WO2017191924A1 - Nano-emulsion composition containing polyglyceryl-based emulsifier - Google Patents

Abstract

The present specification relates to a nano-emulsion composition having improved stability through a combination of polyglyceryl-based emulsifiers and to a method for preparing the same. The nano-emulsion composition according to the present specification has significantly excellent characteristics compared with a conventional nano-emulsion in terms of the size and distribution of particles; the preparation method for the nano-emulsion is cheaper and more convenient than a conventional method; and the nano-emulsion composition is also excellent in terms of safety due to the restriction of the use of a PEG-based compound, and thus, the nano-emulsion composition and the method for preparing the same according to the present specification can be widely utilized in various fields.

Description

Nanoemulsion composition comprising polyglyceryl emulsifier

The present specification relates to a nanoemulsion composition comprising a polyglyceryl-based emulsifier and a preparation method thereof.

Functional materials used in the fields of cosmetics, pharmaceuticals, food and beverages are denatured by external environmental factors (light, heat, oxygen, etc.) despite their excellent effects, or they are insoluble in water and general organic solvents. Often limited. In order to overcome these limitations, surfactants or emulsifiers are used to stabilize the solution through emulsions or encapsulation. In this case, unstable phenomena such as agglomeration of micelles or separation of functional substances often occur. There may be limitations in using it.

In particular, cosmetics are often formulated by combining substances that do not dissolve with each other, such as water-soluble components and fat-soluble components, so that emulsification and dispersion techniques are very important, and the purpose and method of use are also subdivided. Therefore, various emulsification techniques have been developed in the cosmetic field. Has been. Research is continuously underway to add new value to cosmetics using various cosmetic formulation technologies. Emulsions are one of the most representative formulation and research systems in the cosmetic industry. Many researches have been conducted on maintaining stability in emulsion. As the particle size is small and the distribution is uniform, the long-term stability is excellent. Therefore, the nanoemulsion with small particle size and even distribution is actively researched. I'm losing.

Conventional nanoemulsion preparation methods include a high-pressure emulsification method for emulsifying an emulsifier by mechanical force, a full-phase temperature emulsification method, a D-phase emulsification method, etc., which are methods using interfacial chemical properties. The high pressure emulsification method has the advantage of being capable of continuous manufacturing and easy mass production, but it takes a lot of time and place, and it is expensive in terms of equipment because it is expensive. In addition, the method using the interfacial chemical properties has a restriction that must use a polyoxyethylene (polyoxyethylene, POE) system. The emulsifiers used to prepare nanoemulsions have been the mainstream of PEG-based compounds added with ethylene oxide. Recently, a small amount of dioxins may be contained during polymerization of ethylene glycol, which may cause skin irritation. In recent years, there is a need for measures to avoid the use of emulsifiers of concern about irritation in accordance with recent consumer trends that emphasize safety and well-being.

Accordingly, the present inventors have completed the present invention while solving the problems of the prior art as described above, while studying for the production of nanoemulsion excellent in terms of stability.

It is an object of the present specification to provide a nanoemulsion composition that is significantly more stable than conventional nanoemulsions through the combination of polyglyceryl-based emulsifiers. In addition, unlike conventional nanoemulsion manufacturing method, the purpose of preparing nanoemulsion using only homomixer is to save time and cost, and to provide nanoemulsion without skin irritation by limiting PEG-based raw materials. have.

In order to solve the above problems, the present invention provides a nanoemulsion composition comprising polyglyceryl stearate as an emulsifier.

In another aspect, the present invention provides a method including a dispersion using a homomixer as a method of preparing the nanoemulsion composition.

Nanoemulsion composition according to an aspect of the present invention is significantly increased stability compared to the conventional nanoemulsion composition, significantly reduced in terms of time and cost compared to the conventional manufacturing method, to exclude skin irritation by PEG-based compounds It works.

1 is a view showing a distribution over time with respect to the particle size of the nanoemulsion composition according to Example 3 of the present specification at room temperature.

 2 is a view showing the distribution over time in the refrigeration conditions for the particle size of the nanoemulsion composition according to Example 3 of the present specification.

Figure 3 is a view showing the distribution over time in 45 ℃ conditions for the particle size of the nanoemulsion composition according to Example 3 of the present specification.

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

The nanoemulsion disclosed herein refers to an emulsion having an average particle size of nano unit among liquid-liquid dispersion systems in which one or more liquid phases are not mixed in one liquid phase, and generally have a size distribution of several μm to several hundred μm. However, nanoemulsions disclosed herein include those having an average particle size of 400 nm or less. The smaller the particle size and the more uniform the particle size distribution, the more stable it can be seen.

The average particle size disclosed herein refers to the average diameter of the particles, and since the particles are three-dimensional objects, they include particle sizes calculated using the equivalent sphere concept to measure the diameter when the particles are not perfectly spherical. will be. For example, spheres of the same maximum length, spheres of the same minimum length, spheres of the same mass, spheres of the same volume, spheres of the same surface area, spheres passing through the same sieve aperture, spheres having the same sedimentation velocity, and the like. Particle size can be calculated from the equivalent spherical diameter in terms of equivalent spherical shape having the same characteristics, and the average particle size can be seen as an average value for these particle sizes of the particles. The average particle size also includes a particle size measured by a dynamic light scattering (DLS) method. The dynamic light scattering method includes a method of determining particle size by Brownian motion of particles, and a method of determining particle size by reading wavelength intensity of scattered light that changes per predetermined time interval. Light used in the method may include a laser. A formula for determining the particle size may be used as commonly used, and the formula includes a Stoke-Einstein relation regarding the diffusion coefficient.

* PDI disclosed herein refers to a polydispersity index, which means a weight average molecular weight (Mw) divided by a number average molecular weight (Mn) (Mw / Mn). Here, a weight average molecular weight and a number average molecular weight are experimental values which can be obtained by experiment. In general, the larger the PDI, the wider the molecular weight distribution tends to be unstable on the nanoemulsion, and the lower the PDI, the narrower and more uniform the molecular weight distribution.

Analogous ceramides disclosed herein include compounds having the same or similar structure as natural ceramides, including synthetic ceramides having the same or similar function as natural ceramides.

In one aspect, the present invention provides a nanoemulsion composition comprising polyglyceryl stearate as an emulsifier.

In one aspect of the present invention, "polyglyceryl stearate" is a compound belonging to a polyglycerin fatty acid ester, and is a compound obtained by esterifying a stearic acid, which is one of fatty acids, to a polyglycerol polymerized with one or more glycerin, and has a general meaning of poly Includes all glyceryl stearate. In addition, the number of glycerin to be polymerized is not limited, and the number of stearic acid is also not limited, and glycerin or stearic acid includes a substituent, and all of its variants and isomers. Examples of the polyglyceryl stearate used herein include polyglyceryl-4 iso stearate, polyglyceryl-6 mono stearate, polyglyceryl-6 iso stearate, polyglyceryl-10 mono stearate, poly Glyceryl-10 monoisostearate, polyglyceryl-10 distearate, polyglyceryl-10 diiso stearate, polyglyceryl-10 tristearate, polyglyceryl-3 alkylglucose monostearate, polyglycerol Reel-3 alkylglucose distearate, polyglyceryl-3 alkylglucose tristearate, and the like. The polyglyceryl stearate preferably comprises polyglyceryl-10 stearate and polyglyceryl-3 alkylglucose distearate, more preferably polyglyceryl-10 stearate and polyglyceryl-3 methylglucose Distearate.

According to one embodiment of the present invention, the polyglyceryl stearate may be one kind or two or more kinds.

According to another embodiment of the present invention, the polyglyceryl stearate may include polyglyceryl-10 stearate and polyglyceryl-3 alkylglucose distearate.

According to another embodiment of the present invention, the polyglyceryl stearate may be 0.1 to 10% by weight relative to the total weight of the nanoemulsion composition. However, the polyglyceryl stearate is 0.1 wt% or more, 0.2 wt% or more, 0.3 wt% or more, 0.4 wt% or more, 0.5 wt% or more, 0.6 wt% or more, 0.7 wt% or more, based on the total weight of the nanoemulsion composition, At least 0.8 weight percent, at least 0.9 weight percent, at least 1.0 weight percent, at least 1.5 weight percent, at least 2.0 weight percent, at least 2.5 weight percent, at least 3.0 weight percent, at least 3.5 weight percent, at least 4.0 weight percent, at least 4.5 weight percent, At least 5.0 weight percent, at least 5.5 weight percent, at least 6.0 weight percent, at least 6.5 weight percent, at least 7.0 weight percent, at least 7.5 weight percent, at least 8.0 weight percent, at least 8.5 weight percent, at least 9.0 weight percent, at least 9.5 weight percent, Or at least 9.9 wt%, at most 10 wt%, at most 9.5 wt%, at most 9.0 wt%, at most 8.5 wt%, at most 8.0 wt%, at most 7.5 wt%, at most 7.0 wt%, at most 6.5 wt%, 6.0 wt% Or less, 5.5 wt% or less, 5.0 wt% or less, 4.5 wt% or less, 4.0 wt% or less, 3.5 wt% or less, 3.0 wt% or less, 2.5 wt% or less, 2. 0 wt% or less, 1.5 wt% or less, 1.0 wt% or less, 0.9 wt% or less, 0.8 wt% or less, 0.7 wt% or less, 0.6 wt% or less, 0.5 wt% or less, 0.4 wt% or less, 0.3 wt% or less, 0.2 wt% or less, or 0.15 wt% or less, and preferably 2 wt%.

According to another embodiment of the invention, the polyglyceryl stearate may be composed of polyglyceryl-10 stearate and polyglyceryl-3 alkylglucose distearate, polyglyceryl-10 stearate: polyglycerol The weight ratio of reyl-3 alkylglucose distearate may be 7: 1 to 1: 7. However, the weight ratio is not limited thereto, and is not limited to 7: 1 or more, 7: 2 or more, 7: 3 or more, 7: 4 or more, 7: 5 or more, 7: 6 or more, or 1: 1 or 1: 7 or less. , 1: 6 or less, 1: 5 or less, 1: 4.5 or less, 1: 4 or less, 1: 3 or less, or 1: 2 or less, preferably 1: 1.

According to another embodiment of the present invention, the alkyl of the polyglyceryl-3 alkylglucose distearate may be C ₁ to C ₆ alkyl. The alkyl may preferably be methyl. In addition, the stearate includes monostearate, distearate, tristearate, tetrastearate, pentastearate, hexastearate, heptastearate, octastearate, nonastearate, decastearate, preferably May be distearate.

According to another embodiment of the present invention, the nanoemulsion composition may further comprise a lipid component. The lipid component is not particularly limited, and may include all lipid components that can be generally used in the art.

According to another embodiment of the present invention, the lipid component may be any one or more selected from the group consisting of ceramide, cholesterol, and fatty acids. The fatty acid is not particularly limited and includes stearic acid.

According to another embodiment of the present invention, the weight ratio of ceramide to polyglyceryl stearate may be 1: 1 to 1:20. However, the weight ratio is not limited to 1: 1 or more, 1: 2 or more, 1: 3 or more, 1: 4 or more, 1: 5 or more, 1: 6 or more, 1: 7 or more, 1: 8 or more, 1: 9 or less, 1:10 or more, 1:20 or less, 1:15 or less, 1:10 or less, 1: 9 or less, 1: 8 or less, 1: 7 or less, 1: 6 or less, or 1: 5 or less It may be preferably 1:10.

According to another embodiment of the present invention, the ceramide may be 0.01 to 1% by weight relative to the total weight of the nanoemulsion. It is not specifically limited to the said weight%, 0.01 weight% or more, 0.02 weight% or more, 0.03 weight% or more, 0.04 weight% or more, 0.05 weight% or more, 0.06 weight% or more, 0.07 weight% or more, 0.08 weight% or more, At least 0.09 weight percent, at least 0.1 weight percent, at least 0.2 weight percent, at least 0.3 weight percent, at least 0.4 weight percent, at least 0.5 weight percent, at least 0.6 weight percent, at least 0.7 weight percent, at least 0.8 weight percent, at least 0.9 weight percent, Or 0.95 wt% or less, 1.0 wt% or less, 0.9 wt% or less, 0.8 wt% or less, 0.7 wt% or less, 0.6 wt% or less, 0.7 wt% or less, 0.5 wt% or less, 0.4 wt% or less, 0.3 wt% or less , 0.2 wt% or less, 0.1 wt% or less, 0.09 wt% or less, 0.08 wt% or less, 0.07 wt% or less, 0.06 wt% or less, 0.05 wt% or less, 0.04 wt% or less, 0.03 wt% or less, or 0.02 wt% It may be less than, preferably 0.2% by weight.

According to another embodiment of the present invention, the ceramide may include natural ceramide or synthetic ceramide.

According to another embodiment of the present invention, the synthetic ceramide may include pseudoceramide, and may include hydroxypropyl bispalmitamide MEA represented by the following Chemical Formula 1.

[Formula 1]

According to another embodiment of the present invention, the nanoemulsion composition may further include any one or more of C ₂ to C ₈ polyhydric alcohol or glycerin. Preferably, the alcohol is propanol, but is not limited thereto. The polyhydric alcohol may be a dihydric alcohol, more preferably propanediol.

According to another embodiment of the present invention, the nanoemulsion composition may be a cosmetic composition. In one aspect, the present invention may be a cosmetic composition comprising the nanoemulsion composition.

According to another embodiment of the present invention, the nanoemulsion composition may be a mist formulation.

According to another embodiment of the present invention, the nanoemulsion composition may have an average particle size of 400 nm or less. The average particle size is 400 nm or less, 380 nm or less, 350 nm or less, 33 nm or less, 300 nm or less, 280 nm or less, 250 nm or less, 220 nm or less, 200 nm or less, 190 nm or less, 180 nm or less, 170 nm Or less, 160 nm or less, 150 nm or less, 140 nm or less, 130 nm or less, 120 nm or less, 110 nm or less, 100 nm or less, 80 nm or less, 50 nm or less, 30 nm or less, or 10 nm or less, preferably Preferably from 50 to 250 nm, more preferably from 150 to 180 nm.

According to another embodiment of the present invention, the nanoemulsion composition may have a polydispersity index (PDI) of 0.55 or less. The PDI is 0.55 or less, 0.5 or less, 0.45 or less, 0.4 or less, 0.35 or less, 0.3 or less, 0.29 or less, 0.28 or less, 0.25 or less, 0.24 or less, 0.22 or less, 0.21 or less, 0.2 or less, 0.18 or less, 0.15 or less, or 0.1 It may be less than, preferably 0.18 to 0.4, more preferably 0.2 to 0.29.

According to another embodiment of the present invention, the nanoemulsion composition may be stably maintained for at least 16 weeks at a temperature of 4 ℃ or 45 ℃.

In addition, the minimum 16 weeks is not limited thereto, and may be 16 weeks or more, 17 weeks or more, 18 weeks or more, 19 weeks or more, 20 weeks or more, or 25 weeks or more.

According to another embodiment of the present invention, the nanoemulsion composition may be stable for at least 4 weeks under the conditions of 12 hours alternately -10 ℃ and 45 ℃. The minimum 4 weeks is not limited thereto, and may be at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 8 weeks, at least 12 weeks, or at least 16 weeks.

According to another embodiment of the present invention, the nanoemulsion composition may not include a polyethylene glycol (PEG) -based compound.

Formulation of the nanoemulsion composition is not particularly limited, but can be used in hair, nails, and oral cavity including skin, mucous membranes, scalp, hair, and the like, for example, supple cosmetics, nourishing cosmetics, lotions, creams, packs, gels, Compositions selected from patches, sprays or mists, compositions selected from lipsticks, makeup bases, or foundations, compositions selected from shampoos, rinses, body cleansers, toothpastes, mouthwashes, or hair tonics, gels, mousses, etc. It comprises a hair composition selected from hair dressing, wool, hair dye. In addition, it can be used in various forms such as lotions, ointments, gels, creams, plaques, mists, or sprays, and its application includes all cosmetics, food and beverages, dietary supplements, medicines and quasi-drugs. There is no

In one aspect, the present invention may further include surfactants, emulsifiers, excipients, suspending agents, coloring agents, flavoring agents, oils, waxes, polyols and other additives generally used to prepare emulsions, and there is no particular limitation. .

In order to prove that the nanoemulsion composition according to one aspect of the present invention is significantly more stable than other nanoemulsions, stability verification was performed through Examples and Experimental Examples, and as a result, the nanoemulsion composition according to one aspect of the present invention had a particle size. It was found to be very small compared to other nanoemulsions in terms of surface area, and the PDI surface was significantly lower than other nanoemulsions (see Table 3). In addition, as shown in Table 4, Figures 1 to 3, the nanoemulsion composition according to one aspect of the present invention can be seen that the stability is remarkable in terms of stability compared to the conventional nanoemulsion is maintained for more than 16 weeks.

In another aspect, the present invention, as a method of preparing the nanoemulsion composition, it can provide a method including dispersion using a homomixer (homomixer). The homomixer is a device for homogeneously mixing and dispersing two or more materials, and generally, any one used in the art may be used, and the rpm is preferably 500 or more, but is not limited thereto.

An example of the manufacturing method by the said method is as follows.

First, an aqueous phase including a water-soluble physiologically active ingredient, a humectant, and purified water is prepared, and the dissolution is performed in an emulsification tank capable of temperature control and stirring by a conventional method, and may be stirred or heated as necessary. The heating temperature is 50-80 ° C., preferably 70-75 ° C., so that other components can be sufficiently dissolved in the purified water. Next, an oil phase part including a biolipid component, an emulsifier and an oil is prepared. The production of the oil phase can also be stirred or heated as necessary, similarly to the water phase. The heating temperature is 50-80 ° C., preferably 70-75 ° C., so that the other components can be sufficiently dissolved in the oil. Next, an oil phase part is added to the water phase part to prepare a nanoemulsion. At this time, using a homo mixer can be stirred for 5-10 minutes at a speed of 8000 to 12000rpm, preferably 10000rpm to produce a nano-sized emulsion through the primary emulsification. After cooling slowly to prepare a nanoemulsion composition.

In the conventional case, the nanoemulsion is usually used in the manufacture of a high pressure emulsifier (Microfluidizer), because it is not possible to stably manufacture the nanoemulsion using only a homomixer. The high pressure emulsification method is a method of making a nanoemulsion by applying physically strong force, which requires a high pressure emulsifier (Microfluidizer), which consumes a lot of time and money.

When prepared through a high pressure emulsifier, two-step emulsification should be carried out: preparation of the first preemulsion and preparation of the second nanoemulsion. The preparation of the primary preemulsion is to form a micro-sized emulsion via primary emulsification by performing agitation for 3 to 10 minutes at a speed of 2000 to 4000 rpm, preferably 3000 rpm using a homo mixer in a vacuum emulsification tank. Is done. Next, after cooling the preemulsion three times in a high pressure emulsifier at a pressure of 500 to 2500bar to prepare a nanoemulsion. At this time, if the treatment pressure is less than the above range, it is difficult to stably form the nano-size. On the contrary, if the treatment pressure is exceeded, the nano-size emulsion is sufficiently small by causing strong damage to the physiologically active component itself or by uniting particles. Cannot be prepared.

According to one aspect of the present invention, since it is possible to produce a stable nanoemulsion using a homomixer without a high pressure emulsifier, it is much more advantageous than the conventional method for producing a nanoemulsion in terms of time and cost. In addition, in terms of stability, it is possible to manufacture a much more stable nanoemulsion than a nanoemulsion prepared using a conventional high pressure emulsifier, it can be said to be a far more advanced manufacturing method than the prior art.

Hereinafter, preferred examples, experimental examples, and comparative examples are presented to help understand the present invention. However, the following examples are merely provided to more easily understand one aspect of the present invention, and the contents of the present invention are not limited by the following examples.

Example 1-9 and Comparative Example 1-3 Preparation of Nanoemulsion Composition

The aqueous phase containing the water-soluble physiologically active ingredient, humectant and purified water was dissolved in an emulsification tank by heating (70 ° C.) to dissolve. Next, the oil phase portion containing the biolipid component, emulsifier and oil was stirred in another emulsifier and heated (70 ° C.) to dissolve. Next, an oil phase part was added to the water phase part, and a stirring was performed for 5 minutes at a speed of 10000 rpm using a homo mixer to produce a nano-sized emulsion, and then gradually cooled to prepare a nanoemulsion composition.

The weight percentages of the aqueous phase, oil phase, and total nanoemulsion used are shown in the table below. As the ceramide of the biolipid component, hydroxypropyl bispalmitamide MEA, which is a pseudo ceramide, was used.

division	Example 1	Example 2	Example 3	Example 4	Example 5	Example 6	Example 7	Example 8	Example 9
Purified water	Remaining amount	Remaining amount	Remaining amount	Remaining amount	Remaining amount	Remaining amount	Remaining amount	Remaining amount	Remaining amount
Disodium ID	0.02	0.02	0.02	0.02	0.02	0.02	0.02	0.02	0.02
Polyglyceryl-10 Stearate	0.5	One	One	0.2	0.8	One	-	2	-
Polyglyceryl-3 Methylglucose Distearate	0.5	One	One	0.8	0.2	-	One	-	2
Polyglyceryl-10 Behenate / Eicosadiate	-	-	-	-	-	-	-	-	-
Methoxypig-114 / polyepsiloncaprolactone	-	-	-	-	-	-	-	-	-
Hydroxypropyl Bispalmitamide MEA	0.2	0.2	0.2	0.2	0.2	0.2	0.2	0.2	0.2
cholesterol	0.2	0.2	0.2	0.2	0.2	0.2	0.2	0.2	0.2
Stearic acid	0.2	0.2	0.2	0.2	0.2	0.2	0.2	0.2	0.2
Octyldodecanol	1 to 3	1 to 3	1 to 3	1 to 3	1 to 3	1 to 3	1 to 3	1 to 3	1 to 3
Propanediol	-	-	10	-	-	-	-	-	-
glycerin	-	-	3	-	-	-	-	-	-
Glyceryl Caprylate	0.1	0.1	0.1	0.1	0.1	0.1	0.1	0.1	0.1
Ethylhexylglycerin	0.05	0.05	0.05	0.05	0.05	0.05	0.05	0.05	0.05

division	Comparative Example 1	Comparative Example 2	Comparative Example 3
Purified water	Remaining amount	Remaining amount	Remaining amount
Disodium ID	0.02	0.02	0.02
Polyglyceryl-10 Stearate	-	-	-
Polyglyceryl-3 Methylglucose Distearate	-	-	-
Polyglyceryl-10 Behenate / Eicosadiate	One	One	-
Methoxypig-114 / polyepsiloncaprolactone	-	-	One
Hydroxypropyl Bispalmitamide MEA	0.2	0.2	0.2
cholesterol	0.2	0.2	0.2
Stearic acid	0.2	0.2	0.2
Octyldodecanol	1 to 3	1 to 3	1 to 3
Propanediol	-	10	-
glycerin	-	3	-
Glyceryl Caprylate	0.1	0.1	0.1
Ethylhexylglycerin	0.05	0.05	0.05

Experimental Example 1 Measurement of Average Particle Size and Particle Size Distribution

The average particle size and particle size distribution of the nanoemulsions prepared by the above Examples and Comparative Examples were measured using a dynamic light scattering method (Dynamic Light Scattering, Instrument Model: Zetasizer Nano ZS, Malvern, UK). The scattering angle was fixed at 90 degrees and the measurement temperature was maintained at 25 degrees.

The specific results are shown in the table below.

division	Type of surfactant or emulsifier	Average particle size (nm)	PDI value
Example 6	Polyglyceryl-10 Stearate 1%	295.6	0.541
Example 7	Polyglyceryl-3 Methylglucose Distearate 1%	370.3	0.48
Example 1	0.5% polyglyceryl-10 stearate, 0.5% polyglyceryl-3 methylglucose distearate	167.6	0.268
Example 8	Polyglyceryl-10 Stearate 2%	282	0.445
Example 9	Polyglyceryl-3 Methylglucose Distearate 2%	300.5	0.419
Example 2	1% polyglyceryl-10 stearate, 1% polyglyceryl-3 methylglucose distearate	176.6	0.272
Example 3	0.5% polyglyceryl-10 stearate, 0.5% polyglyceryl-3 methylglucose distearate, 10% propanediol, 3% glycerin	158.02	0.219
Comparative Example 1	Polyglyceryl-10 Behenate / Eicosadiate 1%	409.9	0.652
Comparative Example 2	Polyglyceryl-10 Behenate / Eicosadiate 1%, Propanediol 10%, Glycerin 3%	418.4	0.707
Comparative Example 3	Methoxypig-114 / polyepsiloncaprolactone 1%	530.2	0.453
Example 4	Polyglyceryl-10 Stearate 0.2%, Polyglyceryl-3 Methylglucose Distearate 0.8%	187.1	0.271
Example 5	Polyglyceryl-10 Stearate 0.8%, Polyglyceryl-3 Methylglucose Distearate 0.2%	183.02	0.261

Experimental Example 2 Stability Check

In order to determine the stability of the nanoemulsion according to the Examples and Comparative Examples, the prepared nanoemulsion was stored in a thermostat at room temperature (21 ° C-23 ° C) and 45 ° C for 2 months to observe the appearance change of the nanoemulsion. In addition, after keeping for 12 hours in a constant temperature bath and kept for 12 hours, and maintained for 12 hours and then again for 12 hours, and then cooled to -10 ℃ and maintained for 12 hours in a thermostat for 2 months after storage of the nanoemulsion The change in appearance was observed. The results are shown in the table below.

division	Type of surfactant or emulsifier	Stability
		Room temperature			45 degrees			cycle
		1 week	4 Weeks	8 Weeks	1 week	4 Weeks	8 Weeks	3 days	1 week	4 Weeks
Example 1	0.5% polyglyceryl-10 stearate, 0.5% polyglyceryl-3 methylglucose distearate	Good	Good	Good	Good	Good	Good	Good	Good	Good
Example 2	1% polyglyceryl-10 stearate, 1% polyglyceryl-3 methylglucose distearate	Good	Good	Good	Good	Good	Good	Good	Good	Good
Example 3	0.5% polyglyceryl-10 stearate, 0.5% polyglyceryl-3 methylglucose distearate, 10% propanediol, 3% glycerin	Good	Good	Good	Good	Good	Good	Good	Good	Good
Example 4	Polyglyceryl-10 Stearate 0.2%, Polyglyceryl-3 Methylglucose Distearate 0.8%	Good	Good	Good	Good	Good	Good	Good	Good	Good
Example 5	Polyglyceryl-10 Stearate 0.8%, Polyglyceryl-3 Methylglucose Distearate 0.2%	Good	Good	Good	Good	Good	Good	Good	Good	Good
Comparative Example 1	Polyglyceryl-10 Behenate / Eicosadiate 1%	Separation	Separation	Separation	Separation	Separation	Separation	Separation	Separation	Separation
Comparative Example 2	Polyglyceryl-10 Behenate / Eicosadiate 1%, Propanediol 10%, Glycerin 3%	Separation	Separation	Separation	Separation	Separation	Separation	Separation	Separation	Separation
Comparative Example 3	Methoxypig-114 / polyepsiloncaprolactone 1%	Separation	Separation	Separation	Separation	Separation	Separation	Separation	Separation	Separation

As can be seen from the table, Examples 1 to 5 showed good stability at room temperature, 45 ° C., or circulating conditions. Examples 6 and 7 were stable for 1 week at room temperature and 45 ° C., Examples 8 and 9 were stable for 1 week at room temperature and 45 ° C., and up to 3 days in circulating conditions, and Comparative Examples 1 to 3 were room temperature Stable emulsion conditions were not maintained at both 45 ° C. and cycling conditions.

Experimental Example 3 Additional Stability Check for Example 3

Through evaluation of the Examples and Comparative Examples, it was confirmed that the nanoemulsion composition of Example 3 is very good in terms of average particle size and PDI value, and also good in terms of stability regardless of temperature, the nanoemulsion of Example 3 Further stability assessments were made.

Specifically, the particle size and the PDI value of the nanoemulsion of Example 3 were observed to change over time and the results are shown in the table below. This is confirmed by the above-mentioned dynamic laser light scattering method. The results of the table below shows that the average particle size and PDI values of the nanoemulsion of Example 3 were maintained up to 16 weeks after preparation.

Example 3	Average particle size (nm)	PDI value
0 days	145.7	0.235
1 week	154	0.224
2 weeks	151.9	0.23
3 weeks	154.7	0.231
4 Weeks	153.8	0.217
6 Weeks	154.7	0.206
8 Weeks	165.1	0.211
12 Weeks	167.9	0.218
16 Weeks	181.6	0.204

1 is a view showing the particle distribution of the Example 3 nanoemulsion in consideration of the average particle size and PDI value change in the table, it can be seen that the particle size and PDI is maintained even after a time until 16 weeks after the preparation of the nanoemulsion composition .

2 and 3 show the particle distribution of the nanoemulsion of Example 3 at 4 ° C. and 45 ° C., respectively, and it can be seen that the particle distribution is excellently maintained up to 16 weeks even under refrigeration conditions and high temperature conditions.

Experimental Example 4 Skin Irritation Test

In the case of conventional emulsion products, PEG-based emulsifiers to which ethylene oxide has been added have been mainly used. In the case of PEG-based polymers, there is a disadvantage in that ethylene glycol may cause a risk of containing dioxin and skin irritation. The present invention confirmed the skin irritation based on the nanoemulsion of Example 3 to identify the absence of such skin irritation.

Specifically, the nanoemulsion of Example 3 targets 30 healthy adult men and women who do not have psoriasis, acne, eczema, and other skin diseases (except those who are pregnant, nursing mothers, contraceptives or antihistamines). A closed patch test was conducted. 20 μl of the nanoemulsion composition of Example 3 was patched on the back of the subject using an IQ chamber (Chemotechique MB Diagnostics, Sweden). After 48 hours or 72 hours, the patch was removed and the skin reaction was read for 30 minutes to 24 hours. Skin response readings were performed according to the following table, which is a modified test standard referring to the test standards of DTFA guidline (1981) and Frosch & Kligman (1979).

score		Characteristic
0	No response
One	Weak erythema of spotty or diffuse
2	Common erythema
3	Severe erythema with edema
4	Severe erythema with edema and vesicles

As a result, it was confirmed that there is no skin irritation even if the patch for 48 hours to 72 hours as shown in the table below.

Time from patch to patch removal	48 hours				72 hours
score	1 or more	2 or more	3 or more	4 or more	1 or more	2 or more	3 or more	4 or more
Number of subjects	0	0	0	0	0	0	0	0
Mean Score	0.00
Judgment	Non-irritating

Claims (22)

1. Nanoemulsion composition comprising polyglyceryl stearate as emulsifier.
2. The nanoemulsion composition of claim 1, wherein the polyglyceryl stearate is two or more kinds.
3. The nanoemulsion composition of claim 2, wherein the polyglyceryl stearate comprises polyglyceryl-10 stearate and polyglyceryl-3 alkylglucose distearate.
4. The nanoemulsion composition of claim 1, wherein the polyglyceryl stearate is 0.1 to 10% by weight relative to the total weight of the nanoemulsion composition.
5. The method of claim 3, wherein the polyglyceryl stearate is composed of polyglyceryl-10 stearate and polyglyceryl-3 alkylglucose distearate, and polyglyceryl-10 stearate and polyglyceryl-3 alkylglucose. The weight ratio of distearate is 1: 7 to 7: 1, nanoemulsion composition.
6. The nanoemulsion composition of claim 3, wherein the alkyl of the polyglyceryl-3 alkylglucose distearate is C ₁ to C ₆ alkyl.
7. The nanoemulsion composition of claim 1, wherein the nanoemulsion composition further comprises a lipid component.
8. The nanoemulsion composition of claim 7, wherein the lipid component comprises any one or more selected from the group consisting of ceramide, cholesterol, and stearic acid.
9. The nanoemulsion composition of claim 8, wherein the weight ratio of ceramide to polyglyceryl stearate is 1: 3 to 1:20.
10. The nanoemulsion composition of claim 8, wherein the ceramide is 0.01 to 1 wt% based on the total weight of the nanoemulsion.
11. The nanoemulsion composition of claim 8, wherein the ceramide comprises natural ceramide or synthetic ceramide.
12. The nanoemulsion composition of claim 11, wherein the synthetic ceramide comprises a compound represented by Formula 1 below.

    [Formula 1]

    
13. The nanoemulsion composition of claim 1, wherein the nanoemulsion composition further comprises any one or more of C ₂ to C ₈ polyhydric alcohols or glycerin.
14. The nanoemulsion composition of claim 13, wherein the C ₂ to C ₈ polyhydric alcohol is propanediol.
15. The nanoemulsion composition of claim 1, wherein the nanoemulsion composition is a cosmetic composition.
16. The nanoemulsion composition of claim 1, wherein the nanoemulsion composition is a mist formulation.
17. The nanoemulsion composition of claim 1, wherein the nanoemulsion composition has an average particle size of 400 nm or less.
18. The nanoemulsion composition of claim 1, wherein the nanoemulsion composition has a polydispersity index (PDI) of 0.55 or less.
19. The nanoemulsion composition of claim 1, wherein the nanoemulsion composition remains stable at 4 ° C., or 45 ° C. for at least 16 weeks.
20. The nanoemulsion composition of claim 1, wherein the nanoemulsion composition is stable for at least 4 weeks under conditions of 12 hours alternately between −10 ° C. and 45 ° C. 6.
21. The nanoemulsion composition of claim 1, wherein the nanoemulsion composition does not include a polyethylene glycol (PEG) -based compound.
22. 20. A method of preparing a nanoemulsion composition according to any one of claims 1 to 19, comprising a dispersion using a homomixer.

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