KR20220052560A - Cosmetic composition comprising deformable liposome with effects of alleviating skin irritation and promoting skin absorption - Google Patents

Abstract

The present invention relates to a cosmetic composition including elastic liposome with an excellent skin irritation-relieving effect. More specifically, the present invention relates to a skin irritation-relieving composition including a high content of a skin irritation-relieving complex, increasing a skin permeation rate, and enhancing stability of a complex. The present invention relates to an elastic liposome composition including an irritation-relieving complex with an excellent skin irritation-relieving effect. More specifically, the present invention relates to a skin irritation-relieving elastic liposome composition including a high content of a skin irritation-relieving complex which contains a comfrey leaf extract, madecassoside and panthenol, increasing a skin permeation rate and enhancing stability of a complex.

Description

COSMETIC COMPOSITION COMPRISING DEFORMABLE LIPOSOME WITH EFFECTS OF ALLEVIATING SKIN IRRITATION AND PROMOTING SKIN ABSORPTION }

The present invention relates to a cosmetic composition comprising an elastic liposome having an excellent skin irritation alleviation effect and a skin absorption promoting effect, and more particularly, includes a skin irritation alleviation complex in a high content, and increases the skin penetration rate, the complex It relates to a cosmetic composition for alleviating skin irritation comprising elastic liposomes that enhance the stability of the skin.

The skin is the largest organ in the human body and is also the first defense network to protect the external environment. However, the skin is the outermost layer that is directly exposed to the external environment, and the activity of keratinocytes and fibroblasts is reduced by ultraviolet rays, stress, fine dust, and harmful chemicals, and the ability to retain water is reduced, the skin barrier function is weakened, and external sources of infection. It is sensitive to various stimuli due to a decrease in the ability to defend against In the skin that has been sensitized by external stimuli, objective stimuli such as erythema and edema may appear, and subjective inflammatory reactions such as itching, stinging, and burning may occur. irritation may occur.

Cosmetics are used to clean the body, make it beautiful, protect the skin, and keep it healthy. However, looking at the cosmetic composition, ingredients different from the original skin protection purpose are used as essential for product manufacturing and maintenance. These ingredients are indispensable ingredients added to preserve, maintain, and function cosmetics, and include surfactants, preservatives, fragrances, and sunscreens. These ingredients are generally known as the main cause of irritation, inflammation, allergies, pimples, edema, etc. on the skin.

Therefore, in terms of skin safety, cosmetics that reduce skin irritation and inflammation caused by various irritants are required, and the importance of irritation-relieving materials that can protect the skin from various factors is increasing.

The skin consists of three layers: the epidermis, the dermis and the subcutaneous fat and surrounds the whole body. Among them, the epidermis consists of the basal layer, the stratum corneum, the granular layer and the stratum corneum. The stratum corneum, the outermost layer of the skin, plays a role of a strong skin barrier that protects the skin from external stimuli, so it is difficult to permeate the drug. Therefore, various transdermal delivery systems (TDS) have been developed as a way to overcome the skin barrier and enhance the permeation efficiency of intercellular lipids, and a representative one of them is liposomes.

Liposomes are spherical vesicles composed of amphiphilic phospholipids and have a lipid bilayer structure similar to the skin lipid membrane. Therefore, it is a carrier that has high biocompatibility and enhances skin absorption by capturing both hydrophilic or hydrophobic drugs. However, liposomes have several disadvantages, such as low entrapment efficiency, instability in the formulation, low solubility of the active ingredient in water, and the possibility of oxidation and hydrolysis of lipids. In order to improve these problems, studies on the development of new carriers such as etosomes, elastic liposomes, coated liposomes, and cationic liposomes are being actively conducted.

Elastic liposomes are composed of phospholipids and single-chain surfactants. In this system, the surfactant acts as an edge activator, giving it a high radius of curvature and giving the lipid bilayer membrane elasticity and flexibility. Due to these characteristics, elastic liposomes are known to be able to pass through the pores of the stratum corneum smaller than their own size, and thus can effectively deliver active ingredients to the skin compared to conventional liposomes. In the study of elastic liposomes, surfactants such as sodium cholate, Tween 80, and Span 80 were mainly used as edge activators.

Korean Patent Application Laid-Open No. 10-2003-0085941 discloses a liposome containing flavonoids having effects such as antioxidant and skin aging prevention therein and a cosmetic composition containing the liposome.

In addition, Korean Patent Laid-Open No. 10-2018-0013541 discloses an elastic liposome formed of a surfactant such as sodium cholate.

An object of the present invention is to obtain a new skin irritation alleviation complex by combining materials with various different irritation alleviation mechanisms, targeting materials whose safety has already been proven in cosmetics.

In addition, an object of the present invention is to provide a cosmetic composition containing elastic liposomes capable of maintaining a stable state for a long period of time while having excellent deformability, flexibility, skin absorption rate and irritation alleviation complex collection efficiency.

The above object is achieved by a cosmetic composition for alleviating skin irritation comprising an elastic liposome enclosing a skin irritation alleviation complex including comfrey leaf extract, madecassoside and panthenol.

Preferably, the skin irritation alleviation complex may include comfrey leaf extract, madecassoside, and panthenol in a weight ratio of 28:2:70.

Also preferably, the skin irritation alleviation complex may be contained in an amount of 0.1 to 5.0% by weight based on the total weight of the elastic liposome.

Also preferably, the elastic liposome may include a lecithin compound and a surfactant in a weight ratio of 8 to 9: 2 to 1.

Also preferably, the surfactant may be polyglyceryl-3 methylglucose distearate.

The skin irritation alleviation complex according to the present invention not only has an excellent skin barrier recovery and irritation alleviation effect, but also has excellent deformability, flexibility, skin absorption rate, and irritation alleviation complex collection efficiency, and can be applied to an elastic liposome composition to increase stability.

1 is a transmission electron micrograph of an elastic liposome (Example 1) and a general liposome (Comparative Example 1) according to the present invention.
2 is a result of measuring the skin permeation amount of the elastic liposome (Example 1) and the general liposome (Comparative Example 1) according to the present invention.

All technical terms used in the present invention, unless otherwise defined, have the following definitions and have the meanings as commonly understood by one of ordinary skill in the art of the present invention. In addition, although preferred methods and samples are described herein, similar or equivalent ones are also included in the scope of the present invention.

The term "about" means 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, means an amount, level, value, number, frequency, percentage, dimension, size, amount, weight or length varying by 4, 3, 2 or 1%.

Throughout this specification, unless the context requires otherwise, the terms "comprises" and "comprising" include, but are not limited to, a given step or element, or group of steps or elements, but any other step or element, or It is to be understood that a step or group of elements is not excluded.

The present invention relates to a cosmetic composition for alleviating skin irritation comprising elastic liposomes comprising a skin irritation alleviation complex having excellent skin irritation alleviation effect.

The skin irritation relief complex may include comfrey leaf extract, madecassoside and panthenol.

According to one embodiment of the present invention, the skin irritation alleviation complex is characterized by comprising comfrey leaf extract, madecassoside and panthenol in a weight ratio of 28: 2: 70.

Preferably, the skin irritation alleviation complex may be contained in an amount of 0.1 to 5.0% by weight based on the total weight of the elastic liposome.

According to one embodiment of the present invention, the elastic liposome consists of an oil phase and a water phase. The oily part includes a lecithin compound, a surfactant, polyglyceryl-3-methylglucose distearate, and a skin irritation relief complex.

Preferably, the elastic liposome may include a lecithin compound and polyglyceryl-3-methylglucose distearate in a weight ratio of 8 to 9: 2 to 1.

Polyglyceryl-3-methylglucose distearate can impart elasticity and flexibility to elastic liposomes as an edge activator. In particular, since elastic liposomes are easy to deform in the shape of the lipid membrane, even if the particle size is large, unlike general liposomes, it can easily pass through the narrow gap between the stratum corneum and effectively deliver the irritation-relieving complex to the skin.

The water phase may include at least one selected from the group consisting of water, glycerin, polyethylene glycol, propylene glycol, 1,3-butylene glycol, propanediol, and ethyl hexanediol.

According to one embodiment of the present invention, the particles of the elastic liposome may further include a physiologically active substance that helps to alleviate skin irritation. The physiologically active substance further included may be dipotassium glycyrrhizate, beta glucan, oleracea extract or allantoin.

Hereinafter, the present invention will be described in more detail through non-limiting examples. However, the following examples are intended to illustrate the present invention, and the scope of the present invention is not to be construed as being limited by the following examples.

Preparation Example 1: Preparation of Comfrey Leaf Extract

200 g of completely dried comfrey leaves were placed in 3 L of 50% ethanol, and extracted by immersion for 24 hours. 100 mL of 50% ethanol extract was distilled under reduced pressure at 40 °C to obtain an extract (yield: 14.9%).

Preparation Example 2: Preparation of skin irritation alleviation complex

The skin irritation alleviation complex of the present invention is a mixture of comfrey leaf extract, madecassoside and panthenol showing different irritation relief mechanisms, thereby exhibiting a synergistic irritation relief effect. The skin irritation alleviation complex was used by mixing the comfrey leaf extract of Preparation Example 1: madecassoside: panthenol = 28: 2: 70 by weight. This was compared with Formulation Example 1 containing only 0.2% by weight of comfrey leaf extract, Formulation Example 2 containing only 0.01% by weight of madecassoside, and Formulation Example 3 containing only 0.5% by weight of panthenol, as shown in Table 1 below.

Experimental Example 1: Primary irritation evaluation of skin irritation alleviation complex (patch test)

When the skin irritation alleviating complex of the present invention is directly applied to human skin, a human skin patch test was conducted to confirm whether it has an excellent skin irritation alleviation effect. The test subject visited a total of three times (before the start of the test, the date of patch removal, and 30 minutes after removal of the patch) during this human application test period to determine whether or not the skin was irritating. At the first visit, a skin patch test was performed on the subject's back using a Finn chamber (100×10, EPITEST, Finland). For 15 test subjects, the sample was applied between the shoulder blade and the waistline with the spine on the back using a pin chamber.

After wiping the test site with 70% (v/v) ethanol and drying it, 20 μl of the test sample prepared according to Table 1 below was dropped into the pin chamber and fixed on the test site. As a test sample, 0.2% by weight of comfrey leaf extract was added to Formulation Example 1, 0.01% by weight of madecassoside was added to Formulation Example 2, and 0.5% by weight of panthenol was added to Formulation Example 3, and in Formulation Example 4, comfrey leaf extract: madecassoside: panthenol was added. = 28% by weight: 2% by weight: It was mixed and added in a weight ratio of 70% by weight, and Comparative Formulation Example 1 in which no stimulant was added was tested together. They were applied to the skin for 24 hours, and after removal of the patch, the test site was marked with a marking pen, and after 30 minutes, erythema and edema were observed at the test site using a magnifying glass (8MC-150, DAZOR, USA).

Raw material name content (wt%) Formulation Example 1 Formulation Example 2 Formulation Example 3 Formulation Example 4 Formulation Example 5 Formulation Example 6 Comparative Formulation Example 1 Comfrey Leaf Extract 0.2 - - - 0.5 - - Madecassoside - 0.01 - - - 0.5 - panthenol - - 0.5 - - - - alleviation complex
(Production Example 2) - - - 0.5 - - - lactic acid 5 5 5 5 5 5 5 glycerin 2.8 2.8 2.8 2.8 2.8 2.8 2.8 Polyglyceryl-3 Methylglucose Distearate 1.6 1.6 1.6 1.6 1.6 1.6 1.6 PEG-4 Oliveate 0.4 0.4 0.4 0.4 0.4 0.4 0.4 cetearyl alcohol 0.2 0.2 0.2 0.2 0.2 0.2 0.2 squalane 4.5 4.5 4.5 4.5 4.5 4.5 4.5 Caprylic/Capric Triglycerides 4.2 4.2 4.2 4.2 4.2 4.2 4.2 dimethicone 1.3 1.3 1.3 1.3 1.3 1.3 1.3 Hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer 1.0 1.0 1.0 1.0 1.0 1.0 1.0 incense a very small amount a very small amount a very small amount a very small amount a very small amount a very small amount a very small amount Distilled water remaining amount remaining amount remaining amount remaining amount remaining amount remaining amount remaining amount

The skin reaction was determined according to the regulations (Table 2) of the International Contact Dermatitis Research Group (ICDRG), and the average skin reactivity was calculated by Equation 1 below, and the results are shown in Table 3.

- no response 0 . faint light erythema 0.5 ± Mild erythema with well-demarcated borders One + Distinct erythema, papules and vesicles 2 ++ Severe erythema, blistering 6 +++ crust formation 12

The degree of skin irritation in Experimental Example 1 was shown according to the evaluation criteria as shown in Table 2, and the skin irritation rate was calculated by the following calculation formula and shown in Table 3.

The degree of skin irritation is judged as non-irritating if the stimulation rate is 0.0, non-irritating if 0.1-1.0, mild if 1.0-1.7, moderately irritating if 1.7-2.5, and strong if over 2.5.

composition skin irritation rate stimulus degree Formulation Example 1 1.39 mild stimulation Formulation Example 2 1.33 mild stimulation Formulation Example 3 1.00 mild stimulation Formulation Example 4 0.91 mild stimulation Formulation Example 5 1.11 mild stimulation Formulation Example 6 0.97 mild stimulation Comparative Formulation Example 1 2.08 central stimulus

composition Stimulus relief rate (%) Comparative Formulation Example 1 - Formulation Example 1 33.2 Formulation Example 2 36.1 Formulation Example 3 51.9 Formulation Example 4 56.3 Formulation Example 5 46.6 Formulation Example 6 53.4

As can be seen from Experimental Example 1 of the present invention, it was confirmed that the composition formulation containing 5.0% (w/w) lactic acid caused strong irritation to the skin. Referring to Table 3, the present invention It was confirmed that the cosmetic formulation example 4 containing the composite material of the present invention had significantly lower skin irritation than the cosmetic formulation example 1 which did not contain the composite material of the present invention. In particular, compared with the skin irritation rates of Formulation Examples 1, 2, and 3, it was found that the irritation relief effect was further increased when comfrey leaf extract, madecassoside and panthenol were contained together as in the complex of the present invention.

As can be seen from Table 4, it was confirmed that the comfrey leaf extract, madecassoside, and panthenol of the present invention were mixed together in a certain ratio to further increase the irritation-relieving effect against the stimulation of lactic acid.

Example 1: Preparation of elastic liposome composition

The elastic liposome of Example 1 was prepared by mixing lecithin and polyglyceryl-3-methylglucose distearate in wt% of Table 5 below. First, soybean lecithin and polyglyceryl-3-methylglucose distearate were put in a round-bottom flask in a 9:1 weight ratio), and then the irritation relief complex was added to the lecithin and polyglyceryl-3-methylglucose distearate. It is mixed in 0.5 wt% based on the weight and dissolved in methanol and chloroform 1:4 (v/v%) solution. After the organic solvent was completely removed using a rotary evaporator, a thin lipid film was formed on the wall. The formed lipid membrane is hydrated with purified water to form elastic liposomes. In order to uniform the particle size of the thus obtained elastic liposome, glass beads were added thereto, and an ultrasonic wave crusher was applied for 20 min. The prepared liposome suspension was removed using a 0.45 μm syringe filter (Minisart CA 26 mm, Germany) to remove uncollected alleviation complexes.

The general liposome of Comparative Example 1 was prepared in the same manner as in Example 1, except that cholesterol was used instead of polyglyceryl-3-methylglucose distearate.

division lecithin Polyglyceryl-3-methylglucose distearate cholesterol Example 1 90 10 - Comparative Example 1 90 - 10

Experimental Example 2: Particle Size and Zeta Potential

(1) particle size measurement

In order to confirm whether the elastic liposome prepared in Preparation Example 2 was well formed, the particle size was measured using dynamic light scattering (Otsuka ELS-Z2, Otsuka Electronics, Japan). The measurement temperature was 25°C, the scattering angle was 165°, and an Argon laser was used as the light source. The average particle size was expressed by the Cumulative method, and the distribution was analyzed by the Contin method.

(2) Zeta potential measurement

In order to confirm that the elastic liposome prepared in Example 1 was well formed, the zeta potential was measured using a Zetisizer (Malvern Instruments, UK). The particle size was measured three times each 70 times to represent the average, and the zeta potential was measured three times for 10 times.

division Particle size (nm) Zeta potential (mV) Example 1 186 -28 Comparative Example 1 153 -30

As shown in Table 6, the elastic liposome containing the alleviation complex according to the present invention and polyglyceryl-3-methylglucose distearate exhibited a particle size of 186 nm, and the general containing alleviation agent and cholesterol Liposomes exhibited a particle size of 153 nm. The zeta potentials were found to be stable at -28 mV and -30 mV, respectively.

Experimental Example 3: Morphological observation

A transmission electron microscope (transmission electron microscopy, TEM, JEOL-JEM2010 instrument, JEOL Ltd., Japan) was used for morphological observation of the elastic liposome prepared in Example 1. The liposome suspension diluted with distilled water was dripped onto a carbon-coated copper grid, dried, and then the particle surface was stained with 0.2% (w/v%) phosphotungistic acid and measured at an accelerating voltage of 200 kV. shown in From the observation results, it was confirmed that the prepared elastic liposome and general liposome had a spherical structure.

Experimental Example 4: Measurement of collection efficiency

Take 1 mL of the liposome suspension of Example 1 and Comparative Example 1, add 10 mL of ethanol, and destroy the liposome membrane. After evaporating the solvent using a rotary evaporator, 1 mL of ethanol is added again. A UV-vis spectrometer was used to quantitatively analyze the stimulus-relief complex captured in the liposome. The concentration of the alleviation complex captured in the liposome was calculated by creating a standard calibration curve of the alleviation complex for each concentration, and the obtained value was substituted into Equation 3 shown below to calculate the capture efficiency of the liposome.

C _T : Concentration of the stimulus-relief complex first added; C _F : Concentration of irritation relief complex passed through 0.45 μm syringe filter

The collection efficiency of the stimulus-relieving complex collected in the general liposome was 67.5, and the collection efficiency of the stimulus-relieving complex captured in the elastic liposome was 81.2%, indicating that the collection efficiency of the elastic liposome was higher than that of the general liposome. It is considered that when the liposome contains a surfactant, the size of the liposome slightly increases and the capture efficiency also increases.

Experimental Example 5: Determination of variable formation

A mini extruder was used to evaluate the deformation rate of the liposome membrane of Example 1 and Comparative Example 1. That is, when a pressure of 0.2 MPa was applied to the liposome for 1 min, it passed through a polycarbonate membrane having pores of 0.08 μm in size. The particle size of the liposome before and after extrusion was measured using dynamic light scattering. The strain was calculated by substituting Equation (4).

S _B : particle size before extrusion; S _A : particle size after extrusion

As a result of measuring the variable morphology for normal liposomes and elastic liposomes, it was found that the normal liposomes significantly reduced the size of the liposomes to 20.7% and the membrane was ruptured. However, it was confirmed that the flexibility of the membrane was increased by decreasing the deformability of the elastic liposome to 2.8%.

Experimental Example 6: Stability observation

In order to confirm the physical stability of the liposome formulations of Example 1 and Comparative Example 1, the liposome suspension was refrigerated at 4° C. for 4 weeks and observed. Changes in particle size and polydispersity index (PDI) values were measured for 4 weeks, and precipitation formation was observed. At this time, observation of the particle size of the present invention was measured using a particle size analyzer (Otsuka ELS-Z2, Otsuka Electronics, Japan).

Table 7 and Table 8 show the results of observation of its particle size and polydispersity index over time.

Referring to Table 7, the elastic liposome composition containing 0.5% of the irritation relief complex according to the present invention showed excellent stability properties in particle size and polydispersity index for 4 weeks.

As can be seen in Table 8, the general liposome of Comparative Example 1 also showed stable properties in particle size and polydispersity index for 4 weeks. It is considered that the addition of cholesterol helped to stabilize the membrane.

Example 1 0 weeks 1 week 2 weeks 4 weeks particle size 186.0 nm 192.2 nm 195.0 nm 204.8 nm polydispersity index 0.2 0.256 0.276 0.271 Appearance (transparency) translucent translucent translucent translucent

Comparative Example 1 0 weeks 1 week 2 weeks 4 weeks particle size 154.1 nm 161.7 nm 165.4 nm 184.4 nm polydispersity index 0.198 0.255 0.260 0.282 Appearance (transparency) translucent translucent translucent translucent

Experimental Example 7: Skin permeability test

In order to examine the effect of the elastic liposome composition on the skin delivery of the skin irritation alleviation complex, the amount of skin permeation was measured using a Franz diffusion cell, and the results are shown in FIG. 2 . Butylene glycol in which 0.5% by weight of the elastic liposome of Example 1, Comparative Example 1, and the skin irritation alleviation complex of Preparation Example 2 was dissolved as a control was used in the experiment. The results were expressed by quantifying the amount of the skin irritation alleviation complex after 24 hours, and were divided into the amount of substances present in the epidermis and dermis (Skin) and the amount that penetrated the skin (Transdermal).

As a result of using the elastic liposome composition, the amount present in the epidermis and dermis (Skin) was similar, but the amount that penetrated the skin (Transdermal) was significantly increased. As a result, the total skin absorption capacity of the control group, butylene glycol, was 52.2%, which was lower than that of the experimental group, and the general liposome of Comparative Example 1 was 68.8%, indicating significantly improved skin permeability compared to the control group, In the case of the elastic liposome of Example 1, 80.6% showed more improved skin permeability compared to the general liposome.

Through these results, it was confirmed that the case where the stimulus-relieving complex was supported on elastic liposomes delivered the active ingredients to the skin better than general liposomes. It seems that the membrane flexibility of elastic liposomes affected the skin permeability of the alleviation complex. That is, the surfactant added between the lipid membranes of elastic liposomes increases the flexibility of the lipid membranes, and this property can promote the fusion of the liposomes with the biological membranes, thereby enhancing the skin penetration of the alleviating irritation complex.

Claims (5)

A cosmetic composition for alleviating skin irritation comprising an elastic liposome encapsulated in a skin irritation relief complex comprising comfrey leaf extract, madecassoside and panthenol. The cosmetic composition for alleviating skin irritation according to claim 1, wherein the skin irritation alleviation complex comprises comfrey leaf extract, madecassoside, and panthenol in a weight ratio of 28:2:70. The cosmetic composition for alleviating skin irritation according to claim 1, wherein the skin irritation alleviation complex is contained in an amount of 0.1 to 5.0% by weight based on the total weight of the elastic liposome. The cosmetic composition for alleviating skin irritation according to claim 1, wherein the elastic liposome contains a lecithin compound and a surfactant in a weight ratio of 8 to 9: 2 to 1. The cosmetic composition for alleviating skin irritation according to claim 4, wherein the surfactant is polyglyceryl-3 methylglucose distearate.

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