KR20230164334A - Niosome comprising 7-dehydrocholesterol, Cosmetic compositions comprising the same as an active ingredient, and Manufacturing method thereof - Google Patents

Abstract

The present invention relates to a niosome containing 7-dehydrocholesterol, a vitamin D derivative, and a cosmetic composition containing it as an active ingredient, wherein 7-dehydrocholesterol and pentaerythrityltetra-di-t-butylhydroxyhydrocinna are added. By additionally adding mate, niosomes containing 7-dehydrocholesterol have excellent dispersion stability, thereby providing a new delivery system.

Description

Niosome comprising 7-dehydrocholesterol, cosmetic composition comprising the same as an active ingredient, and manufacturing method thereof {Niosome comprising 7-dehydrocholesterol, Cosmetic compositions comprising the same as an active ingredient, and Manufacturing method thereof}

The present invention relates to a niosome containing 7-dehydrocholesterol, a vitamin D derivative, and a cosmetic composition containing it as an active ingredient, and more specifically, to 7-dehydrocholesterol and pentaerythrityltetra-di-t-butyl. It relates to niosomes with improved dispersion stability by additionally adding hydroxyhydrocinnamate, a cosmetic composition containing the same, and a method for manufacturing the same.

In general, the skin acts as a primary penetration barrier for skin penetration of cosmetic active ingredients. Therefore, a lot of research is being done on effective delivery systems to effectively deliver active ingredients to the skin, and liposome technology using phospholipids is being widely used.

Liposomes are closed vesicles formed by a lipid bilayer, and contain cosmetic ingredients in the water phase within the vesicle space. Types of liposomes can be classified according to the size of the liposome, and can be broadly divided into SUV (small unilamellar Vesicle), LUV (Large unilamellar Vesicle), and GUV (giant unilamellar Vesicle). Among them, liposomes composed of five or more double membrane structures are called multilamellar vesicles (MLV).

Meanwhile, nanoemulsions, which can contain oily cosmetic ingredients, are characterized by a single-membrane structure, unlike liposomes. In such nanoemulsions, the encapsulated oil phase components may be destroyed by osmosis with the external water phase. To prevent this, SLN (soiled lipid nanoparticles) are made by turning the oily component of the liquid into a solid lipid. These SLNs have little osmotic effect with the outside, so the active ingredients are well preserved. However, since the oil component is a solid lipid, the nanoemulsion hardens over time.

Niosome is a double membrane transporter composed of nonionic surfactant, is biodegradable, can encapsulate polar and non-polar substances, and is more stable than liposomes, so it was developed as an alternative to overcome problems related to large-scale production and stability of liposomes. there is.

Although niosomes and liposomes are structurally similar, differences in properties exist between liposomes and niosomes because niosomes are manufactured from uncharged single-chain surfactants and cholesterol, while liposomes are manufactured from double-chain phospholipids. The stabilization of these endoplasmic reticulum depends on the cholesterol component that maintains the membrane. Niosomes composed of non-ionic surfactants cannot be expected to play the same role as lipids with the non-ionic surfactants alone, and must be made to resemble natural lipid components. For this purpose, phosphate derivatives are mainly used to graft the glycerine skeleton. It is used to make it have amphipathic properties. Niosomes have the advantage of being able to encapsulate polar and non-polar substances, being osmotically active, and requiring no special conditions for storage and handling of the surfactant used during production.

7-dehydrocholesterol (7-DHC) is a provitamin form of vitamin D3 and is converted to vitamin D3 by sunlight. However, 7-dehydrocholesterol is very unstable to light and heat, and is easily converted into various other substances by ultraviolet rays and temperature. In addition, it has a structural problem in that it reacts with oxygen in the air and denatures, making it less active. However, stabilization studies on 7-dehydrocholesterol are very limited.

Accordingly, the present applicant has devised the present invention as a result of repeated research on niosomes that contain 7-dehydrocholesterol but can provide excellent long-term dispersion stability.

Public Patent Publication No. 10-2016-0103718 Registered Patent Publication No. 10-2307408

The purpose of the present invention is to prepare niosomes encapsulated by additionally mixing unstable 7-dehydrocholesterol with pentaerythrityltetra-di-t-butylhydroxyhydrocinnamate, thereby ensuring dispersion stability despite containing 7-dehydrocholesterol. The object is to provide improved niosomes and a cosmetic composition containing them as an active ingredient.

In order to achieve the above object, the niosome with improved stability according to the present invention contains a nonionic surfactant, an auxiliary surfactant, a lipophilic antioxidant, phytosterol, vegetable cholesterol, polyol, oil, 7-dehydrocholesterol, and purified water. It can be configured to include.

Here, the content of each component is 1-10% by weight of nonionic surfactant, 0.001-5% by weight of auxiliary surfactant, 0.01-0.5% by weight of lipophilic antioxidant, and phytosterol based on the total weight of niosomes. 1-10% by weight of silver, 1-10% by weight of vegetable cholesterol, 5-10% by weight of polyol, 5-20% by weight of oil, 0.001-20% by weight of 7-dehydrocholesterol, and 50-85% by weight of purified water. It may include weight percent.

In the present invention, 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 include an emulsifier (emulsifier or emulsifying agent), More specifically, a nonionic surfactant that has the properties of a water-soluble emulsifier and can dissolve cholesterol, etc. in an aqueous solvent can be used.

Specifically, nonionic surfactants include polyglyceryl-10 laurate, sorbitan esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene alkyl ether, It is at least one selected from the group consisting of poloxamer, saccharose diester, or mixtures thereof, but is not limited thereto, and any known nonionic surfactant with similar properties can be used without limitation.

Additionally, the auxiliary surfactant may include sodium stearoyl glutamate, which is an anionic surfactant.

Additionally, the lipophilic antioxidant may include pentaerythrityl tetra-di-t-butylhydroxyhydrocinnamate.

The phytosterol may be one or more selected from the group consisting of beta-sitosterol, β campesterol, and stigmasterol, and is preferably campesterol, but is not limited thereto.

The polyol may be one or more selected from the group consisting of glycerin, propanediol, hexanediol, dipropylene glycol, propylene glycol, butylene glycol, and pentylene glycol, preferably glycerin and propane. It may be diol, but is not limited thereto.

The oil is a hydrocarbon-based oil consisting of squalane, hydrogenated polyisobutene, hydrogenated poly(C6-14 olefin), C13-15 alkane, etc.; Ester oils consisting of isopropyl palmitate, isopropyl myristate, butyloctyl salicylate, etc.; Vegetable oils such as macadamia seed oil, sunflower seed oil, argan kernel oil, and meadowfoam seed oil; and glyceride-based oils consisting of caprylic/capric triglyceride, etc.; preferably one or more selected from the group consisting of squalane, macadamia seed oil, cetyl ethyl hexanoate, and caprylic/capric. It may be at least one type selected from triglycerides, but is not limited thereto.

In addition, niosomes may include a preservative, and the preservative may contain 0.01-2% by weight based on the total weight of niosomes, including 1,2-hexanediol, ethylhexylglycerin, and glyceryl caprylate. , caprylyl glycol, and phenoxyethanol, but is not limited thereto.

In a specific embodiment of the present invention, polyglyceryl-10 laurate is used as a nonionic surfactant, sodium stearoyl glutamate, an anionic surfactant, is used as an auxiliary surfactant, and pentaerythrityl is used as a lipophilic antioxidant. By using tetra-di-t-butylhydroxyhydrocinnamate, the permeability of the active substance and the stability of niosomes could be greatly improved.

Niosomes containing 7-dehydrocholesterol according to the present invention are characterized by having a particle size of 100 to 200 nm, preferably 150 to 180 nm. Here, if the particle size is less than 100 nm, the collection efficiency of the active ingredient is low, and if the particle size is more than 200 nm, there is a problem of reduced stability.

Additionally, a cosmetic composition containing niosomes according to the present invention as an active ingredient can be prepared.

At this time, the content of niosomes may be 0.001 to 50% by weight, preferably 0.01 to 40% by weight, and more preferably 0.1 to 30% by weight, based on the total weight of the cosmetic composition. Here, if it is less than 0.001% by weight, the efficacy provided by the active ingredient may be insufficient, and if it exceeds 50% by weight, the efficacy provided by the active ingredient does not increase in proportion to the amount added, which is economically undesirable.

In addition, it was confirmed that the cosmetic composition containing niosomes containing 7-dehydrocholesterol according to the present invention has an excellent skin moisturizing effect, and therefore can be used to improve skin moisturizing ability.

The cosmetic composition containing such 7-dehydrocholesterol-containing niosomes may be in the form of skin care, body care, cream, hair care, emulsion, essence, or makeup base.

The method for producing niosomes containing 7-dehydrocholesterol according to the present invention includes nonionic surfactant, auxiliary surfactant, lipophilic antioxidant, phytosterol, vegetable cholesterol, polyol, oil, 7-dehydrocholesterol and purified water. It is done by mixing and can be done in the following steps.

Preparing a base by dissolving nonionic surfactant, vegetable cholesterol, and phytosterol and then cooling (S1);

Dissolving the prepared base (S2);

Heating polyol, auxiliary surfactant, and purified water and adding them to the melt of step S2 (S3);

Step (S4) of dissolving 7-dehydrocholesterol, pentaerythrityltetra-di-t-butylhydroxyhydrocinnamate and oil by heating;

It includes a step (S5) of adding the resultant dissolved in step S4 to the lysate in step S3, emulsifying it, followed by cooling and defoaming to obtain niosomes.

At this time, in step S1, the nonionic surfactant, vegetable cholesterol, and phytosterol are melted and dissolved at a temperature of 90 to 100°C, and cooled at room temperature to prepare the base.

Additionally, the prepared base is dissolved by heating to 90 to 100°C in step S2.

Additionally, in step S3, the heating temperature of the polyol, auxiliary surfactant, and purified water is 80°C or higher.

In addition, in step S5, the resultant dissolved in step S4 is added to the dissolved product in step S3 to emulsify and then passed through a high-pressure microemulsifier three times in succession at 1000 bar, followed by cooling and defoaming to obtain niosomes.

Here, the content of each ingredient used in each step is 1-10% by weight of nonionic surfactant, 0.001-5% by weight of auxiliary surfactant, 0.01-0.5% by weight of lipophilic antioxidant, and phytosterol based on the total weight of niosomes. It consists of 1-10% by weight, vegetable cholesterol 1-10% by weight, polyol 5-10% by weight, oil 5-20% by weight, 7-dehydrocholesterol 0.001-20% by weight, and purified water 50-85% by weight.

Niosomes prepared according to the present invention can be mixed in a certain amount with a cosmetic composition of a specific formulation to produce a cosmetic composition containing niosomes.

At this time, niosomes containing 7-dehydrocholesterol of the present invention may be included in an amount of 0.001 to 50% by weight based on the total weight of the cosmetic composition.

The niosome according to the present invention has the effect of providing a new delivery system by having excellent dispersion stability of unstable 7-dehydrocholesterol.

Figure 1 is a graph showing the particle size distribution of niosomes in Example 1, Comparative Example 1, and Comparative Example 2 according to the present invention.
Figure 2 is a graph showing the zeta potential difference distribution of niosomes of Example 1, Comparative Example 1, and Comparative Example 2 according to the present invention.
Figure 3 is a graph showing the results of the Turbiscan long-term stability test of the niosomes of Example 1, Comparative Example 1, and Comparative Example 2 according to the present invention.
Figure 4 is a graph evaluating the moisturizing and sustained moisturizing power of niosomes of Example 1, Comparative Example 1, and Comparative Example 2 according to the present invention.
Figure 5 is a graph evaluating the improvement in transepidermal water loss of niosomes of Example 1, Comparative Example 1, and Comparative Example 2 according to the present invention.
Figure 6 is a graph evaluating the moisturizing and sustained moisturizing power of the cosmetic containing Example 1 and the comparative example cosmetic according to the present invention.
Figure 7 is a graph evaluating the improvement in transepidermal water loss of the niosome-containing cosmetic of Example 1 and the comparative example cosmetic according to the present invention.
Figure 8 is a graph evaluating the cytotoxicity of the niosome of Example 1 according to the present invention (Figure 8(a) is NHF, Figure 8(b) is HaCaT, Figure 8(c) is B16F10, Figure 8( d) is RAW264.7)
Figure 9 is a graph evaluating (a) cell death inhibition, (b) NO production inhibition ability, and (c) MMP-1 production inhibition of the niosome of Example 1 according to the present invention.

Hereinafter, a detailed description of preferred embodiments of the present invention will be described with reference to the attached drawings. However, the present invention is not limited to the embodiments described herein and may be embodied in other forms.

The term "niosome" used in the present invention refers to a non-ionic surfactant-based vesicle, which is a closed double cell with a hydrophilic space formed on the inside and a hydrophobic property on the outside. It refers to a fine molecular sieve with a lipid membrane.

The term “non-ionic surfactant” used in the present invention refers to a surfactant that does not separate into ions, and is also called a non-ionic surfactant or non-ionic surfactant. Unlike ionic surfactants, nonionic surfactants can be freely mixed with other surfactants or electrolytes. It is harmless to the skin and has characteristics such as thickening of the shampoo base, improved stability at low temperatures, excellent cleaning action and less foaming, so it can be used for various purposes such as a dispersant, emulsion agent, detergent, and dyeing aid. .

The term “phytosterol” used in the present invention is a phytosteroid similar to cholesterol, produced in plants (corn, soybeans, vegetable oil seeds, etc.), and includes plant sterols and plant stanols. Phytosterols are essential components that form part of plant cell membranes, just as cholesterol is one of the components of cell membranes in the human body. Because phytosterols are structurally similar to cholesterol, they are known to repair the protective film of the stratum corneum, normalize its function, prevent skin from becoming rough, and have a strong anti-inflammatory effect.

<Example 1> Preparation of niosomes containing 7-dehydrocholesterol and pentaerythrityltetra-di-t-butylhydroxyhydrocinnamate

Table 1 below shows the composition for producing niosomes containing 7-dehydrocholesterol and pentaerythrityltetra-di-t-butylhydroxyhydrocinnamate according to the present invention.

ingredient Example 1 content(%) Sodium Stearoyl Glutamate 0.80 Pentaerythrityltetra-di-t-butylhydroxyhydrocinnamate 0.50 7-dehydrocholesterol 1.00 Polyglyceryl-10 Laurate 4.50 vegetable cholesterol 2.25 Phytosterols 2.25 Purified water remaining amount glycerin 7.00 1,2-hexanediol 2.00 squalane 5.00 Macadamia seed oil 10.00 Sum 100

Polyglyceryl-10 laurate, vegetable cholesterol, and phytosterol (campesterol) are melted at a temperature of 90 to 100°C and then cooled to room temperature to prepare the base.

After melting the prepared base by heating to 90℃, glycerin, sodium stearoyl glutamate, purified water, and 1,2-hexanediol were heated to above 80℃ and added to the dissolved area, and 7-dehydrocholesterol, squalane, Macadamia seed oil and pentaerythrityl tetra-di-t-butylhydroxyhydrocinnamate were dissolved and added to emulsify by heating, and then passed through a high-pressure microemulsifier three times in succession at 1000 bar, followed by cooling and degassing to obtain niosomes.

<Formulation Example 1> Preparation of toner containing Example 1

Disodium EDTA, glycerin, propanediol, and carbomer were dispersed in purified water and the dissolved emulsification system was added to the aqueous phase heated to 70°C to 75°C and stirred for 5 minutes with an azimixer. Tromethamine was added at 60°C to 65°C and then stirred for 3 minutes with an azimixer to neutralize. 1,2-hexanediol and ethylhexylglycerin were added at 45°C, stirred for 3 minutes, and then cooled to 30°C. Afterwards, the niosomes of Example 1 were added and stirred and defoamed for 3 minutes to prepare a toner formulation. Table 2 below shows the composition for producing a toner containing niosomes of Example 1 according to the present invention.

ingredient Formulation example 1 content(%) Example 1 20.00 Purified water remaining amount Propanediol 8.00 glycerin 5.00 1,2-hexanediol 2.00 carbomer 0.10 Tromethamine 0.08 Ethylhexylglycerin 0.05 Disodium EDTA 0.02 Sum 100

<Formulation Example 2> Preparation of lotion containing Example 1

Cetyl ethyl hexanoate, cetearyl alcohol, glyceryl stearate, C14-22 alcohol, C12-20 alkyl glucoside, glucose, and caprylic/capric triglyceride are heated and dissolved at 75℃ to 80℃ to create a transparent emulsion. A system was prepared.

Disodium EDTA, glycerin, propanediol, and carbomer are dispersed in purified water, and the transparent emulsifying system dissolved in the water phase heated to 70°C to 75°C is added and emulsified for 5 minutes using a homomixer under conditions of 3500 to 5000 rpm. did.

After adding tromethamine at 60°C to 65°C, it was neutralized by stirring for 3 minutes using a homomixer under conditions of 3000 to 3500 rpm. 1,2-hexanediol and ethylhexylglycerin were added at 45°C, stirred for 3 minutes, and then cooled to 30°C. Afterwards, the niosomes of Example 1 were added and stirred and defoamed for 3 minutes to prepare a lotion formulation.

Table 3 below shows the composition for producing a lotion containing niosomes of Example 1 according to the present invention.

ingredient Formulation example 2 content(%) Example 1 10.00 Purified water remaining amount Propanediol 5.00 glycerin 5.00 Caprylic/Capric Triglyceride 3.00 Cetyl Ethyl Hexanoate 3.00 1,2-hexanediol 2.00 C14-22Alcohol 1.59 Glyceryl Stearate 1.00 Cetearyl alcohol 0.50 C12-20 Alkyl Glucoside 0.40 carbomer 0.30 Tromethamine 0.24 Ethylhexylglycerin 0.05 Disodium EDTA 0.02 glucose 0.004 Sum 100

<Formulation Example 3> Preparation of cream containing Example 1

A transparent emulsion system was prepared by heating and dissolving cetyl ethyl hexanoate, cetearyl alcohol, and glyceryl stearate at 75°C to 80°C.

Disodium EDTA, glycerin, propanediol, cetearyl olivate, sorbitan olivate, and carbomer were dispersed in purified water and the dissolved emulsifying system was added to the water phase heated to 70°C to 75°C, then mixed with a homomixer. Emulsification was performed for 5 minutes under conditions of 3500 to 5000 rpm.

Tromethamine was added at 60°C to 65°C and then neutralized by stirring for 3 minutes using a homomixer under conditions of 3000 to 3500 rpm. 1,2-hexanediol and ethylhexylglycerin were added at 45°C, stirred for 3 minutes, and then cooled to 30°C. Afterwards, the niosomes of Example 1 were added and stirred and defoamed for 3 minutes to prepare a cream formulation.

Table 4 below shows the composition for preparing cream containing niosomes of Example 1 according to the present invention.

ingredient Formulation example 3 content(%) Example 1 10.00 Purified water remaining amount glycerin 5.00 Propanediol 3.00 Cetyl Ethyl Hexanoate 3.00 Cetearyl alcohol 2.00 Cetearyl olivate 2.00 Sorbitan Olivate 2.00 1,2-hexanediol 2.00 Glyceryl Stearate 0.50 carbomer 0.30 Tromethamine 0.24 Ethylhexylglycerin 0.05 Disodium EDTA 0.02 Sum 100

<Comparative Example 1> Preparation of niosomes without addition of 7-dehydrocholesterol and pentaerythrityltetra-di-t-butylhydroxyhydrocinnamate

Niosomes were prepared in the same manner as in Example 1, except that 7-dehydrocholesterol and pentaerythrityltetra-di-t-butylhydroxyhydrocinnamate were not added.

Table 5 below shows the composition for producing niosomes without adding 7-dehydrocholesterol and pentaerythrityltetra-di-t-butylhydroxyhydrocinnamate according to the present invention.

ingredient Comparative Example 1 content(%) Sodium Stearoyl Glutamate 0.80 Pentaerythrityltetra-di-t-butylhydroxyhydrocinnamate - 7-dehydrocholesterol - Polyglyceryl-10 Laurate 4.50 vegetable cholesterol 2.25 Phytosterols 2.25 Purified water remaining amount glycerin 7.00 1,2-hexanediol 2.00 squalane 5.00 Macadamia seed oil 10.00 Sum 100

<Comparative Example 2> Preparation of niosomes containing 7-dehydrocholesterol

Niosomes were prepared in the same manner as in Example 1, except that pentaerythrityltetra-di-t-butylhydroxyhydrocinnamate was not added.

Table 6 below shows the composition for preparing niosomes containing 7-dehydrocholesterol.

ingredient Comparative example 2 content(%) Sodium Stearoyl Glutamate 0.80 Pentaerythrityltetra-di-t-butylhydroxyhydrocinnamate - 7-dehydrocholesterol 1.00 Polyglyceryl-10 Laurate 4.50 vegetable cholesterol 2.25 Phytosterols 2.25 Purified water remaining amount glycerin 7.00 1,2-hexanediol 2.00 squalane 5.00 Macadamia seed oil 10.00 Sum 100

<Experimental Example 1> Particle distribution and potential measurement

The particle distribution of Example 1, Comparative Example 1, and Comparative Example 2 was measured by Photal. The results of measurement using ELS-Z are shown in Figure 1.

As shown in Figures 1(a), 1(b), and 1(c), the particle sizes were measured to be approximately 162.1 nm, 164.7 nm, and 179.5 nm, respectively. In addition, the potential of the particles was -78.7 mV, -71.5 mV, and -58.9 mV, respectively, as shown in Figures 2(a), 2(b), and 2(c), confirming that Example 1 had the best dispersion stability. .

<Experimental Example 2> Long-term stability measurement

To numerically evaluate the change in dispersion stability of the entire niosome sample, it was analyzed for about 4 hours at 40°C using Turbiscan, and the results are shown in Figure 3. The larger the Turbiscan Stability Index (TSI) value, the more unstable the stability, and the phenomenon of decreased stability can be quantitatively derived.

As a result of the analysis, as shown in Figure 3, Example 1, which contains the antioxidant pentaerythrityltetra-di-t-butylhydroxyhydrocinnamate, has TSI higher than Comparative Example 2, which contains only 7-dehydrocholesterol. Considering that the TSI value was low and similar to that of Comparative Example 1, which did not contain 7-dehydrocholesterol, pentaerythrityl tetra-di-t-butylhydroxyhydrocinnamate was additionally mixed into the niosome. It was found that if it was encapsulated more stably, it would be stable for a long period of time.

<Experimental Example 3> Evaluation of moisturizing power and continuous moisturizing power

In the preparation stage, to ensure that the measurement conditions were the same for the subjects, the test area was kept clean and dry, and the skin was stabilized in a place where constant temperature and humidity (22±2℃R.H. 40-60%) was maintained for at least 30 minutes before proceeding. In the measurement stage, the test product was applied in an amount of 2 mg/cm2 to the selected test area (5 cm x 4 cm) of the forearm using a micro pipette. Measurements were made three times: before using the product, after using the product, and 3 hours later, and the average value was calculated using the three values. Skin moisture was measured using the Aphrodite moisture checker MC-1000.

As a result of the experiment, as shown in Figure 4, the moisturizing power increased by about 90.8% immediately after application of Example 1, and after 3 hours of application, the moisturizing power increased by about 67.4% and continued. It was confirmed that the moisturizing effect of Example 1 3 hours after application was about 36.2% better than Comparative Example 1 and about 24.5% better than Comparative Example 2.

In addition, when this was applied to the formulation, as shown in Figure 6, the moisturizing power increased by about 92.2% immediately after application of the formulation containing Example 1, and after 3 hours of application, the moisturizing power increased by about 67.2% and persisted. Compared to the formulation that did not contain Example 1, it was confirmed that the moisturizing effect of the formulation containing Example 1 was about 23.2% better 3 hours after application.

<Experimental Example 4> Evaluation of transepidermal water loss

In the preparation stage, to ensure that the measurement conditions were the same for the subjects, the test area was kept clean and dry, and the skin was stabilized in a place where constant temperature and humidity (22±2℃R.H. 40-60%) was maintained for at least 30 minutes before proceeding. In the measurement stage, the test product was applied in an amount of 2 mg/cm2 to the selected test area (5 cm x 4 cm) of the forearm using a micro pipette. Measurements were made three times: before using the product, after using the product, and 3 hours later, and the average value was calculated using the three values. Transepidermal water loss was measured using a Tewameter®TM 300 device.

As a result of the experiment, as shown in Figure 5, the transepidermal water loss was improved by about 39.5% immediately after application of Example 1, and was improved by about 37.9% 3 hours after application. It was confirmed that the water loss improvement effect of Example 1 3 hours after application was about 16.3% better than Comparative Example 1 and about 7.4% better than Comparative Example 2.

In addition, when this was applied to the formulation, as shown in Figure 7, the transepidermal water loss was improved by about 39.4% immediately after application of the formulation containing Example 1, and was improved by about 43.6% 3 hours after application. This showed that compared to the formulation that did not contain Example 1, the improvement in moisture loss 3 hours after application of the formulation containing Example 1 was about 12.1% better.

<Experimental Example 5> Cytotoxicity evaluation

For the cytotoxicity test, Example 1 was tested at a concentration ranging from a minimum of 0.0625% to a maximum of 1%.

As a result, the highest concentration at which cell viability was 90% or more was found to be 0.5% in NHF, 0.5% in HaCaT, 0.5% in B16F10, and 1% in RAW264.7 in Example 1, respectively.

For this efficacy test, four concentrations without cytotoxicity were selected to confirm the concentration dependence of the efficacy, and these are shown in Table 7 and Figure 8.

test substance density Cell survival rate (%) NHF HaCaT B16F10 RAW264.7 Control 100.0±1.1 100.0±1.0 100.0±1.0 100.0±1.2

Example 1 One 74.0±3.8 78.8±2.9 68.8±3.6 98.7±0.6 0.5 99.2±2.7 94.6±5.8 90.1±2.3 97.5±2.3 0.25 108.6±1.4 94.5±3.9 103.3±0.7 98.9±1.4 0.125 108.1±1.7 101.5±1.3 101.0±1.9 98.6±0.8 0.0625 107.6±4.4 103.3±2.7 103.0±1.4 98.6±1.3

<Experimental Example 6> Evaluation of cell death inhibition

HaCaT was dispensed at 1.5 × 10 ⁴ cells/well into a 96-well plate and cultured under cell culture conditions. After 24 hours, the culture medium was discarded, washed with PBS, and the cells were starved using DMEM medium without FBS. The next day, the test substance at a certain concentration was treated with a certain amount of sodium dodecyl sulfate (SDS), an anionic surfactant, and cultured for 24 hours. 100 ul of WST-1 reagent diluted 10 times in the medium was added to each well, and after 2 hours of incubation, the absorbance was measured at 450 nm and is shown in Figure 9(a).

As a result of the experiment, it was found that the cell viability, which was reduced by 26.4% by SDS, increased in a concentration-dependent manner by Example 1, with a maximum of 16.1% of cells surviving. Therefore, it was indirectly confirmed that it was a substance with irritation-relieving effects.

<Experimental Example 7> Evaluation of NO production inhibition ability

RAW 264.7 was dispensed at 6 × 10 ⁴ cells/well into a 96-well plate and cultured under cell culture conditions. After 24 hours, the culture medium was discarded, washed with PBS, and the cells were starved using DMEM medium without FBS. The next day, the test substances were treated with a certain concentration along with 1 ug/ml of LPS (Lipopolysaccaride) and cultured. After 24 hours, equal amounts of cell culture medium and griess reagent were mixed and reacted at room temperature for 15 minutes. Absorbance was measured at 560 nm, and the amount of nitric oxide (NO), an inflammation mediator, was determined using a standard curve obtained from sodium nitrite. The final amount of NO was converted to the amount of NO per certain protein and compared with the negative control group, and is shown in Figure 9(b).

As a result of the experiment, the amount of NO production, which increased by 37.5% due to LPS, decreased in a concentration-dependent manner in Example 1, and Example 1 showed a maximum decrease of 40.8%. Therefore, it was indirectly confirmed that it was a substance with anti-inflammatory effects.

<Experimental Example 8> Evaluation of inhibition of MMP-1 production

HaCaT cells were distributed at 2.5 × 10 ⁵ cells/well in a 6-well plate and cultured under cell culture conditions. After 24 hours, the medium was discarded, washed with PBS, and the cells were starved using DMEM medium (serum free medium) that does not contain FBS, and then cultured under UVB irradiation the next day.

NHF was dispensed at 6 × 10 ³ cells/well into a 96-well plate and cultured under cell culture conditions. After 24 hours, the cells were starved using FBM medium without supplements, and the next day, the UVB-stimulated HaCaT culture medium was treated with the samples and cultured with human fibroblasts. After culturing for 24 hours, the absorbance was measured at 450 nm after experiment using the MMP-1 Elisa kit. The final amount of MMP-1 was converted to the amount of MMP-1 per certain protein and compared with the negative control group, and is shown in Figure 9(c).

The experimental results showed that the amount of MMP-1 production, which increased by 26.8% due to UVB, decreased in a concentration-dependent manner due to niosomes, decreasing by up to 23.6%. Therefore, it was indirectly confirmed that it was a substance with anti-aging effects.

Although the present invention has been described above with reference to one embodiment, those skilled in the art may make various modifications and changes to the present invention without departing from the spirit and scope of the present invention as set forth in the patent claims described below. You can do it. Therefore, if the modified implementation basically includes the elements of the claims of the present invention, it should be considered to be included in the technical scope of the present invention.

Claims (16)

Niosomes with improved dispersion stability, characterized by comprising nonionic surfactants, auxiliary surfactants, lipophilic antioxidants, phytosterols, plant cholesterol, polyols, oils, 7-dehydrocholesterol, and purified water.
According to clause 1,
The content of each of the above components is 1-10% by weight of nonionic surfactant, 0.001-5% by weight of auxiliary surfactant, 0.01-0.5% by weight of lipophilic antioxidant, and 1-10% by weight of phytosterol, based on the total weight of niosomes. , 1-10% by weight of vegetable cholesterol, 5-10% by weight of polyol, 5-20% by weight of oil, 0.001-20% by weight of 7-dehydrocholesterol, and 50-85% by weight of purified water. a little.
According to clause 1,
The nonionic surfactant includes polyglyceryl-10 laurate, sorbitan esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene alkyl ether, and poloxamer. Niosome with improved dispersion stability, characterized in that it is at least one selected from the group consisting of (poloxamer), saccharose diester, or mixtures thereof.
According to clause 1,
Niosomes with improved dispersion stability, characterized in that the auxiliary surfactant is sodium stearoyl glutamate, an anionic surfactant.
According to clause 1,
Niosome with improved dispersion stability, characterized in that the lipophilic antioxidant is pentaerythrityl tetra-di-t-butylhydroxyhydrocinnamate.
According to clause 1,
A niosome with improved dispersion stability, wherein the phytosterol is at least one selected from the group consisting of beta-sitosterol, beta campesterol, and stigmasterol.
According to clause 1,
The polyol has improved dispersion stability, characterized in that at least one selected from the group consisting of glycerin, propanediol, hexanediol, dipropylene glycol, propylene glycol, butylene glycol, and pentylene glycol. a little.
According to clause 1,
The oil is a hydrocarbon oil consisting of squalane, hydrogenated polyisobutene, hydrogenated poly(C6-14 olefin), and C13-15 alkane; Ester oils consisting of isopropyl palmitate, isopropyl myristate, and butyloctyl salicylate; Vegetable oil consisting of macadamia seed oil, sunflower seed oil, argan kernel oil, and meadowfoam seed oil; A niosome with improved dispersion stability, characterized in that it is at least one selected from the group consisting of glyceride-based oil consisting of caprylic/capric triglyceride.
According to clause 1,
The niosome has improved dispersion stability, characterized in that the niosome has a particle size of 100 to 200 nm.
A cosmetic composition containing the niosome of any one of claims 1 to 9 as an active ingredient.
According to clause 10,
A cosmetic composition characterized in that the niosome is contained in an amount of 0.001 to 50% by weight based on the total weight of the cosmetic composition.
According to clause 10,
A cosmetic composition, characterized in that the formulation of the cosmetic composition is skin care, body care, cream, hair care, emulsion, essence, or makeup base.
Preparing a base by dissolving nonionic surfactant, vegetable cholesterol, and phytosterol and then cooling (S1);
Dissolving the prepared base (S2);
Heating polyol, auxiliary surfactant, and purified water and adding them to the melt of step S2 (S3);
Step (S4) of dissolving 7-dehydrocholesterol, pentaerythrityltetra-di-t-butylhydroxyhydrocinnamate and oil by heating;
Manufacture of niosomes with improved dispersion stability, comprising: adding the resultant dissolved in step S4 to the lysate in step S3, emulsifying it, followed by cooling and defoaming to obtain niosomes (S5); method.
According to clause 13,
In step S1, the dissolution temperature is 90 to 100°C, the cooling temperature is room temperature,
In step S2, the dissolution temperature is 90 to 100°C,
A method for producing niosomes with improved dispersion stability, characterized in that the heating temperature in step S3 is 80°C or higher.
According to clause 13,
The nonionic surfactant includes polyglyceryl-10 laurate, sorbitan esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene alkyl ether, and poloxamer. (poloxamer), saccharose diester, or at least one selected from the group consisting of mixtures thereof,
The auxiliary surfactant is sodium stearoyl glutamate, an anionic surfactant,
The phytosterol is at least one selected from the group consisting of beta-sitosterol, beta campesterol, and stigmasterol,
The polyol is at least one selected from the group consisting of glycerin, propanediol, hexanediol, dipropylene glycol, propylene glycol, butylene glycol, and pentylene glycol,
The oil is a hydrocarbon oil consisting of squalane, hydrogenated polyisobutene, hydrogenated poly(C6-14 olefin), and C13-15 alkane; Ester oils consisting of isopropyl palmitate, isopropyl myristate, and butyloctyl salicylate; Vegetable oil consisting of macadamia seed oil, sunflower seed oil, argan kernel oil, and meadowfoam seed oil; A method for producing niosomes with improved dispersion stability, characterized in that at least one selected from the group consisting of glyceride-based oil consisting of caprylic/capric triglyceride.
According to clause 13,
The content of each of the above components is 1-10% by weight of nonionic surfactant, 0.001-5% by weight of auxiliary surfactant, and 0.01% by weight of pentaerythrityltetra-di-t-butylhydroxyhydrocinnamate based on the total weight of niosomes. 0.5% by weight, 1-10% by weight of phytosterol, 1-10% by weight of vegetable cholesterol, 5-10% by weight of polyol, 5-20% by weight of oil, 0.001-20% by weight of 7-dehydrocholesterol, and 50-85% by weight of purified water. A method for producing niosomes with improved dispersion stability, characterized in that %.