P(VP-APS)(a/b)) of the present invention. Panel (A) shows the hydrogen nuclear magnetic resonance analysis results for P(VP-APS) (100/0), and panel (B) shows hydrogen nuclei for Oxi-P(VP-APS) (100/0). Shows the magnetic resonance analysis results, panel (C) shows the hydrogen nuclear magnetic resonance analysis results for P(VP-APS) (98/2), and panel (D) shows the results of Oxi-P(VP-APS) ( 98/2) shows the results of hydrogen nuclear magnetic resonance analysis.
3 shows the XPS spectral analysis results for poly(vinylpyrrolidone-co-allylphenylsulfide) (P(VP-APS)(a/b)) of the present invention. Panel (A) shows the XPS spectrum (solid line) for P(VP-APS) (100/0) and the XPS spectrum (dashed line) for Oxi-P(VP-APS) (100/0), panel ( B) shows the XPS spectrum (solid line) for P(VP-APS) (96/4) and the XPS spectrum (dashed line) for Oxi-P(VP-APS) (96/4).
4 is a homopolymer P (VP-APS) (100/0) solution (●), homopolymer Oxi-P (VP-APS) (100/0) solution (○), copolymer P (VP-) of the present invention. APS)(98/2) solution(▼), copolymer Oxi-P(VP-APS)(98/2) solution(▽), copolymer P(VP-APS)(97.5/2.5) solution(■), Copolymer Oxi-P(VP-APS)(97.5/2.5) solution (□), copolymer P(VP-APS)(96/4) solution(♦) and copolymer Oxi-P(VP-APS)(96) /4) It shows the optical density change according to the temperature of the solution (◇).
5 is a homopolymer P (VP-APS) (100/0) solution (●), homopolymer Oxi-P (VP-APS) (100/0) solution (○), copolymer P (VP-) of the present invention. APS)(98/2) solution(▼), copolymer Oxi-P(VP-APS)(98/2) solution(▽), copolymer P(VP-APS)(97.5/2.5) solution(■), Copolymer Oxi-P(VP-APS)(97.5/2.5) solution (□), copolymer P(VP-APS)(96/4) solution(♦) and copolymer Oxi-P(VP-APS)(96) /4) It shows the air/water interface tension analysis result of the solution (◇).
6 shows the results of measuring the change in droplet diameter of the oxidation-responsive emulsion of the present invention. Panel (A) uses mineral oil as an oil phase and distilled water as a water phase, but P(VP-APS)(100/0)(●), P(VP-APS) of the present invention (98/2)(▲), P(VP-APS)(97.5/2.5)(■) and P(VP-APS)(96/4)(♦) of O/W emulsion stabilized using emulsifier It shows the result of measuring the change in droplet diameter over time, and panel (B) uses mineral oil as an oil phase and 10% H ₂ O ₂ solution as a water phase. P(VP-APS)(100/0)(○), P(VP-APS)(98/2)(Δ), P(VP-APS)(97.5/2.5)(□) or P( VP-APS) (96/4) (◇) was used as an emulsifier to measure the change in droplet diameter with time of an O/W emulsion stabilized is shown.
7 shows the results of evaluating the stability (%) of the oxidation-responsive emulsion of the present invention. Panel (A) uses mineral oil as an oil phase and distilled water as a water phase, but P(VP-APS)(100/0)(●), P(VP-APS) of the present invention (98/2)(▲), P(VP-APS)(97.5/2.5)(■) and P(VP-APS)(96/4)(♦) of O/W emulsion stabilized using emulsifier Shows the results of evaluating stability (%), and panel (B) uses mineral oil as an oil phase and 10% H ₂ O ₂ solution as a water phase, and P (VP) of the present invention -APS)(100/0)(○), P(VP-APS)(98/2)(Δ), P(VP-APS)(97.5/2.5)(□) or P(VP-APS)(96 /4) Shows the results of evaluating the stability (%) of the O/W emulsion stabilized using (◇) as an emulsifier.

The present invention provides an oxidation-responsive emulsion containing poly(vinyl pyrrolidone-co-allyl phenyl sulfide) as an emulsifier.

The poly (vinyl pyrrolidone-co-allyl phenyl sulfide) (poly (vinyl pyrrolidone-co-allyl phenyl sulfide) is amphiphilic as an emulsifier, and the allylphenyl sulfide residue is oxidized to an allylphenyl sulfone residue in an oxidizing environment to become amphiphilic. As this decreases, fusion and phase separation of the droplets are induced.

The poly(vinylpyrrolidone-co-allylphenylsulfide) is characterized in that the vinylpyrrolidone monomer and the allylphenylsulfide monomer are composed of a molar ratio of 100: 3 to 10, and the interfacial tension of the stabilized group in the aqueous solution is 55 to 66 dyne/ It is characterized in that it is cm. Preferably, the poly(vinylpyrrolidone-co-allylphenylsulfide) is composed of a vinylpyrrolidone monomer and an allylphenylsulfide monomer in a molar ratio of 100:3 to 5, more preferably a vinylpyrrolidone monomer and It is characterized in that the allylphenyl sulfide monomer consists of 100: 3.4, 3.6 or 4.8. Poly(vinylpyrrolidone-co-allylphenylsulfide) in which the molar ratio of the vinylpyrrolidone monomer to the allylphenylsulfide monomer is less than 100:3 has a disadvantage in that the stability of the emulsion is low due to low amphiphilicity, and the vinylpyrrolidone monomer Poly(vinylpyrrolidone-co-allylphenylsulfide) in which the molar ratio of the and allylphenylsulfide monomers exceeds 100:10 has a disadvantage in that the reactivity of the active ingredient is lowered due to low reactivity to the oxidizing environment.

The oxidation-responsive emulsion of the present invention comprises a hydrophilic solution containing 0.5% poly(vinylpyrrolidone-co-allylphenylsulfide) emulsifier as a water phase and an oil containing oil as an oil phase It is characterized in that it is an in water (O/W) type emulsion. The O/W type emulsion uses a water phase as a continuous phase or a dispersion medium and an oil phase as a dispersion phase, and the oil phase is a water phase by an emulsifier. means distributed in According to an embodiment of the present invention, the emulsifier used in the emulsion of the present invention may be poly(vinylpyrrolidone-co-allylphenylsulfide), which is an amphipathic copolymer, and the aqueous phase may be water or a 10% aqueous hydrogen peroxide solution, and oil The phase may be mineral oil. Poly(vinylpyrrolidone-co-allylphenylsulfide), which is the emulsifier of the present invention, is a polymerization of a vinylpyrrolidone monomer and an allylphenylsulfide monomer, and has amphiphilic properties. However, when the allylphenylsulfide is oxidized, it becomes allylphenylsulfone masculinity will disappear. Therefore, in the oxidation-responsive emulsion of the present invention, the amphiphilicity of poly(vinylpyrrolidone-co-allylphenylsulfide) is maintained in a reducing environment to maintain the emulsion in a stable state, but in an oxidizing environment, poly(vinylpyrrolidone-co- allylphenyl sulfide) disappears, oil droplets are fused and a phase transition occurs, separating the aqueous phase and the oil phase.

According to an embodiment of the present invention, in the oxidation-responsive emulsion of the present invention, the diameter of the oil droplets was at a level of 3 to 4 μm in a reducing environment and increased to 30 to 15 to 35 μm after 300 hours, and in an oxidizing environment, the oil liquid It is characterized in that the diameter of the enemy was at the level of 3 to 4 μm and then increased to 30 to 40 to 100 μm after 300 hours. %) to a level of 55 to 80%.

The oxidation-responsive emulsion of the present invention can be used as a drug delivery system or used as a raw material for cosmetics by loading an additional hydrophobic active ingredient into oil droplets. The drug delivery system is a drug delivery system that can increase the surface area to increase the solubility of poorly soluble active ingredients (drugs) and improve absorption to improve biocompatibility. As a homogeneous mixture in a liquid or solid state from which the aqueous phase has been removed, the active ingredient can be delivered by meeting the aqueous phase such as body fluid when taking it to form an emulsion (o/w) in water. The cosmetic means an emulsification product and can be used in creams, lotions, foundations, and the like, mainly having a milky white shape.

The present invention will be described in detail through the following examples.

Example

1. Experimental method

1.1. test material

Vinyl pyrrolidone (VP) and mineral oil were purchased from Sigma-Aldrich Chemiccal Co. Allyl phenyl sulfide (allyl phenyl sulfide, APS) was purchased from Tokyo Chemical Industry Co., Ltd.. α,α'-azobisisobutyronitrile (α,α'-azobisisobutyronitrile, AIBN) was purchased from Junsei Chemical Co. Tetrahydrofuran (tetrahydrofuran), hexane (hexane), H ₂ O ₂ solution (30%) was purchased from popular chemical.

1.2. Preparation of copolymers and homopolymers

Poly(vinyl pyrrolidone-co-allyl phenyl sulfide, P(VP-APS)) as copolymers and polyvinylpyrrolidone as homopolymers (poly(vinyl pyrrolidone), P(VP)) was prepared using a free radical reaction. Various ratios of VP monomer, APS monomer, and 50 ml of tetrahydrofuran were placed in a 250 ml round-bottom flask and mixed, followed by VP:APS. A mixture having a molar ratio of 98:2 (Example 1), 97.5:2.5 (Example 2), or 96:4 (Example 3) was prepared so that the total mass of the monomer was 5.557 g. In the same manner, homopolymers having a VP:APS molar ratio were prepared of 100: 0. The mixture containing the VP monomer and the APS monomer in various molar ratios was degassed using an N2-stream for 30 minutes, and each mixture was degassed. 40 mg of AIBN was further added to .The mixture with AIBN was placed in a round bottom flask in an oil bath, heated to reflux and 75° C., and stirred for 12 hours using a magnetic bar. Copolymer P For precipitation of (VP-APS) and the homopolymer P(VP), each reaction mixture was cooled to room temperature, poured into a 1ℓ beaker containing 600 ml of hexane, mixed, and then filtered using filter paper (Whatman No. 2). A first cake (1 ^st cake) containing the copolymer or homopolymer was obtained.

For purification of the copolymer or homopolymer, the cake was re-dissolved in tetrahydrofuran and re-precipitated in hexane to prepare a second cake (1 ^nd cake) and dried in a vacuum oven at 50°C. A copolymer or homopolymer obtained from a reaction mixture having a VP/APS molar ratio a/b was named P(VP-APS)(a/b) and is shown in Table 1 below. The molar ratio of the monomers actually present after preparation in Table 1 below is the result of analysis through hydrogen nuclear magnetic resonance.

name Molar ratio of monomers used in the preparation (VP:APS) Molar ratio of monomers present after preparation (VP:APS) Comparative Example 1 P(VP-APS)(100/0) 100:0 100:0 Example 1 P(VP-APS)(98/2) 98:2 100:3.4 Example 2 P(VP-APS) (97.25/2.5) 97.25:2.5 100:3.6 Example 3 P(VP-APS)(96/4) 96:4 100:4.8

1.3. Oxidation of copolymers and homopolymers

Homopolymer (Comparative Example 1: P(VP-APS) (100/0)) or copolymer (Example 1: :P(VP-APS) (98/2), Example 2) prepared above in a 20 mL vial : P (VP-APS) (97.52.5), Example 3: P (VP-APS) (96/4)) 0.2 g and H ₂ O ₂ solution (10%, distilled water) 10㎖ by mixing the same After dissolving the polymer or copolymer, it was left at room temperature for 3 days. The H ₂ O ₂ solution in which the copolymer or homopolymer was dissolved was lyophilized to obtain only an oxidation-treated copolymer or homopolymer. The oxidation-treated copolymer was named Oxi-P (VP-APS) (a/b) and is shown in Table 2 below. The molar ratio of the monomers actually present after preparation in Table 2 below is the result of analysis through hydrogen nuclear magnetic resonance.

name Molar ratio of monomers used in preparation (VP:APS) Molar ratio of monomers present after preparation (VP:APS) Comparative Example 1-1 Oxi-P (VP-APS) (100/0) 100:0 100:0 Example 1-1 Oxi-P (VP-APS) (98/2) 98:2 100:3.4 Example 2-1 Oxi-P (VP-APS) (97.25/2.5) 97.25:2.5 100:3.6 Example 3-1 Oxi-P (VP-APS) (96/4) 96:4 100:4.8

1.4. hydrogen nuclear magnetic resonance

The compounds of Examples and Comparative Examples were dried overnight in a vacuum oven at 50° C. together with phosphorus pentoxide as a drying agent. The dried copolymer and homopolymer were dissolved in DMSO-d6 to prepare an NMR sample having a concentration of 12 mg/ml. The sample was placed in an NMR tube (outer diameter of 0.5 mm, length of 180 mm) and sealed, and then a hydrogen nuclear magnetic resonance spectrum was obtained using an FT-NMR spectrometer (Bruker DPX 400 MHz (9.4T), Bruker Analytik GmbH).

1.5. X-ray photoelectron spectroscopy

In order to confirm whether the compounds of Comparative Examples and Examples of the present invention are oxidized by H ₂ O ₂ treatment, X-ray photoelectron spectroscopy (XPS) analysis was performed. The XPS analysis is Comparative Example 1, Comparative Example 1 -1, Example 3, and Example 3-1 were performed. The XPS analysis was performed by using a 180° bifocal hemispherical analyzer equipped with a 128-channel position sensor to analyze the binding energy (eV) of electrons. XPS spectra of the copolymers and homopolymers were investigated using A MaKa (1253.6 eV) colorless X-ray source, and Tien spectra were obtained at room temperature of 5x10 ^-8 mbar or less. The binding energy of atomic electrons was determined based on the observed binding energy of C1s electrons (284.5 eV).

1.6. Optical density change according to temperature of homopolymer solution or copolymer solution

A solution of a homopolymer or copolymer having a concentration of 2% (w/v) was prepared by dissolving 60 mg of a compound of Comparative Example or Example of the present invention in 3 ml of distilled water in a 10 ml glass bottle. 0.8 ml of the homopolymer solution or copolymer solution is placed in a cuvette and a temperature controller (Peltier Controller, JENWAY, Staffordshire, UK) is installed in a 7315 spectrophotometer (Jenway, Staffordshire, UK) in a temperature range of 20 to 50 ° C. The optical density (600 nm) was measured while heating at a rate of minutes.

1.7. Air/water interface tension measurement

20 mg of the compound of Comparative Example or Example of the present invention was placed in a 30 ml glass vial, and 20 ml of distilled water was added to prepare a homopolymer solution and a copolymer solution having a concentration of 1 mg/ml. After that, the homopolymer solution or the copolymer solution was diluted twice so that the concentration was 0.0039 mg/ml, and then the air/water interface was used using the ring method and a tensiometer (DST 60, SEO Co., Gunpo, South Korea). The tension was measured.

1.8. Preparation of emulsions

An emulsifier solution was prepared by dissolving the compounds of Comparative Examples and Examples of the present invention in distilled water or 10% H ₂ O ₂ solution to be 0.5% (w/v), respectively. After putting 4.5 ml of the emulsifier solution in a 10 ml vial, 0.5 ml of mineral oil was added to prepare an emulsion. The emulsion was sonicated at a density of 27% for 90 seconds using a tip-type ultrasonicator (VC 505, Sonic & Materials, Newtown, USA). The prepared emulsion is an emulsion containing 10% oil phase and 0.5% (w/v) emulsifier, and the types of emulsifiers, types of oil phases and types of water phase are shown in Table 3 below.

emulsifier oil phase Awards Comparative Example 2 P(VP-APS)(100/0) mineral oil distilled water (H ₂ O) Comparative Example 2-1 P(VP-APS)(100/0) mineral oil hydrogen peroxide solution
(10% H ₂ O ₂ +90% H ₂ O) Example 4 P(VP-APS)(98/2) mineral oil distilled water (H ₂ O) Example 4-1 P(VP-APS)(98/2) mineral oil hydrogen peroxide solution
(10% H ₂ O ₂ +90% H ₂ O) Example 5 P(VP-APS) (97.25/2.5) mineral oil distilled water (H ₂ O) Example 5-1 P(VP-APS) (97.25/2.5) mineral oil hydrogen peroxide solution
(10% H ₂ O ₂ +90% H ₂ O) Example 6 P(VP-APS)(96/4) mineral oil distilled water (H ₂ O) Example 6-1 P(VP-APS)(96/4) mineral oil hydrogen peroxide solution
(10% H ₂ O ₂ +90% H ₂ O)

1.9. Determination of stability of emulsions

The stability of the emulsions prepared in Comparative Examples and Examples was evaluated by measuring the size of oil droplets and the degree of phase separation. First, the emulsion was placed in a vial, filled with nitrogen, tightly sealed, and left in the dark at 25°C for 28 days. The emulsion was photographed with a microscope over time, and the diameter of the oil droplets was analyzed using an image analyzer (Image-Pro Plus Version 5.1, Media Cybernetics, Rockville, USA). In addition, the degree of phase separation of the emulsion was determined using Equation 1 below.

2. Experimental results and discussion

2.1. Hydrogen Nuclear Magnetic Resonance Analysis Results

Panel (A) of FIG. 2 shows the 1H-NMR spectrum analysis result for P(VP-APS) (100/0) of Comparative Example 1 of the present invention. As a result of the analysis, the hydrogen (proton) residue contained in the vinyl group methylene of P(VP-APS) (100/0) was 1.3 ppm, the hydrogen residue contained in methine was 3.7 ppm, and the 2 adjacent to the carbonyl group of the pyrrolidone group Hydrogen residues included in methylene are found at 1.8 ppm and 2.1 ppm, and hydrogen residues included in methylene next to nitrogen are found at 3.2 ppm.

Panel (B) of FIG. 2 shows the 1H NMR spectrum analysis result of Oxi-P (VP-APS) (100/0) of Comparative Example 1-1. The NMR signal for the hydrogen residue of Oxi-P(VP-APS) (100/0) was confirmed at the same position as that of P(VP-APS) (100/0) of Comparative Example 1. Therefore, the homopolymer P(VP-APS) (100/0) of the present invention is judged to be stable to an oxidizing agent (H ₂ O ₂ ). Indeed, it is confirmed that the structure of P(VP-APS) (100/0) does not contain oxidizable residues.

Panel (C) of FIG. 2 shows the result of analyzing the 1H NMR spectrum of P(VP-APS)(98/2) of Example 1 of the present invention. As a result of the analysis, with respect to the APS contained in P(VP-APS)(98/2), the hydrogen residue contained in the methylene of the vinyl group was at 1.6 ppm, the hydrogen residue contained in the methine was at 1.9 ppm, and the methylene next to the sulfur atom was The hydrogen residue included in 2.4 ppm, the hydrogen residue included in phenyl is confirmed at 7.3 to 7.6 ppm. The NMR signal of the hydrogen residue associated with the VP of P(VP-APS) (98/2) is found at the same position as the P(VP-APS) (100/0), which indicates that the VP is copolymerized with APS without chemical degradation. means that A value obtained by integrating the NMR signal area of a hydrogen residue contained in methine and a hydrogen residue contained in methylene located next to the nitrogen atom of VP, and a value obtained by integrating the NMR signal area of a hydrogen residue contained in aromatics at position 4 of APS As a result of calculating the molar ratio of the VP monomer and the APS monomer included in the copolymer by comparing The molar ratio of the VP monomer and the APS monomer used in the reaction mixture for preparing the P(VP-APS)(98/2) copolymer is only VP:APS=98:2. Therefore, it is determined that the reactivity of APS is higher than that of VP in the preparation of the P(VP-APS)(98/2) copolymer.

Panel (D) of FIG. 2 shows the 1H NMR spectrum analysis result of Oxi-P(VP-APS) (98/2) of Example 1-1. The NMR signal associated with the VP of Oxi-P(VP-APS) 98/2 is identified at the same position as that of P(VP-APS) 98/2. However, the NMR signal of the hydrogen residue contained in phenyl and the hydrogen residue contained in methylene located next to the sulfur atom of Oxi-P(VP-APS)(98/2) is that of P(VP-APS)(98/2). It is identified in the downfield than the NMR signal. Specifically, the hydrogen residue included in the phenyl of Oxi-P(VP-APS) (98/2) is found at 7.6 to 7.7 ppm, whereas the hydrogen residue included in the phenyl of P(VP-APS) (98/2) was found between 7.3 and 7.6 ppm.

Sulfide is oxidized to sulfoxide and sulfone under oxidizing conditions. The APS of the P(VP-APS) 98/2 may be oxidized by an oxidizing agent such as H ₂ O ₂ . When the sulfide is oxidized, oxygen with negative electronegativity is attached to the sulfur, and electron density of adjacent hydrogen atoms is reduced and the shield is released. When the shielding is released, the NMR signal of the hydrogen residue contained in phenyl and the NMR signal of the hydrogen residue contained in methylene located next to sulfur are shifted down field fh. Additionally, P(VP-APS) (97.5/2.5) of Example 2 and P(VP-APS) (96/4) of Example 3 are NMR at the same position as the P(VP-APS) (98/2) It is confirmed that the signal is visible.

The copolymer of the present invention is composed of monomers, and since the composition ratio (VP/APS molar ratio) of the VP monomer and the APS monomer used in the synthesis process is different from each other, the amounts of the VP monomer and the APS monomer included in the synthesized copolymer are different from each other. can do. In the NMR spectrum, using the area calculated by integrating the NMR signal of hydrogen contained in VP and the area calculated by integrating the NMR signal of hydrogen contained in APS, the VP/APS molar ratio contained in the copolymer can be calculated. . As a result of integrating and analyzing the NMR signals of VP and APS, the VP:APS molar ratios of P(VP-APS)(97.5/2.5) and P(VP-APS)(96/4) are 100:3.6 and 100:4.8, respectively. was confirmed to be The above results show that P(VP-APS) (97.5/2.5) and P(VP-APS) (96/4) are also VP:APS of the reaction mixture used in the preparation in the same manner as P(VP-APS) (98/2). As it was confirmed that the molar ratio of VP:APS in the synthesized state was higher than the molar ratio, it means that the reactivity of ASP is higher than that of VP. As a result of NMR spectrum analysis, P(VP-APS) (97.5/2.5) and P(VP-APS) (96/4) were oxidized by H ₂ O ₂ in the same manner as P(VP-APS) (98/2). It was confirmed that the NMR signals of the hydrogen residues contained in phenyl and the hydrogen residues contained in methylene moved to the down field after the conversion. The above result means that the chemical shift of the hydrogen residue contained in the phenyl and the hydrogen residue contained in the methylene is affected by the phenomenon that the shielding is reduced due to oxidation of the surrounding hydrogen residue.

2.2. X-ray photoelectron spectroscopy analysis result

Panel (A) of FIG. 3 shows the XPS spectrum of P(VP-APS) (100/0) of Comparative Example 1 and Oxi-P(VP-APS) (100/0) of Comparative Example 1-1 of the present invention. Show the analysis results. No significant signal was found in the XPS spectrum of P(VP-APS) (100/0) and the XPS spectrum of Oxi-P(VP-APS) (100/0). This is because the above result is a scan of the binding energy of electrons in the range in which the signal of the sulfur atom appears. APS was not used for the P(VP-APS) (100/0). Therefore, no sulfur was found in the XPS spectra of P(VP-APS) (100/0) and Oxi-P(VP-APS) (100/0).

Panel (B) of Figure 3 shows the results of analyzing XPS spectra of P (VP-APS) (96/4) of Example 3 and Oxi-P (VP-APS) (96/4) of Example 3-1 shows In the XPS spectrum of P(VP-APS) (96/4), a peak of about 163 eV corresponding to ally phenyl sulfide, which is the sulfide of APS, is found, and Oxi-P(VP-APS) (96/4) ) In the XPS spectrum, a sharp peak near 168 eV corresponding to ally phenyl sulfone, which is a sulfide of Oxi-P(VP-APS) (96/4), is confirmed.

Sulfide is oxidized to sulfoxide and further oxidized to sulfone. The sulfone signal was found in the XPS spectrum of Oxi-P(VP-APS)(96/4), which is ally phenyl sulfide of P(VP-APS)(96/4) before oxidation under current oxidizing conditions. ) was oxidized to ally phenyl sulfone.

2.3. Analysis result of optical density change according to the temperature of the copolymer solution

4 is a solution of homopolymer P(VP-APS) (100/0) of the present invention, solution of homopolymer Oxi-P(VP-APS) (100/0), copolymer P(VP-APS) (98/2) ) solution, copolymer Oxi-P(VP-APS)(98/2) solution, copolymer P(VP-APS)(97.5/2.5) solution, copolymer Oxi-P(VP-APS)(97.5/2.5) The optical density change according to the temperature of the solution, the copolymer P(VP-APS)(96/4) solution, and the copolymer Oxi-P(VP-APS)(96/4) solution is shown.

Copolymers of hydrophilic equivalents and hydrophobic monomers are known to have a low critical solution temperature (LCST). In the present invention, VP is a hydrophilic monomer and APS is a type of hydrophobic monomer. Therefore, it is judged that the copolymers P(VP-APS)(a/b) and Oxi-P(VP-APS)(a/b) of the present invention in which VP and APS are used will show LCST behavior. In order to confirm the prediction, the copolymer was prepared as a solution and optical density change according to temperature change was observed. As a result of the analysis, it was confirmed that all the copolymer solutions of the present invention did not show LCST behavior by maintaining an almost constant optical density in the experimental temperature range. The above result is presumed to be because the content of APS, which is a hydrophobic monomer included in the copolymer of the present invention, was not suitable for exhibiting LCST behavior in a temperature window. In this regard, it is judged that additional research should be conducted.

Interestingly, it was confirmed that the optical density of the copolymer solution of the present invention was highly dependent on the APS content. According to the analysis results, P(VP-APS)(100/0) solution, P(VP-APS)(98/2) solution, P(VP-APS)(97.5/2.5) solution, and P at 20°C The optical densities of the (VP-APS) (96/4) solution were found to be 0.01, 0.23, 0.38 and 0.5, respectively. Since VP is a hydrophilic monomer and APS is a lipophilic (hydrophobic) monomer, P(VP-APS)(a/b), except for P(VP-APS)(100/0), is likely to be amphiphilic. Amphiphilic molecules can be generated by self-assembly in aqueous solution by an entropy-driven process. Therefore, it is judged that the copolymer of the present invention is self-assembled into polymer micelles, and the optical density analysis result of the copolymer solution supports that the copolymer of the present invention is due to the formation of self-assembly.

The APS is a hydrophobic monomer, and when used in a copolymer together with a hydrophilic monomer, amphiphilicity is imparted. Therefore, the degree of amphiphilicity and self-assembly of the copolymer is proportional to the content of the hydrophobic monomer. The above results explain why the optical density increased as the APS content of the copolymer increased. The P(VP-APS)(100/0) solution is not amphiphilic as it is a homopolymer composed only of the hydrophilic monomer, VP. Therefore, since P(VP-APS)(100/0) does not self-assemble in aqueous solution, an optical density close to zero is measured.

The optical density of the Oxi-P(VP-APS)(a/b) solution was also measured as a value exceeding 0 in the copolymer solutions except for the Oxi-P(VP-APS)(100/0) solution, and Oxi-P The optical densities of the (VP-APS) (98/2) solution, the Oxi-P (VP-APS) (97.5/2.5) solution and the Oxi-P (VP-APS) (96/4) solution were 0.07 and 0.11, respectively. And it is confirmed to be 0.34, and it is confirmed that it shows an optical density proportional to the content of APS.

As described above, sulfides (sulfides) are oxidized to sulfides and sulfones under oxidizing conditions. APS of copolymer P(VP-APS) (96/4) of FIG. 3 was oxidized to sulfone through H ₂ O ₂ treatment. When APS is oxidized, it changes to hydrophilicity, so the amphiphilicity of the copolymer decreases, which leads to a decrease in self-assembly. As a result, the optical density of the Oxi-P (VP-APS) (96/4) solution is decreased compared to the optical density of the P (VP-APS) (96/4) solution.

2.4. Air/water interface tension measurement result

5 is P(VP-APS)(100/0) solution, Oxi-P(VP-APS)(100/0) solution, P(VP-APS)(98)/2 solution, Oxi-P of the present invention (VP-APS)(98/2) solution, P(VP-APS)(97.5/2.5) solution, Oxi-P(VP-APS)(97.5/2.5) solution, P(VP-APS)(96/4) ) and Oxi-P (VP-APS) (96/4) solutions show the results of air/water interfacial tension analysis. It was confirmed that the interfacial tension of the P(VP-APS)(100/0) solution decreased from 72dyne/cm to 70dyne/cm with increasing concentration in the range of 0 to 1.0mg/ml, and Oxi-P(VP-APS) It was confirmed that the interfacial tension of the )(100/0) solution also showed almost the same trend as the interfacial tension measurement result of the P(VP-APS(100/0). The result was P(VP-APS)(100/0). ), which means that the surface activity of the solution was not affected by the oxidation treatment because it did not contain APS that was oxidized by the H ₂ O ₂ treatment.

It is confirmed that the interfacial tension of the P (VP-APS) (98/2) solution rapidly decreases from 72.5 dyne/cm to 64.5 dyne/cm as the concentration increases in the concentration range of 0 to 0.25 mg/ml, and the concentration range At 0.25 to 1 mg/ml, it is confirmed that the plateau interfacial tension is maintained almost constantly at 64.5 dyne/cm. As shown in FIG. 5, the interfacial tension profile expressed in an L-shape having a stabilized interfacial tension is a typical profile of a surfactant. The stabilized interfacial tension of the P(VP-APS)(100/0) solution of the present invention is at a level of 70 dyne/cm, whereas the stabilized interfacial tension of the P(VP-APS)(98/2) solution of the present invention is 64.5 dyne/cm level is found to be smaller. This means that the surface activity of P(VP-APS)(98/2) is higher than that of the homopolymer P(VP-APS)(100/0. VP is a hydrophilic monomer and APS is a hydrophobic monomer, so VP When APS and APS form a copolymer, an amphiphilic and surface active copolymer is formed, so P(VP-APS) (98/2) of the present invention has a more surface activity than P(VP-APS) (100/0) is considered to be higher.

It was confirmed that the interfacial tension profile of the Oxi-P(VP-APS)(98/2) solution of the present invention was similar to that of the P(VP-APS)(98/2) solution. However, the Oxi-P(VP-APS)(98/2) solution had a plateau interfacial tension of 67.1 dyne/cm, which was significantly higher than that of the P(VP-APS)(98/2) solution, 70 dyne/cm. Confirmed. The above results show that the surface activity of the H ₂ O ₂ treated copolymer, Oxi-P(VP-APS) (98/2), is less than that of the non-oxidized copolymer, P(VP-APS) (98/2). it means. As shown in FIG. 3 , the sulfide of APS in the copolymer composed of VP and APS is oxidized to sulfone by H ₂ O ₂ treatment, and the oxidation reduces the hydrophobicity of APS, thereby reducing the amphipathic properties of the copolymer. . Therefore, it is determined that the surface activity of Oxi-P(VP-APS) 98/2 is decreased because the sulfide of APS is oxidized to sulfone.

It was confirmed that the interfacial tension of the P(VP-APS) (97.5/2.5) solution of the present invention also decreased in an L-shaped saturation manner. The plateau interfacial tension of the P(VP-APS) (97.5/2.5) solution of the present invention is 62.3 dyne/cm, which is significantly lower than that of the P(VP-APS) (98/2) solution of 64.5 dyne/cm is confirmed, which means that the surface activity of P(VP-APS) (97.5/2.5) is higher than that of P(VP-APS) (98/2). The APS content of P(VP-APS) (97.5/2.5) is 3.55%, which is higher than the APS content of 3.39% of P(VP-APS) (98/2), so it is judged that the amphiphilicity of the copolymer is stronger. Like the P(VP-APS)(98/2) solution, it was confirmed that the plateau interfacial tension of the Oxi-P(VP-APS)(97.5/2.5) solution was further increased, because the surface activity was decreased due to the oxidation treatment. is judged as For example, the plateau interfacial tension of Oxi-P(VP-APS) (97.5/2.5) was 63.6 dyne/cm, whereas that of P(VP-APS) (97.5/2.5) was 62.3 dyne/cm. found to be significantly higher. This means that the oxidation of APS contained in P(VP-APS) (97.5/2.5) was responsible for the decrease in surface activity.

The P(VP-APS)(96/4) solution also showed an L-shaped interfacial tension profile and showed the lowest interfacial tension among the copolymer solutions. This means that the P(VP-APS) (96/4) has the highest surface activity, which means that P(VP-APS) (96/4) has the highest APS content of 4.8%, showing the strongest amphipathic properties. supported by the results of having Oxi-P (VP-APS) (96/4) solution also increased the interfacial tension was confirmed to decrease the surface activity. Specifically, the minimum interfacial tension of the Oxi-P(VP-APS)(96/4) solution was 61.5 dyne/cm, which was significantly higher than that of the P(VP-APS)(96/4) solution of 57.0 dyne/cm. was found to be high.

2.5. Results of stability analysis of emulsion

Panel (A) of Figure 6 uses mineral oil as an oil phase and distilled water as a water phase, but P (VP-APS) (100/0), P (VP-APS) of the present invention Droplet diameter over time of O/W emulsions stabilized using (98/2), P(VP-APS)(97.5/2.5) and P(VP-APS)(96/4) as emulsifiers Shows the result of measuring change. As a result of the experiment, it was confirmed that the droplet diameter of the O/W emulsion (Comparative Example 2) containing the P(VP-APS)(100/0) emulsifier rapidly increased from 2㎛ to 55㎛ for 24 hours, and after 24 hours, the droplet diameter Almost no increase in diameter was found. The rapid increase in the droplet diameter means that the oil droplets were fused for a short period of time. According to the result of FIG. 5, P(VP-APS) (100/0) is a homopolymer of VP, and it is confirmed that it has low surface activity due to weak amphipathic properties. Therefore, when a homopolymer such as P(VP-APS) (100/0) is used as a stabilizer (emulsifier), it is determined that the O/W interfacial energy cannot be reduced and thus the oil droplets cannot be stabilized.

In contrast, the increase in droplet diameter of the emulsion containing the P(VP-APS)(98/2) emulsifier (Example 4) proceeded much more slowly than the emulsion containing the P(VP-APS)(100/0) emulsifier. was confirmed to be Specifically, the droplet diameter of the emulsion containing P(VP-APS)(98/2) emulsifier slowly increased from 4㎛ to 31㎛ for 336 hours. According to the results of FIG. 5 , it is confirmed that the surface activity of P(VP-APS) (98/2) is significantly higher than that of P(VP-APS) (100/0). Therefore, when P(VP-APS) (98/2) is used as an emulsifier, it reduces the air/water interface energy and stabilizes the droplets more effectively. The droplet diameter increase of the emulsion containing P(VP-APS) (97.5/2.5) emulsifier (Example 5) increased slowly from 3 μm to 28 μm over 336 hours, and P(VP-APS) (96/4) emulsifier It was confirmed that the increase in the droplet diameter of the emulsion containing Emulsion (Example 6) slowly increased from 3 μm to 16 μm for 336 hours.

In summary, the rate of increase in the droplet diameter of the emulsion using the homopolymer or copolymer of the present invention as an emulsifier is P(VP-APS)(100/0) Emulsion containing emulsifier > P(VP-APS)(98/2) emulsifier Emulsions with > P(VP-APS) (97.5/2.5) Emulsions with emulsifiers > P(VP-APS) (96/4) Emulsions with emulsifiers > P(VP-APS) (100/0) It is confirmed that the emulsion containing the emulsifier is in order. Thus, the efficacy of the homopolymer or copolymer of the present invention to stabilize droplets as an emulsifier is P(VP-APS) (94/4) > P(VP-APS) (97.5/2.5) > P(VP-APS) (98 /2) > P(VP-APS)(100/0). In general, the higher the surfactant, the higher the droplet stabilization efficacy of the surfactant. According to the results of Figure 5, the surface activity of the homopolymer or copolymer of the present invention is P(VP-APS) (96/4) > P(VP-APS) (97.5/2.5) > P(VP-APS) ( 98/2) > P(VP-APS)(100/0).

Panel (B) of Figure 6 uses mineral oil as an oil phase and a 10% H ₂ O ₂ solution as a water phase, and P(VP-APS) (100/0) of the present invention (100/0), Time dependence of O/W emulsions stabilized using P(VP-APS)(98/2), P(VP-APS)(97.5/2.5) or P(VP-APS)(96/4) as emulsifiers The measurement result of the droplet diameter change is shown. The panel (B) of FIG. 6 uses a 10% H ₂ O ₂ solution as an aqueous phase, so P(VP-APS)(100/0), P(VP-APS)(98/2), P added as an emulsifier (VP-APS) (97.5/2.5) or P(VP-APS) (96/4) exists as an oxidized form.

As in the case of using distilled water as the aqueous phase, the droplet diameter of the emulsion (Example 2-1) containing Oxi-P (VP-APS) (100/0) as an emulsifier is due to the low stabilization efficacy of P (VP-APS). As a result, it was confirmed that the droplet diameter rapidly increased from 2 μm to 51 μm in 24 hours. The droplet diameter of the emulsion containing Oxi-P(VP-APS) (98/2) (98/2) as an emulsifier (Example 4-1) slowly increased from 2 μm to 16 μm during the first 170 hours, and then rapidly increased to 73 μm during the rest of the period. increased. In addition, the droplet diameter of the emulsion (Example 5-1) containing Oxi-P (VP-APS) (97.5/2.5) as an emulsifier is the emulsion containing Oxi-P (VP-APS) (98/2) as an emulsifier. and the droplet diameter increase profile was almost identical to that of the emulsion containing Oxi-P(VP-APS) (98/2) as an emulsifier.

The droplet diameter of the emulsion (Example 6-1) containing Oxi-P (VP-APS) (96/4) as an emulsifier is the emulsion containing Ox-P (VP-APS) (98/2) as an emulsifier. and Oxi-P (VP-APS) (97.5/2.5) as an emulsifier increased in a pattern similar to that of the emulsifier, but the rate of increase was the emulsion containing Oxi-P (VP-APS) (98/2) as an emulsifier. and Oxi-P(VP-APS) (97.5/2.5) as an emulsifier. The results show that the content of APS contained in P(VP-APS) (96/4) is higher than the content of APS contained in P(VP-APS) (98/2) and P(VP-APS) (97.5/2.5). It is determined that this is because it has a higher interfacial activity (see FIG. 5). The droplet diameter increase rate of the emulsion prepared by using the H ₂ O ₂ solution as the aqueous phase was confirmed to be higher than that of the emulsion prepared using distilled water (see FIG. 6 ). When the H ₂ O ₂ solution is treated, the sulfoxide residue of the APS contained in the copolymer is oxidized to sulfone, so that the surface activity of the copolymer is greatly reduced (see FIGS. 3 and 5 ). Therefore, when an emulsion is prepared using the copolymer of the present invention and a H ₂ O ₂ solution, the copolymer is oxidized, so it will show lower surface activity than the copolymer contained in the emulsion prepared using the copolymer of the present invention and distilled water. is judged to be The above result explains why the emulsion prepared using the H ₂ O ₂ solution is unstable than the emulsion prepared using distilled water and shows a higher droplet diameter increase rate.

Panel (A) of Figure 7 uses mineral oil as an oil phase and distilled water as a water phase (water pahse) of the present invention P (VP-APS) (100/0), P (VP-APS) (98/2), P(VP-APS) (97.5/2.5) and P (VP-APS) (96/4) were used as emulsifiers to evaluate the stability (%) of the O/W emulsion stabilized. show It is confirmed that the stability (%) of the emulsion (Comparative Example 2) containing P (VP-APS) (100/0) as an emulsifier fell very rapidly to 0% in 48 hours due to the low surfactant activity of the homopolymer. . Since the emulsion containing P(VP-APS) (100/0) as an emulsifier could not stabilize the oil droplets, fusion occurred easily and it is judged that it led to rapid phase separation, that is, a decrease in stability. Emulsions containing P(VP-APS) (98/2) as emulsifiers (Example 4), emulsions containing P(VP-APS) (97.5/2.5) as emulsifiers (Example 5) and P(VP- The emulsion (Example 6) containing APS) (96/4) as an emulsifier gradually decreased in stability and reached 0% after 650 hours. It was confirmed that P(VP-APS)(a/b) had a surface activity, and it was confirmed that the copolyer stabilized oil droplets more effectively than the homopolyer (see FIGS. 5 and 6 ). The above results explain why the stability of emulsions stabilized with copolymers is higher than that of emulsions stabilized with homopolymers.

Considering the slope of the curve shown in Fig. 7, it is determined that the stability of the emulsion containing the copolymer of the present invention is in the following order: Emulsion containing P(VP-APS) (96/4) as an emulsifier > P Emulsion with (VP-APS) (97.5/2.5) as emulsifier > Emulsion with P(VP-APS) (98/2) as emulsifier > With P(VP-APS) (100/0) as emulsifier emulsion that does. As a result of the analysis, it was confirmed that the emulsion stability evaluated based on the phase separation of the emulsion containing the copolymer of the present invention and the stability evaluated based on the fusion of oil droplets were in the same order (panel (A of FIG. 6) and FIG. 7 see panel (A)).

Panel (B) of Figure 7 uses mineral oil as an oil phase and H ₂ O ₂ solution as an aqueous phase, and P(VP-APS)(100/0), P(VP) of the present invention Evaluate the stability (%) of O/W emulsions stabilized using -APS)(98/2), P(VP-APS)(97.5/2.5) and P(VP-APS)(96/4) as emulsifiers show one result. The stability of the emulsion is determined by using distilled water as the aqueous phase, P(VP-APS)(100/0), P(VP-APS)(98/2), P(VP-APS)(97.5/2.5), or P(VP -APS) (96/4) was confirmed to show a similar pattern to the stability evaluation results of the O/W emulsion. However, it was confirmed that the stability of the emulsion using the H ₂ O ₂ solution decreased more rapidly than the emulsion using distilled water. Specifically, while it was confirmed that the emulsion containing distilled water and P(VP-APS)(98/2) had decreased stability to 45% after 350 hours, H ₂ O ₂ as an aqueous phase and P(VP) It was confirmed that the emulsion (Example 4-1) containing -APS) (98/2) had decreased stability to 0% after 350 hours. As described above, using H ₂ O ₂ solution and emulsion containing P(VP-APS)(a/b), the sulfide of APS contained in P(VP-APS)(a/b) is sulfone oxidized to lower the surface activity and droplet stabilization ability of the copolymer, so coalescence and phase separation of the droplets are induced.

3. Conclusion

The oxidation responsive emulsions of the present invention are prepared using an oxidizable copolymer such as P(VP-APS)(a/b) as the emulsifier. When the emulsion containing P(VP-APS)(a/b) of the present invention as an emulsifier is exposed to an oxidizing environment, the APS contained in P(VP-APS)(a/b) is oxidized, resulting in improved surface activity and droplet stabilization ability. As it is lowered, coalescence of droplets and phase separation are induced.

As a result of hydrogen nuclear magnetic resonance and X-ray photoelectron spectroscopy analysis, it was confirmed that the sulfide of APS was oxidized to sulfone as a result of oxidation treatment using H ₂ O ₂ . Through UV spectroscopy and tensiometer studies, it was confirmed that the amphiphilic properties and surface activity of the copolymer were significantly weakened by the oxidizing agent. The destabilization of the emulsion stabilized with P(VP-APS)(a/b) was accelerated when a H ₂ O ₂ solution (10%, v/v) was used as the aqueous phase, which resulted in the weakened surfactant activity due to oxidation of APS. is considered to be due to

When the P(VP-APS)(a/b) of the present invention is used as an oxidizable emulsifier, an O/W emulsion that can be easily demulsified as needed can be prepared. The O/W emulsion prepared by using P(VP-APS)(a/b) of the present invention as an emulsifier decreases amphiphilicity and surface activity when exposed to an oxidizing environment, thereby reducing the stabilization ability of oil droplets. As enemies coalesce, more phase separation occurs and they are released. Therefore, when an active ingredient is included in the oil droplet or the oil droplet is replaced with a hydrophobic active ingredient, it is possible to prepare an O/W emulsion that releases the sexual active ingredient in response to oxidation.

Specific examples described herein are meant to represent preferred embodiments or examples of the present invention, and the scope of the present invention is not limited thereby. It will be apparent to those skilled in the art that modifications and other uses of the present invention do not depart from the scope of the invention as set forth in the claims herein.

Claims (7)

An oxidation-responsive emulsion comprising poly(vinyl pyrrolidone-co-allyl phenyl sulfide) as an emulsifier.
The method of claim 1, wherein the poly(vinyl pyrrolidone-co-allyl phenyl sulfide) (poly (vinyl pyrrolidone-co-allyl phenyl sulfide) is an emulsifier and is amphiphilic and in an oxidizing environment, the allylphenylsulfide residue is allylphenylsulfone. Oxidation-responsive emulsion, characterized in that the fusion of droplets and phase separation are induced because the amphiphilicity is reduced by oxidation to a residue.
The oxidation-responsive emulsion according to claim 2, wherein the poly(vinylpyrrolidone-co-allylphenylsulfide) contains a vinylpyrrolidone monomer and an allylphenylsulfide monomer in a molar ratio of 100:3 to 10.
[4] The oxidation-responsive emulsion according to claim 3, wherein the poly(vinylpyrrolidone-co-allylphenylsulfide) has a stable interfacial tension of 55 to 66 dyne/cm in an aqueous phase.
The oxidation responsive emulsion of claim 1, wherein the oxidation responsive emulsion comprises a hydrophilic solution comprising 0.5% poly(vinylpyrrolidone-co-allylphenylsulfide) emulsifier as water phase and oil as oil phase. Oxidation-responsive emulsion, characterized in that it is an oil in water (O/W) type emulsion containing
[Claim 6] The oxidation-responsive emulsion according to claim 5, wherein, in the case of a reducing environment, the diameter of oil droplets is at a level of 3 to 4 μm, and increases to 30 to 15 to 35 μm after 300 hours, and in an oxidizing environment, the diameter of oil droplets is 3 Oxidation-responsive emulsion, characterized in that the level of ∼ 4 µm increases to 30 to 40 µm to 100 µm after 300 hours.
The oxidation responsiveness of claim 5, wherein the oxidation responsive emulsion has a phase separation stability (stability, 50%) in an oxidizing environment is reduced to a level of 55 to 80% of a phase separation stability (stability, 50%) in a reducing environment. emulsion.

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