KR102621819B1 - Nano multilamella liposome containg skin lipid ingredient and manufacturing method thereof - Google Patents

Abstract

The present invention relates to nano multilayer liposomes that are biocompatible and stably encapsulate ceramides, bio-derived peptides, and hyaluronic acid, and have excellent skin absorption and permeability for overall skin improvement, such as improving skin moisturization, preventing skin aging, and improving skin wrinkles. Provided are nano multilayer liposomes suitable for cosmetic compositions and a method for producing the same.

Description

Nano multilamella liposome containing skin lipid ingredient and manufacturing method thereof}

The present invention relates to a nano multilayer liposome that is biocompatible, has little skin irritation, and effectively stabilizes effective substances such as bio-derived peptides, and can be applied to cosmetics for moisturizing the skin and preventing aging, and a method for manufacturing the same.

The skin, which first comes into contact with the outside of the human body and provides the first barrier against the external environment, has an important aesthetic impact in addition to its simple defensive function. The composition of the skin is divided into the epidermis and the dermis, and among these, the epidermis has been observed to change most clearly depending on skin aging and moisture content, and has been the main target of research for skin beauty.

The main component of skin is lipid, and various skin components, including lipids, form a solid skin barrier to maintain the shape of the skin and defend against foreign environments. Representative lipids that form the skin barrier include cholesterol, fatty acids, and ceramides. It is known that it is very difficult for water-soluble components to penetrate into the skin due to the lipid components of the skin barrier and the skin barrier containing them.

Among various methods to penetrate water-soluble ingredients into the skin, the method using liposomes is widely used to prevent skin aging, moisturize, and improve wrinkles. The main reason for using liposomes is that stable delivery is possible without changes in the active ingredients contained in the liposomes, and the active ingredients can be delivered into the skin through liposomes regardless of whether they are fat-soluble or water-soluble.

Types of liposomes can be divided into multilamella or unilamella liposomes, and unilamella liposomes can be further divided into large-lamella liposomes or small-lamella liposomes depending on their size. In general, multilayer liposomes are 400 to 3,500 nm in size and can encapsulate about 5 to 15% of the components of the liposome, while single-layer liposomes have a size of 100 to 1,000 nm in the case of large membranes and can encapsulate about 30 to 65% of the components. In the case of a small membrane, the size is 20 to 50 nm and can contain about 0.5 to 1.0% of the liposome.

Large-membrane liposomes can encapsulate the largest amount of ingredients, but are unstable, and small-membrane liposomes are stable, but the amount of ingredients that can be encapsulated is very small. On the other hand, multilayer liposomes have a sufficient amount of ingredients that can be encapsulated in liposomes and have good affinity for the skin, which has a multilayer structure. However, in the case of multilayer liposomes, their size is so large that it is difficult to maintain stability and there is a problem in that they do not have excellent penetrability into the skin.

In addition to liposomes, a method of infiltrating water-soluble ingredients into the skin through niosomes is also used. Niosomes are 10 to 200 nm in size, contain non-ionic surfactants and cholesterol as main ingredients, have a closed double-layer structure through high-pressure emulsification, etc., and are relatively stable compared to liposomes that transport ingredients by lipid particles such as phospholipids. It is easy to produce and inexpensive, but has the disadvantage of being easy to aggregate or fuse and not being biocompatible.

Among the lipid components used in liposome production, lecithin is known to be effective in reducing the size of liposomes and improving skin absorption in the case of non-hydrogenated lecithin, but due to the nature of liposomes existing in a water dispersed state, it has chemical instability due to unsaturated groups. , it is accompanied by changes in color and scent due to acidification, and has the disadvantage of low long-term stability. On the other hand, hydrogenated lecithin has excellent chemical stability as the unsaturated group is removed, and has the advantage of excellent long-term stability, such as no oxidation or odor change even if it is in a water dispersed state. However, due to the rigidity of the saturated hydrocarbon group, it has a large radius of curvature. It is difficult to manufacture nano-level liposomes, but there is a problem in that they transfer to a lamellar phase.

To solve these problems or shortcomings, it is necessary to develop multilayer liposomes that are stable and small in size, can stably capture various substances, and have excellent biocompatibility and long-term stability.

Republic of Korea Public Patent 2004-0078500

In order to solve the problems of technology using multilayer liposomes, the present invention was completed by developing a nano multilayer liposome and a manufacturing method thereof that are biocompatible, have excellent skin permeability, and can stably capture various effective substances, including skin lipid components.

The present invention can be used as a cosmetic composition for improving skin, such as improving skin moisturization and preventing skin aging, and can be applied not only to the cosmetics field but also to the pharmaceutical and food fields.

The present inventors recognized the problems of existing known liposomes and, by using hydrogenated lecithin, not only had chemical stability and long-term stability, but also introduced polyglyceryl-based surfactants substituted with acyl groups and fatty acids to form multilayer liposomes in nano size. We have invented a multilayer nanoliposome that can be formed stably, is biocompatible, and can stably capture effective substances.

The present invention provides a nano multilayer liposome containing a polyglyceryl-based surfactant substituted with an acyl group of C ₁₆ to C ₂₂ , hydrogenated lecithin, and fatty acid, and in which an effective substance is stably captured.

The present invention includes the following steps: a) mixing oil phase components containing a polyglyceryl-based surfactant substituted with an acyl group of C ₁₆ to C ₂₂ , hydrogenated lecithin, and fatty acid, b) adding the oil phase components to the water phase component and emulsifying them, c. ) A high-pressure emulsification step to form nano-sized liposomes, and d) a step of stabilizing the liposomes by dispersing a thickener and cooling.

The nano multilayer liposome of the present invention is biocompatible, has little irritation to the skin, is safe, and effectively captures the effective substances in a very stable manner. It has excellent moisturizing power and skin permeability, thereby improving the skin, including skin moisturizing effect, skin aging prevention, and skin wrinkle improvement. It can be used in a variety of ways.

Figures 1 (a) to (d) show the structure and size of the nano multilayer liposome according to the present invention.

The specific details of the present invention will be described. In the description and drawings of the present invention, descriptions of well-known content that may obscure the gist of the invention may be omitted, and terms not separately defined throughout the specification may be used by those skilled in the art to which the present invention pertains. It can be interpreted in the usual sense.

The present invention relates to a nano multilamella liposome containing a polyglyceryl-based surfactant substituted with an acyl group of C ₁₆ to C ₂₂ , hydrogenated lecithin, and fatty acid, and in which an effective substance is stably captured, and a method for producing the same. The present invention provides nano multilayer liposomes that are biocompatible, have excellent skin permeability and skin absorption, and are effective in improving skin, and a method for manufacturing the same.

The content of polyglyceryl-based surfactant substituted with an acyl group of C ₁₆ to C ₂₂ included in the nano multilayer liposome of the present invention is 1 to 15% by weight, preferably 3 to 12% by weight, more preferably, compared to the nano multilayer liposome dispersion. is 5 to 10% by weight. According to an embodiment of the present invention, when the amount is less than 3% by weight, the multilayer liposome is not manufactured firmly and the stability over time may deteriorate, and when it is more than 12% by weight, the emulsifying power of the surfactant increases, resulting in the creation of a fine emulsion. Multilamellar liposomes may not be produced.

The number of glycerol added in the polyglyceryl-based surfactant is 6 to 20, preferably 8 to 12, but is not limited thereto. Within this range, it can be effective in reducing the size of multilayer liposomes and further improving stability. Specifically, the polyglyceryl-based surfactant substituted with an acyl group of C ₁₆ to C ₂₂ is one or more of polyglyceryl-based stearate, polyglyceryl-based palmitate, and polyglyceryl-based behenate. may include.

In the present invention, the stability and biocompatibility of nano multilayer liposomes can be improved and the total amount of surfactant can be reduced by including lecithin, a major component of phospholipids, as an auxiliary emulsifier. Lecithin can be divided into lecithin that has an unsaturated group and hydrogenated lecithin in which the unsaturated group is removed by hydrogenating the unsaturated group. In the present invention, hydrogenated lecithin is preferably used.

Lecithin is manufactured by extracting from soybeans or eggs and then refining, and is composed of phospholipids with a fatty acid chain of 12 to 24 carbon atoms, such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, and phosphatidic acid. It is a mixture containing. The fatty acid chain constituting the hydrophobic group of the extracted lecithin is an unsaturated lecithin with an average distribution of 0 to 3 double bonds, and depending on the degree of purification, a mixture containing 70 to 95% of phosphatidylcholine can be used. While the double bond of the fatty acid chain present in lecithin is easily oxidized by water or active oxygen, hydrogenated lecithin is characterized by high chemical stability by reducing the number of unsaturated groups through hydrogenation.

The content of hydrogenated lecithin is 0.05 to 10% by weight, 0.5 to 6% by weight, preferably 1 to 5% by weight, and more preferably 4 to 5% by weight, based on the nano multilayer liposome dispersion. The desired content of hydrogenated lecithin may be important for the stability of nanomultilayer liposomes, especially for maintaining long-term stability. In addition, when hydrogenated lecithin that satisfies a specific content range is used, emulsification is maintained and low-temperature stability, high-temperature stability, discoloration prevention, and high satisfaction when used on the skin can be achieved. According to an embodiment of the present invention, if the hydrogenated lecithin content is less than 1%, the stability of the nano multilayer liposome may be very low, and if the hydrogenated lecithin content exceeds 5%, discoloration may occur too easily.

According to the present invention, the multilayer structure of the nano multilayer liposome can be further stabilized by further including fatty acids. The fatty acid is a fatty acid having a carbon chain of 14 to 24 carbon atoms, preferably 16 to 22 carbon atoms, but is not limited thereto. For example, the fatty acid may include one or more of lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, arachidonic acid, and behenic acid. The content of fatty acid is 0.1 to 5% by weight, 1 to 5% by weight, 1 to 2% by weight, and 1.5 to 2.5% by weight relative to the nano multilayer liposome dispersion, but is not limited thereto.

The effective substance captured and stabilized in the present invention is not limited as long as it can be stably captured in the nano multilayer liposome of the present invention, and is a substance that exhibits water-soluble or fat-soluble properties. Preferably, at least one of bio-derived peptides, ceramides, tocopherol, and hyaluronic acid is captured and stabilized as an effective substance.

In the present invention, bio-derived peptide refers to a protein existing in the body found in human blood, saliva, etc., and includes any one or more of water-soluble copper peptide, argireline, palmitoyl oligopeptide, and palmitoyl tetrapeptide. The content of the bio-derived peptide is 0.001 to 1% by weight, 0.1 to 0.5% by weight, preferably 0.01 to 0.1% by weight, compared to the nano multilayer liposome dispersion, but is not limited thereto.

In the present invention, high molecular weight (HMW) hyaluronic acid can be used to continuously supply moisture to the skin, and low molecular weight (LMW) hyaluronic acid can be used for absorption into the skin. You can. The high molecular weight hyaluronic acid preferably has a molecular weight of 30,000 to 100,000 daltons, and the low molecular weight hyaluronic acid preferably has a molecular weight of 10,000 daltons or less. The content of hyaluronic acid is preferably different for high molecular weight and low molecular weight. For high molecular weight hyaluronic acid, it is 0.001 to 0.1% by weight compared to the nano multilayer liposome dispersion, and for low molecular weight hyaluronic acid, it is 0.001 to 0.1% by weight compared to the nano multilayer liposome dispersion. It is preferably 0.05 to 1% by weight, but is not limited thereto.

In the present invention, tocopherol can further improve skin absorption and provide an antioxidant effect to further improve the skin improvement effect. The content of tocopherol is 0.001 to 0.01% by weight, 0.01 to 5% by weight, and preferably 0.1 to 3% by weight relative to the nano multilayer liposome dispersion, but is not limited thereto.

In the present invention, ceramide can improve skin compatibility as one of the skin lipid components and can further improve the stability of multilayer liposomes by combining with fatty acids. Ceramide may be included in its precursor form, phytosphingosine, or may include both ceramide and phytosphingosine. The content of ceramide is 0.1 to 10% by weight, preferably 1 to 5% by weight, compared to the nano multilayer liposome dispersion, but is not limited thereto.

The size of the nano multilayer liposome of the present invention is 50 to 500 nm, which is smaller than that of existing multilayer liposomes, has excellent stability, and has an excellent content of ingredients that can be contained. According to one embodiment of the present invention, the multilayer liposome has 5 to 7 layers and has a multilayer structure including a lamellar structure with an interlayer spacing of 20 to 50 nm.

The nano multilayer liposome of the present invention has a smaller size than typical multilayer liposomes, has high skin absorption and permeability, and maintains a stable multilayer structure, thereby maintaining excellent skin affinity. In addition, according to one embodiment of the present invention, the amount that can be encapsulated in nano multilayer liposomes is about 5 to 15%, so that effective substances such as bioactive ingredients can be captured and delivered.

The nano multilayer liposome of the present invention can improve biocompatibility and long-term stability by using a polyglyceryl-based surfactant substituted with an acyl group of C ₁₆ to C ₂₂ , hydrogenated lecithin, and fatty acid, and the size of the multilayer liposome is 50 to 500 nm. It can be manufactured and stabilized while maintaining a sufficient content of effective substances that can be captured. In addition, by adjusting the content of hydrogenated lecithin, the content of polyglyceryl-based surfactant can be adjusted, making it possible to manufacture liposomes that are more biocompatible, have a good feeling of use, and are excellent in long-term stability and discoloration prevention.

The method for producing nano-multilayer liposomes of the present invention includes the steps of a) mixing oil phase components containing a polyglyceryl-based surfactant substituted with an acyl group of C ₁₆ to C ₂₂ , hydrogenated lecithin, and fatty acid, b) adding the oil phase component to the aqueous phase component. This is a method for producing nano multilayer liposomes, which includes the steps of emulsifying by adding, c) high pressure emulsification to form nano-sized liposomes, and d) dispersing the thickener and cooling to stabilize the liposomes.

In step a) of the nano multilayer liposome production method, the surfactant substituted with an acyl group of C ₁₆ to C ₂₂ is used in an amount of 1 to 15% by weight, preferably 3 to 12% by weight, more preferably 5 to 10% by weight, relative to the nano multilayer liposome dispersion. It is weight %. According to an embodiment of the present invention, when the amount is less than 3% by weight, the multilayer liposome is not manufactured firmly and the stability over time may deteriorate, and when it is more than 12% by weight, the emulsifying power of the surfactant increases, resulting in the creation of a fine emulsion. Multilamellar liposomes may not be produced.

In step a) of the nano multilayer liposome production method, the content of hydrogenated lecithin is 0.05 to 10% by weight, 0.5 to 6% by weight, preferably 1 to 5% by weight, more preferably 4 to 5% by weight, relative to the nano multilayer liposome dispersion. %am. The desired content of hydrogenated lecithin may be important for the stability of nanomultilayer liposomes, especially for maintaining long-term stability. In addition, when hydrogenated lecithin that satisfies a specific content range is used, emulsification is maintained and low-temperature stability, high-temperature stability, discoloration prevention, and high satisfaction when used on the skin can be achieved. According to an embodiment of the present invention, if the hydrogenated lecithin content is less than 1%, the stability of the nano multilayer liposome may be very low, and if the hydrogenated lecithin content exceeds 5%, discoloration may occur too easily.

In step a) of the nano multilayer liposome manufacturing method, effective substances such as ceramide and tocopherol may be added to the oil phase components and mixed by dissolving and mixing at 60 to 80°C. The emulsification step b) can be performed by a general emulsification method, and efficacious substances and preservatives such as water-soluble peptides and hyaluronic acid can be added to the aqueous phase components, and the aqueous phase components are also mixed and dissolved in water at 60 to 80 ° C.

The high-pressure emulsification in c) is a process for creating a nanoemulsion state, in which a multi-layered nano-liposome form with a stable nano-size in the micro size is formed, and is carried out at 50-60° C. and under a pressure of 500-1500 bar using a high-pressure emulsifier. . The thickening agent in step d) is guar gum, gellan gum, cellulose, agar, pectin, carbomer, poloxamer, xanthan gum, carrageenan gum, locust bean gum, plant-based polymer, microbial polymer, animal-based polymer, starch-based polymer, and are. One or more of phosphoric acid-based polymers, vinyl-based polymers, polyoxyethylene-based polymers, polyoxyethylene-polyoxypropylene copolymer-based polymers, acrylic polymers, and inorganic water-soluble polymers may be included, and the cooling temperature is cooled to 25 to 35°C. This is desirable for stabilization of multilayer liposomes.

In the manufacturing method, if a thickener is added before the high-pressure emulsification step of c), the efficiency of high-pressure emulsification is lowered, making it impossible to prepare the stable nano multilayer liposome targeted in the present invention. Additionally, in order to satisfy the stability desired in the present invention, it is preferable that each step of the manufacturing method be carried out in a continuous process.

The nano multilayer liposome of the present invention may further include vegetable oil, vegetable sterol, or skin softener as an oily component. The nano multilayer liposome of the present invention may further include alcohol, skin conditioning agent, dispersing agent, emulsifying agent, wetting agent, moisturizing agent, or whitening agent as an aqueous phase component. In addition, the nano multilayer liposome of the present invention may further include a preservative component.

Hereinafter, specific examples for carrying out the present invention will be described, but the present invention is not limited or construed as limited by the following examples.

[ Examples 1-8] Preparation of nano multilayer liposomes

The ingredient contents of Examples 1 to 8 and Comparative Examples 1 to 6 are shown in Tables 1 and 2 below.

Example 1 Example 2 Example 3 Example
4 Comparative Example 1 Comparative Example 2 Comparative Example 3 paid
ingredient Meadowfoam seed oil
(Limnanthes Alba Seed Oil) 5 5 5 5 5 5 5 Cetyl octaphosphate
(CETYL OCTANOTE) 5 5 5 5 5 5 5 Palmitic acid 2 2 2 2 2 2 2 PEG-5 Rape Seed Sterol
(PEG-5 Rapeseed Sterol) 2 2 2 2 2 2 2 Polyglyceryl-10 Stearate
(Polyglyceryl-10 Stearate) 8 8 8 8 8 8 8 Hydrogenated Lecithin
(Hydrogenated Lecithin) 5 One 3 4 0.1 7 9 Ceramide 3B
(Ceramide 3B) 5 5 5 5 5 5 5 Phytosphingosine
(Phytosphingosine) One One One One One One One tocopherol
(Tocopherol) 0.01 0.01 0.01 0.01 0.01 0.01 0.01 Awards
Ingredient 2 Propanediol 9 9 9 9 9 9 9 Potassium Seryl Phosphate
(POTASSIUM
CETYL PHOSPHATE) 0.3 0.3 0.3 0.3 0.3 0.3 0.3 Acetyl Glucosamine
(Acetyl Glucossamine) 7 7 7 7 7 7 7 Sodium Hyaluronate
(Sodium Hyaluronate) 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Low molecular weight sodium hyaluronate
(LMW sodium Hyaluronate) 0.2 0.2 0.2 0.2 0.2 0.2 0.2 Peptide 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Niacinamide
(Niacinamide) 5 5 5 5 5 5 5 thickener Polyacrylate-13*polyisobutene*polysorbate 20
(Polyacrylate-13*Polyisobutene *Polysorbate 20) 0.1 0.1 0.1 0.1 0.1 0.1 0.1 embalming
ingredient Phenoxyethanol
(Phenoxyethanol) 0.4 0.4 0.4 0.4 0.4 0.4 0.4 Ethylhexylglycerin
(Ethylhexylglycerin) 0.05 0.05 0.05 0.05 0.05 0.05 0.05 Awards
Ingredient 1 Purified water
(DI Water) to 100 to 100 to 100 to 100 to 100 to 100 to 100 Total 100 100 100 100 100 100 100

Example 5 Example 6 Example 7 Example
8 Comparative Example 4 Comparative Example 5 Comparative Example 6 paid
ingredient Meadowfoam seed oil
(Limnanthes Alba Seed Oil) 5 5 5 5 5 5 5 Cetyl octaphosphate
(CETYL OCTANOTE) 5 5 5 5 5 5 5 Palmitic acid 2 2 2 2 2 2 2 PEG-5 Rape Seed Sterol
(PEG-5 Rapeseed Sterol) 2 2 2 2 2 2 2 Polyglyceryl-10 Stearate
(Polyglyceryl-10 Stearate) 3 6 9 12 2 13 16 Hydrogenated Lecithin
(Hydrogenated Lecithin) 4 4 4 4 4 4 4 Ceramide 3B
(Ceramide 3B) 5 5 5 5 5 5 5 Phytosphingosine
(Phytosphingosine) One One One One One One One tocopherol
(Tocopherol) 0.01 0.01 0.01 0.01 0.01 0.01 0.01 Awards
Ingredient 2 Propanediol 9 9 9 9 9 9 9 Potassium Seryl Phosphate
(POTASSIUM
CETYL PHOSPHATE) 0.3 0.3 0.3 0.3 0.3 0.3 0.3 Acetyl Glucosamine
(Acetyl Glucossamine) 7 7 7 7 7 7 7 Sodium Hyaluronate
(Sodium Hyaluronate) 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Low molecular weight sodium hyaluronate
(LMW sodium Hyaluronate) 0.2 0.2 0.2 0.2 0.2 0.2 0.2 Peptide 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Niacinamide
(Niacinamide) 5 5 5 5 5 5 5 thickener Polyacrylate-13*polyisobutene*polysorbate 20
(Polyacrylate-13*Polyisobutene *Polysorbate 20) 0.1 0.1 0.1 0.1 0.1 0.1 0.1 embalming
ingredient Phenoxyethanol
(Phenoxyethanol) 0.4 0.4 0.4 0.4 0.4 0.4 0.4 Ethylhexylglycerin
(Ethylhexylglycerin) 0.05 0.05 0.05 0.05 0.05 0.05 0.05 Awards
Ingredient 1 Purified water
(DI Water) to 100 to 100 to 100 to 100 to 100 to 100 to 100 Total 100 100 100 100 100 100 100

Nano multilayer liposomes of Examples 1 to 8 and Comparative Examples 1 to 6 were prepared according to the following method. The oil phase components were uniformly mixed and dissolved at 70°C. Water phase component 2 and preservative ingredient were added to water phase component 1 and mixed and dissolved at 70°C. After mixing and dissolving, the oil phase component was slowly added to the water phase component while homomixing to emulsify. Afterwards, nanoemulsion was created by high-pressure emulsification in a high-pressure emulsifier at 55°C and 1000 bar. After high-pressure emulsification, the thickener was added to the resulting nanoemulsion while homomixing to completely disperse it, and then cooled to 30°C to obtain stabilized nano multilayer liposomes.

thickener Comparison of stability and particle size depending on the time of injection

The time of addition of the thickener should be after high-pressure emulsification, and if the time of addition of the thickener was before high-pressure emulsification, nano multilayer liposomes with the desired stability and size could not be obtained. The only difference was that the thickener was added before high-pressure emulsification, and the other manufacturing methods were the same as Examples 1 to 8. Stability tests and average sizes of multilayer membranes were measured. The size of each nano multilayer liposome obtained by varying the time of addition of the thickener and the results of the stability test conducted at 45°C for 14 days are shown in Table 3. I also confirmed that multilayer liposomes were formed uniformly and remained stable.

45℃ stability and particle size according to the time of thickener addition Input before high pressure emulsification Input after high pressure emulsification Stability at 45℃/14 days upper layer separation Good average particle size 10㎛ 100 nm

Comparison of stability by surfactant combination

In Examples 1 to 4, the contents of hydrogenated lecithin were set to 1, 3, 4, and 5% by weight, respectively, and in Comparative Examples 1 to 3, the contents of hydrogenated lecithin were set to 0.01, 7, and 9% by weight, respectively. In Examples 5 to 8, the content of polyglyceryl-based surfactant was 3, 6, 9, and 12% by weight, respectively, and in Comparative Examples 4 to 6, the content of polyglyceryl-10 stearate, a polyglyceryl-based surfactant, was set to 3, 6, 9, and 12% by weight, respectively. It was set at 2, 13, and 16% by weight. Comparison of low-temperature stability of Examples 1 to 8 and Comparative Examples 1 to 6 was carried out by storing at -17°C for 1 day and then thawing for 1 day, and for high-temperature stability testing, the samples were checked daily at 45°C and 60°C. did. The freezing stability of Comparative Example 1 was excellent for one week, but the high temperature stability decreased, especially when stored at 60°C for more than 2 days, as the emulsification was broken. And in the case of Comparative Examples 2 and 3, discoloration occurred at high temperature, and the feeling of use was not good due to the excessive lecithin content. As a result of the stability evaluation of Examples 1 to 4 and Comparative Examples 1 to 3, multilayer liposomes with a lecithin content of 1 to 5% by weight had excellent stability, but when the lecithin content exceeded 1 to 5% by weight, the stability was not good. . In addition, in Table 4, Examples 1 and 4 showed very good stability and discoloration evaluation results among the examples, and the stability and discoloration degree of the multilayer liposome were particularly excellent when the lecithin content was included in 4 to 5%. Comparative Example 4 had excellent freezing stability for one week, but when stored at both 45°C and 60°C for more than 2 days, the stability decreased as the emulsification was broken, and in Comparative Examples 5 and 6, multilayer nano liposomes were not produced normally. As a result of the stability evaluation of Examples 5 to 8 and Comparative Examples 4 to 6, it was confirmed that when the content of polyglyceryl-based surfactant exceeded 3 to 12% by weight, stability was poor or multilayer nano liposomes were not produced normally. The experimental results for stability and discoloration were shown in Table 4 below.

stability discoloration Example 1 5 5 Example 2 4 5 Example 3 4 5 Example 4 5 5 Example 5 5 5 Example 6 5 5 Example 7 4 5 Example 8 5 5 Comparative Example 1 One 3 Comparative Example 2 2 One Comparative Example 3 2 One Comparative Example 4 One 4 Comparative Example 5 Not manufactured 4 Comparative Example 6 Not manufactured 4 1: bad, 2: slightly bad, 3: average, 4: slightly good, 5: very good

multi-layer liposome Formation confirmation

After preparing nano multilayer liposomes using the ingredients according to Examples 1 to 8, the microstructure of the liposomes was confirmed. A lamellar structure of about 5 to 7 layers was formed in a multilayered form and the length was about 200 nm, the interlayer spacing was formed relatively regularly within 20 to 50 nm, and the size of the liposome was 50 to 500 nm (Figure 1). When manufacturing nano multilayer liposomes using the ingredients according to Comparative Examples 5 and 6, a large number of fine emulsions of 20 to 40 nm were produced, and multilayer nano liposomes were not produced.

stability test

The stability of nano multilayer liposomes prepared by the manufacturing method according to Examples 1 to 8 was evaluated on 10 subjects through an in vitro patch test, and the results are shown in Table 5.

test substance degree of stimulation average stimulation score (-)control (-) 0.00 0.3% SDS ++ 6.55 Examples 1 to 4 (-) 0.00 (-): No response / stimulation score 0
·: Faint mild erythema/irritation score 0.5
±: mild erythema with well-defined boundaries/irritation score 1
+: Marked erythema, papules and vesicles / irritation score 2
++: severe erythema, blisters / irritation score 6
+++: crust formation/irritation score 12

For the moisturizing power test, a moisture measuring probe of the ARAMO-TS (Aram Huvis Co., Ltd., Korea) device was used, and for TEWL, the average moisturizing power was measured by 10 people using the subject's forearm using an AquaFlux. (Biox, UK) device. Measurements were made, and the results are shown in Tables 6 and 7.

test substance Before processing 1 day 5 days 15th 20th 30 days Examples 1 to 4 33.40 +8.60 +5.90 +3.63 +5.73 +6.47

It was confirmed that the moisturizing power increased to more than 8 after just one day of using the liposome, and when used continuously, an improved moisturizing power of 6.47 compared to the previous one was confirmed even on the 30th day.

test substance Before processing 1 day 5 days 15th 20th 30 days Examples 1 to 4 12.64 -7.13 -2.48 0.14 -1.8 -0.48

In the case of the average transepidermal water loss (TEWL) value, it was confirmed that the amount of loss decreased by more than 7 in 1 day compared to before treatment.

Claims (13)

It includes a polyglyceryl-based surfactant substituted with a C ₁₆ to C ₂₂ acyl group, hydrogenated lecithin, and a fatty acid, and the content of the polyglyceryl-based surfactant substituted with a C ₁₆ to C ₂₂ acyl group is 3 to 12% compared to the nano multilayer liposome dispersion. % by weight, the hydrogenated lecithin content is 4 to 5% by weight compared to the nano multilayer liposome dispersion, the polyglyceryl-based surfactant substituted with an acyl group of C ₁₆ to C ₂₂ has a glycerin added number of 6 to 20, and the effective substance This stably captured nano multilamella liposome. According to paragraph 1,
The effective substance is a nano multilayer liposome containing one or more of bio-derived peptides, hyaluronic acid, ceramide, and tocopherol. According to paragraph 1,
The polyglyceryl-based surfactant substituted with an acyl group of C ₁₆ to C ₂₂ is a nano multilayer liposome containing one or more of polyglyceryl stearate, polyglyceryl palmitate, and polyglyceryl behenate. delete delete According to paragraph 2,
The bio-derived peptide is a nano multilayer liposome containing one or more of copper peptide, argireline, palmitoyl oligopeptide, and palmitoyl tetrapeptide. According to paragraph 1,
The nano multilayer liposome has a size of 50 to 500 nm. According to paragraph 1,
The nano multilayer liposome has a lamellar structure of 5 to 7 layers and an interlayer spacing of 20 to 50 nm. A cosmetic composition for skin moisturizing comprising the nano multilayer liposome of any one of claims 1 to 3 and 6 to 8. a) mixing oil phase components including a polyglyceryl-based surfactant substituted with an acyl group of C ₁₆ to C ₂₂ , hydrogenated lecithin, and fatty acid;
b) adding the oil phase component to the water phase component and emulsifying it;
c) high-pressure emulsification step to form nano-sized liposomes; and
d) dispersing the thickener and cooling to stabilize the liposome;
Including,
In step a), the content of polyglyceryl-based surfactant substituted with acyl groups of C ₁₆ to C ₂₂ is 3 to 12% by weight compared to the nano multilayer liposome dispersion,
In step a), the hydrogenated lecithin content is 4 to 5% by weight compared to the nano multilayer liposome dispersion,
The polyglyceryl-based surfactant substituted with an acyl group of C ₁₆ to C ₂₂ has 6 to 20 glycerol added, a method for producing a nano multilayer liposome. delete delete According to clause 10,
The high-pressure emulsification step is a nano multilayer liposome production method performed at 50 to 60°C and 500 to 1500 bar.