KR20220094630A - Niosome composition for stabilizing egf and method for manufacturing of niosome for stabilizing egf - Google Patents

Abstract

The present invention relates to a technology for stabilizing an epidermal growth factor (EGF), a skin regeneration material and, more specifically, to a method for increasing the stabilization of EGF by forming niosomes by means of various surfactants. As a result of measuring niosomes encapsulated with EGF through particle size, Turbiscan Lab, zeta-potential, and an electron microscope, vesicles have been formed favorably, and each of the measured stability is excellent. Consequently, when applying cosmetic ingredients as well as EGF to a niosome formulation prepared using various surfactants, it is possible to obtain various types of niosomes.

Description

EGF-stabilized niosome composition and method for producing the niosome {NIOSOME COMPOSITION FOR STABILIZING EGF AND METHOD FOR MANUFACTURING OF NIOSOME FOR STABILIZING EGF}

The present invention relates to a technique for stabilizing EGF, which is a material for skin regeneration, and more particularly, to a method for increasing the stabilization of EGF by forming niosomes using various surfactants.

EGF (Epidermal growth factor) is a protein that acts on the cell nucleus to promote the division and proliferation rate of epidermal cells, regulates the secretion of collagen synthetase, and is involved in skin regeneration such as skin damage recovery. Although EGF is used in cosmetics for improving skin condition, there is a problem in that durability and stability are relatively low. Therefore, there is a need for new techniques to increase the stability of EGF.

Niosomes composed of nonionic surfactants cannot be expected to play the same role as lipids by themselves, so they must be made similar to natural lipid components. In this case, a phosphate derivative is grafted onto the mainly used glycerine backbone to have amphiphilic properties.

Republic of Korea Patent No. 10-1815316

The present invention relates to a niosome composition capable of stabilizing EGF, comprising: any one of a sucrose-based surfactant, a sorbitan-based surfactant, or a polyethylene glycol cetyl ether; phytosterol; And an object of the present invention is to provide a niosome base composition for stabilizing EGF containing cholesterol, a niosome composition for stabilizing EGF comprising the base composition, and a method for producing niosomes stabilizing EGF.

The technical problems to be achieved by the present invention are not limited to the technical problems mentioned above, and other technical problems not mentioned can be clearly understood by those of ordinary skill in the art to which the present invention belongs from the description below. There will be.

In order to achieve the above technical object, an embodiment of the present invention is a nonionic surfactant of any one of sucrose-based surfactant, sorbitan-based surfactant, or polyethylene glycol cetyl ether; Phytosterol (Phytosterol); And it provides a niosome base composition for EGF stabilization comprising cholesterol (Cholesterol).

The sucrose-based surfactant is sucrose myristate, sucrose laurate, sucrose palmitate, sucrose stearate, sucrose distearate, and sucrose dilaurate. It may be one or more selected from the group consisting of sucrose dilaurate, but is not limited thereto, and preferably sucrose stearate.

The sorbitan-based surfactant is sorbitan olivate (Sorbitan Olivate), sorbitan stearate (Sorbitan Stearate), sorbitan isostearate (Sorbitan Isostearate), sorbitan tristearate (Sorbitan Tristearate), sorbitan sesqui Sorbitan Sesquistearate, Sorbitan Palmitate, Sorbitan Laurate, Sorbitan Oleate, Sorbitan Sesquioleate, Sorbitan Trioleate (Sorbitan Trioleate), Sorbitan Stearate and Sorbityl Laurate, Polysorbate 20, Polysorbate 40, Polysorbate 60, Polysorbate 65, Polysorbate 80 And it may be at least one selected from the group consisting of polysorbate 85, but is not limited thereto, and preferably sorbitan stearate.

The polyethylene glycol cetyl ether is Ceteth-1, Ceteth-2, Ceteth-3, Ceteth-4, Ceteth-5, Ceteth 6, Ceteth-10, Ceteth-12, Ceteth-14, It may be at least one selected from the group consisting of Ceteth-15, Ceteth-16, Ceteth-10, Ceteth-24, Ceteth-25, Ceteth-30 and Ceteth-45, but is not limited thereto, Preferably it is Ceteth-3 or Ceteth-5.

The base composition may include 40 to 60% by weight of a nonionic surfactant, 20 to 40% by weight of phytosterol, and 15 to 25% by weight of cholesterol relative to the total weight of the composition.

According to another embodiment of the present invention, there is provided a niosome composition for EGF stabilization comprising the base composition, wherein the niosome composition may include a base composition, an anionic surfactant, polyol, EGF, oil and water. have.

The anionic surfactant may be at least one selected from the group consisting of sodium stearoyl glutamate, disodium stearoyl glutamate, sodium auroyl glutamate, sodium lauryl glucose carboxylate, sodium methyl cocoyl taurate, and sodium cetyl phosphate. However, it is not limited thereto, and preferably sodium stearoyl glutamate.

The polyol is sorbitol (SORBITOL), polyethylene glycol (POLYETHYLENE GLYCOL), polypropylene glycol (POLYPROPYLENE GLYCOL), dipropylene glycol (DIPROPYLENE GLYCOL), propylene glycol (PROPYLENE GLYCOL), 1,3-butylene glycol (1,3-butylene glycol) BUTYLENE GLYCOL), glycerin (GLYCERIN), propanediol (PROPANEDIOL), ethylhexanediol (ETHYL HEXANEDIOL), 1,2-hexanediol (1,2-HEXANEDIOL), PEG/Sebum/Polybutylene glycol-8/ 5/3 glycerin (PEG/PPG/POLYBUTYLENE GLYCOL-8/5/3 GLYCERIN) and pentylene glycol (PENTYLENE GLYCOL) may be at least one selected from the group consisting of, but not limited thereto, preferably glycerin and 1 ,2-hexanediol mixture.

The oil is cyclomethicone, dimethicone, dimethicone/vinyldimethicone crosspolymer, phenyltrimethicone, polyisobutene, squalane, cetylethylhexanoate, caprylic/capric triglyceride, cococaprylate / Caprate, octyldodecanol, dicaprylyl carbonate, triethylhexanoin, olive oil, may be at least one selected from the group consisting of macadamia seed oil, but is not limited thereto, preferably cetylethylhexano Eight, dimethicone and macadamia seed oil mixture.

When the nonionic surfactant of the base composition is polyethylene glycol cetyl ether, the niosome composition for EGF stabilization may further include a phospholipid.

The phospholipids are egg yolk lecithin (phosphatidylcholine), soybean lecithin, hydrogenated lecithin, lysolecithin, sphingomyelin (Sphingomyelin), phosphatidic acid, phosphatidylserine, phosphatidyl glycerol, phosphatidylinositol, phosphatidylinositol, It may be at least one selected from the group consisting of diphosphatidylglycerol, cardiolipin, and plasmalogen, but is not limited thereto, and preferably lysolecithin.

Specifically, the niosome composition for stabilizing EGF contains 5 to 15% by weight of the base composition of claim 1, 0.1 to 1% by weight of anionic surfactant, 5 to 15% by weight of polyol, 40 to 60% by weight of EGF, oil based on the total weight of the composition 15 to 25% by weight and 10 to 15% by weight of water.

When the nonionic surfactant of the base composition is polyethylene glycol cetyl ether, the niosome composition for stabilizing EGF may further include 0.1 to 1% by weight of phospholipids based on the total weight of the composition.

According to another embodiment of the present invention, any one of nonionic surfactants of sucrose-based surfactants, sorbitan-based surfactants or polyethylene glycol cetyl ether; phytosterol; and mixing cholesterol to prepare a base composition; mixing anionic surfactant, polyol and water and then adding to the base composition; It provides a method for producing a niosome in which EGF is stabilized, comprising the step of adding EGF; and adding oil.

Preferred examples and contents of the materials used in the manufacturing method are the same as those of the composition, and since they have been specifically described above, they are omitted to avoid overlapping descriptions.

In another embodiment of the present invention, by providing a niosome prepared by the above manufacturing method, the EGF is stabilized inside the niosome.

The niosomes prepared by the composition and manufacturing method can be used for improving skin elasticity.

The cosmetic composition according to the present invention is selected from the group consisting of solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, wax foundations and sprays. It may have a formulation.

The present inventors used various surfactants to form various types of vesicle raw materials EGF NIOSOME-1, EGF NIOSOME-2, EGF NIOSOME-3, and EGF NIOSOME-4. All niosomes encapsulated with EGF had very well formed vesicles as a result of particle size, turbiscan, zeta potential, and electron microscopy measurements, and each had excellent stability. Afterwards, niosome formulations made using various surfactants can be applied with EGF as well as cosmetic ingredients to obtain various types of niosomes.

1 is a graph showing the particle size measurement results of EGF NIOSOME samples.
2 is a graph showing the zeta potential measurement results of EGF NIOSOME samples.
3 is a graph showing the results of Turbiscan measurement of EGF NIOSOME samples.
4 is a TEM photograph of EGF NIOSOME samples.
5 is a graph showing the viscosity of EGF NIOSOME samples.
6 is a graph showing the elasticity of EGF NIOSOME samples.
7 is a graph showing Solid Liquid Balance of EGF NIOSOME samples.

Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention in more detail, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .

<Example>

1. Preparation of NSV (Non-ionic Surfactant Vesicle)-base using various non-ionic surfactants

A total of three formulations were prepared for NSV-base using different surfactants (Table 1). The A and B phases are directly heated respectively. After each phase is completely melted, slowly add phase B to phase A, stir and cool at room temperature.

NSV production using nonionic surfactants Phase Ingredient % by weight A nonionic surfactant 50.00 B Phytosterol
Cholesterol 30.20
19.80

- Nonionic surfactants: (a) sucrose stearate (S570), (b) sorbitan stearate (Arlacel60), (c) Ceteth-3, Ceteth-5 (Emalex 103, Emalex 105)

2. Manufacturing EGF NIOSOME

Based on the three NSV-bases made, a total of four niosomes were prepared using EGF (Tables 2 and 3). First, after transparently dissolving phase B (80°C), heat the phase A directly to completely melt it. Slowly add phase B to phase A and emulsify. After that, the temperature is cooled down to 30° C., and then phase C is added and mixed. After adding phase D (40° C.), emulsify for 5 minutes at 3,000 rpm using a Homer mixer (T.K Auto Homomixer Mark ±, Tokushukikakogyo, Japan). The emulsified emulsion was subjected to high pressure emulsification with a microfludizer (M-110Y, Microfluidics, USA) three times at 1000 bar to prepare niosomes.

NIOSOME formulation Phase Ingredient % by weight A NSV base 10.00 B Sodium Stearoyl Glutamate
water
glycerin
1,2-Hexanediol 0.80
12.20
7.00
2.00 C EGF 50.00 D Cetylethylhexanoate
dimethicone
Macadamia Seed Oil 6.00
6.00
6.00

- NSV base: (a) sucrose stearate (S570), (b) sorbitan stearate (Arlacel60), (c) Ceteth-3, Ceteth-5 (Emalex 103, Emalex 105) 1:1 weight ratio mixture

Elastic NIOSOME formulation Phase Ingredient % by weight A Ceteth-3, Ceteth-5(1:1) NSV base
lyzolecithin 10.00
0.50 B Sodium Stearoyl Glutamate
water
glycerin
1,2-Hexanediol
Sodium Cholate 0.80
11.20
7.00
2.00
0.50 C EGF 50.00 D Cetylethylhexanoate
dimethicone
Macadamia Seed Oil 6.00
6.00
6.00

sample notation NSV base NSV base Remark Notation EGF S570 EGF NIOSOME-1 Arlacel60 EGF NIOSOME-2 Ceteth-3, Ceteth-5 EGF NIOSOME-3 Ceteth-3, Ceteth-5 Lysolecithin
Sodium Cholate EGF NIOSOME-4

<Experimental example>

1. Particle size measurement

After preparing a 10% solution using purified water for the purpose of measuring the average size of the formed particles, the particle size was measured using a laser light scattering system (Photal, ELS-Z, Japan).

Referring to FIG. 1 , it was found that the particle size of the formed EGF NIOSOME samples was different depending on the type of surfactant, and the particle size range was 60 - 750 nm.

Raw material name Particle size [nm] EGF NIOSOME-1 95.3 EGF NIOSOME-2 146.9 EGF NIOSOME-3 67.0 EGF NIOSOME-4 718.4

2. Zeta potential measurement

After preparing a 10% solution using purified water for the purpose of measuring the particle surface charge of the formed particles, the zeta potential was measured using a laser light scattering system (Photal, ELS-Z, Japan).

Referring to FIG. 2 , the zeta potential was generally seen to be in a stable state at a value of |40|mV or more, and EGF NIOSOME-1 had the highest zeta potential value.

Raw material name Zeta potential [mV] EGF NIOSOME-1 -78.74 EGF NIOSOME-2 -73.26 EGF NIOSOME-3 -66.17 EGF NIOSOME-4 -59.78

3. Stability evaluation using Turbiscan

As an emulsion itself without concentration dilution of the prepared sample solution, it was measured under conditions of 40° C., 4 hours, and 50 scans using Turbiscan (Turbiscan LAB, Formulaction, France) for the purpose of checking stability under high temperature conditions.

If the graph does not fluctuate much over time at 40°C, it can be considered stable. Referring to FIG. 3 , it can be seen that all four graphs are relatively stable as there is no significant change in the graph.

4. Check NIOSOME

For the purpose of confirming the presence or absence of NIOSOME formation, it was investigated using Cryo-Transmission Electron Microscopy (Cryo-TEM). Structural analysis was performed in a frozen state by maintaining the sample at -176°C using liquid nitrogen.

Referring to FIG. 4 , vesicles were formed in all four EGF NIOSOMEs.

5. Check Rheology

For the purpose of confirming the rheology of the formed NIOSOMEs, it was investigated using a rheometer. The analysis was performed at room temperature for 2 days as it was without concentration dilution.

Referring to FIG. 5 , the higher the EI of the Y-axis, the higher the elasticity of the sample. Comparing the four samples, the sample EGF NIOSOME-4 was observed to have the highest elasticity, and the sample EGF NIOSOME-2. The least elastic aspect was observed.

Referring to Figure 6, the higher the MVI of the Y-axis, the higher the viscous aspect can be seen as a sample. .

Referring to FIG. 7 , the lower the Y-axis SLB value is, the more solid-like system can be seen. From the SLB results, all samples except EGF NISOME-4 had an SLB value of 0.5 or higher. EGF NIOSOME-4 was evaluated as a solid-like system, and the remaining three types were evaluated as a liquid-like system. The NIOSOME-4 is a solid-like system, and since it exhibits less osmotic pressure, it is judged to be more preferable for stabilizing EGF.

6. Results

Elasticity: EGF NIOSOME-4 > EGF NIOSOME-3 > EGF NIOSOME-1 > EGF NIOSOME-2

Viscosity: EGF NIOSOME-4 > EGF NIOSOME-3 > EGF NIOSOME-2 > EGF NIOSOME-1

Solid like system : EGF NIOSOME-4

Liquid like system: EGF NIOSOME-1, EGF NIOSOME-2, EGF NIOSOME-3

As described above in detail a specific part of the present invention, for those of ordinary skill in the art, this specific description is only a preferred embodiment, and it is clear that the scope of the present invention is not limited thereto. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

Claims (16)

Any one of a sucrose-based surfactant, a sorbitan-based surfactant, or polyethylene glycol cetyl ether;
phytosterol; and
Niosome-based composition for stabilizing EGF containing cholesterol.
The method of claim 1,
A niosome base composition for stabilizing EGF comprising 40 to 60% by weight of a nonionic surfactant, 20 to 40% by weight of phytosterol, and 15 to 25% by weight of cholesterol relative to the total weight.
The method of claim 1,
The sucrose-based surfactant is sucrose myristate, sucrose laurate, sucrose palmitate, sucrose stearate, sucrose distearate, and sucrose dilaurate. Niosome base composition for stabilizing at least one EGF selected from the group consisting of sucrose dilaurate.
The method of claim 1,
The sorbitan-based surfactant is sorbitan olivate (Sorbitan Olivate), sorbitan stearate (Sorbitan Stearate), sorbitan isostearate (Sorbitan Isostearate), sorbitan tristearate (Sorbitan Tristearate), sorbitan sesqui Sorbitan Sesquistearate, Sorbitan Palmitate, Sorbitan Laurate, Sorbitan Oleate, Sorbitan Sesquioleate, Sorbitan Trioleate (Sorbitan Trioleate), Sorbitan Stearate and Sorbityl Laurate, Polysorbate 20, Polysorbate 40, Polysorbate 60, Polysorbate 65, Polysorbate 80 And at least one selected from the group consisting of polysorbate 85 niosome base composition for EGF stabilization.
The method of claim 1,
The polyethylene glycol cetyl ether is Ceteth-1, Ceteth-2, Ceteth-3, Ceteth-4, Ceteth-5, Ceteth 6, Ceteth-10, Ceteth-12, Ceteth-14, A niosome base composition for stabilizing EGF at least one selected from the group consisting of Ceteth-15, Ceteth-16, Ceteth-10, Ceteth-24, Ceteth-25, Ceteth-30 and Ceteth-45.
The niosome composition for stabilizing EGF comprising the base composition of claim 1, an anionic surfactant, polyol, EGF, oil and water.
7. The method of claim 6,
The anionic surfactant is EGF at least one selected from the group consisting of sodium stearoyl glutamate, disodium stearoyl glutamate, sodium auroyl glutamate, sodium lauryl glucose carboxylate, sodium methyl cocoyl taurate, and sodium cetyl phosphate. A niosome composition for stabilization.
7. The method of claim 6,
The polyol is sorbitol (SORBITOL), polyethylene glycol (POLYETHYLENE GLYCOL), polypropylene glycol (POLYPROPYLENE GLYCOL), dipropylene glycol (DIPROPYLENE GLYCOL), propylene glycol (PROPYLENE GLYCOL), 1,3-butylene glycol (1,3-butylene glycol) BUTYLENE GLYCOL), glycerin (GLYCERIN), propanediol (PROPANEDIOL), ethylhexanediol (ETHYL HEXANEDIOL), 1,2-hexanediol (1,2-HEXANEDIOL), PEG/Sebum/Polybutylene glycol-8/ 5/3 glycerin (PEG/PPG/POLYBUTYLENE GLYCOL-8/5/3 GLYCERIN) and pentylene glycol (PENTYLENE GLYCOL) A niosome composition for stabilizing EGF at least one selected from the group consisting of.
7. The method of claim 6,
The oil is cyclomethicone, dimethicone, dimethicone/vinyldimethicone crosspolymer, phenyltrimethicone, polyisobutene, squalane, cetylethylhexanoate, caprylic/capric triglyceride, cococaprylate / Caprate, octyldodecanol, dicaprylyl carbonate, triethylhexanoin, olive oil, niosome composition for stabilizing EGF at least one selected from the group consisting of macadamia seed oil.
7. The method of claim 6,
the anionic surfactant is sodium stearoyl glutamate; the polyol is a mixture of glycerin and 1,2-hexanediol; The oil is cetyl ethyl hexanoate, dimethicone, and a niosome composition for stabilizing EGF which is a mixture of macadamia seed oil.
7. The method of claim 6,
When the nonionic surfactant of the base composition is polyethylene glycol cetyl ether, the niosome composition for EGF stabilization further comprising a phospholipid.
12. The method of claim 11,
The phospholipids are egg yolk lecithin (phosphatidylcholine), soybean lecithin, hydrogenated lecithin, lysolecithin, sphingomyelin (Sphingomyelin), phosphatidic acid, phosphatidylserine, phosphatidyl glycerol, phosphatidylinositol, phosphatidylinositol, Diphosphatidylglycerol, cardiolipin (Cardiolipin) and at least one selected from the group consisting of plasmalogen niosome composition for stabilizing EGF.
7. The method of claim 6,
Based on the total weight of the composition, 5 to 15% by weight of the base composition of claim 1, 0.1 to 1% by weight of anionic surfactant, 5 to 15% by weight of polyol, 40 to 60% by weight of EGF, 15 to 25% by weight of oil, and 10 to 15% by weight of water A niosome composition for stabilizing EGF comprising wt%.
Any one of a sucrose-based surfactant, a sorbitan-based surfactant, or polyethylene glycol cetyl ether; phytosterol; and mixing cholesterol to prepare a base composition;
mixing anionic surfactant, polyol and water and then adding to the base composition;
adding EGF; and
A method for producing a niosome stabilizing EGF comprising the step of adding oil.
A niosome prepared by the method of claim 14 .
A cosmetic composition comprising the niosome of claim 15.

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