KR101807548B1 - Whitening cosmetic compositions containing nano liposome included extract of schisandra chinensis and manufacturing method of its nano liposome - Google Patents

Whitening cosmetic compositions containing nano liposome included extract of schisandra chinensis and manufacturing method of its nano liposome Download PDF

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KR101807548B1
KR101807548B1 KR1020150173312A KR20150173312A KR101807548B1 KR 101807548 B1 KR101807548 B1 KR 101807548B1 KR 1020150173312 A KR1020150173312 A KR 1020150173312A KR 20150173312 A KR20150173312 A KR 20150173312A KR 101807548 B1 KR101807548 B1 KR 101807548B1
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extract
omija
skin
weight
nanoliposome
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KR20170051099A (en
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김은종
홍재화
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한국콜마주식회사
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/02Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/14Liposomes; Vesicles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34Alcohols
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/55Phosphorus compounds
    • A61K8/553Phospholipids, e.g. lecithin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/68Sphingolipids, e.g. ceramides, cerebrosides, gangliosides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/02Preparations for care of the skin for chemically bleaching or whitening the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/41Particular ingredients further characterized by their size

Abstract

The present invention relates to a composition for skin whitening comprising a nanoliposome encapsulated with an extract of Omija, and a method for producing a nanoliposome encapsulating an Omija extract.
The present invention provides a nanoliposome capable of effectively delivering an extract of Omija, which has not only skin moisturizing effect but also melanin production inhibitory activity, to the skin dermis layer by formulating the Omija extract in a form encapsulated in liposome, It is possible to maximize the efficacy of Omija extract having no skin discoloration and irritation due to stable formulation of nanoliposome and having low skin irritation, skin moisturizing effect and melanin production inhibitory activity of Omiza extract.

Description

TECHNICAL FIELD [0001] The present invention relates to a skin whitening composition containing a nanoliposome containing an extract of Omija, and a method for producing a nanoliposome encapsulated with an extract of Omija. BACKGROUND ART [0002]

The present invention relates to a nanoliposome-containing skin whitening composition encapsulated with an extract of Omija and a method for producing a nanoliposome encapsulated with an extract of Omija. More particularly, the present invention relates to a liposome composition encapsulated in a liposome, The present invention relates to a nanoliposome-containing skin whitening composition encapsulated with an extract of Omija, which is useful as a composition for effectively whitening skin, and to a method for producing a nanoliposome encapsulated with an Omija extract.

In general, depending on the skin moisturizing condition, the skin condition can be largely classified into dryness, neutrality, intellect, complexity and dryness. Depending on the skin moisturizing condition, the progress of skin aging may be changed.

The most prominent phenomenon of skin aging is wrinkle formation and skin keratinization. Such aging phenomena may be affected or promoted by the environment, although the skin itself gradually develops as the inherent function decreases.

The main cause of aging according to the environment is photodegradation by sunlight. Specifically, due to the free radicals generated by ultraviolet rays of the sunlight, abnormal cross-linking and cleavage of the connective tissue causes wrinkle formation, skin elasticity decrease, cause.

In addition, it is one of the causes to reduce the water retention capacity of the stratum corneum by promoting the cleavage and low molecular weight of hyaluronic acid, which plays a major role in the water retention ability of the skin.

The stratum corneum of the skin contains about 20% of the moisture, and the moisture content is an important factor in determining the flexibility and the luster which determine the skin condition. When the water content of the stratum corneum is less than 10%, the physiological action of the skin is lowered, and the skin loses its original function, becomes rough, and causes various kinds of skin troubles.

Many attempts have been made to solve moisture loss of the skin which causes skin troubles. Particularly, researches on materials for improving the moisturizing power have been actively carried out with few side effects.

Skin is the largest tissue in the human body and plays a primary role in protecting the skin from external stimuli as a primary barrier. These skin types vary in color depending on the person or age, and are determined by the concentration and distribution of melanin in the skin.

Skin melanogenesis is a defense mechanism against stimuli such as ultraviolet light in melanocyte-producing cells (melanocyte), and a large amount of melanin produced by the melanin is transferred to keratinocyte and accumulated on the skin surface layer Results. Such melanin causes hyperpigmentation of the skin, causing spots, freckles, skin darkening after skin inflammation, and aging pigmentation spots.

Generally, the melanin production process is made by a nonenzymatic oxidation reaction in which an enzyme called tyrosinase acts on tyrosine, which is a kind of amino acid, and is converted into dopa (DOPA) or dopaquinone (dopaquinone).

Accordingly, various compositions for inhibiting melanin production of skin have been reported. Korean Patent Laid-Open Publication No. 2014-0105799, for example, discloses a coloring agent such as hydroquinone and derivatives thereof, ascorbic acid and derivatives thereof, kojic acid and derivatives thereof, nicotinic acid derivatives, serotonin derivatives, salicylic acid derivatives, astaxanthin, An extract having a whitening effect, a plant extract having a whitening effect, a polyphenol having a whitening effect, an unsaturated fatty acid having a whitening effect, a peptide having a whitening effect, an amino acid having a whitening effect, a nucleic acid derivative having a whitening effect, An alkylphenol having a whitening effect is disclosed. As the extracts, Korean traditional patent application No. 2014-0082276, Korean patent application No. 2010-0097857, Japanese patent application No. 1041403, and Japanese patent application No. 10-40313 disclose a mixture of green tea, alfalfa and licorice Fermented products are reported.

However, L-ascorbic acid is easily oxidized to cause irritation to the skin. The cosmetic composition containing the L-ascorbic acid causes discoloration and irritation, and the plant extracts derived from various plant materials have a great effect on the dermis It is difficult to effectively deliver the active ingredient, so that homogeneity of the product is difficult to maintain, and arbutin has a disadvantage of low effectiveness.

Accordingly, the inventors of the present invention have searched for a group of plant materials useful for skin. As a result, it has been confirmed that not only the skin moisturizing effect but also the melanin production inhibitory activity of the extract of Omija is confirmed, and the Omija extract is formulated into a liposome- Thereby effectively delivering the composition to the skin dermis layer, and optimizing the skin whitening effect of the Omiza extract, thereby completing the present invention.

It is an object of the present invention to provide a nano liposome-containing skin whitening composition containing an extract of Omija.

Another object of the present invention is to provide a method for producing a nanoliposome encapsulated with an extract of Omija.

In order to attain the above object, the present invention relates to a cosmetic composition comprising 0.1 to 34% by weight of an Omija extract and 1 to 15% by weight of an aqueous and skin phospholipid-like component consisting of purified water, 0.1 to 10% by weight of oil and 1 to 40% Which is emulsified and encapsulated with an extract of Omija, to provide a composition for skin whitening comprising a nanoliposome.

In the composition for skin whitening, the particle size of the nanoliposome encapsulated with the extract of Omija is 50 to 200 nm, and the content of the nanoliposome encapsulated with the extract of Omiza is preferably 2 to 50% by weight.

The present invention provides a skin whitening composition having a melanin synthesis inhibitory activity, wherein the hypermethylated N component represented by the following Formula 1 is isolated from an extract of Omija do.

Formula 1

Figure 112015119590038-pat00001

In the nanoliposome-containing skin whitening composition encapsulated with the extract of Omija of the present invention, the skin phospholipid-like component in the oily phase contains one or more components selected from the group consisting of lecithin, ceramide, cholesterol and derivatives thereof.

In addition, the oil component contained in the oily phase is selected from caprylic / caprylic triglyceride, isopropyl myristate, isopropyl palmitate, tocopherol, triglyceride, ethyl oleate, octyl methoxy cinnamate, octocrylene, salicylate, homo-year-old rate, 12~ C 15 alkyl benzoate, isostearyl benzoate, PPG-2-isopropyl-iso having access -7-carboxylate, dibutyl adipate, dI isopropyl adipate, diisopropyl sebacate , Polyglycerol-isostearate, diethylhexyl maleate, polyglycerol-2 diisostearate, ethylhexyl ethylhexanoate, propylene glycol dicaprylate / caprate, cocoglyceride, butylene glycol dicaprylate / Dicaprate, isopropyl myristate, octyl stearate, dicaprylyl carboen- nite and propylene glycol Monocaprylate, and the like.

Also, the oil component contained in the oil phase may be at least one selected from the group consisting of 1,3-butylene glycol, dipropylene glycol, propylene glycol, butylene glycol, dipropylene glycol, propylene glycol, Glycerin, diglycerin, ethylhexyl glycerin, polyglycerin, 1,6-hexanediol, 1,6-hexanediol, glycerin, glycerin, 1,2-hexanediol, 1,2-pentanediol, D-panthenol, and 1,2-octanediol.

Also, the present invention provides a method for preparing a water-soluble extract, comprising the steps of: (1) warming a water-containing part containing purified water and 0.1 to 34% by weight of an Omija extract to a temperature of 30 to 90 캜;

(2) adding an oily portion containing 1 to 15% by weight of a skin phospholipid-like component to the upper part of the water, stirring the mixture at a temperature of 30 to 90 DEG C at a speed of 1,000 to 4,000 rpm for 1 to 30 minutes; And

(3) stirring the mixture at a temperature of 30 to 65 ° C at a speed of 1,000 to 3,000 rpm for 1 to 20 minutes to encapsulate the lipase with an extract of Omija.

In addition, the manufacturing method of the present invention can perform the nanoization step (4) of treating at a pressure of 500 to 3,000 bar at 15 to 60 ° C after the step (3).

The composition for skin whitening of the present invention can effectively deliver the above-mentioned Omija extract to the skin dermis layer by providing the nanoliposome of the present invention in which the Omija extract having the skin moisturizing effect as well as the melanin production inhibitory activity is encapsulated in the liposome, .

In addition, the present invention can provide a method for producing a nanoliposome formulation in which the above-mentioned Omiza extract is encapsulated in a liposome.

1 is an electron micrograph of a nanoliposome encapsulating an extract of Omija of the present invention,
FIG. 2 shows the results of suppressing the tyrosinase and TRP-1 protein expression of the extract of Omija and the hypermucin N component of the present invention,
FIG. 3 shows the results of suppressing the MITF protein expression of the Omija extract and the hypermucin N component of the present invention,
Fig. 4 shows the results of suppressing the expression of phosphorylated proteins of CREB and CREB of the extract of Omija and the hypermucin N component of the present invention.

Hereinafter, the present invention will be described in detail.

The present invention relates to a cosmetic composition comprising 0.1 to 34% by weight of an extract of Omija and 1 to 15% by weight of an aqueous and phospholipid-like component comprising purified water, 0.1 to 10% by weight of an oil and 1 to 40% by weight of a polyol, The present invention provides a composition for skin whitening comprising the nanoliposome.

Liposomes are a typical formulation technique for skin penetration, and are stabilized formulations in which a hydrophilic substance is wrapped in a lipid-bilayer membrane in the most similar form to a cell membrane, and the liquid crystal is again maintained in a colloid state in a hydrophilic liquid. Liposomes composed of a lipid bilayer exhibit a strong ability to infiltrate hydrophilic substances and oil-soluble substances through the keratin skin cell gap formed by the double lipid membrane or directly through the cells to the dermal layer.

FIG. 1 is an electron micrograph of a nanoliposome encapsulating an extract of Omija of the present invention. As a result, the particle size of a nanoliposome encapsulating an Omija extract is 50 to 200 nm, more preferably 70 to 150 nm.

The content of the Omiza extract encapsulated in the nanoliposome is preferably 0.1 to 34% by weight. If the content is less than 0.1% by weight, the moisturizing effect is insufficient, which is not worthy of use as a moisturizing cosmetic, and if it exceeds 34% by weight, liposomes are not formed. More preferably, the content of the Omija extract is from 1 to 33% by weight.

Further, the composition for skin whitening of the present invention contains 2 to 50% by weight, preferably 2 to 40% by weight, more preferably 2 to 35% by weight of the content of the nanoliposome encapsulated in the above Omiza extract.

At this time, if the content of the nanoliposome encapsulated with the extract of Omija is less than 2% by weight, the moisturizing ability is insufficient, and if it exceeds 50% by weight, irritation to the skin is given and the formulation stability of the cosmetic composition deteriorates.

As the Omiza extract of the present invention, any commonly used Omiza extract may be used without limitation. Examples of the Omiza extract include alcohol omija extract, apple omija extract, grape omija extract, mala omija extract, sour cherry omija extract, distilled omija extract, An extract of Omija, an extract of Omija, a extract of Omija, an extract of Omija, an extract of Omija, an extract of Omija, a extract of Omija, and a mixture of two or more of them.

More preferably, the extract of Omija in the present invention contains hyperinsin N represented by the following formula (1).

Accordingly, the composition for skin whitening with nanoliposome encapsulated with the extract of Omiza of the present invention includes those containing Omija extract or hypericin N, which is separated from the above Omija extract, represented by the following formula (1).

Formula 1

Figure 112015119590038-pat00002

The hypermutin N inhibits the activity of chitin synthase II, a cell wall synthesizing enzyme of fungi, and inhibits the activity of cholesterol acyltransferase (Planta med. 1999, 65: 74-76) [Korean Pharmacological Association, 1999, 43, pp.509-515]. However, there has been no report on skin whitening of hypermucin N yet.

Accordingly, the present invention provides a possibility for a skin whitening composition by confirming the melanin synthesis inhibitory activity of the hypermucin N component isolated from the Omiza extract and the Omiza extract.

Specifically, FIG. 2 is a graph showing the results of inhibition of tyrosinase and TRP-1 protein expression of the extract of Omija and hypermucin of the present invention, and that of Schizandra chinensis extract (SCH) and Schizosaccharide fraction (SCH) Or whitening effect, and it is possible to confirm whitening effect of the hypotonic N.

Fig. 3 shows the results of suppressing the expression of MITF protein of the Omija extract and the hypermucin N component of the present invention. The MITF is an important transcription factor that regulates the expression of tyrosinase in melanin-forming cells. The inhibitory effect on the expression of MITF is supported by the action of Omiza extract and hypermucin N component, thereby supporting melanin production inhibitory effect.

4 shows the results of suppressing the expression of phosphorylated proteins of CREB and CREB of the extract of Omija and the hypermucin N component of the present invention. Particularly, from the above results, it can be confirmed that the hexane fraction of the Omiza extract of the present invention has the best inhibitory effect according to the pathway of CREB / MITF.

In the nanoliposome encompassed by the above-mentioned Omija extract of the present invention, the skin phospholipid-like component in the oily phase contains at least one component selected from the group consisting of lecithin, ceramide, cholesterol and derivatives thereof.

More preferably, the skin phospholipid-like component may comprise both lecithin, ceramide and cholesterol, wherein the mixing weight ratio of lecithin, ceramide and cholesterol may be from 5 to 15: 1 to 5: 1.

At this time, lecithin is also called a phosphatidylcholine as a phospholipid component. Lecithin is used as an emulsifier because it has an amphipathic nature as a constituent of a cell membrane, and is also used as a drug delivery substance in the medical field.

Ceramides can function to protect the skin from stresses by removing damaged cells due to internal and external stresses. For example, ceramide can be used to treat skin such as ceramide 1, ceramide 2, ceramide 3, ceramide 4, ceramide 5, ceramide 6, Ceramide 7, and ceramide 8, and one kind or two or more kinds of them may be used in combination.

When the amount of the ceramides is included in the above weight ratio, it is possible to perform an appropriate skin protecting function and to prevent the stability of the liposome composition or the occurrence of gelation.

Cholesterol is a major component of the cell membrane (membrane system), together with ceramides and fatty acids in the keratin structure of the skin, and plays a major role in membrane structure and function. Wherein the cholesterol or derivative thereof is selected from the group consisting of cholesterol, cholesteryl chloride, cholesteryl octanoate, cholesteryl nonanoate, cholesteryl isoleuconate, cholesteryl isostearyl carbonate, and mixtures thereof Lt; / RTI >

At this time, the content of the skin phospholipid-like component may be 1 to 15% by weight, preferably 1 to 10% by weight, more preferably 3 to 10% by weight, based on the total weight of the nanoliposome.

The oil component contained in the oil phase portion is not particularly limited as far as it is an oil used in the cosmetic composition, but is preferably caprylic / caprylic triglyceride, isopropyl myristate, isopropyl palmitate, tocopherol, triglyceride, ethyl Octyl methoxycinnamate, octocrylene, octyl salicylate, homosalate , C 12-15 alkyl benzoate, isostearyl benzoate, isopropyl PPG-2 isodeceth-7 carboxylate, di Butyl adipate, diisopropyl adipate, diisopropyl sebacate, polyglycerol-isostearate, diethylhexyl maleate, polyglycerol-2 diisostearate, ethylhexyl ethylhexanoate, propylene glycol dicaprylate / Caprate, cocoglyceride, butylene glycol dicaprylate / dicaprate, isopropyl May contain at least one member selected from the group consisting of stearate, octyl stearate, dicaprylyl carboen- nite and propylene glycol monocaprylate.

The polyol may be contained in an amount of 1 to 40% by weight, preferably 5 to 30% by weight, more preferably 10 to 25% by weight based on the total weight of the liposome composition.

The polyol component contained in the oil phase portion may be at least one selected from the group consisting of 1,3-butylene glycol, dipropylene glycol, propylene glycol, butyleneglycol, dipropylene glycol, propylene glycol, Diethylene glycol, hexylene glycol, polyethylene glycol, glycerin, diglycerin, ethylhexyl glycerin, polyglycerin, 1,6-hexanediol, 1, At least one selected from the group consisting of 2-hexanediol, 1,2-pentanediol, D-panthenol and 1,2-octanediol can be used.

The oil may be contained in an amount of 0.1 to 10% by weight, more preferably 0.1 to 8% by weight, based on the total weight of the nanoliposome.

The composition for skin whitening according to the present invention may further comprise an organic solvent, a solubilizing agent, a thickening agent and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a perfume, a surfactant , Water, ionic or nonionic emulsifiers, fillers, sequestering agents and chelating agents, preservatives, vitamins, barrier agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or cosmetics Any other ingredients used may additionally contain adjuvants commonly used in the cosmetics field.

The formulation of the skin whitening composition according to the present invention is not limited as long as it is a conventional cosmetic formulation, but it may be formulated into various forms such as a softening agent, a skin such as a convergent lotion or a nutritional lotion, a nutritional cream, a massage cream, an essence, , A cleansing foam, a cleansing water, a pack, a powder, a body lotion, a body cream, a body oil or a body essence.

Specifically, the cosmetic composition comprises 0.1 to 5% by weight of a humectant, 2 to 50% by weight of the liposome composition of the present invention, 0.01 to 1% by weight of a carbomer, 0.1 to 5% by weight of a solubilizer, 0.1 to 5% To 1% by weight of the composition.

Also, the present invention provides a method for preparing a water-soluble extract, comprising the steps of: (1) warming a water-containing part containing purified water and 0.1 to 34% by weight of an Omija extract to a temperature of 30 to 90 캜;

(2) adding an oily portion containing 1 to 15% by weight of a skin phospholipid-like component to the upper portion of the water, and emulsifying the mixture at a temperature of 30 to 90 ° C at a rate of 1,000 to 4,000 rpm for 1 to 30 minutes while stirring; And

(3) stirring the mixture at a temperature of 30 to 65 ° C at a speed of 1,000 to 3,000 rpm for 1 to 20 minutes to encapsulate the lipase with an extract of Omija.

In addition, the manufacturing method of the present invention can perform the nanoization step (4) of treating at a pressure of 500 to 3,000 bar at 15 to 60 ° C after the step (3).

In the method for producing a nanoliposome encapsulated with the extract of Omiza, steps (1) and (2) are steps of emulsifying the upper part and the upper part of liposomes and forming a bulky spherical liposome. In step (2) May be 2,000 to 3,000 rpm, and may be stirred for 5 to 15 minutes.

The polyol may be further added in the step (1), and the amount of the polyol to be added is not limited to 1 to 40% by weight, preferably 5 to 30% by weight, more preferably 10 to 25% by weight, % ≪ / RTI >

In addition, the oil may be further added in the step (2). The amount of the oil to be added is not limited thereto, but may be 0.1 to 10% by weight, and preferably 0.1 to 8% by weight based on the total weight of the liposome composition .

The extract of Omija is enclosed in the liposome through the step (3), cooled to a temperature of 35 to 60 DEG C, more preferably 45 to 55 DEG C, and then cooled at a rate of 1,000 to 3,000 rpm, preferably 1,500 to 2,500 rpm At a rate of 1 to 20 minutes, preferably 5 to 10 minutes.

The extract of Omija and the lipid component of the cell membrane may be 0.1 to 34% by weight and 1 to 15% by weight, respectively, based on the total weight of the liposome composition, and the detailed description of the components is the same as described in the liposome composition according to the present invention.

The method for preparing a liposome composition of the present invention may further comprise the step of (4) treating the liposome produced in the step (3) with a pressure of 500 to 3,000 bar at a temperature of 15 to 60 ° C.

Through the step (4), the bulky spherical liposome encapsulated with the extract of Omiza may be secondarily emulsified to prepare a nano-sized liposome containing the extract of Omiza.

More specifically, the bulky spherical liposomes containing the Omiza extract are heated at a temperature of 15 to 60 DEG C, preferably 20 to 50 DEG C, more preferably 30 to 40 DEG C, to 500 to 3,000 bar, preferably 700 to 2,000 bar preferably from 2 to 3 times at a pressure of from 800 to 1,500 bar, more preferably from 800 to 1,500 bar, to reduce the size of the bulky spherical liposome into nano-size, A nano-sized phospholipid liposome can be produced.

Hereinafter, the present invention will be described in more detail with reference to Examples.

The present invention is intended to more specifically illustrate the present invention, and the scope of the present invention is not limited to these embodiments.

< Manufacturing example  1> ethanol extract of Schizandra chinensis ( SCE ) Produce

1 kg of Omija was added to 7 L of 95% ethanol and extracted at room temperature for 3 days. Then, the ethanol extract obtained by filtration was concentrated with a concentrator to obtain 303 g of a concentrate.

< Manufacturing example  2> From the ethanol extract of Omija High superstition  N separation

The concentrated osmia ethanol extract (SCE) obtained in Preparation Example 1 was dissolved in 3 L of 20% ethanol, and then fractionated with n-hexane, methylene chloride and ethyl acetate to obtain 60.6 g of n-hexane fraction. The n-hexane fraction (SCH) was separated into a silica gel column and used as a developing solvent of n-hexane / ethyl acetate (20: 1 to 1: 2) to obtain 10 fractions (HF1 to HF10).

The fractions obtained above were separated by developing solvent (CH 2 Cl 2 / MeOH (1: 1)) using Sephadex LH-20 and recrystallized from ethyl acetate to give gomisin N (310 mg) &Lt; RTI ID = 0.0 &gt;[&lt; / RTI &gt; 1 H-NMR (700MHz, CDCl 3 )?: 0.74 (3H, d, J = 7.2Hz, CH3-17), 0.97 (3H, d, J = 7.0Hz, CH3-18) H-7), 1.80 (2H , m, H-8), 2.02 (1H, brd, J = 13.2Hz, H-6), 2.28 (1H, dd, J = 13.2,9.6Hz, H-9), 2.55 (2H, m, H- 9), 2.58 (2H, m, H-6), 3.57,3.84,3.92 (3H, s, OCH 3 × 4), 5.94 (2H, s, OCH 2 O), N6 .47 (1H, s, H-11), 6.58 (1H, s, H-4); 13 C-NMR (175MHz, CDCl 3): 151.5 (C-1), 140.3 (C-2), 152.0 (C-3), 111.0 (C-4), 134.8 (C-5), 39.3 (C- 6), 33.3 (C-7), 40.6 (C-8), 35.9 (C-9), 136.9 ), 140.9 (C-14) , 121.1 (C-15), 123.8 (C-16), 21.6 (CH3-17), 12.2 (CH3-18), 101.0 (OCH 2 O), 61.0, 60.4, 59.8, 56.0 (OCH 3 x 4).

&Lt; Examples 1 to 5 > Manufacture of nanoliposome encapsulated with Omija extract

Using the compositions shown in Table 1 below, nanoliposomes encapsulated with Omiza extract were prepared. Specifically, in Table 1, the water phase was charged into a vacuum emulsification tank capable of temperature control and agitation, heated to a temperature of 75 ° C, and the oily phase was separately introduced into an oily dissolution tank capable of heating and stirring. The oily phase prepared in the vacuum emulsification tank containing the water phase was charged and stirred for 8 minutes at a rate of 2,500 rpm using a homomixer while keeping the temperature at 75 DEG C to perform primary emulsification to form bulky spherical liposomes.

The mixture was cooled to 50 DEG C and stirred at a speed of 2,000 rpm using a homomixer to enclose the Omiza extract in a bulky spherical liposome. After that, a bulky spherical liposome was put into a high pressure type microfluidizer at 35 and treated three times at a pressure of 1,000 bar for secondary emulsification to prepare a skin cosmetic composition containing an omija extract stabilized with nanoliposome.

< Comparative Example  1 to 5>

The nanoliposome encapsulated with the extract of Omija was prepared in the same manner as in Example 1, except that the composition was changed to the composition shown in Table 1 below.

Figure 112015119590038-pat00003

As shown in the electron micrographs of the nanoliposome (Example 1) in which the prepared Omiza extract of Fig. 1 was enclosed, as a result of Examples 1 to 5 prepared with the composition of Table 1, It was confirmed that the nanoliposome was stably formed.

On the other hand, in Comparative Example 1, the amount of Omija extract was so small that the moisturizing effect was insignificant, and in Comparative Example 2, the liposome was not formed well. From the results shown in Table 1, it was determined that the effective content of the extract of Omija in the liposome-forming composition was 0.1 to 34% by weight. When the range was satisfied, it was confirmed that the liposome was well formed with moisturizing effect.

< Example  6 ~ 9> The extract of Omija Enclosed Nanoliposome  Preparation of skin whitening composition containing

Skin cosmetic compositions having the compositions shown in the following Table 2 were prepared using nanoliposome encapsulated with the extract of Omija in Example 1.

Figure 112015119590038-pat00004

In Examples 6 to 9 and Comparative Example 5, there was no irritation to the skin, but in Comparative Examples 6 to 9, a strong irritation to the skin was felt. On the other hand, in Comparative Example 5, there was no irritation to the skin, but even after applying to the skin, the face shrinkage continues to be felt, and the moisturizing power is very small.

In Comparative Examples 6 to 9, discoloration and alteration were confirmed at a high temperature (40 ° C), but in Examples 6 to 9, no discoloration or alteration occurred.

From the results shown in Table 2, it can be seen that Examples 6 to 9 are suitable in terms of formulation stability, skin irritation and moisturizing effect. From the results, it can be seen that the nanoliposome encapsulated with the extract of Omija according to the present invention It was confirmed that it is preferable to contain 2 to 35% by weight based on the total weight of the composition.

EXPERIMENTAL EXAMPLE 1 Evaluation of whitening effect of Omiza extract and hypermycin N component

1. Measurement of tyrosinase, TRP-1 protein expression

Tyrosinase, tyrosinase-related protein-1, TRP-1, TRP-2 and MITF are known to be important proteins in melanogenesis. Among them, tyrosinase is an enzyme that plays a pivotal role in melanin biosynthesis and is an enzyme that converts L-tyrosine to L-waveope in melanoma and then oxidizes L-dopa to dopaquinone. TRP-1 is an enzyme that oxidizes 5,6-DHICA (dihydroxyindole-2-carboxylic acid) to indole-5,6-quinone-2-carboxylic acid.

In order to measure the expression level of tyrosinase and TRP-1 protein of Omija extract and hypermucin N, the following method was performed.

B16F10 cells were plated at a density of 1 × 10 5 cells / well in a 6-well plate with DMEM containing 10% FBS and stabilized in a 5% CO 2 incubator at 37 ° C. for 24 hours. After pretreatment of diluted samples, the stimulants were treated for the time each protein was phosphorylated or expressed. The culture medium was removed, washed three times with PBS, and cells were collected by treatment with trypsin-EDTA. 100 ml of RIPA buffer solution was treated, and the cells were lysed by stirring for 10 minutes on ice for 30 minutes. The supernatant was obtained by centrifugation at 12,000 rpm and 4 ° C for 15 minutes, and quantified by the Bradford method. 20 mg protein was mixed with sample loading buffer solution, heated at 100 캜 for 3 minutes, and subjected to SDS-PAGE. After electrophoresis, the proteins in the gel were transferred to PVDF (polyvinylidene fluoride) membrane and blocked for 1 hour in TBST buffer containing 5% skim milk. Anti-thyrosinase, anti-TRP-1, anti-MITF and anti-b-actin primary antibody were added and the membrane was left overnight at 4 ° C. After the primary antibody reaction, the cells were washed three times with TBST buffer. Secondary antibody conjugated with HRP (horseradish peroxidase) was reacted on 5% skim milk for 2 hours at room temperature. After washing three times with TBST buffer, the membrane was reacted with ECL (enhanced chemiluminescence) solution and each band was identified using instrument (ChemiDocTM XRS +, Hercules, Calif.).

As shown in FIG. 2, the effect of tyrosinase and TRP-1 protein expression was examined by treating SCE (Schizandra chinensis extract), SCH (Schizophyllum hexane fraction) and GoN As a result, the expression of tyrosinase and TRP-1 was inhibited by 65% and 58%, respectively, when treated with the positive control arbutin. In the case of SCE and SCH, the expression inhibition rate of tyrosinase was 49% and 99%, respectively, and the expression inhibition rate of TRP-1 was 34% and 94%, respectively.

In addition, the inhibition rates of tyrosinase and TRP-1 expression were 15% and 10%, respectively, when the hyperinsin N inhibited 88% of the melanin production at 5 μM concentration. Therefore, hyperinsulinemic N has confirmed strong whitening efficacy through SCE, SCH and other mechanisms.

2. Measurement of MITF and CREB protein expression

MITF is an important transcription factor that regulates tyrosinase expression in melanocytes and is regulated by a variety of mechanisms. When stimulated by a-MSH, CREB phosphorylation is induced by the increase of cAMP, inducing MITF expression and promoting tyrosinase expression, thereby inducing melanogenesis. In addition, when SCF and endothelin-1 are activated by IL-1 and TNF-a secreted by ultraviolet light, they are bound to c-kit and EDNRB. When SCF binds to c-kit of melanocytic cells, it activates ras, raf, MEK1 / 2, ERK and activates RSK to phosphorylate CREB. The phosphorylated CREB induces tyrosinase expression by inducing MITF. Endothelin-1 binds to EDNRB of melanocytes and G-protein becomes GTP-type, activating phospholipase Cg, which degrades PIP 2 into DAG and IP 3 . DAG phosphorylates CREB through ras, raf, MEK1 / 2, ERK, and RSK by activating PKC. By inhibiting the expression of MITF induced by these various mechanisms, it is possible to effectively inhibit the production of melanin.

Melanogenesis cells were stimulated with 250 nM a-MSH, and SCE, SCH and GoN were treated at different concentrations to examine the effect of MITF on the expression of MITF protein. As a result, positive control group arbutin showed 36% inhibition of MITF expression and GoN showed a low inhibition rate of 13%. SCE and SCH showed 55% and 96% MITF protein inhibition rates, respectively. In addition, we examined the effect of p-CREB protein on MITF expression, which induces the expression of MITF protein.

As a result, SCH alone inhibited phosphorylation of CREB in a concentration-dependent manner. This suggests that the omiza n-hexane extract inhibits CREB / MITF pathway and inhibits melanogenesis. However, the ethanol extract of Omiza inhibited the expression of MITF only and the inhibitory effect of GoN on MITF expression was insufficient. Therefore, it could be expected that melanogenesis would be suppressed by a pathway other than the CREB / MITF pathway.

As described above, the present invention provides a nano liposome-containing skin whitening composition encapsulated with an extract of Omija, thereby effectively delivering the Omija extract to the skin dermis layer, thereby providing skin moisturizing effect without skin irritation, Maximizing the efficacy of Omija extract with inhibitory activity. Accordingly, the present invention relates to a cosmetic composition which is useful for application of a cosmetic composition to a nanoliposome encapsulated with an extract of Omija, and which has no discoloration and alteration due to the stable formulation of nanoliposome, has a hypoallergenic effect, skin moisturizing effect and skin whitening effect Lt; / RTI &gt;

While the invention has been shown and described with reference to certain exemplary embodiments thereof, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention as defined by the appended claims.

Claims (8)

1 to 33% by weight of an Omija extract,
Lipid-lowering reaction consisting of 1 to 15% by weight of a skin phospholipid-like component mixed with lecithin: ceramide: cholesterol in a weight ratio of 5 to 15: 1 to 5: 1, 0.1 to 10% by weight of oil and 1 to 40% by weight of polyol The present invention relates to a skin whitening composition containing a nanoliposome, wherein the extract of Omija is encapsulated in a nanoliposome.
The composition for skin whitening according to claim 1, wherein the nanoparticles encapsulated with the extract of Omiza have a particle diameter of 50 to 200 nm. The composition for skin whitening according to claim 1, wherein the composition contains 3 to 30% by weight of nanoliposome encapsulated with the extract of Omiza. delete delete delete (1) warming the water phase containing purified water and 1 to 33% by weight of the Omija extract to a temperature of 30 to 90 캜;
(2) an oil phase containing 1 to 15% by weight of a skin phospholipid-like component mixed in a weight ratio of lecithin: ceramide: cholesterol of 5 to 15: 1 to 5: 1 is placed on the water, At 1,000 to 4,000 rpm for 1 to 30 minutes;
(3) stirring the mixture at a temperature of 30 to 65 ° C at a rate of 1,000 to 3,000 rpm for 1 to 20 minutes to inoculate the liposome with the extract of Omija; And
And performing a nanoization step (4) at a temperature of 15 to 60 DEG C at a pressure of 500 to 3,000 bar after the step (3).
delete
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KR20230126061A (en) 2022-02-22 2023-08-29 주식회사 코씨드바이오팜 Cosmetic composition for skin whitening by personal DTC gene comprising schisandra chinensis extract as active ingredient

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