Bicelle and liposome composition comprising same

Abstract

The present invention relates to a bicelle and a liposome composition comprising same and, more specifically, to a bicelle and a liposome composition comprising same, the bicelle comprising: an active ingredient; hydrogenated lecithin as a long-chain lipid; cholesterol, ceramide, lysolecithin, or a mixture thereof as a short-chain lipid; PEG-5 phytosterol, PEG-10 phytosterol, PEG-20 phytosterol, PEG-30 phytosterol, phytosteryl / behenyl / octyldodecyl lauroyl glutamate, phytosteryl / isostearyl / cetyl / stearyl / behenyl dimer dilinoleate, or a mixture thereof as a nonionic surfactant; and polyglyceryl-10 laurate, PEG-10 rapeseed sterol, or a mixture thereof as an auxiliary stabilizer.

Description

Bicell and liposome composition containing same

[0001] The present invention relates to a bicel and a liposome composition comprising the same, and more particularly, to a bicel and a liposome composition comprising the same, comprising: an active ingredient; hydrogenated lecithin as a long-chain lipid; cholesterol, ceramide, lysolecithin or a mixture thereof as a short-chain lipid; PEG-5 phytosterol, PEG-10 phytosterol, PEG-20 phytosterol, PEG-30 phytosterol, phytosteryl / behenyl / octyldodecyl lauroyl glutamate, phytosteryl / isostearyl / cetyl / stearyl / behenyl dimer dilinoleate or a mixture thereof as a nonionic surfactant; and polyglyceryl-10 laurate, PEG-10 rapeseed sterol or a mixture thereof as an auxiliary stabilizer.

[0002] The stratum corneum (stratum corneum) of the skin is the outermost layer and functions as a biological barrier. It consists of cells and intercellular lipids, forming a brick-and-mortar structure. Ceramides and cholesterol are the main components of this structure. Ceramides and cholesterol, along with other lipids, form a planar lamellar structure within the intercellular lipids. Cholesterol and ceramides are known to play a crucial role in protecting the body from external irritants and transepidermal moisture loss. In particular, their lamellar structure significantly contributes to strengthening the skin barrier. However, they have the disadvantage of being difficult to incorporate into cosmetic formulations with high crystallinity and low oil content.

[0003] Bicelle is a disc-shaped lipid delivery system consisting of a flat plate composed of long-chain lipids and an end portion composed of short-chain lipids (Figure 1). Bicelle is a lamellar lipid delivery system capable of carrying active substances. Bicelle has the property of selectively penetrating the intercellular space of stratum corneum to reach the target skin layer. There are various methods for manufacturing the Bicelle structure, including ultrasound, stirring, and high-pressure microemulsification. Among these, high-pressure microemulsification uses a device called a microfluidizer. According to Bernoulli's theorem, high pressure rapidly decreases, resulting in increased flow velocity, which in turn causes cavitation and turbulent flow, thereby breaking down emulsified particles into very fine particles. Particle size can be controlled by adjusting the pressure difference. Bicelle is a delivery system that can form a structure similar to a cell membrane and is attracting attention as a model for stably formulating highly crystalline cholesterol and ceramides.

[0004] Liposomes are defined as spherical phospholipid vesicles of self-assembled colloidal particles. Alec Bangham first discovered their formation in water in the early 1960s. Liposomes, spherical vesicles composed of phospholipids, can simultaneously entrap hydrophilic and lipophilic components, and are therefore being studied as delivery systems for active ingredients such as vitamins and pharmaceuticals. Since phospholipids are a major component of biological membranes, the phospholipid membrane of liposomes exhibits physiological functions and properties similar to those of biological membranes. Therefore, liposomes are skin-friendly and have excellent safety, making them effective delivery systems for active ingredients in fields such as the pharmaceutical and cosmetic industries.

[0005] The present invention has as its technical task the provision of a bicell-based transdermal delivery system (TDS) capable of efficiently delivering an active ingredient of a cosmetic into the skin in a stable form.

[0006] In addition, another technical object of the present invention is to provide a cosmetic composition comprising the above-described cell-based transdermal delivery system.

[0007] In order to solve the above problems, the present invention provides a bisulphite comprising: an active ingredient; hydrogenated lecithin as a long-chain lipid; cholesterol, ceramide, lysolecithin or a mixture thereof as a short-chain lipid; PEG-5 phytosterol, PEG-10 phytosterol, PEG-20 phytosterol, PEG-30 phytosterol, phytosteryl / behenyl / octyldodecyl lauroyl glutamate, phytosteryl / isostearyl / cetyl / stearyl / behenyl dimer dilinoleate or a mixture thereof as a nonionic surfactant; and polyglyceryl-10 laurate, PEG-10 rapeseed sterol or a mixture thereof as an auxiliary stabilizer.

[0008] In addition, the present invention provides a liposome composition containing the above-described bicelles.

[0009] In addition, the present invention provides a cosmetic composition comprising the above-described bicell-containing liposome composition.

[0010]

[0011] The present invention is described in detail below.

[0012]

[0013] According to one aspect of the present invention,

[0014] Active ingredient;

[0015] Hydrogenated lecithin as a long-chain lipid;

[0016] Cholesterol, ceramide, lysolecithin or mixtures thereof as short-chain lipids;

[0017] PEG-5 phytosterol, PEG-10 phytosterol, PEG-20 phytosterol, PEG-30 phytosterol, phytosteryl / behenyl / octyldodecyl lauroyl glutamate, phytosteryl / isostearyl / cetyl / stearyl / behenyl dimer dilinoleate or a mixture thereof as a nonionic surfactant; and

[0018] A bicelle is provided comprising polyglyceryl-10 laurate, PEG-10 rapeseed sterol or a mixture thereof as an auxiliary stabilizer.

[0019]

[0020] Lecithin refers to a mixture of various phospholipids, the composition of which can vary depending on their origin. Hydrogenated lecithin can be obtained by adding hydrogen to lecithin.

[0021] Ceramides are a family of lipids composed of sphingosine and fatty acids.

[0022] The term lyso- in lysolecithin means to dissolve, and is created when the fatty acid at position 2 is removed from lecithin.

[0023] Phytosterols are phytosteroids produced in plants that are similar to cholesterol, differing only in the presence or absence of a carbon side chain or double bond.

[0024] Phytosteryl / behenyl / octyldodecyl lauroyl glutamate is a mixed ester of phytosterol, behenyl alcohol, and octyldodecanol with lauroyl glutamic acid.

[0025] Phytosteryl / isostearyl / cetyl / stearyl / behenyl dimer dilinoleate is an ester of dilinoleic acid with a mixture of phytosterols, isostearyl alcohol, cetyl alcohol, stearyl alcohol, and behenyl alcohol.

[0026] Polyglyceryl-10 laurate is an ester of lauric acid and polyglycerin-10.

[0027] PEG-10 rapeseed sterol is a polyethylene glycol ether of rapeseed sterol with an average of 10 moles of ethylene oxide.

[0028]

[0029] According to one specific example of the present invention, the biscell may comprise 0.1 to 60 wt% of an active ingredient, 5 to 60 wt% of a long-chain lipid, 2 to 50 wt% of a short-chain lipid, 10 to 65 wt% of a nonionic surfactant, and 5 to 40 wt% of an auxiliary stabilizer.

[0030] According to another embodiment of the present invention, the biscell may comprise 0.2 to 55 wt% of an active ingredient, 8 to 55 wt% of a long-chain lipid, 3 to 45 wt% of a short-chain lipid, 12 to 60 wt% of a nonionic surfactant, and 7 to 38 wt% of an auxiliary stabilizer.

[0031] According to another embodiment of the present invention, the bicelle may comprise 0.5 to 50 wt% of an active ingredient, 10 to 50 wt% of a long-chain lipid, 5 to 40 wt% of a short-chain lipid, 15 to 55 wt% of a nonionic surfactant, and 8 to 35 wt% of an auxiliary stabilizer.

[0032]

[0033] There is no particular limitation on the active ingredient in the present invention. The active ingredient in the present invention may be, for example, one or more selected from the group consisting of moisturizers, whitening agents, anti-wrinkle agents, UV blockers, hair growth agents, vitamins or derivatives thereof, amino acids or peptides, anti-inflammatory agents, acne treatment agents, bactericidal agents, female hormones, exfoliating and dissolving agents, and natural products, but is not limited thereto. In addition, cosmetic ingredients such as oils, waxes, butters, paraffins, higher fatty acids such as palmitic acid, esters such as cetyl ethylhexanoate, and silicones may also be used as active ingredients.

[0034] Humectants include, but are not limited to, creatine, polyglutamic acid, sodium lactate, hydroxyproline, 2-pyrroidone-5-carboxylic acid (PCA), hyaluronic acid, sodium hyaluronate, ceramides, collagen, phytosterols, cholesterol, beta-sitosterol, pullulan, proteoglycans, etc. Whitening agents include, but are not limited to, arbutin and arbutin derivatives, kojic acid, bisabolol, niacinamide, vitamin C and vitamin C derivatives, placenta, allantoin, tranexamic acid, etc. Anti-wrinkle agents include, but are not limited to, retinol, retinol derivatives, adenosine, licorice extract, red ginseng extract, and ginseng extract. Sunscreens include, but are not limited to, benzophenone derivatives, para-aminobenzoic acid derivatives, methoxycinnamate derivatives (e.g., octyl methoxycinnamate), salicylic acid derivatives, and octocrylene. There are no particular limitations on hair growth agents, but circulation promoters and / or local irritants are preferred. Circulation promoters include, but are not limited to, dandelion root extract, cepharanthine, vitamin E and its derivatives, and gamma-oryzanol. Local irritants include, but are not limited to, capsicum tincture, ginger tincture, cantharides tincture, and nicotinic acid benzyl ester.Vitamins or their derivatives include, for example, vitamin A (retinol) and its derivatives, retinal, hydroxypinacolone retinoate (HPR), retinyl palmitate, vitamins B1, B2, B6, vitamin C, vitamin E and its derivatives, vitamin D, vitamin H, vitamin K, pantothenic acid and its derivatives, biotin, panthenol, coenzyme Q. 10, idebenone, etc., but are not limited thereto. Amino acids or peptides include, for example, cysteine, methionine, serine, lysine, tryptophan, epidermal growth factor (EGF), insulin-like growth factor (IGF), fibroblast growth factor (FGF), Cooper tripeptide-1, tripeptide-29, tripeptide-1, acetyl hexapeptide-8, nicotinoyl tripeptide-35, hexapeptide-12, hexapeptide-9, palmitoyl pentapeptide-3, palmitoyl pentapeptide-4, palmitoyl tetrapeptide-7, palmitoyl tripeptide-29, palmitoyl tripeptide-1, nonapeptide-7, tripeptide-10 citrulline, sh-polypeptide-15, palmitoyl tripeptide-5, diaminopropioyl Examples include, but are not limited to, tripeptide-33, r-spider polypeptide-1, and dipeptide-8. Anti-inflammatory agents include, but are not limited to, beta-glycyrrhetinic acid, glycyrrhetinic acid derivatives, aminocaproic acid, hydrocortisone, beta-glucan, and licorice. Acne treatments include, but are not limited to, estradiol, estrogen, ethinyl estradiol, triclosan, and azelaic acid. Antibacterial agents include, but are not limited to, benzalkonium chloride and benzethonium chloride. There are no specific restrictions on female hormones, but estrogen is suitable, and estradiol, ethinyl estradiol, and isoflavones, which are plant estrogens, are preferable. Examples of exfoliating and dissolving agents include, but are not limited to, sulfur, salicylic acid, alpha hydroxy acid (AHA), beta hydroxy acid (BHA), and resorcin.Extracts of natural products or ingredients obtained from them, such as extracts of Korean ginseng, common angelica, white chrysanthemum, rhubarb, licorice, aloe, chamomile, rosehip, horse chestnut, ginseng, loofah, cucumber, laver, seaweed, hemp, snail, young lady, and centella asiatica, as well as hinokitiol, beta-carotene, and bakuchiol, are not limited thereto. In addition, there are yeast extracts, collagen, elastin, DHA, EPA, and fragrance ingredients.

[0035]

[0036] According to another embodiment of the present invention, the bicelle may further comprise a solvent. According to another embodiment of the present invention, the solvent may be selected from, but is not limited to, 1,2-hexanediol, butylene glycol, propylene glycol, dipropylene glycol, pentylene glycol, diglycerin, propanediol, purified water, and mixtures thereof.

[0037]

[0038] According to another aspect of the present invention, a liposome composition containing a bicelle is provided, comprising the bicelle, a lipid component, a stabilizer and a solvent.

[0039]

[0040] According to another specific embodiment of the present invention, the bicell-containing liposome composition may comprise 0.5 to 40 wt% of bicell, 0.5 to 40 wt% of lipid component, 1 to 40 wt% of stabilizer, and 10 to 80 wt% of solvent.

[0041] According to another specific embodiment of the present invention, the lipid component may be selected from, but is not limited to, hydrogenated lecithin, phosphatidylcholine, cholesterol, phytosterol, lecithin, cholesterol ester, phytosterol ester and mixtures thereof.

[0042] According to another specific embodiment of the present invention, the stabilizer may be selected from, but is not limited to, glycerin, butylene glycol, propylene glycol, pentylene glycol, dipropylene glycol, diglycerin, propanediol and mixtures thereof.

[0043] According to another specific embodiment of the present invention, the solvent may be selected from, but is not limited to, 1,2-hexanediol, purified water, and mixtures thereof.

[0044] According to another specific embodiment of the present invention, the liposome composition containing the bicelles may further comprise one or more ingredients selected from preservatives, antioxidants, and fragrances.

[0045]

[0046] In the liposome composition containing bicelles according to the present invention, the stability of the active ingredient can be improved through double encapsulation by first encapsulating the active ingredient in bicelles, and then secondarily encapsulating bicelles containing the active ingredient within the liposomes. In addition, by forming an outer membrane with liposomes, it can have the effect of enhancing skin penetration and alleviating skin irritation. Since both bicelles and liposomes can be composed of ingredients similar to skin components, it can also have skin-friendly properties. The liposome composition containing bicelles according to the present invention is a model that mimics the skin lamellar structure. After contact with the skin, the outer liposome membrane fuses with the skin, and the lamellar bicelles selectively pass through the intercellular space to reach the target skin layer, efficiently delivering the active ingredient into the cells. Thereafter, the bicelles can be fused with the skin matrix to strengthen the skin barrier.

[0047]

[0048] According to another aspect of the present invention, a cosmetic composition comprising the above-described bicell-containing liposome composition is provided.

[0049] In the present invention, the cosmetic composition may be formulated as, for example, a skin, lotion, body lotion, cream, essence, BB (Blemish Balm) cream, etc., but is not limited thereto. In the present invention, the cosmetic composition may include a bicell-containing liposome composition in various contents depending on the formulation needs, and for example, may include a bicell-containing liposome composition in a content of 0.1 to 50 wt%.

[0050] According to the present invention, the active ingredient is double-encapsulated into a vicell and a liposome, thereby efficiently delivering the active ingredient into the skin in a very stable form and increasing bioavailability, thereby enabling excellent efficacy to be exhibited even with a small amount of the active ingredient.

[0051] Figure 1 is a schematic diagram showing the structure of a bicelle.

[0052] Figure 2 is a photograph of the bicell of Example 22 and the bicell-liposome of Example 23.

[0053] Figure 3 shows the results of measuring the particle diameter size of the bicelles of Example 22 and the bicelles-liposomes of Example 23 using Photal and ELS-Z.

[0054] Figure 4 shows the results of measuring the zeta potential of the bicelles of Example 22 and the bicelles-liposomes of Example 23 using Photal, ELS-Z.

[0055] Figure 5 is a photograph of the bicelles of Example 22 and the bicelles-liposomes of Example 23 taken using cryo-transmission electron microscopy.

[0056] Manufacturing Examples 1 to 4: Manufacturing of a bicell containing ceramide

[0057] A bicelle was prepared using ceramide as a short-chain lipid. Each component was introduced into a container according to the composition shown in Table 1 below, dissolved at 90°C, mixed for 5 minutes using an Agi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0058] [Table 1]

[0059]

[0060]

[0061] Manufacturing Examples 5 to 7: Manufacturing of a bicell containing cholesterol

[0062] Bicelles were prepared using cholesterol as a short-chain lipid. Each component was introduced into a container according to the composition shown in Table 2 below, dissolved at 90°C, and mixed for 5 minutes using an Azi homomixer. The mixture was then passed through a high-pressure microemulsifier once at 1,000 bar and cooled to obtain Bicelles.

[0063] [Table 2]

[0064]

[0065]

[0066] Manufacturing Examples 8 to 10: Manufacturing of a bisel containing lysolecithin

[0067] A bisel was prepared using lysolecithin as a short-chain lipid. Each component was introduced into a container according to the composition shown in Table 3 below, dissolved at 90°C, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bisel.

[0068] [Table 3]

[0069]

[0070]

[0071] Example 1: Preparation of a bicell containing natural products 1

[0072] Each component was introduced into a container according to the composition in Table 4 below, dissolved at a temperature of 90°C, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0073] [Table 4]

[0074]

[0075]

[0076] Example 2: Preparation of a bicell containing natural products 2

[0077] Each component was introduced into a container according to the composition in Table 5 below, dissolved at a temperature of 90°C, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0078] [Table 5]

[0079]

[0080]

[0081] Example 3: Preparation of oil-containing bisel

[0082] Each component was introduced into a container according to the composition in Table 6 below, dissolved at a temperature of 90°C, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0083] [Table 6]

[0084]

[0085]

[0086] Example 4: Preparation of oil-containing bisel 2

[0087] Each component was introduced into a container according to the composition in Table 7 below, dissolved at a temperature of 90°C, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0088] [Table 7]

[0089]

[0090]

[0091] Example 5: Preparation of a bicell containing wax

[0092] Each component was introduced into a container according to the composition of Table 8 below, dissolved at a temperature of 90°C, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0093] [Table 8]

[0094]

[0095]

[0096] Example 6: Preparation of a bisel containing butter

[0097] Each component was introduced into a container according to the composition in Table 9 below, dissolved at a temperature of 90°C, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0098] [Table 9]

[0099]

[0100]

[0101] Example 7: Preparation of bicelles containing paraffin

[0102] Each component was introduced into a container according to the composition of Table 10 below, dissolved at a temperature of 90°C, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0103] [Table 10]

[0104]

[0105]

[0106] Example 8: Preparation of bisel containing high-grade fatty acids

[0107] Each component was introduced into a container according to the composition of Table 11 below, dissolved at a temperature of 90℃, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0108] [Table 11]

[0109]

[0110]

[0111] Example 9: Preparation of a bicell containing ester

[0112] Each component was introduced into a container according to the composition of Table 12 below, dissolved at a temperature of 90℃, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0113] [Table 12]

[0114]

[0115]

[0116] Example 10: Preparation of a bicell containing a moisturizer

[0117] Each component was introduced into a container according to the composition of Table 13 below, dissolved at a temperature of 90℃, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0118] [Table 13]

[0119]

[0120]

[0121] Example 11: Preparation of a bicell containing a whitening agent

[0122] Each component was introduced into a container according to the composition of Table 14 below, dissolved at a temperature of 90℃, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0123] [Table 14]

[0124]

[0125]

[0126] Example 12: Preparation of a bicell containing a sunscreen agent

[0127] Each component was introduced into a container according to the composition of Table 15 below, dissolved at a temperature of 90℃, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0128] [Table 15]

[0129]

[0130]

[0131] Example 13: Preparation of a vitamin-containing vicelle 1

[0132] Each component was introduced into a container according to the composition of Table 16 below, dissolved at a temperature of 90℃, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0133] [Table 16]

[0134]

[0135]

[0136] Example 14: Preparation of a vitamin-containing vicelle 2

[0137] Each component was introduced into a container according to the composition of Table 17 below, dissolved at a temperature of 90℃, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0138] [Table 17]

[0139]

[0140]

[0141] Example 15: Preparation of a peptide-containing biscell 1

[0142] Each component was introduced into a container according to the composition of Table 18 below, dissolved at a temperature of 90℃, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0143] [Table 18]

[0144]

[0145]

[0146] Example 16: Preparation of a peptide-containing biscell 2

[0147] Each component was introduced into a container according to the composition of Table 19 below, dissolved at a temperature of 90℃, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0148] [Table 19]

[0149]

[0150]

[0151] Example 17: Preparation of a bisel containing an anti-inflammatory agent

[0152] Each component was introduced into a container according to the composition of Table 20 below, dissolved at a temperature of 90℃, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0153] [Table 20]

[0154]

[0155]

[0156] Example 18: Preparation of a vicell containing an acne treatment agent

[0157] Each component was introduced into a container according to the composition of Table 21 below, dissolved at a temperature of 90℃, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0158] [Table 21]

[0159]

[0160]

[0161] Example 19: Preparation of a biocide containing a bactericide

[0162] Each component was introduced into a container according to the composition of Table 22 below, dissolved at a temperature of 90℃, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0163] [Table 22]

[0164]

[0165]

[0166] Example 20: Preparation of a bicell containing natural products 3

[0167] Each component was introduced into a container according to the composition of Table 23 below, dissolved at a temperature of 90℃, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0168] [Table 23]

[0169]

[0170]

[0171] Example 21: Preparation of a bisel containing retinol

[0172] Each component was introduced into a container according to the composition of Table 24 below, dissolved at a temperature of 90℃, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0173] [Table 24]

[0174]

[0175]

[0176] Example 22: Preparation of a bicell containing retinal

[0177] Each component was introduced into a container according to the composition of Table 25 below, dissolved at a temperature of 90℃, mixed for 5 minutes using an Azi homomixer, passed once through a high-pressure microemulsifier at 1,000 bar, and cooled to obtain a bicelle.

[0178] [Table 25]

[0179]

[0180]

[0181] Example 23: Preparation of liposomes containing bicelles (bicell-liposomes)

[0182] Liposomes loaded with the bicelles obtained in Example 22 were prepared. Each component was introduced into a container according to the composition in Table 26, dissolved at a temperature of 80°C, mixed for 5 minutes using an Azi homomixer, and then passed through a high-pressure microemulsifier at 1,000 bar three times in succession, cooled, and defoamed to obtain bicelle-liposomes.

[0183] [Table 26]

[0184]

[0185]

[0186] Comparative Example: Preparation of a typical liposome containing retinal.

[0187] After introducing each component into a container according to the composition of Table 27 below, they were dissolved at a temperature of 80°C, mixed for 5 minutes using an Azi homomixer, and then passed through a high-pressure microemulsifier at 1,000 bar three times in succession, and then cooled and defoamed to obtain a liposome composition.

[0188] [Table 27]

[0189]

[0190]

[0191] Experimental Example 1: Particle Distribution Measurement

[0192] To confirm the particle distribution, the bicelles of Example 22 and the bicelles-liposomes of Example 23 were diluted by 10%, and 10 mL was placed in a Photal, ELS-Z (Japan Photal) cell and measured (Fig. 3). The measurement results showed that the average particle sizes of the bicelles of Example 22 and the bicelles-liposomes of Example 23 were 25 nm and 360 nm, respectively.

[0193]

[0194] Experimental Example 2: Stability Measurement

[0195] To confirm the surface charge of the particles, the bicelles of Example 22 and the bicelles-liposomes of Example 23 were diluted by 10%, and 1 mL was placed in a Photal, ELS-Z (Japan, Photal) cell and measured (Fig. 4). The measurement results showed that the particle potentials of the bicelles of Example 22 and the bicelles-liposomes of Example 23 were stable at -28.89 mV and -36.51 mV, respectively.

[0196]

[0197] Experimental Example 3: Electron Microscopy

[0198] To confirm whether the bicelles of Example 22 and the bicell-liposomes of Example 23 were well formed, cryo-transmission electron microscopy (cryo-TEM) analysis was performed (Fig. 5). As a result, it was confirmed that the bicelles and bicell-liposomes were well formed.

[0199]

[0200] Experimental Example 4: Experiment on the effect of promoting percutaneous absorption

[0201] Neoderm, an artificial skin from Taego Science, was mounted on a Franz-type diffusion cell (Lab Fine Instruments, Korea) for an experiment. 50 mM phosphate buffer (pH 7.4, 0.1 M NaCl) was added to the receptor vessel (5 mL) of the Franz-type diffusion cell, and the diffusion cell was mixed and dispersed at 32°C and 600 rpm. The bicell-liposome containing retinal of Example 23 and the general liposome of the comparative example were placed in the donor vessel so that the retinal content was the same. Absorption and diffusion were allowed according to a predetermined time, and 0.64 cm of the skin where absorption and diffusion occurred 2 After the absorption and diffusion of the active ingredient was completed, the emulsions remaining on the skin that were not absorbed were washed away with dried kimwipes or 10 mL of ethanol, and the skin where the active ingredient was absorbed and diffused was ground using a tip-type equalizer, and the retinal absorbed into the skin was extracted using 4 mL of dichloromethane. After that, the extract was filtered through a 0.45 μm nylon membrane, and the content was measured by HPLC under the following conditions, and the results are shown in Table 28.

[0202] [Table 28]

[0203]

Claims

1. Active ingredient; Hydrogenated lecithin as a long-chain lipid; Cholesterol, ceramide, lysolecithin or mixtures thereof as short-chain lipids; PEG-5 phytosterol, PEG-10 phytosterol, PEG-20 phytosterol, PEG-30 phytosterol, phytosteryl / behenyl / octyldodecyl lauroyl glutamate, phytosteryl / isostearyl / cetyl / stearyl / behenyl dimer dilinoleate or mixtures thereof as nonionic surfactants; and A bis-cell comprising polyglyceryl-10 laurate, PEG-10 rapeseed sterol or a mixture thereof as an auxiliary stabilizer.

2. A bicelle characterized in that it comprises 0.1 to 60 wt% of an active ingredient, 5 to 60 wt% of a long-chain lipid, 2 to 50 wt% of a short-chain lipid, 10 to 65 wt% of a nonionic surfactant, and 5 to 40 wt% of an auxiliary stabilizer in the first paragraph.

3. A bicelle characterized in that it comprises 0.2 to 55 wt% of an active ingredient, 8 to 55 wt% of a long-chain lipid, 3 to 45 wt% of a short-chain lipid, 12 to 60 wt% of a nonionic surfactant, and 7 to 38 wt% of an auxiliary stabilizer in the second paragraph.

4. A bicelle characterized in that it comprises 0.5 to 50 wt% of an active ingredient, 10 to 50 wt% of a long-chain lipid, 5 to 40 wt% of a short-chain lipid, 15 to 55 wt% of a nonionic surfactant, and 8 to 35 wt% of an auxiliary stabilizer in the third paragraph.

5. In the first paragraph, a Bycell characterized in that the active ingredient is at least one selected from the group consisting of a moisturizer, a whitening agent, an anti-wrinkle agent, a UV blocker, a hair growth agent, a vitamin or a derivative thereof, an amino acid or peptide, an anti-inflammatory agent, an acne treatment agent, a sterilizing agent, a female hormone agent, an exfoliating and dissolving agent, a natural product, an oil, a wax, a butter, a paraffin, a higher fatty acid, and an ester.

6. A bicell according to claim 1, characterized in that it further comprises a solvent.

7. A bisel according to claim 6, characterized in that the solvent is selected from 1,2-hexanediol, butylene glycol, propylene glycol, dipropylene glycol, pentylene glycol, diglycerin, propanediol, purified water, and mixtures thereof.

8. A liposome composition containing a bicelle, a lipid component, a stabilizer and a solvent according to any one of claims 1 to 7.

9. A liposome composition containing bicel, characterized in that it comprises 0.5 to 40 wt% of bicel, 0.5 to 40 wt% of lipid component, 1 to 40 wt% of stabilizer, and 10 to 80 wt% of solvent in the 8th paragraph.

10. A liposome composition containing a bisphenol A, characterized in that the lipid component is selected from hydrogenated lecithin, phosphatidylcholine, cholesterol, phytosterol, lecithin, cholesteryl ester, phytosterol ester, and mixtures thereof, according to claim 8.

11. A liposome composition containing a bicelle, characterized in that the stabilizer in the 8th paragraph is selected from glycerin, butylene glycol, propylene glycol, pentylene glycol, dipropylene glycol, diglycerin, propanediol and mixtures thereof.

12. A liposome composition containing bis-cells, characterized in that the solvent in claim 8 is selected from 1,2-hexanediol, purified water, and a mixture thereof.

13. A liposome composition containing a bicell, characterized in that it further comprises at least one selected from a preservative, an antioxidant, and a fragrance according to claim 8.

14. A cosmetic composition comprising a liposome composition containing a bicell according to Article 8.

15. A cosmetic composition characterized in that it comprises 0.1 to 50 wt% of a liposome composition containing biscelles in accordance with claim 14.

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