CN117122525A

CN117122525A - Lipid vesicles containing 7-dehydrocholesterol, cosmetic composition containing the same as active ingredient, and preparation method thereof

Info

Publication number: CN117122525A
Application number: CN202310572279.XA
Authority: CN
Inventors: 徐在龙; 柳知秀; 李叡智; 朴宁娥; 姜有真
Original assignee: Cosymanja Cosmetics China Co ltd; Cosmecca Korea Co Ltd
Current assignee: Cosymanja Cosmetics China Co ltd; Cosmecca Korea Co Ltd
Priority date: 2022-05-25
Filing date: 2023-05-19
Publication date: 2023-11-28
Also published as: KR20230164334A

Abstract

Lipid vesicles containing 7-dehydrocholesterol, cosmetic compositions containing the same as an active ingredient, and methods of preparing the same. The present application relates to a lipid vesicle containing 7-dehydrocholesterol, which is a microbial D derivative, and a cosmetic composition containing the same as an active ingredient, wherein the lipid vesicle containing 7-dehydrocholesterol is excellent in dispersion stability by further adding pentaerythritol tetra-di-t-butylhydroxyhydrocinnamate to 7-dehydrocholesterol, thereby providing a novel delivery system.

Description

Lipid vesicles containing 7-dehydrocholesterol, cosmetic composition containing the same as active ingredient, and preparation method thereof

Technical Field

The present application relates to a lipid vesicle containing 7-dehydrocholesterol, which is a microbial D derivative, and a cosmetic composition containing the same as an active ingredient, and more particularly, to a lipid vesicle, which has improved dispersion stability by further adding pentaerythritol tetra-di-t-butylhydroxyhydrocinnamate to 7-dehydrocholesterol, a cosmetic composition containing the same, and a method for preparing the same.

Background

In general, the skin acts as a barrier to penetration of the cosmetic active ingredient. Therefore, an effective delivery system for effectively delivering an active ingredient to the skin has been studied, and liposome technology using phospholipids has been applied in many cases.

Liposomes are closed vesicles formed from lipid bilayer membranes, the vesicle space of which contains aqueous cosmetic ingredients. The types of liposomes can be classified according to their size, and are largely classified into small unilamellar vesicles (SUV, small unilamellar Vesicle), large unilamellar vesicles (LUV, large unilamellar Vesicle), and giant phospholipid vesicles (GUV, giant unilamellar Vesicle). Among them, liposomes composed of 5 or more bilayer membrane structures are called multilamellar vesicles (MLV, multilamellar Vesicle).

In addition, the nanoemulsion can be loaded with a milky cosmetic ingredient, and is characterized by being formed into a single membrane structure unlike liposomes. The included milky components of the nanoemulsion may be destroyed due to the permeation with the external water phase. In order to prevent this, the solid lipid nanoparticles (SLNs, soild Lipid Nanoparticle) change the liquid emulsion component into solid lipid, and the SLNs have little permeation from the outside, so that the active ingredient can be well preserved. However, the emulsion component is changed into solid lipid, and the coagulation of the nanoemulsion occurs with the passage of time.

Lipid vesicles (niosomes) are bilayer membrane transporters composed of nonionic surfactants, are biodegradable, can encapsulate polar and nonpolar substances, and are more stable than liposomes, thus becoming an alternative for solving problems related to mass production and stability of liposomes.

Lipid vesicles are similar in structure to liposomes, but lipid vesicles are prepared from uncharged single-chain surfactants and cholesterol, whereas liposomes are prepared from double-chain phospholipids, and thus there are differences in the properties of liposomes and lipid vesicles. The cholesterol content of the vesicle-stabilizing membrane (Membranes) is determined. Lipid vesicles are composed of nonionic surfactants, and they cannot function like lipids only by the nonionic surfactants themselves, and need to be prepared as components similar to natural lipids, and for this purpose, the following methods are mainly used: the main chain of glycerin (glycerin) is grafted with Phosphate (Phosphate) derivative, so that the glycerin (glycerin) has amphipathy for standby. The lipid vesicles can encapsulate polar and nonpolar substances and have osmotic pressure activity, and have the advantage that the surfactant adopted in the preparation process does not need to have special conditions in storage and use.

7-dehydrocholesterol (7-DHC) is converted into vitamin D3 by sunlight as a provitamin (provitamin) form of vitamin D3. 7-dehydrocholesterol has the following structural drawbacks: is very unstable to light and heat, is easily converted into other various substances by ultraviolet rays and temperature, and reacts with oxygen in the air to exhibit deterioration, resulting in a decrease in activity. However, little research has been done on how to stabilize 7-dehydrocholesterol.

In view of this, the present inventors have repeatedly studied lipid vesicles containing 7-dehydrocholesterol and giving excellent long-term dispersion stability, and have devised the present application.

[ Prior Art literature ]

(patent document 1) Korean laid-open patent publication No. 10-2016-0103718

(patent document 2) Korean registered patent publication No. 10-2307408

Disclosure of Invention

Problems to be solved

The purpose of the present application is to provide lipid vesicles which are obtained by further mixing pentaerythritol tetra-di-t-butylhydroxyhydrocinnamate with unstable 7-dehydrocholesterol and encapsulating the lipid vesicles, and to provide lipid vesicles which contain 7-dehydrocholesterol but have improved dispersion stability, and to provide cosmetic compositions containing the lipid vesicles as active ingredients.

Solution to the problem

In order to achieve the above object, according to the present application, the lipid vesicles having increased stability may contain nonionic surfactants, cosurfactants, lipophilic antioxidants, phytosterols (phytosterols), phytocholesterol, polyols (polyols), oils, 7-dehydrocholesterol and purified water.

Wherein the contents of the components are as follows: the total weight of the lipid vesicles is 1-10 wt%, the cosurfactant is 0.001-5 wt%, the lipophilic antioxidant is 0.01-0.5 wt%, the phytosterol (phytosterol) is 1-10 wt%, the phytocholesterol is 1-10 wt%, the polyol (polyol) is 5-10 wt%, the oil is 5-20 wt%, the 7-dehydrocholesterol is 0.001-20 wt%, and the purified water is 50-85 wt%.

In the present application, the nonionic surfactant may have a Hydrophilic-lipophilic balance (HLB) of 3 to 6, specifically 4 to 6, but is not necessarily limited thereto, and may be an emulsifier (emulsifier or emulsifying agent), more specifically, a nonionic surfactant having the property of a water-soluble emulsifier and capable of dissolving cholesterol or the like in an aqueous solvent may be used.

Specifically, the nonionic surfactant is at least one or more selected from the group consisting of: polyglycerol-10 laurate, sorbitan esters (sorbitan esters), polyoxyethylene sorbitan fatty acid esters (polyoxyethylene sorbitan fatty acid esters), polyoxyethylene alkyl ethers (polyoxyethylene alkyl ether), poloxamers (poloxamers), sucrose diesters (Saccharose diester), or mixtures thereof, but are not limited thereto and may be used as long as they have similar properties and are known nonionic surfactants.

And, the cosurfactant may contain sodium stearoyl glutamate (sodium stearoyl glutamate) as a negative ion surfactant.

And, the lipophilic antioxidant may comprise pentaerythritol tetra-di-t-butyl hydroxy hydrocinnamate.

The phytosterol (phytosterol) may be one or more selected from the group consisting of: beta-sitosterol, beta-campesterol and stigmasterol are preferably, but not limited to, campesterol.

The polyol (polyol) may be one or more selected from the group consisting of: glycerol, 1, 3-propanediol (propanediol), hexanediol, dipropylene glycol, propylene glycol, butylene glycol, and pentylene glycol are preferable, but glycerol, 1, 3-propanediol are not limited thereto.

The oil may be one or more selected from the group consisting of: hydrocarbon oils composed of squalane (squarane), hydrogenated polyisobutene (hydrogenated polyisobutene), hydrogenated poly (C6-14 olefin) (hydrogenated poly (C6-14 olefin)), C13-15 alkane (alkane), and the like; ester oil composed of isopropyl palmitate (iospropyl palmitate), isopropyl myristate (isopropyl myristate), butyl octanol salicylate (butyloctyl salicylate) and the like; vegetable oil comprising macadamia nut seed oil, sunflower seed oil, argan kernel oil, white pool flower seed oil (meadowfoam seed oil), etc.; and glyceride oil (glyceride oil) composed of caprylic/capric triglyceride (capric/capric triglyceride) and the like, preferably, at least one or more selected from the following components: squalane (squarane), macadamia nut seed oil, cetyl ethyl hexanoate (cetyl ethylhexanoate), caprylic/capric triglyceride (capric/capric triglyceride), but are not so limited.

And, the lipid vesicle may contain a preservative in an amount of 0.01 to 2% by weight, based on the total weight of the lipid vesicle, and the preservative may be at least one or more selected from the following components: 1, 2-hexanediol, ethylhexyl glycerol (ethylhexyl glycerin), caprylic acid glyceride (glyceryl caprylate), caprylyl glycol (capryl glycol), phenoxyethanol (phenoxythanol), but is not limited thereto.

In a specific embodiment of the present application, polyglycerol-10 laurate is used as a nonionic surfactant, sodium stearyl glutamate (sodium stearoyl glutamate) as a negative ion surfactant is used as a cosurfactant, and pentaerythritol tetra-di-t-butylhydroxyhydrocinnamate is used as a lipophilic antioxidant, whereby the permeability of an active material and the stability of lipid vesicles can be greatly improved.

According to the application, the lipid vesicles contain 7-dehydrocholesterol and are characterized in that: the particle size is 100 to 200nm, preferably 150 to 180nm. Wherein, when the particle size is less than 100nm, the capturing efficiency of the active ingredient is low, and when the particle size exceeds 200nm, the stability is lowered.

Also, a cosmetic composition containing the lipid-like vesicle of the present application as an active ingredient can be produced.

At this time, the content of the lipid vesicles may be 0.001 to 50 wt%, preferably may be 0.01 to 40 wt%, and further preferably may be 0.1 to 30 wt% in the total weight of the cosmetic composition. Wherein, at a content of less than 0.001 wt%, the efficacy provided by the active ingredient is very small, and at a content of more than 50 wt%, the efficacy provided by the active ingredient is not increased as compared with the added amount thereof, and thus, the economical efficiency is not preferable.

In addition, it was confirmed that the cosmetic composition including the lipid vesicles containing 7-dehydrocholesterol according to the present application can achieve excellent moisturizing effect on skin, and thus, the lipid vesicles containing 7-dehydrocholesterol can be used to improve skin moisturizing ability.

As described above, the cosmetic composition in which the lipid vesicles containing 7-dehydrocholesterol are contained may be in the form of skin care, body skin care, face cream, hair care, emulsion, essence or foundation.

According to the present application, in a method for producing a lipid vesicle containing 7-dehydrocholesterol,

mixing nonionic surfactant, cosurfactant, lipophilic antioxidant, phytosterol (phytosterol), vegetable cholesterol, polyalcohol (polyol), oil, 7-dehydrocholesterol and purified water,

the next stage comprises the steps of:

step S1: dissolving nonionic surfactant, plant cholesterol and phytosterol (phytosterol), cooling, and preparing substrate;

step S2: dissolving the prepared substrate;

step S3: heating polyol (polyol), cosurfactant and purified water, and adding the polyol, cosurfactant and purified water into the dissolved substance in the step S2;

step S4: heating 7-dehydrocholesterol, pentaerythritol tetra-di-tert-butyl hydroxy hydrocinnamate and oil to dissolve the same;

step S5: and (3) adding the dissolved product in the step (S4) into the dissolved product in the step (S3) to realize emulsification, and then cooling and defoaming to obtain the lipid-like vesicles.

In this case, the step S1 melts and dissolves the nonionic surfactant, the plant cholesterol and the plant sterol (phytosterol) at a temperature of 90 to 100 ℃ and cools the mixture at room temperature to prepare the substrate.

And, the step S2 heats the prepared substrate to 90 to 100 ℃ to dissolve it.

In the step S3, the heating temperature of the polyol (polyol), the cosurfactant and purified water is 80 ℃ or higher.

And, in the step S5, the dissolved product in the step S4 is put into the dissolved product in the step S3 to realize emulsification, and then the dissolved product is continuously passed through a high-pressure micro-emulsifier for 3 times at 1000bar, and then the dissolved product is cooled and defoamed to obtain the lipid-like vesicle.

Wherein, the content of each component adopted in each step is as follows: the total weight of the lipid vesicles is 1-10 wt%, the cosurfactant is 0.001-5 wt%, the lipophilic antioxidant is 0.01-0.5 wt%, the phytosterol (phytosterol) is 1-10 wt%, the phytocholesterol is 1-10 wt%, the polyol (polyol) is 5-10 wt%, the oil is 5-20 wt%, the 7-dehydrocholesterol is 0.001-20 wt%, and the purified water is 50-85 wt%.

The lipid vesicles prepared according to the application may be mixed with a cosmetic composition of a specific dosage form in a certain amount to prepare a cosmetic composition containing the lipid vesicles.

In this case, the content of the lipid vesicles containing 7-dehydrocholesterol in the present application may be 0.001 to 50% by weight in the entire weight of the cosmetic composition.

Effects of the application

The lipid-like vesicles according to the application can provide excellent dispersion stability of labile 7-dehydrocholesterol to provide novel delivery systems.

Drawings

FIG. 1 is a graph showing the particle size distribution of lipid vesicles in example 1, comparative example 1 and comparative example 2 according to the present application.

FIG. 2 is a graph showing the zeta potential difference distribution of lipid vesicles in example 1, comparative example 1 and comparative example 2 according to the present application.

FIG. 3 is a graph showing the results of long-term stability test of lipid vesicles in example 1, comparative example 1 and comparative example 2 according to the present application.

FIG. 4 is a graph showing evaluation of moisturizing and continuous moisturizing ability of lipid-like vesicles in example 1, comparative example 1, and comparative example 2 according to the present application.

FIG. 5 is a graph showing the evaluation of improvement in the amount of moisture loss of the hard skin of lipid vesicles in example 1, comparative example 1 and comparative example 2 according to the present application.

FIG. 6 is a graph showing evaluation of moisturizing ability of cosmetics according to example 1 and cosmetics according to comparative example of the present application.

FIG. 7 is a graph showing evaluation of improvement in the moisture loss of the hard skin of a cosmetic containing lipid vesicles in example 1 according to the application and a comparative cosmetic.

FIG. 8 is a graph showing cytotoxicity test of lipid vesicles according to example 1 of the application (NHF in FIG. 8 (a), haCaT in FIG. 8 (B), B16F10 in FIG. 8 (c), and RAW264.7 in FIG. 8 (d)).

FIG. 9 is a graph showing evaluation of (a) apoptosis inhibition, (b) NO production inhibition ability, and (c) MMP-1 production inhibition by lipid-like vesicles in example 1 according to the present application.

Detailed Description

Hereinafter, preferred embodiments of the present application will be described in detail with reference to the accompanying drawings. However, the present application is not limited to the embodiments described herein, and may be embodied in other forms.

The term "lipid vesicle" used in the present application is a vesicle (non-ionic surfactant-based vesicle) based on a nonionic surfactant, and means a micro-device having a hydrophilic space formed inside and a hydrophobic outside and having a closed bilayer lipid membrane.

The term "nonionic surfactant" as used herein is a surfactant that cannot be dissociated into ions, also referred to as a nonionic surfactant or nonionic surfactant. The nonionic surfactant has properties different from those of the ionic surfactant and may be optionally mixed with other surfactants or electrolytes. The shampoo has the characteristics of improving the thickening performance of shampoo matrix, improving the stability at low temperature, having excellent cleaning effect, little foam and the like, and can be used for various purposes such as dispersing agents, emulsion agents, detergents, dyeing aids and the like.

The term "phytosterol" as used herein is generated from plants (corn, soybean, vegetable oil seed, etc.) as cholesterol-like phytosterols, and includes phytosterols and phytostanols. As cholesterol is one of the components of cell membranes in humans, phytosterol (phytosterol) is a necessary component in the formation of parts of plant cell membranes. The structure of the phytosterol (phytosterol) is similar to that of cholesterol, so that the phytosterol can repair the protective film of the stratum corneum, normal functions can be realized, skin roughening is avoided, and the phytosterol has a strong anti-inflammatory effect.

< example 1> preparation of lipid vesicles containing 7-dehydrocholesterol and pentaerythritol tetra-di-t-butylhydroxyhydrocinnamate

The compositions for preparing lipid vesicles containing 7-dehydrocholesterol and pentaerythritol tetra-di-tert-butylhydroxyhydrocinnamate according to the present application are shown in Table 1 below.

[ Table 1 ]

The substrate is prepared by melting polyglycerol-10 laurate, plant cholesterol, phytosterol (campesterol) at a temperature of 90 to 100deg.C, and then cooling at room temperature.

Heating the prepared base material to 90 ℃ for melting, then heating glycerol, sodium stearoyl glutamate (sodium stearoyl glutamate), purified water and 1, 2-hexanediol to more than 80 ℃, putting the base material into a dissolution place, heating and dissolving 7-dehydrocholesterol, squalane (squarane), macadamia nut seed oil and pentaerythritol tetra-di-tert-butyl hydroxy hydrocinnamate, putting the base material into the dissolution place, and continuously passing through the base material for 3 times at 1000bar by using a high-pressure micro-emulsifier after emulsification, and then cooling and defoaming the base material to obtain the lipid-like vesicles.

< formulation example 1> toner containing example 1 was prepared

Disodium EDTA (discodium EDTA), glycerin, 1, 3-propanediol, carbomer (carbomer) were dispersed in purified water, an emulsifying system was added, which was dissolved in an aqueous phase heated to 70 to 75 ℃, and then stirred for 5 minutes using an AGI mixer. Tromethamine is added at a temperature of 60 ℃ to 65 ℃ and then stirred with an AGI mixer for three minutes and neutralization is carried out. 1, 2-hexanediol and ethylhexyl glycerol (ethylhexyl glycerin) were added at 45℃and stirred for three minutes, followed by cooling to 30 ℃. Then, the lipid vesicles of example 1 were put into the vessel, stirred and deaerated for 3 minutes to prepare a toner formulation. The components for preparing the toner containing the lipid-like vesicles in example 1 according to the present application are shown in table 2 below.

[ Table 2 ]

< formulation example 2> preparation of skin lotion containing example 1

Transparent emulsion systems were prepared by heating cetyl ethylhexanoate (cetyl ethylhexanoate), cetostearyl alcohol, glyceryl stearate, C14-22 alcohol, C12-20 alkyl glycoside, glucose, caprylic/capric triglyceride (capric/capric triglyceride) to 75℃to 80℃and dissolving.

Disodium EDTA (disodium EDTA), glycerin, 1, 3-propanediol, carbomer (carbomer) were dispersed in purified water, a transparent emulsifying system was added, which was dissolved in an aqueous phase heated to 70 to 75 ℃, and then emulsification was performed using a homomixer at 3500 to 5000rpm for five minutes.

Tromethamine is added at a temperature of 60 ℃ to 65 ℃ and then, with a homomixer, stirred at 3000 to 3500rpm for three minutes and neutralization is carried out. 1, 2-hexanediol and ethylhexyl glycerol (ethylhexyl glycerin) were added at 45℃and stirred for three minutes, and then cooled to 30 ℃. Then, the lipid vesicles of example 1 were put into the skin care solution, stirred and deaerated for three minutes to prepare a skin care lotion formulation.

The compositions for preparing lotions containing the lipid-like vesicles of example 1 described herein are shown in Table 3 below.

[ Table 3 ]

< formulation example 3> preparation of face cream containing example 1

Cetyl ethyl hexanoate (cetyl ethylhexanoate), cetostearyl alcohol, glycerol stearate were heated to 75 ℃ to 80 ℃ to dissolve, and a transparent emulsion system was prepared.

Disodium EDTA (dis EDTA), glycerin, 1, 3-propanediol, cetostearyl oleate, sorbitan olivate, carbomer (carbomer) are dispersed in purified water, an emulsifying system is added, which is dissolved in an aqueous phase heated to 70 ℃ to 75 ℃, and then, emulsification is performed at 3500 to 5000rpm using a homomixer for five minutes. Tromethamine is added at a temperature of 60 ℃ to 65 ℃ and then, a homomixer is used, stirred for three minutes at 3000 to 3500rpm, and neutralization is performed. 1, 2-hexanediol and ethylhexyl glycerol (ethylhexyl glycerin) were added at 45℃and stirred for three minutes, followed by cooling to 30 ℃. Then, the lipid vesicles of example 1 were put into the vessel, stirred and deaerated for three minutes to prepare a cream formulation.

The components for preparing the cream containing the lipid-like vesicles of example 1 according to the application are shown in table 4 below.

[ Table 4 ]

Comparative example 1 preparation of lipid vesicles without added 7-dehydrocholesterol and pentaerythritol tetra-di-t-butylhydroxyhydrocinnamate

Lipid vesicles were prepared in the same manner as in example 1, except that 7-dehydrocholesterol and pentaerythritol tetra-di-t-butylhydroxyhydrocinnamate were not added.

The composition of the lipid vesicles to which the 7-dehydrocholesterol and pentaerythritol tetra-di-t-butylhydroxyhydrocinnamate according to the present application were not added was prepared as shown in Table 5 below.

[ Table 5 ]

Comparative example 2 preparation of lipid vesicles containing 7-dehydrocholesterol

Lipid vesicles were prepared in the same manner as in example 1, except that pentaerythritol tetra-di-t-butylhydroxyhydrocinnamate was not added.

The components of the lipid vesicles prepared with 7-dehydrocholesterol are shown in Table 6 below.

[ Table 6 ]

< test example 1> particle distribution and potential detection

The particle distributions of example 1, comparative example 1 and comparative example 2 were examined using photo, ELS-Z, and the results are shown in fig. 1.

As shown in FIG. 1 (a), FIG. 1 (b) and FIG. 1 (c), the particle sizes were about 162.1nm, 164.7nm and 179.5nm, respectively. As shown in FIG. 2 (a), FIG. 2 (b) and FIG. 2 (c), the potential of the particles was-78.7 mV, -71.5mV and-58.9 mV, respectively, and it was confirmed that the dispersion stability of example 1 was most excellent.

Test example 2 detection of long-term stability

To evaluate the dispersion stability of the whole lipid vesicle sample by numerical value, a stability analyzer (turbinan) was used, and analysis was performed at a temperature of 40 ℃ for about four hours, and the results thereof are shown in fig. 3. The higher the dispersion stability index (stability analyzer stability index (turbiscan Stability Index, TSI)) value, the worse the stability, and the phenomenon of stability degradation can be quantitatively derived.

From the analysis results, as shown in FIG. 3, it was found that the TSI value of example 1 was lower than that of comparative example 2 containing only 7-dehydrocholesterol and similar to comparative example 1 containing no 7-dehydrocholesterol, and that long-term stability was achieved by further mixing pentaerythritol tetra-di-t-butylhydroxyhydrocinnamate and encapsulating lipid vesicles more stably.

< test example 3> evaluation of moisturizing ability and continuous moisturizing ability

In the preparation stage, in order to unify the detection conditions of the subjects, the test parts are kept clean and dry, and after the skin is kept calm for a minimum of 30 minutes, the test is started in a place where the constant temperature and humidity (22+/-2 ℃ R.H.40-60%) can be maintained. In the detection phase, the test product was applied at a concentration of 2mg/cm using a micropipette (micropipette) ² Is applied to a selected test site (5 cmX cm) of the forearm portion. The products were tested before, after and 3 hours after use, 3 times in total, and the average value was determined from the 3 values. Skin moisture was detected using an aversion moisture detector (Aphrodite moisture checker) MC-1000.

As a result of the test, as shown in fig. 4, the moisturizing force was increased by about 90.8% after the application of example 1, and the moisturizing force was increased by about 67.4% and continued after the application for 3 hours. It was confirmed that the moisturizing effect was more excellent than comparative example 1 by about 36.2% and more excellent than comparative example 2 by about 24.5% after 3 hours of application of example 1.

When applied to a dosage form, the moisture retention was increased by about 92.2% after the dosage form of example 1 was applied, and the moisture retention was increased by about 67.2% and continued after 3 hours of application, as shown in fig. 6. It was confirmed that the moisturizing effect was more excellent by about 23.2% after the formulation of example 1 was applied for 3 hours than the formulation not containing example 1.

< test example 4> evaluation of moisture loss amount of hard skin

In the preparation stage, in order to unify the detection conditions of the subjects, the test parts are kept clean and dry, and after the skin is kept calm for a minimum of 30 minutes, the test is started in a place where the constant temperature and humidity (22+/-2 ℃ R.H.40-60%) can be maintained. In the detection phase, the test product was applied at a concentration of 2mg/cm using a micropipette (micropipette) ² Is applied to a selected test site (5 cmX cm) of the forearm portion. The products were tested before, after and 3 hours after use, 3 times in total, and the average value was determined from the 3 values. The amount of skin moisture loss was measured using a moisture meter (Tewameter) TM 300 instrument.

As a result of the test, as shown in FIG. 5, the amount of the moisture loss of the crust was improved by about 39.5% after the application of example 1, and by about 37.9% after the application for 3 hours. It was confirmed that the effect of improving the water loss amount after 3 hours of application of example 1 was more excellent than comparative example 1 by about 16.3%, and more excellent than comparative example 2 by about 7.4%.

When applied to a dosage form, the dosage form of example 1 was applied, as shown in fig. 7, with an improvement in the moisture loss of the crust of about 39.4% and an improvement of about 43.6% after 3 hours of application. The improvement effect of the amount of water loss after 3 hours of application of the dosage form containing example 1 was about 12.1% more excellent than that of the dosage form not containing example 1.

< test example 5> cytotoxicity evaluation

To conduct the cytotoxicity test, the concentration of example 1 was brought to the minimum of 0.0625% to the maximum of 1%, and the test was conducted.

As a result, the highest concentration at which the cell viability of example 1 was 90% or more was 0.5% NHF, 0.5% HaCaT, 0.5% B16F10 and 1% RAW264.7, respectively.

In the present utility test, the concentration dependence of utility was confirmed by selecting 4 concentrations without cytotoxicity, and the results are shown in table 7 and fig. 8.

[ Table 7 ]

< test example 6> evaluation of apoptosis inhibition

At 1.5X10 in 96well plate (96 well plate) ⁴ cell/well isolates HaCaT, then cultured under cell culture conditions. After 24 hours, the culture medium was poured off, washed with PBS, and then the cells were starved with DMEM medium without FBS. The next day, a certain amount of sodium dodecyl sulfate (Sodium Dodecyl Sulfate, SDS), a negative ion surfactant, was treated with a certain concentration of the test substance and incubated for 24 hours. WST-1 reagent diluted 10-fold was injected into each well (well) at 100ul in the medium and cultured for 2 hours, and then absorbance was measured at 450nm, and the results are shown in FIG. 9(a)。

As a result of the test, the cell viability was increased by 26.4% due to SDS decrease, and was 16.1% at the highest due to the concentration-dependent increase in example 1. From this, it can be indirectly confirmed that the substance has an effect of relieving the stimulus.

< test example 7> evaluation of NO production inhibition ability

At 6X 10 in 96well plate (96 well plate) ⁴ cell/well isolate RAW264.7, and then culturing under cell culture conditions. After 24 hours, the culture medium was poured off, washed with PBS, and then the cells were starved with DMEM medium without FBS. The next day, 1ug/ml of LPS (Lipopolysaccaride) was treated and incubated with a concentration of the test substance. After 24 hours, the cell culture solution and griess reagent (griess reagent) were added in equal amounts and mixed, and then reacted at room temperature for 15 minutes. Absorbance was measured at 560nm and the amount of inflammatory mediator Nitric Oxide (NO) was determined using a standard curve obtained from Sodium nitrite (Sodium nitrite). The final amount of NO was converted into the amount of NO in a certain protein, which was compared with a negative control group, and the result thereof was shown in FIG. 9 (b).

As a result of the test, the concentration-dependent decrease in the amount of NO produced by the increase in LPS by 37.5% was found to be 40.8% at the maximum in the amount of NO produced by the increase in LPS in example 1. It can thus be indirectly confirmed that the substance has anti-inflammatory effect.

< test example 8> evaluation of inhibition of MMP-1 production

At 2.5X10 in 96well plate (96 well plate) ⁵ cells/well are isolated from HaCaT cells and then cultured under cell culture conditions. After 24 hours, the medium was poured off, washed with PBS, and then the cells were starved with DMEM medium (serum free medium) containing no FBS, and then UVB was irradiated the next day for culturing.

At 6X 10 in 96well plate (96 well plate) ³ cell/well-separated NHF, and then cultured under cell culture conditions. After 24 hours, the cells were starved using FBM medium without additives (supplements) and then, the next day, on human fibroblasts, were subjected to UVB stimulationThe HaCaT broth of (C) was treated with the reagent and cultured. After incubation for 24 hours, an assay was performed using MMP-1 enzyme-linked immunosorbent assay kit (Elisa kit), and then absorbance was measured at 450 nm. The final MMP-1 amount was converted to the amount of MMP-1 in a protein, compared to the negative control, and the results are shown in FIG. 9 (c).

As a result of the test, MMP-1 production was reduced by 26.8% due to the concentration-dependent decrease in lipid-like vesicles, with a maximum reduction of 23.6%. It can be indirectly confirmed that the substance has an anti-aging effect.

The foregoing has been described with reference to an embodiment of the present application, but it should be apparent to those skilled in the art that the present application can be variously modified and altered without departing from the spirit and scope of the present application as set forth in the following claims. Therefore, as long as the implementation of the modification substantially includes the constituent elements of the claims of the present application, it should be regarded as being included in the technical scope of the present application.

Claims

1. A lipid vesicle having increased dispersion stability, characterized in that: comprises nonionic surfactant, cosurfactant, lipophilic antioxidant, phytosterol (phytosterol), vegetable cholesterol, polyalcohol (polyol), oil, 7-dehydrocholesterol and purified water.

2. The lipid vesicle of claim 1, wherein the lipid vesicle has increased dispersion stability, and is characterized by: the contents of the components are as follows: the total weight of the lipid vesicles is 1-10 wt%, the cosurfactant is 0.001-5 wt%, the lipophilic antioxidant is 0.01-0.5 wt%, the phytosterol (phytosterol) is 1-10 wt%, the phytocholesterol is 1-10 wt%, the polyol (polyol) is 5-10 wt%, the oil is 5-20 wt%, the 7-dehydrocholesterol is 0.001-20 wt%, and the purified water is 50-85 wt%.

3. The lipid vesicle of claim 1, wherein the lipid vesicle has increased dispersion stability, and is characterized by: the nonionic surfactant is at least one or more selected from the group consisting of: polyglycerol-10 laurate, sorbitan esters (sorbitan esters), polyoxyethylene sorbitan fatty acid esters (polyoxyethylene sorbitan fatty acid esters), polyoxyethylene alkyl ethers (polyoxyethylene alkyl ether), poloxamers (poloxamers), sucrose diesters (Saccharose diester), or mixtures thereof.

4. The lipid vesicle of claim 1, wherein the lipid vesicle has increased dispersion stability, and is characterized by: the cosurfactant is sodium stearoyl glutamate (sodium stearoyl glutamate) as a negative ion surfactant.

5. The lipid vesicle of claim 1, wherein the lipid vesicle has increased dispersion stability, and is characterized by: the lipophilic antioxidant is pentaerythritol tetra-di-tert-butyl hydroxy hydrocinnamate.

6. The lipid vesicle of claim 1, wherein the lipid vesicle has increased dispersion stability, and is characterized by: the phytosterol (phytosterol) is one or more selected from the group consisting of: beta-sitosterol, beta-campesterol, stigmasterol.

7. The lipid vesicle of claim 1, wherein the lipid vesicle has increased dispersion stability, and is characterized by: the polyol (polyol) is one or more selected from the group consisting of: glycerol, 1, 3-propanediol, hexylene glycol, dipropylene glycol, propylene glycol, butylene glycol, and pentylene glycol.

8. The lipid vesicle of claim 1, wherein the lipid vesicle has increased dispersion stability, and is characterized by: the oil is one or more selected from the group consisting of: hydrocarbon oils consisting of squalane (squarane), hydrogenated polyisobutene (hydrogenated polyisobutene), hydrogenated poly (C6-14 olefins) (hydrogenated poly (C6-14 olefin)), C13-15 alkanes (alkane); ester oil composed of isopropyl palmitate (iospropyl palmitate), isopropyl myristate (isopropyl myristate), butyl octanol salicylate (butyloctyl salicylate); vegetable oil comprising macadamia nut seed oil, sunflower seed oil, argan kernel oil, and white pool seed oil (meadowfoam seed oil); and glyceride oil (glyceride oil) composed of caprylic/capric triglyceride (capric/capric triglyceride).

9. The lipid vesicle of claim 1, wherein the lipid vesicle has increased dispersion stability, and is characterized by: the particle size of the lipid vesicles is 100 to 200nm.

10. A cosmetic composition comprising the lipid-like vesicle of any one of claims 1 to 9 as an active ingredient.

11. The cosmetic composition of claim 10, wherein: the lipid vesicles are present in an amount of 0.001 to 50 wt% based on the total weight of the cosmetic composition.

12. The cosmetic composition of claim 10, wherein: the cosmetic composition is in the form of skin care, body skin care, face cream, hair care, lotion, essence or foundation.

13. A method for producing lipid vesicles having increased dispersion stability, comprising:

step S2: dissolving the prepared substrate;

14. The method for producing a lipid vesicle with increased dispersion stability according to claim 13, wherein:

in the step S1, the dissolution temperature is 90 to 100 ℃, the cooling temperature is normal temperature,

in said step S2, the dissolution temperature is 90 to 100 c,

in the step S3, the heating temperature is 80 ℃ or higher.

15. The method for producing a lipid vesicle with increased dispersion stability according to claim 13, wherein:

the nonionic surfactant is at least one or more selected from the group consisting of: polyglycerol-10 laurate, sorbitan esters (sorbitan esters), polyoxyethylene sorbitan fatty acid esters (polyoxyethylene sorbitan fatty acid esters), polyoxyethylene alkyl ethers (polyoxyethylene alkyl ether), poloxamers (poloxamers), sucrose diesters (Saccharose diester) or mixtures thereof,

the cosurfactant is sodium stearyl glutamate (sodium stearoyl glutamate) serving as a negative ion surfactant,

the phytosterol (phytosterol) is one or more selected from the group consisting of: beta-sitosterol, beta-campesterol, stigmasterol,

the polyol (polyol) is one or more selected from the group consisting of: glycerol, 1, 3-propanediol, hexanediol, dipropylene glycol, propylene glycol, butylene glycol, and pentylene glycol,

the oil is one or more selected from the group consisting of: hydrocarbon oils consisting of squalane (squarane), hydrogenated polyisobutene (hydrogenated polyisobutene), hydrogenated poly (C6-14 olefins) (hydrogenated poly (C6-14 olefin)), C13-15 alkanes (alkane); ester oil composed of isopropyl palmitate (iospropyl palmitate), isopropyl myristate (isopropyl myristate), butyl octanol salicylate (butyloctyl salicylate); vegetable oil comprising macadamia nut seed oil, sunflower seed oil, argan kernel oil, and white pool seed oil (meadowfoam seed oil); and glyceride oil (glyceride oil) composed of caprylic/capric triglyceride (capric/capric triglyceride).

16. The method for producing a lipid vesicle with increased dispersion stability according to claim 13, wherein: the contents of the components are as follows: the total weight of the lipid vesicles is 1 to 10% by weight of nonionic surfactant, 0.001 to 5% by weight of cosurfactant, 0.01 to 0.5% by weight of pentaerythritol tetra-di-t-butylhydroxyhydrocinnamate, 1 to 10% by weight of phytosterol (phytosterol), 1 to 10% by weight of vegetable cholesterol, 5 to 10% by weight of polyol (polyol), 5 to 20% by weight of oil, 0.001 to 20% by weight of 7-dehydrocholesterol, and 50 to 85% by weight of purified water.