WO2015065100A1

WO2015065100A1 - Spherical hydrogel particles using mpc and water-soluble crosslinking agent

Info

Publication number: WO2015065100A1
Application number: PCT/KR2014/010359
Authority: WO
Inventors: 김민아; 김도훈; 임형준; 남개원; 신송석
Original assignee: 주식회사 아모레퍼시픽
Priority date: 2013-10-31
Filing date: 2014-10-31
Publication date: 2015-05-07

Abstract

The present invention relates to spherical hydrogel particles of methacryloyl phosphoryl choline (MPC) and, more specifically, to hydrogel particles which are prepared in an aqueous solution of a water-in-oil (w/o) type emulsion using MPC and a water-soluble cross-linking agent, and to a method for preparing the same.

Description

【Specification】

[Name of invention]

Spherical Hydrogel Particles Using MPC and Water-soluble Crosslinker

Technical Field

<1> The present invention is a methacryloyl phosphoryl choline,

MPC) relates to spherical hydrogel particles, and more particularly, to hydrogel particles made from an aqueous solution of a water-in-oil (w / o) emulsion dog using MPC and a water-soluble crosslinking agent and a method of preparing the same.

Background Art

<2> The study of hydrogel particles from the late 1980s to the 1990s involved embolization, enzyme immobilization, and drug delivery by granulating polymer materials into micro-sized particles and chemically modifying surfaces and interiors. drug delivery). Entering the 2000s, with the development of nanotechnology, research on the preparation and use of nano-sized particles using water-soluble polymers is in progress. To date, most studies on hydrogel particles use biodegradable polymers for their purpose in biopharmaceuticals and bio-organs, and are manufactured in an injectable structure for non ^¬ invasive procedures. It is focused on things. The field includes drug delivery systems, embolization® tissue engineering scaffolds, bulking agents and implant donuts. It is also widely used in the fields of protein isolation, concentration and stabilization, immunoassays, bioreactors, sensors, biospecific chromatography, and cosmetic fillers. These hydrogel particles are made by chemical methods such as emulsified coacervation, physical methods of spray drying, and heterogeneous polymerization. One example is the preparation of microcapsules with walls composed of polysaccharides through crosslinking reactions occurring at the interface using w / o emulsions (MC Levy et al., Int. J. Pharm., 62, 1990, 27-35; PCT / FR93 / 00237). The method uses a microcapsule having a size of several microns or more, in which only an interface portion is crosslinked through an interfacial crosslinking reaction resulting from an interface where an oil phase containing a crosslinking agent and a polysaccharide aqueous phase contact in a w / o emulsion. How to get.

<3> Conventionally, using a carbodiimide crosslinker (carbodiimide crosslinker),

It has been found that crosslinking of MPC and PEG-diacrylate and hydrogels can be made, but a method for preparing hydrogels in an aqueous solution of a water-in-oil emulsion has not been disclosed. Although high molecular networks have been studied using MPC crosslinked with PEG-diacrylate, a method for preparing hydrogels in an aqueous solution of w / o emulsion dogs has not been disclosed (see, eg, W02011 / 038485). "Col agen-phosphorylchol ine interpenetrat ing network hydrogel s as corneal subst i tutes", Wenguang Liu et al., Biomater i al s 30 (2009) 1551-1559). MPC hydrogels formed by these conventional methods are limited to bulky amorphous hydrogel forms, which are difficult to use for cosmetic applications.

[Detailed Description of the Invention]

[Technical problem]

Thus, the present inventors proceeded a study to manufacture the MPC spherical hydrogel particles by chemically cross-linking the MPC present in the aqueous solution of w / o emulsion dog while adjusting a number of manufacturing parameters in order to solve the conventional problems. Specifically, all kinds of manufacturing parameters such as oil type, ratio of oil phase solution and water phase solution of w / o emulsion dog, type and concentration of surfactant were determined.

As a result, when hydrogel particles are spherically prepared using MPC and a specific water-soluble crosslinking agent, moisture feeling is much improved than that of MPC hydrogel formed by conventional manufacturing methods, and it is easy to disperse on an emulsion without a surfactant. And the present invention was completed.

Accordingly, an object of the present invention is to provide an MPC spherical hydrogel particle having an improved moisture feeling and easy to disperse on an emulsion dog, and a method for preparing the same.

Technical Solution

In order to achieve the above object, the present invention provides a hydrogel particles and a method for producing the same in the aqueous solution of w / o emulsion dog using MPC and a water-soluble crosslinking agent.

Advantageous Effects

The present invention relates to a hydrogel particle made from an aqueous solution of a w / o emulsion dog using MPC and a specific water-soluble crosslinking agent, and to a method for preparing the same. Since the particles of size and (30 ~ 50 μ ηι), the moisture is much improved than the conventional MPC hydrogel, it can be dispersed on the emulsion without the surfactant, it can be easily used in cosmetics. [Brief Description of Drawings]

1 is when the MPC spherical hydrogel according to the present invention is dispersed in an oily solution, It is a photograph showing that it is stably dispersed without a surfactant.

Figure 2 is a micrograph showing that the MPC spherical hydrogel according to the present invention is stably dispersed in both w / o, o / w formulation.

Figure 3 is a micrograph showing the change in size before and after drying the MPC spherical hydrogel.

Figure 4 is a graph showing the change in water change rate according to the addition of MPC spherical hydrogel according to the present invention to w / o.

[Best form for implementation of the invention]

The present invention relates to spherical hydrogel particles made in an aqueous solution of a w / o emulsion using MPC and a specific water-soluble crosslinking agent and a method for preparing the same.

Hereinafter, the present invention will be described in more detail.

Method for producing spherical hydrogel particles using MPC and a water-soluble crosslinking agent according to the present invention

a) dissolving a surfactant in an oil component to prepare an oil phase solution;

b) dissolving the MPC and the water soluble crosslinker in a solvent to prepare an aqueous solution; c) injecting the solution of b) into the solution of a) to form a w / o emulsion;

d) advancing the crosslinking reaction of the crosslinking agent on the aqueous solution with MPC while heating the w / o emulsion of c) to 40 ^° C. to 150 ^° C .; And

e) recovering MPC spherical hydrogel particles from the w / o emulsion of d).

The oil component used to prepare the MPC spherical hydrogel particles according to the present invention may be selected from one or more selected from the group consisting of vegetable, mineral, silicone and synthetic oils, preferably cetyl ethylnucleoanoate (Cetyl ethyl hexanoate, CEH), dodecane, heptane, and the like can be used.

As the surfactant used to prepare the MPC spherical hydrogel particles according to the present invention, at least one of surfactants capable of stabilizing w / o emulsions may be generally used, and preferably cetyl PEG / PPG. -10/1 dimethicone (Cetyl PEG / PPG-10 / 1 dimethi cone (ABIL EM-90)), sorbitan sesquioleate (ARLACEL 83), polyethylene glycol dipolyhydroxy stearate (Polyethylene glycol dipolyhydroxy stearate (ARLACEL P135)). In the present invention, the content of the surfactant is 1 to 10% by weight, preferably 2 to 6% by weight, based on the total weight of the mixture of the oil phase and the water phase of the w / o emulsion dog. The concentration of the surfactant is a factor that affects the size and stability of the w / o emulsion dog particles. If the concentration is less than 1 wt%, the size of the particles increases and the stability of the particles becomes unstable. Emulsion dog particles are stabilized, but since the surfactant becomes an impurity component that is not necessary in the finally obtained particles, there is a disadvantage in that the purity is lowered.

In preparing the MPC spherical hydrogel particles according to the present invention, the solvent used for preparing the aqueous phase solution is not particularly limited, but is preferably purified water.

In the present invention, MPC (Methacryloyl phosphoryl cholene) is used in an amount of 0.1 to 20 weight ¾) based on the total weight of the oil and water mixtures.

The water-soluble crosslinking agent used to prepare the MPC spherical hydrogel particles according to the present invention may be used by selecting one or more from crosslinking agents having the characteristic of forming crosslinking with the natural polymer polysaccharide. When bisepoxide is used as the crosslinking agent, an ether bond is formed instead of an ester bond, which is a crosslink, which is conventionally used through ester esters. In addition, when the crosslinked structure is dispersed in water, in order to make the components forming the crosslinked structure more familiar with water, it is considered to use PEG chain as a main chain of the crosslinking agent. Preference (Polypropylene glycol diacrylate, PPG-DA) or polyethylene glycol diacrylate (PEG-DA) is preferable, and polyethylene glycol diacrylate is more preferable. MPC spherical hydrogel particles crosslinked with the material show a fast and high degree of swelling in the water phase.

In the present invention, the water-soluble crosslinking agent is used in an amount of 0.1 to 10% by weight based on the total weight of the mixture of the oil phase and the water phase.

In the present invention, the MPC and the water-soluble crosslinking agent are preferably mixed in a weight ratio of 1: 9.

In the present invention, the mixing ratio of the oil phase solution in which the surfactant used to constitute the w / o emulsion and the aqueous phase solution in which the MPC and the water-soluble crosslinking agent are dissolved is based on the weight of the oil phase solution: aqueous solution = 1: 1 to 1 ~. 7: 3 is preferred.

Recovery of the MPC spherical hydrogel particles of e) is to wash the emulsion cross-linked emulsion with an organic solvent, to obtain the MPC spherical hydrogel particles in the aqueous phase solution, This is done by vacuum drying at 70 ~ 90 ^° C to remove the residual organic solvent. The organic solvent is not limited as long as it is compatible with water, but is preferably selected from ethanol, methane, isopropyl alcohol, acetone and tetrahydrofuran.

Optionally, an aqueous solution containing dispersed MPC spherical hydrogel particles in order to completely remove impurities such as oils, surfactants, and anti-crosslinking agents that may be present in the MPC spherical hydrogel particles washed with an organic solvent. It may further comprise the step of washing it using an organic solvent.

The MPC spherical hydrogel particles obtained through the preparation method described above can be used for the type and concentration of the crosslinking agent, the ratio of the aqueous solution of the w / o emulsion to the oil phase solution, the type of oil used in the w / o emulsion, and the surfactant. By controlling the manufacturing parameters of the type and concentration, the particle size can range from tens to hundreds of nanometers in the dry state.

MPC spherical hydrogel particles prepared according to the present invention can be stably dispersed in the emulsion composition such as oil, w / o or o / w without a surfactant, and thus can be efficiently used in the external composition of the skin such as cosmetic composition Can be.

When the MPC spherical hydrogel particles of the present invention are used in the external preparation composition for skin, the content may vary depending on the intended purpose and use, but may be preferably used in an amount of about 20% by weight based on the total weight of the composition.

[Form for implementation of invention]

The present invention will be described in more detail by the following examples and test examples. However, the following examples and test examples are only to help the understanding of the present invention, the scope of the present invention in any sense is not limited by these examples and test examples.

Reference Example 1 Preparation of MPC Hydrogel

Hydrogels of Examples 1 and 2 and Comparative Example 1 were prepared in the compositions shown in Table 1 below (parts by weight). Specifically, Examples 1 and 2 are prepared in the aqueous solution of the w / o emulsion dog according to the present invention, Comparative Example 1 is a hydrogel prepared in the water phase.

Table 1

1) An oily solution was prepared by mixing PEG-30 dipolyhydroxy stearate as a surfactant in a nucleic acid.

2) MPG and PEG-M or PPG-DA are mixed with purified water to prepare an aqueous solution.

3) While slowly adding the solution of 2) to the solution of 1), the mixture is stirred for 10 minutes at a speed of 1800 to 2000 rpm with an emulsifier to prepare an emulsion.

4) Heat the mixture at 70 ^° C while stirring at 1800 ~ 2000rpm to maintain the emulsion.

5) After the reaction, precipitate the emulsion in isopropyl alcohol and separate the precipitated MPC spherical hydrogel particles.

6) Make an aqueous solution in which the separated MPC spherical hydrogel particles of 5) are dispersed and precipitate it again in isopropyl alcohol to remove impurities such as oil, surfactant, and unbound crosslinking agent.

7) The obtained MPC spherical hydrogel particles are vacuum dried at 70-90 ^° C. for 24 hours to completely remove residual solvent.

MPC and PEG-DA are dissolved in water and warmed at 70 ^° C. Reference Example 2 Preparation of Composition Containing MPC Hydrogel

Hydrogelols of Formulation Examples 1 to 4 and Comparative Formulation Examples 1 and 2 were prepared in the compositions shown in Tables 2 and 3 below (weight%). Specifically, Formulation Examples 1 and 2 include the hydrogelols of Examples 1 and 2, respectively, as w / o formulations, and Formulation Examples 3 and 4 include the hydrogels of Examples 1 and 2, respectively, as o / w formulations. It is. Comparative Formulation Examples 1 and 2 are also compositions of w / o and o / w formulations comprising the hydrogelol of Comparative Example 1. [Table 2]

w / o formulation

Table 3

o / w formulation

Test Example 1 Characteristics of MPC Spherical Hydrogel

Examples 1-2 or comparative examples in a single oil phase (using hydrogenated polydecene) 1 MPC hydrogel, or the same amount of water and the hydrogel was dispersed and the dispersion state was observed, and the microscopic picture measured for Example 1 and the visual observation for Comparative Example 1 are shown in FIG. In addition, the dispersion state of Formulation Examples 1 to 4, and Comparative Formulation Examples 1 and 3 in which the hydrogel particles according to the present invention were dispersed in a composition of the w / ο or o / w formulation was measured, and Formulation Examples 1 and 3 The micrograph measured about is shown in FIG.

In the case of dispersing Example 1 or Example 2 on a single oil, in both cases the hydrogel particles were stably dispersed. In particular, referring to Figure 1 showing the dispersion state of the hydrogel particles of Example 1, in the dispersion of MPC spherical hydrogel prepared according to the present invention in an oil phase solution, it was stably dispersed without a surfactant, but the same amount of water in the oil phase When added, it can be seen that separation occurs. In addition, when the MPC hydrogel dispersion of Comparative Example 1, it can be confirmed that the dispersion does not occur without using a surfactant.

In addition, referring to Figure 2, the formulation of the dispersion of the MPC spherical hydrogel particles prepared according to the present invention, both w / o formulations or o / w formulations are all dispersed in a stable state without separation without using a surfactant It can be confirmed.

Test Example 2 Measurement of Water Content of MPC Spherical Hydrogel

In order to measure the moisture content of the MPC spherical hydrogel particles according to the present invention, the weight change before and after drying the hydrogel particles of Example 1 using a halogen humidity analyzer (Mett ler To ledo) after drying the MPC spherical hydrogel Was measured at 5 minute intervals while heating at 105 ^° C. for 60 minutes. The particle size change was observed in a microscope (Olympus, x200) and is shown in FIG. 3.

The MPC spherical hydrogel particles remained 8.19 ± 0.16% after drying, indicating that the weight change indicated that the MPC spherical hydrogel was bound with about 11.2 times moisture. In addition, looking at Figure 3, after drying the MPC spherical hydrogel it can be seen that the size is significantly smaller, which can be seen that the result of the decrease in the amount of water combined with the MPC spherical hydrogel throughout the drying process. .

Test Example 3 Measurement of Moisturizing Power of MPC Spherical Hydrogel

In order to measure the moisturizing power of the MPC spherical hydrogel particles according to the present invention, Formulation Example 1 and Comparative Formulation Example 2 were applied to the skin to measure the change in moisture content. moisture To measure the amount, 10 subjects 20 to 50 years of age were washed with both soaps with soap, and the skin was depressed for about 15 minutes under constant temperature and humidity conditions (20 ^° C, RH 40%). The moisture content before application was measured using a moisture content measuring instrument (Corneometer ® CM825, C + K, Germany), and then in Formulation Example 1 on one forearm and Comparative Formulation Example 2 on the other forearm in an amount of 2 μ1 per 1 cm ² . After applying evenly, after the application, after 1 hour, after 3 hours the amount of water was measured to calculate the increase and decrease is shown in Table 4,

Table 4

As can be seen in Table 4, Formulation Example 1 containing the MPC spherical hydrogel prepared according to the present invention is compared to Comparative Formulation Example 2 containing no MPC spherical hydrogel, immediately after the application, 1 hour after application, the application 3 After 24 hours, the amount of water increased significantly (144.0%, 124.0%, 96.0). This means that the MPC spherical hydrogel according to the present invention has a high water retention, and thus can realize high moisturizing power when applied to various formulations.

Claims

【Scope of Claim】

【Claim 1】

i) An oil-like solution in which a surfactant is dissolved in an oil component; and i i) MPC spherical hydrogel particles crosslinked in a w/o emulsion mixed with an aqueous solution in which methacryloyl phosphoryl choline (MPC) and a water-soluble crosslinking agent are mixed.

【Claim 2】

In item U, the mixing ratio of the oil-phase solution in which the surfactant is dissolved and the aqueous solution in which methacryloyl phosphorylcholine (MPC) and the water-soluble cross-linking agent are dissolved is, based on weight, oil phase solution: aqueous solution = 1 : MPC spherical hydrogel particles characterized in that the ratio is 1~7:3.

【Claim 3】

The MPC spherical hydrogel according to claim 1, wherein the oil component is at least one selected from the group consisting of cetyl ethylhexanoate (CEH), dodecane, and heptane. particle.

[Claim 4]

The method of claim 1, wherein the surfactant is cetyl PEG/PPG-10/1 dimethicone, sorbitan sesquioleate, and polyethylene glycol dipolyhydroxy. MPC spherical hydrogel particles characterized by containing at least one type selected from the group consisting of stearate (polyethylene glycol dipolyhydroxy stearate).

[Claim 5]

The MPC spherical hydrogel particle according to claim 1, wherein the content of the surfactant is 1 to 10 weight y. based on the total weight of the mixture of the oil phase solution and the water phase solution of the w/o emulsion.

【Claim 6】

The MPC spherical hydrogel particle according to claim 1, wherein the content of the MPC is 0.1-20% by weight based on the total weight of the mixture of the oil phase and the water phase.

[Claim 7]

The MPC spherical hydrogel particle according to claim 1, wherein the water-soluble crosslinking agent is at least one selected from the group consisting of polypropylene glycol diacrylate and polyethyl¾ glycol diacrylate.

【Claim 8】 The MPC spherical hydrogel particle according to claim 1, wherein the content of the water-soluble crosslinking agent is 0.1 to 10% by weight based on the total weight of the mixture of the oil phase and the water phase.

[Claim 9]

The MPC spherical hydrogel particle of claim 1, wherein the particle has a size of 30 to 50 μ πι.

[Claim 10]

i) w/o emulsion obtained by mixing an oil phase solution in which a surfactant is dissolved in an oil component and Π) an aqueous solution in which methacryloyl phosphoryl chol ine (MPC) and a water-soluble cross-linking agent are dissolved. Method for producing MPC spherical hydrogel particles, comprising the step of crosslinking.

【Claim 11】

The method of claim 10, wherein the MPC spherical hydrogel particles are produced through the following steps:

a) preparing an oil-like solution in which a surfactant is dissolved in an oil component;

b) preparing an aqueous solution in which MPC and a water-soluble crosslinking agent are dissolved;

c) adding the solution of b) to the solution of a) to form w/o emulsion;

d) heating the w/o emulsion of c) to 40-150 ^° C while conducting a cross-linking reaction between the cross-linking agent in the aqueous solution and MPC; and

e) Recovering the MPC spherical hydrogel particles from the w/o emulsion of d) above.

【Claim 12】

A cosmetic composition comprising the MPC spherical hydrogel particles of any one of claims U to 9.

【Claim 13】

The cosmetic composition according to claim 12, wherein the composition is in the form of an oil or a w/o or o/w emulsion type.

[Claim 14]

The cosmetic composition of claim 13, wherein the composition does not contain a surfactant.