KR101867210B1

KR101867210B1 - amphiphilic triblock copolymer surfactants with enhanced emulsion stability and the composition comprising thereof

Info

Publication number: KR101867210B1
Application number: KR1020170002993A
Authority: KR
Inventors: 고정남; 김진국; 김희식; 김영희; 김진웅; 이진용
Original assignee: 에스케이바이오랜드 주식회사
Priority date: 2017-01-09
Filing date: 2017-01-09
Publication date: 2018-06-12

Abstract

The present invention relates to a method for producing a hydrophilic polymer, wherein methoxypolyethylene glycol (A) as a hydrophilic polymer and polycaprolactone (B) as a hydrophobic polymer are linked to each other via a urethane linkage group derived from a cyclic diisocyanate compound, And a composition containing the same. BACKGROUND OF THE INVENTION [0002] The present invention relates to an amphipathic polymer surfactant and a composition containing the same.

Description

[0001] The present invention relates to an amphiphilic polymer surfactant and a composition containing the amphiphilic triblock copolymer surfactant,

The present invention relates to a water-insoluble polymer which is composed of methoxypolyethylene glycol (A) as a hydrophilic polymer and polycaprolactone (B) as a hydrophobic polymer, which are linked to each other via a urethane linkage group derived from a cyclic diisocyanate compound, Block type (ABA) amphipathic polymer surfactant and a composition containing the same.

Surfactants are typically amphiphilic compounds that have two opposing functional groups, one hydrophilic group and one hydrophobic group, in one molecule. They are adsorbed at the interface of different phases and have surface tension, emulsion, refers to a class of materials exhibiting properties such as dispersion, wettability, foaming, defoaming and solubilization. Because of these unique and diverse properties, surfactants are widely used in various fields such as textile, cosmetics, food, medicine industry.

In particular, in cosmetics and pharmaceuticals, an amphipathic polymer surfactant is used as an insoluble active ingredient that is insoluble in water or other solvents, thereby protecting the active ingredient from external conditions such as light, heat, air or physiologically active ingredients Thereby producing a highly stable product. In general, active ingredients having skin whitening, wrinkle reduction and antioxidative effects contained in functional cosmetics are poor in stability against light, heat or air, so that the central part of the particles can serve as a reservoir through the above- It is produced in the form of polymeric micelles or nano emulsions to enhance the stability of the active ingredient.

Recently, a technique of producing a block polymer surfactant using a biodegradable polymer has attracted attention, and since it has high skin affinity and is easy to be absorbed into skin, it can be developed as a transdermal absorption transducer, and the weight of a hydrophilic and hydrophobic block Ratio, and the molecular weight of the triple block polymer, it is possible to develop new type cosmetics through application of cosmetic raw materials, surfactant, transdermal absorption promoter, etc., and various technologies using the same are being developed.

Polylactide, polycaprolactone, and poly (lactide-co-glycolide) are used as biodegradable polymers. Most amphipathic polymer surfactants are prepared by using polyethylene oxide as the hydrophilic moiety and aliphatic polyester, polystyrene, and polypropylene oxide as the hydrophobic moieties. Generally, the reaction is carried out through initiation and growth processes, Polymerization reaction in which a chain transfer or a stop reaction does not occur and growth activity is retained for a long time even after polymerization.

In this regard, Korean Patent Registration No. 10-0967114 discloses an emulsion-type external preparation for skin using amphiphilic polymers having only polycaprolactone as a hydrophobic segment, and Korean Patent Publication No. 10-1054731 discloses a composition for external application Discloses a composition for external application for skin prepared by using an amphiphilic polymer having a self-assembly of a block copolymer (AB) prepared by bonding a polyester polymer (A) and a hydrophilic polymer (B).

In the above-mentioned prior art, the hydrophobic block forms a thin crystalline film at the interface while the hydrophobic block is oriented toward the oily phase and the hydrophilic block is structurally stabilized at the water-water interface toward the water phase Therefore, when strong external physical stimulation is applied, the membrane is broken and the freeze-thaw stability is very low.

In addition, there is a problem in that the amphiphilic block polymer surfactant prepared by ring-opening polymerization from cyclic ether or cyclic amide (lactam) or a complex polymer polymerization process of several stages is produced. The degree of dispersion during synthesis is not constant and since the effect of oxygen can not be exerted during the synthesis process, there is a problem that the surfactant performance of the amphiphilic block polymer surfactant is not consistently expressed.

Accordingly, the inventors of the present invention intend to develop an amphiphilic surfactant in which a linear hydrophobic block does not form a thin crystalline film at the water-water interface, and it has been proposed to remove an existing radical polymerization and to use a simple condensation reaction We propose a new method for preparing amphipathic triblock polymer with improved stability.

Korean Registered Patent No. 10-0967114 (issued on July 5, 2010) Korean Registered Patent No. 10-1054731 (issued on August 5, 2011)

Disclosure of Invention Technical Problem [8] In order to solve the above problems, the present invention has been made to solve the above-mentioned problems, and has as its object to provide a water- (ABA) amphiphilic polymer surfactant which is connected to each other and which is more excellent in emulsion stability, and a composition containing the same.

In order to achieve the above object, the present invention provides a process for producing a polyurethane foam, which comprises reacting methoxypolyethylene glycol (A) as a hydrophilic polymer and polycaprolactone (B) as a hydrophobic polymer via a urethane linkage group derived from a cyclic diisocyanate compound The present invention provides a triple block type amphiphilic polymer surfactant having improved emulsion stability, which is a triblock copolymer (ABA) connected to each other.

The diisocyanate compound may be isophorone diisocyanate.

The tri-block copolymer (A-B-A) may have a molecular weight ratio (A: B) of 1: 0.1 to 2:10.

The triblock copolymer may have a structure represented by the following formula (1).

[Chemical Formula 1]

(Wherein m is an integer of 10 to 350 and n is an integer of 2 to 100).

The present invention also provides a cosmetic or pharmaceutical composition comprising the amphiphilic polymer surfactant.

The present invention also provides a process for preparing a PCL-NCO intermediate having urethane groups introduced therein by reacting polycaprolactone with a diisocyanate compound in the form of a ring and a tin (Sn) catalyst; And

And a second step of reacting the PCL-NCO intermediate with methoxypolyethylene glycol and a tin (Sn) catalyst to prepare a triblock copolymer having a hydrophilic group introduced thereinto. There is provided a process for preparing an amphiphilic polymer surfactant in an improved triblock form.

The diisocyanate compound may be isophorone diisocyanate.

The tin (Sn) catalyst may be dibutyltin dilaurate.

The reaction temperature of the first step and the second step may be 20 to 70 ° C.

The present invention also provides an amphiphilic polymer surfactant prepared by the above method.

The amphiphilic polymer surfactant of the triple block type (ABA) having improved stability according to the present invention is obtained by reacting methoxypolyethylene glycol (A) as a hydrophilic polymer and polycaprolactone (B) as a hydrophobic polymer in a cyclic diisocyanate compound Linking group via urethane linkage group, and thus the emulsion stability is more excellent.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic view illustrating a method for producing an amphipathic polymeric surfactant according to an embodiment of the present invention; FIG.
Figure 2 shows a double block polymer AB.
3 is a view showing a triblock polymer ABA.
4 is a view showing an oil-water interface of the triblock polymer ABA.
5 is a graph showing the measurement result of the droplet stability of an emulsion containing an amphiphilic polymer surfactant according to an embodiment of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described in detail, and a detailed description of known functions and configurations that may unnecessarily obscure the gist of the present invention will be omitted.

The diisocyanate compound may be isophorone diisocyanate.

Considering the characteristics of the amphiphilic polymer surfactant, the number average molecular weight ratio of the hydrophilic polymer, methoxypolyethylene glycol (A) and the hydrophobic polymer, polycaprolactone (B) can be 1: 0.1 to 2:10, In detail, it is preferable that the number average molecular weight ratio of the constituent components of the triblock copolymer (ABA) is in the range of 1: 0.1: 1 to 1: 10: 1. The above ratio sufficiently satisfies solubility in water of the triblock copolymer (A-B-A) prepared according to one embodiment of the present invention, and sufficiently secures the hydrophobicity of the core to facilitate collection of the active ingredient.

In addition, the tri-block copolymer (A-B-A) may be one in which two methoxy polyethylene glycols (A) are linked by a urethane bond to the terminal hydroxyl groups of the polycaprolactone (B), which is a hydrophobic polymer.

[Chemical Formula 1]

(Wherein m is an integer of 10 to 350 and n is an integer of 2 to 100).

The above-mentioned triblock copolymer (ABA) is not particularly limited in the formulation, and it can be used in the form of hair tonic, scalp treatment, hair cream, general ointment, softening lotion, convergent lotion, Body lotion, body cream, body oil, body essence, makeup base, foundation, hair dye, shampoo, rinse, body cleanser, lotion, gel, patch or spray. It is possible to formulate it.

In addition, the above-mentioned triblock copolymer (ABA) can be used in the form of collecting various active ingredients which can be solubilized therein. There is no particular limitation on such active ingredient, but for example, catechin, isoflavone, danazol, haloperidol, furosemide, isosorbide dinitrate, chloramfenicol, sulfamethoxazole, caffeine, cymidine cimethidine, diclofenac Na, ursolic acid, oleanolic acid, rosmarinic acid, glabridin, polyphenol, esculin, Ginsenosides, centella asiatica, asiaticoside, farnesol, resveratrol, vineatrol, vitamin A (retinol), vitamins A, B ₁ (thiam ine), vitamin B ₂ (riboflavin), vitamin B ₃ (niacin), vitamin B ₅ (pantothenicacid), vitamin B ₆ (pyridoxine), vitamin C (ascorbic acid), vitamin D (calciferol) and vitamin E (tocopherol) Can be used.

The kind and content of the active ingredient can be suitably selected and used by those skilled in the art depending on the purpose, and is not particularly limited, but it is generally preferable to use 1 to 40% by weight based on the total weight of the triblock block copolymer. That is, the content of the above-mentioned active ingredient should be 40 wt% or less with respect to the total weight of the triblock block copolymer. If it exceeds 40 wt%, the effective ingredient may not be effectively collected and the effective ingredient may be outflowed and aggregated or denatured. It is more preferable to use the range.

The cosmetic or pharmaceutical composition may be prepared by dissolving the ampholytic polymeric surfactant according to an embodiment of the present invention in an organic solvent, and then adding water to disperse and emulsify the mixture. An ultrasonic wave irradiator And a nano-emulsion prepared by dissolving the nano-emulsion.

The nano emulsion may comprise 1 to 30 parts by weight of an amphiphilic polymer surfactant, 1 to 20 parts by weight of an organic solvent, and 1 to 20 parts by weight of an oil in 100 parts by weight of water.

The amount of the oil is not particularly limited as long as it is usually used in the production of the emulsion composition. If the content of the oil is less than 1 part by weight, there is a problem that the feeling of moisturization and feeling of use are lowered. When the amount of the oil is more than 20 parts by weight, It is not preferable because there is a problem of falling.

If the content of the amphiphilic polymer surfactant is less than 1 part by weight, the emulsion particles become too large and the stability of emulsification becomes poor. When the content of the ampholytic polymer surfactant is more than 30 parts by weight, the mixing ratio is not suitable and the viscosity becomes too high. Can not do it.

When the content of the organic solvent is out of the above range, it is difficult to obtain a stable nano emulsion, which is not preferable.

When an amphiphilic polymer surfactant prepared in one embodiment of the present invention is used to make a nanoemulsion in an aqueous solution, organic solvents that can be used include, for example, acetone, dimethylsulfoxide, dimethylformamide, N-methylpiperazine But are not limited to, acetonitrile, methyl ethyl ketone, methylene chloride, chloroform, methanol, ethanol, ethyl ether, diethyl ether, hexane, petroleum ether and butylene glycol. But is not limited thereto.

The nanoemulsion can be used in various cosmetic compositions such as creams, milky lotions, lotions and the like as well as the product itself because the active ingredient added to the external preparation for skin does not directly contact the emulsified product or the skin product. The nanoemulsion prepared as described above was found to retain the effect of the collected active ingredient without being denatured, and in particular, the emulsion stability of the formulation was excellent, and separation phenomenon of oil or water did not appear.

The average particle diameter of the prepared nanoemulsion may be 1 to 1,000 nanometers, more preferably 10 to 500 nanometers.

When the nanoemulsion is produced by collecting the active ingredient according to the above-described production method, the active ingredient is collected in the hydrophobic core portion and the hydrophilic polymer chain is oriented on the surface, and is dispersed stably in the aqueous phase.

The diisocyanate compound may be isophorone diisocyanate.

The tin (Sn) catalyst may be dibutyltin dilaurate.

The reaction temperature in the first step and the second step may be 20 to 70 ° C, preferably 30 to 60 ° C, more preferably 40 to 50 ° C. If the temperature is out of the above range, have.

As the organic solvent, methylene chloride, chloroform, tetrahydrofuran, ethanol, acetone, toluene and the like can be used, but toluene is more preferably used.

The particles thus dispersed are small in size, excellent in colloidal stability, can be used for various formulations, and have excellent skin absorption. Furthermore, the amphiphilic polymer surfactant of the present invention contained in the nanoemulsion is a biocompatible material and is biodegraded safely in vivo, thus being harmless to the human body. In addition, the active ingredient is not directly contacted with the emulsified product or the skin product, and the product itself is stable, so that it can be used in various forms of cosmetic composition such as cream, milky lotion, lotion and the like.

The triblock copolymer (ABA) of the present invention is composed of a hydrophilic block (A) and a hydrophobic block (B), and the hydrophobic block portion is located in the core to fill the space and the hydrophilic block portion It is possible to achieve a much more stable interface by sufficiently filling the opposite interface.

Considering the characteristics of the amphiphilic polymer surfactant, the number average molecular weight ratio of the hydrophilic polymer, methoxypolyethylene glycol (A) and the hydrophobic polymer, polycaprolactone (B) can be 1: 0.1 to 2:10, In detail, it is preferable that the number average molecular weight ratio of the constituent components of the triblock copolymer (ABA) is in the range of 1: 0.1: 1 to 1: 10: 1. The above ratio satisfies not only the solubility of the triblock copolymer (A-B-A) prepared according to one embodiment of the present invention in water but also the hydrophobicity of the core sufficiently and the collection of the effective component is easier.

Hereinafter, the present invention will be described in more detail with reference to examples, but these examples are for illustrative purposes only and are not intended to limit the scope of protection of the present invention.

< Example 1>

IPDI linked mPEG- b - PCL - b -mPEG Tri-Blocked Polymer Surfactant

In a 500 mL glass flask in an argon atmosphere, 25 mL of toluene, 2.2 g of isophorone diisocyanate (IPDI) and 0.3 g of dibutyltin dilaurate were added, and the mixture was stirred at 45 캜. Next, 5 g of polycaprolactone (Mn = 10,000) was dissolved in 50 mL of toluene, and then added dropwise to the flask and stirred at 45 DEG C for 6 hours. After the temperature of the reaction solution was lowered to room temperature, 350 mL of petroleum ether was added to precipitate the reaction product. The precipitate was collected by filtration and vacuum dried to obtain 4.1 g of PCL-NCO. 4.1 g of PCL-NCO synthesized in the above and 0.3 g of dibutyltin dilaurate were dissolved in 50 mL of toluene, and 4.1 g of methoxypolyethylene glycol (Mn = 5,000) was added to 40 mL of toluene And the mixture was stirred at 45 ° C for 6 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and 300 mL of petroleum ether was added to precipitate the reaction product. The precipitate was collected by filtration and vacuum dried to obtain an IPDI linked mPEG- b -PCL- b- mPEG tri-block polymer. The obtained IPDI-linked mPEG- b- PCL- b- mPEG triblock polymer was found to have an Mn of 19,500 by molecular weight analysis (GPC) and a molecular weight ratio of about 1: 2: 1 by nuclear magnetic resonance analysis.

Nano emulsion Produce

IPDI linked mPEG- b- PCL- b- mPEG triblock polymer was completely dissolved in 10 g of butylene glycol (1,3-BG) at high temperature (80 ° C). Then, 100 g of water was added, and the mixture was dispersed for 1 minute using a homogenizer. 10 g of olive oil was added and emulsified with a homogenizer. In order to reduce the size of the emulsion particles, a nano-emulsion composition containing IPDI-linked mPEG- b- PCL- b- mPEG triblock polymer was prepared by irradiating ultrasonic wave for 5 minutes using a probe type ultrasonic wave irradiator.

< Comparative Example 1>

HMDI linked PEG- b -PCL- b -PEG Preparation of Trimeric Block Polymer Surfactant

25 mL of toluene, 2.9 g of hexamethylene diisocyanate (HMDI) and 0.3 g of dibutyltin dilaurate were added to a 500 mL glass flask in an argon atmosphere, and the mixture was stirred at 45 캜. Next, 5 g of polycaprolactone (Mn = 10,000) was dissolved in 50 mL of toluene, and then added dropwise to the flask and stirred at 45 DEG C for 6 hours. After the temperature of the reaction solution was lowered to room temperature, 350 mL of petroleum ether was added to precipitate the reaction product. The precipitate was collected by filtration and vacuum dried to obtain 3.9 g of PCL-NCO. Then, 3.9 g of PCL-NCO synthesized in the above and 0.3 g of dibutyltin dilaurate were dissolved in 50 mL of toluene and stirred at 45 ° C. in 40 mL of toluene with 3.9 g of polyethylene glycol (Mn = 5,000) And the mixture was stirred at 45 ° C for 6 hours. After the reaction was completed, the reaction mixture was cooled to room temperature and 300 mL of petroleum ether was added to precipitate the reaction product. The precipitate was collected by filtration and vacuum dried to obtain HMDI linked PEG- b -PCL- b- PEG tri-block polymer. The obtained HMDI-linked PEG- b- PCL- b- PEG triblock polymer was Mn 18,900 by molecular weight analysis (GPC) and its molecular weight ratio was confirmed to be about 1: 2: 1 by nuclear magnetic resonance analysis.

Nano emulsion manufacturing

HMDI-linked PEG- b- PCL- b- PEG triblock polymer was completely dissolved in 10 g of butylene glycol (1,3-BG) at high temperature (80 ° C). Then, 100 g of water was added, and the mixture was dispersed for 1 minute using a homogenizer. 10 g of olive oil was added and emulsified with a homogenizer. In order to reduce the size of the emulsion droplet, a nano-emulsion composition containing HMDI-linked PEG- b- PCL- b- PEG triblock polymer was prepared by irradiating ultrasonic wave for 5 minutes using a probe-type ultrasonic wave irradiator.

&Lt; Comparative Example 2 &

HMDI linked mPEG-PCL- b -Preparation of PCL-mPEG Triblock Polymer Surfactant

10 g of methoxypolyethylene glycol (Mn = 5,000), 10 g of epsilon caprolactone and 0.2 g of octanoic acid tin catalyst were placed in a 500 mL glass flask in an argon atmosphere, and the mixture was stirred at 120 ° C for 6 hours. The reaction solution was cooled to room temperature and dissolved in 60 mL of methylene chloride. The reaction product was precipitated with 180 mL of methanol. The precipitate was collected by filtration and vacuum dried to obtain 16 g of PEG- b- PCL. Then, 16 g of PEG- b- PCL synthesized in the above and 0.2 g of hexamethylene diisocyanate (HMDI) were introduced into an argon atmosphere and stirred at 80 ° C for 6 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, dissolved in 50 mL of methylene chloride, precipitated with 150 mL of excess methanol, and the precipitate was collected by filtration, dried under vacuum and connected with each other via a urethane linker derived from hexamethylene diisocyanate 12 g of HMDI linked mPEG-PCL- b -PCL-mPEG tri-block polymer was obtained. Molecular weight analysis (GPC) of the HMDI linked mPEG-PCL- b -PCL-mPEG triblock polymer showed Mn of 19,900 and molecular weight ratio of about 1: 2: 1 through nuclear magnetic resonance analysis.

Nano emulsion manufacturing

HMDI-linked mPEG-PCL- b -PCL-mPEG triblock polymer was completely dissolved in 10 g of butylene glycol (1,3-BG) at high temperature (80 ° C). Then, 100 g of water was added, and the mixture was dispersed for 1 minute using a homogenizer. 10 g of olive oil was added and emulsified with a homogenizer. In order to reduce the size of the emulsion particle, a nano-emulsion composition containing HMDI-linked mPEG-PCL- b -PCL-mPEG triblock polymer was prepared by irradiating ultrasonic wave for 5 minutes using a probe type ultrasonic wave irradiator.

< Comparative Example 3>

Preparation of mPEG-PCL Double Block Polymer Surfactant

10 g of methoxypolyethylene glycol (Mn = 5,000), 20 g of epsilon caprolactone and 0.2 g of octanoic acid tin catalyst were placed in a 500 mL glass flask in an argon atmosphere, and the mixture was stirred at 120 ° C for 6 hours. The reaction solution was cooled to room temperature and dissolved in 90 mL of methylene chloride. The reaction product was precipitated with 270 mL of methanol, and the precipitate was collected by filtration and vacuum-dried to obtain 24 g of mPEG-PCL double block polymer. Molecular weight analysis (GPC) of the mPEG-PCL double-block polymer showed Mn of 14,400, and it was confirmed by nuclear magnetic resonance analysis that the molecular weight ratio was about 1: 2.

Nano emulsion manufacturing

The mPEG-PCL double block polymer was completely dissolved in 10 g of butylene glycol (1,3-BG) at high temperature (80 ° C). Then, 100 g of water was added, and the mixture was dispersed for 1 minute using a homogenizer. 10 g of olive oil was added and emulsified with a homogenizer. In order to reduce the size of the emulsion particle, a nano-emulsion composition including an mPEG-PCL double block polymer was prepared by irradiating ultrasonic wave for 5 minutes using a probe type ultrasonic wave irradiator.

< Comparative Example 4>

IPDI linked PEG- b -PCL- b -PEG Preparation of Trimeric Block Polymer Surfactant

In a 500 mL glass flask in an argon atmosphere, 25 mL of toluene, 3.8 g of isophorone diisocyanate (IPDI) and 0.3 g of dibutyltin dilaurate were added, and the mixture was stirred at 45 캜. Next, 5 g of polycaprolactone (Mn = 10,000) was dissolved in 50 mL of toluene, and then added dropwise to the flask and stirred at 45 DEG C for 6 hours. After the temperature of the reaction solution was lowered to room temperature, 350 mL of petroleum ether was added to precipitate the reaction product. The precipitate was collected by filtration and vacuum dried to obtain 5.1 g of PCL-NCO. Thereafter, 5.1 g of PCL-NCO synthesized above and 0.3 g of dibutyltin dilaurate were dissolved in 50 mL of toluene, and while stirring at 45 캜, 5.1 g of polyethylene glycol (Mn = 5,000) was added to 40 mL of toluene And the mixture was stirred at 45 ° C for 6 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, and 300 mL of petroleum ether was added to precipitate the reaction product. The precipitate was filtered to obtain an IPDI-linked PEG- b -PCL- b -PEG 8.3 g of a triblock polymer was obtained. The obtained IPDI-linked PEG- b- PCL- b- PEG triblock polymer was Mn 19,300 as a result of molecular weight analysis (GPC) and confirmed by nuclear magnetic resonance analysis to have a molecular weight ratio of about 1: 2: 1.

Nano emulsion manufacturing

IPDI linked PEG- b- PCL- b- PEG The triblock polymer was completely dissolved in 10 g of butylene glycol (1,3-BG) at a high temperature (80 ° C). Then, 100 g of water was added, and the mixture was dispersed for 1 minute using a homogenizer. 10 g of olive oil was added and emulsified with a homogenizer. In order to reduce the size of the emulsion droplet, ultrasonic waves were irradiated for 5 minutes using a probe-type ultrasonic wave irradiator to obtain IPDI linked PEG- b- PCL- b- PEG A nanoemulsion composition comprising a triblock polymer was prepared.

< Comparative Example 5>

HMDI linked mPEG- b -PCL- b -mPEG Tri-Blocked Polymer Surfactant

In a 500 mL glass flask in an argon atmosphere, 25 mL of toluene, 1.7 g of hexamethylene diisocyanate (HMDI) and 0.3 g of dibutyltin dilaurate were added, and the mixture was stirred at 45 캜. Next, 5 g of polycaprolactone (Mn = 10,000) was dissolved in 50 mL of toluene, and then added dropwise to the flask and stirred at 45 DEG C for 6 hours. After the temperature of the reaction solution was lowered to room temperature, 350 mL of petroleum ether was added to precipitate the reaction product. The precipitate was collected by filtration and vacuum dried to obtain 3.0 g of PCL-NCO. 3.0 g of PCL-NCO synthesized above and 0.3 g of dibutyltin dilaurate were dissolved in 50 mL of toluene and stirred at 45 캜 in 3.0 g of methoxypolyethylene glycol (Mn = 5,000) in toluene And the mixture was stirred at 45 ° C for 6 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, and 300 mL of petroleum ether was added to precipitate the reaction product. The precipitate was collected by filtration and dried under vacuum to obtain HMDI linked mPEG- b -PCL- b- mPEG 5.5 g of a tri-block polymer was obtained. The obtained HMDI linked mPEG- b- PCL- b- mPEG Molecular weight analysis (GPC) revealed that the triple block polymer had an Mn of 19,200 and a molecular weight ratio of about 1: 2: 1 through nuclear magnetic resonance analysis.

Nano emulsion manufacturing

HMDI linked mPEG- b- PCL- b- mPEG The triblock polymer was completely dissolved in 10 g of butylene glycol (1,3-BG) at a high temperature (80 ° C). Then, 100 g of water was added, and the mixture was dispersed for 1 minute using a homogenizer. 10 g of olive oil was added and emulsified with a homogenizer. In order to reduce the size of the emulsion droplet, ultrasonic waves were irradiated for 5 minutes using a probe type ultrasonic wave irradiator to obtain HMDI linked mPEG- b- PCL- b- mPEG A nanoemulsion composition comprising a triblock polymer was prepared.

< Test Example 1: Confirmation of formulation stability>

The stability test of the nanoemulsion composition comprising the amphiphilic polymer surfactant prepared in Example 1 and Comparative Examples 1 to 3 was carried out. In order to test the stability of the formulation, a test was conducted at room temperature (25 ± 2 ° C), a cold temperature chamber (4 ± 2 ° C), a high temperature chamber (45 ± 2 ° C) and a freeze- 1 cycle), and the stability of each sample was tested after 7 days, 30 days and 60 days. The results are summarized in Table 1 below.

Condition Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 4 ℃ 1 day ◎ ◎ ◎ ◎ ◎ ◎ 7 days ◎ ◎ ◎ △ ◎ ◎ 30 days ◎ ○ ○ × ○ ○ 60 days ○ △ △ × ○ △ 25 ℃ 1 day ◎ ◎ ◎ ◎ ◎ ◎ 7 days ◎ ◎ ◎ ○ ◎ ◎ 30 days ◎ ◎ ○ × ◎ ◎ 60 days ◎ ○ △ × ○ ○ 45 ° C 1 day ◎ ◎ ◎ ◎ ◎ ◎ 7 days ◎ ◎ ◎ ○ ◎ ◎ 30 days ◎ ○ ○ × ○ ○ 60 days ○ △ △ × △ △ Cycle 1 day ◎ ◎ ◎ △ ◎ ◎ 7 days ◎ ◎ ○ × ◎ ◎ 30 days ○ ○ △ × ○ ○ 60 days △ × × × △ ×

◎: stable; No separation of oil or water

?: Relatively stable; Very little separation of oil or water

B: Relatively bad; Slightly separated oil or water

X: very bad; Oil or water is severely separated to form a layer

As shown in Table 2, the emulsion stability measured at 4 ° C, 25 ° C, 45 ° C and a cycle chamber was higher than that of Example 1 and Comparative Example 1, Comparative Example 2, Comparative Example 4 and Comparative Example 5 The stability of the emulsion composition was very poor. As a result, it was observed that the oil or water was severely separated to form a layer over time. As a result, it was confirmed that the stability was improved by forming a more stable interface with the triple block form.

The emulsion composition prepared in Example 1 and Comparative Example 1, Comparative Example 4 and Comparative Example 5, in which the number of urethane linking groups was 2, exhibited higher stability than the emulsion composition prepared in Comparative Example 2 in which the number of urethane linking groups was 1 , And it was confirmed that the more the number of urethane linking groups, the higher the stability.

As a result of comparison between Example 1 and Comparative Example 4 in which the number of urethane couplers was the same but hydrophilic groups were different, it was found that the emulsion composition of Comparative Example 4 prepared using polyethylene glycol was superior to the emulsion composition of Example 1 prepared using methoxypolyethylene glycol It has been observed that higher stability in the emulsion composition is observed because methoxypolyethylene glycol has a relatively high solubility in water and organic solvents.

As a result of comparison between Example 1 and Comparative Example 5 in which the structure of the urethane coupler was different, it was found that the structure of the urethane coupler in Example 1 was lower than that of the emulsion composition prepared in Comparative Example 5 using HMDI having a linear urethane linker structure It has been observed that in the emulsion composition prepared using the cyclic IPDI, separation of oil or water is hardly observed and that the IPDI is maintained for a longer period of time, thereby increasing the rigidity of the polymer chains in the cyclic fixed IPDI film formation It was confirmed that the stability was remarkably improved by minimizing the phenomenon of breaking or cracking of the external factor.

Finally, it was confirmed that the emulsion composition of Example 1 had the highest stability under various conditions.

< Test Example 2 : Amphibian Block polymer Containing Emulsion Droplet Stability measurement>

In order to measure the liquid stability of the emulsion containing the amphiphilic block polymer prepared in Example 1 and Comparative Examples 1 to 5, freeze-thaw cycling (1 cycle = 12h at -20 ℃, 12h at RT) method was used. cycle was performed up to 10 times, and the particle size was measured by using a Dynamic Light Scattering machine at the end of each cycle. The results are shown in FIG. 5 as a graph. In the figure, the hydrodynamic diameter of 0 indicates that the emulsion droplet was broken due to the occurrence of oil-water layer separation, and the particle size of the emulsion particle was not analyzed.

As shown in FIG. 5, in the case of the double-block type polymer surfactant prepared in Comparative Example 3, water-water phase separation or particle densification occurred in only one cycle, whereas in Example 1, Comparative Example 1 and Comparative Example 2 , And the emulsion compositions prepared in Comparative Example 4 and Comparative Example 5 were observed to maintain stability from a minimum of 6 cycles to a maximum of 10 cycles.

In addition, the emulsion compositions prepared in Example 1 and Comparative Example 1, Comparative Example 4 and Comparative Example 5, in which the number of urethane linking groups was relatively higher than that of the emulsion composition prepared in Comparative Example 2, maintained stability for 8 cycles and 10 cycles , And it was confirmed that there was a difference in stability depending on the number of urethane linking groups.

As a result of comparing the stability of Example 1 and Comparative Example 4 in which the number of urethane couplers was the same but hydrophilic groups were different, the emulsion composition prepared in Example 1 using methoxypolyethylene glycol showed 10 cycles It has been observed that high stability is maintained thereafter.

In addition, the stability of the urethane coupler of Example 1 and Comparative Example 5 was measured and compared with that of the emulsion composition prepared in Example 1 using IPDI in which the structure of the urethane linkage group was cyclic. High stability was observed, and finally, it was confirmed that the emulsion composition of Example 1 had the highest stability under various conditions.

The above results show that the stability can be different according to the area of the hydrophobic group forming the membrane and the ratio of the hydrophilic group constituting both the AB pattern double block polymer and the ABA pattern triple block polymer, and the AB double block Unlike polymer, ABA triblock polymer, which has relatively large area, seems to improve stability by forming more firm film.

In addition, in the case of the ABA pattern of the triple-block polymer, the stability may vary depending on the difference in the hydrophilic group. In the case of using methoxypolyethylene glycol, the solubility in water and the organic solvent is higher than that in the case of using polyethylene glycol. .

In addition, even in the case of the ABA patterned triblock polymer, stability can be improved in the interface depending on the structure and number of urethane. In the case of diisocyanate fixed in a ring form than in the case of linear diisocyanate, The stability is improved by minimizing the phenomenon that the external factors are released or broken.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the inventive concept as defined by the appended claims. It will be possible. The scope of the present invention is defined by the appended claims, and all differences within the scope of the claims are to be construed as being included in the present invention.

Claims

1. A ternary block copolymer (ABA) comprising a hydrophilic polymer, methoxypolyethylene glycol (A) and a hydrophobic polymer, polycaprolactone (B) linked together via a urethane linkage group derived from a cyclic diisocyanate compound, 1 < / RTI > of an amphiphilic polymer surfactant in the form of a triblock block having improved emulsion stability.
[Chemical Formula 1]

(Wherein m is an integer of 10 to 350 and n is an integer of 2 to 100).

The method according to claim 1,
Wherein the diisocyanate compound is isophorone diisocyanate.

The method according to claim 1,
Wherein the triblock copolymer (ABA) has a molecular weight ratio (A: B) of 1: 0.1 to 2:10.

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