KR20230115787A - Cosmetic Composition For Skin Damage Prevention And Wrinkle Improvement With Improved Skin Permeability Of Ginseng-derived Saponin - Google Patents

Abstract

The present invention is a ginseng-derived saponin; It provides a cosmetic composition for preventing skin damage and improving wrinkles with improved skin permeability of ginseng-derived irradiation ponin, comprising; and cochleatesome containing a nonionic surfactant.
According to the present invention, a cochleatesome prepared by emulsifying a composition containing a solvent, a natural emulsifier, a softener, a nonionic surfactant, an anionic surfactant, a preservative, ginseng-derived sazoponin, and a divalent cation salt may have excellent stability. In addition, since ginseng-derived irradiated saponin is trapped in cochleatesomes, it has an effect of being blocked or protected from the external environment, so that the skin permeability of irradiated ginseng is greatly improved and it can penetrate more deeply into the skin. As described above, the cosmetic composition of the present invention has the advantage of maximizing the effect of preventing skin damage and improving wrinkles through the ginseng-derived irradiation by stably penetrating the ginseng-derived irradiation deep into the skin.

Description

Cosmetic Composition For Skin Damage Prevention And Wrinkle Improvement With Improved Skin Permeability Of Ginseng-derived Saponin}

The present invention relates to a cosmetic composition for preventing skin damage and improving wrinkles with improved skin permeability of ginseng-derived irradiated ponin, and a pharmaceutical composition for preventing or treating skin diseases caused by ultraviolet rays.

The skin functions to protect internal organs from external environmental stimuli such as changes in temperature and humidity and ultraviolet rays (UV). In particular, irritation caused by ultraviolet rays reduces skin function and promotes photoaging of the skin, and photoaging of the skin is accompanied by overall deterioration of skin components. Reduction of fibroblasts and impaired activity of these cells is an important part of the skin photoaging process.

The skin is composed of three layers: the epidermis, dermis, and subcutaneous fat layer, and the epidermis is further classified into the stratum corneum, the granular layer, the spinous layer, and the basal layer. The outermost layer of the skin, the stratum corneum, plays an important role in protecting the human body from the external environment by moisturizing the skin, controlling sebum secretion, controlling pH, and maintaining oil-moisture balance. do it too Therefore, in the field of pharmaceuticals and cosmetics, research on skin delivery systems for effectively penetrating active ingredients into the skin has been continuously conducted.

Among these dermal delivery systems, liposomes are vesicles composed of lipid bilayers, and have high biocompatibility and biodegradability, and can contain both hydrophilic and hydrophobic substances therein, and thus have been used in various fields of medicine and cosmetics. However, liposomes have very low entrapment efficiency, solvents and preservatives used in liposome manufacturing cause skin irritation, and cholesterol, which is used as a raw material of liposomes, forms a solid lipid film of liposomes and inhibits the release of trapping substances. Rather, there was a problem of lowering the cell membrane permeability of the trapping material (Patent Document 1).

Ginseng (Panax ginseng C.A. Meyer) is a perennial herb belonging to the genus Panax of the Araliaceae family. It has herbal medicinal properties such as strengthening the lungs.

The main physiologically active substances of ginseng include saponin, also called ginsenoside, essential oil components, polyacetylene, phenol components, glycosides and acid peptides, and various other components such as vitamins, sugars, and minerals. The physiological activity of ginseng in general has been reported to include central nervous system action, immune function enhancement action, and anticancer action. In particular, about 40 types of ginsenosides have been discovered so far, and it has been confirmed that they have a wide range of effects on the central nervous system, endocrine system, immune system, metabolic system, etc. These ginsenosides may have actions similar to or opposite to each other, and it is known that certain components exert various efficacies alone or through interactions of several types.

Accordingly, while the present inventors were researching a bio-delivery system capable of effectively infiltrating ginseng-derived radioactive ponin into the skin, ginseng-derived radioactive ponin was incorporated into a cochleatesome prepared with a hydrophilic nonionic surfactant. When collected, the stability of cochleatesomes is improved, the skin permeability of irradiation is improved, and irradiation is penetrated deeper into the skin, thereby maximizing the effect of preventing skin damage and improving wrinkles by irradiation. confirmed and completed the present invention.

Republic of Korea Patent Registration No. 1740136 (2017.05.19.)

An object of the present invention is to provide a cosmetic composition with improved cochleatesome stability and skin permeability of ginseng-derived irradiation.

One aspect of the present invention is ginseng-derived irradiation ponin; It provides a cosmetic composition for preventing skin damage and improving wrinkles with improved skin permeability of ginseng-derived irradiation ponin, comprising; and cochleatesome containing a nonionic surfactant.

Another aspect of the present invention is ginseng-derived irradiation ponin; It provides a pharmaceutical composition for preventing or treating skin diseases caused by ultraviolet rays with improved skin permeability of ginseng-derived irradiation ponin, comprising; and cochleatesome containing a nonionic surfactant.

According to the present invention, a composition containing a solvent, a natural emulsifier, a softener, a nonionic surfactant, an anionic surfactant, a preservative, a ginseng-derived josaponin, and a divalent cation salt is emulsified to provide excellent stability when preparing some cochleate. In addition, since ginseng-derived irradiated saponin is captured in cochleatesomes, it has an effect of being blocked or protected from the external environment, so that the skin permeability of irradiated ginseng is greatly improved and can penetrate more deeply into the skin.

As described above, the cosmetic composition of the present invention has the advantage of maximizing the effect of preventing skin damage and improving wrinkles through the ginseng-derived irradiation by stably penetrating the ginseng-derived irradiation deep into the skin.

Figure 1 shows the results of evaluating the skin damage protection effect from ultraviolet rays according to Example 1 and the irradiated ponin control group.
Figure 2 shows the results of evaluating the pro-collagen synthesis enhancement effect according to Example 1 and the irradiated ponin control group.
Figure 3 shows a photograph of the sample taken after standing for one month at a high temperature (50 ° C.) for a stability test for each sample of Examples and Comparative Examples.

Hereinafter, the present invention will be described in more detail to aid understanding of the present invention.

Terms or words used in this specification and claims should not be construed as being limited to ordinary or dictionary meanings, and the inventor may appropriately define the concept of terms in order to explain his or her invention in the best way. It should be interpreted as a meaning and concept consistent with the technical idea of the present invention based on the principle that there is.

1. Cosmetic composition for preventing skin damage and improving wrinkles with improved skin permeability of ginseng-derived irradiated saponin

One aspect of the present invention is ginseng-derived irradiation ponin; It provides a cosmetic composition for preventing skin damage and improving wrinkles with improved skin permeability of ginseng-derived irradiation ponin, comprising; and cochleatesome containing a nonionic surfactant.

In the present invention, "improvement of permeability" is The composition may be used as a meaning that includes an increase in the ratio of the active ingredient penetrating the skin and penetrating into the skin of the subject to whom the composition is administered, or more deeply penetrating into the skin. For example, it means that the skin permeability of ginseng-derived radioactive ponin is improved by 40 to 80 times, or 45 to 75 times, or 50 to 70 times compared to the control group of ginseng-derived radioactive ponin not captured by cochleatesomes, or ginseng-derived radioactive ponin. It may mean that the skin penetration depth of irradiated ponin is improved by 1.2 times or more, or 1.3 times or more, or 1.4 times or more, or 1.5 times or more compared to the control group of irradiated ponins not captured in cochleatesomes.

As the skin permeability of ginseng-derived irradiation is improved, the skin damage prevention and wrinkle improvement effects that can be expected through irradiation can be more effectively achieved.

Specifically, the cochleatesome encapsulating the ginseng-derived radioponin of the present invention can exhibit an effect of preventing skin damage induced by ultraviolet rays. Reactive oxygen species (ROS) are generated by the action of ultraviolet rays and act as the main cause of skin aging. It can show the effect of preventing skin damage caused by

In addition, it can be seen that the collagen synthesis ability of skin fibroblasts is directly related to skin regeneration, skin elasticity, skin wrinkle formation, and tissue repair or regeneration upon skin damage. That is, when the synthesis of procollagen in skin fibroblasts is promoted, the amount of collagen synthesis increases, and effects such as skin wrinkle improvement, skin elasticity enhancement, repair and regeneration of damaged skin tissue, and prevention of skin aging can be obtained. The cochleaatesome containing the ginseng-derived radioponin of the present invention promotes the synthesis of pro-collagen in skin fibroblasts, thereby improving skin wrinkles, enhancing skin elasticity, restoring and regenerating damaged skin tissue, and preventing skin aging. can have

In the present invention, cochleatesomes are formed by ionic interactions of phospholipid bilayers and cations, and are formed in elongated shapes such as spiral cylinders to minimize interactions between these phospholipid bilayers. The ginseng-derived irradiated saponin of the present invention is stably protected from the external environment by constituting a cochleatesome in a form where it is located between phospholipid bilayers and trapped in cochleatesomes or partially interposed in the phospholipid bilayers, thereby stably protecting ginseng-derived saponin from the external environment. The possibility of saponin passing through the skin barrier and penetrating into the skin increases.

The cochleatesome of the present invention is composed of a solvent, a natural emulsifier, a softening agent, a nonionic surfactant, an anionic surfactant, a preservative and a divalent cation salt. In particular, the cochleatesome of the present invention contains a hydrophilic nonionic surfactant to form a uniform cochleatesome, thereby improving the skin permeability of ginseng-derived radioponin and allowing it to penetrate more deeply into the skin. .

The nonionic surfactant used in the present invention may be a hydrophilic nonionic surfactant of HLB 8 to 20, or HLB 8 to 16, or HLB 13 to 16, or HLB 16 to 20, or HLB 16 to 18. When such an HLB value is satisfied, it may be advantageous to uniformly form the size or shape of cochleatesomes by forming uniform emulsified particles having excellent dispersibility in a hydrophilic solvent.

For example, the nonionic surfactant is selected from the group consisting of polyglyceryl-10 laurate, polyglyceryl-10 oleate, polyglyceryl-10 stearate, and polyglyceryl-10 disostearate One or more may be included, and polyglyceryl-10 laurate is most preferred in terms of excellent dispersibility, high stability in a wide range of pH and temperature.

The nonionic surfactant may be included in 0.01 to 15% by weight, or 0.05 to 12% by weight, or 0.1 to 10% by weight, or 3 to 10% by weight, or 3 to 7% by weight, based on the total weight of the cochleate. .

The solvent may include at least one selected from the group consisting of purified water, glycerin, ethanol, butylene glycol, and propanediol.

The cochleatesome may contain 55 to 99% by weight, or 65 to 95% by weight, or 80 to 90% by weight of the solvent based on the total weight of the cochleatesome.

The natural emulsifier may include phospholipids and saturated fatty acids. The phospholipids include at least one selected from the group consisting of phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, hydrogenated phosphatidylcholine, phosphatidylic acid, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, and hydrogenated products thereof, preferably It is phosphatidylserine. The phosphatidylserine can be extracted by various methods, and for example, it can be prepared from lecithin extracted from soybeans (soybeans).

The cochleatesome may contain 0.1 to 10% by weight, or 0.5 to 7% by weight, or 2 to 5% by weight of phospholipids based on the total weight of the cochleatesome.

In addition, the saturated fatty acid may include at least one selected from the group consisting of palmitic acid, stearic acid, oleic acid, linoleic acid, and linolenic acid.

The cochleatesome may contain 0.0001 to 2% by weight, or 0.001 to 3% by weight, or 0.001 to 1% by weight of a saturated fatty acid based on the total weight of the cochleatesome.

The softening agent may include one selected from the group consisting of caprylic capric triglyceride, cetylethylhexanoate, dicaprylyl ether, ceramide, and ceramide NP.

The cochleatesome may contain 0.1 to 10% by weight, or 0.3 to 9% by weight, or 3 to 7% by weight of a softening agent based on the total weight of the cochleatesome.

The anionic surfactant may include at least one selected from the group consisting of sodium stearoyl glutamate, disodium stearoyl glutamate, sodium lauroyl glutamate, sodium lauryl glucose carboxylate, and sodium methyl cocoyl taurate. It may, but is not limited thereto.

The cochleatesome may contain 0.01 to 7% by weight, or 0.1 to 3% by weight, or 0.1 to 1.5% by weight of an anionic surfactant based on the total weight of the cochleatesome.

The preservative may include at least one selected from the group consisting of pentylene glycol, 1,2-hexanediol, caprylyl glycol, phenoxyethanol, and ethylhexyl glycerin.

The cochleatesome may contain 0.1 to 10% by weight, or 0.5 to 7% by weight, or 1 to 3% by weight of a preservative based on the total weight of the cochleatesome.

The cations of the divalent cation salt are used to form cochleatesomes by ionic interaction with the phospholipid bilayer and precipitate them. At this time, the cation of the divalent cation salt serves as a bridge between the phospholipid bilayers. The divalent cation salt may be a chloride salt of calcium, zinc, barium or magnesium, preferably calcium chloride.

The cochleatesome may contain 0.0001 to 2% by weight, or 0.001 to 3% by weight, or 0.001 to 1% by weight of a divalent cation salt based on the total weight of the cochleatesome.

In the present invention, the cochleatesome mixes and emulsifies an oil phase containing a water phase containing a solvent, a nonionic surfactant, an anionic surfactant, a preservative and a divalent cation salt, phospholipids and saturated fatty acids as natural emulsifiers, and a softening agent. However, at this time, by adding ginseng-derived radioactive ponin to the aqueous phase, cochleatesomes in which ginseng-derived radioactive ponin is trapped can be prepared. The ginseng-derived irradiation ponins are mainly located between phospholipid bilayers, and some of them constitute cochleatesomes in the form of being sandwiched in phospholipid bilayers.

The emulsification is performed at 600 to 1500 bar, or 700 to 1400 bar, or 800 to 1200 bar using a device such as a high-pressure fine emulsifier, at 1200 to 2400 rpm, or 1300 to 2200 rpm, or 1500 to 2000 rpm, at 30 to 70 ° C., or It can be carried out by high-pressure homogenization of the mixture of the aqueous phase and the oil phase by stirring at 40 to 65 ° C., or 50 to 60 ° C. for 3 to 12 minutes, or 5 to 10 minutes. As a result, it is possible to stably capture ginseng-derived radioactive ponin in cochleatesomes. can

The ginseng-derived saponin of the present invention may be obtained through a conventional fractionation process from ginseng extract or steamed ginseng liquid.

In the present invention, ginseng can be used without limitation, such as cultivated or commercially available. The ginseng includes variously processed ones, for example, at least any one selected from the group consisting of fresh ginseng, misam, black ginseng, wild ginseng, camphor ginseng, wild ginseng, dehydrated ginseng, enzyme-treated fine ginseng, fermented ginseng, red ginseng, and fermented red ginseng. It may be one, but is not limited thereto. Fresh ginseng refers to raw ginseng that has maintained its original form, misam refers to the thin root of ginseng, and red ginseng refers to raw ginseng steamed, cooked, and dried, and a browning reaction occurs during the drying process, resulting in a light yellowish brown to reddish brown color.

When obtaining an extract from the ginseng, at least one selected from the group consisting of water, organic solvents, supercritical fluids, and mixtures thereof may be used as an extraction solvent. The organic solvent is an alcohol, preferably a C ₁ -C ₄ lower alcohol, hexane (n-hexane), ether, glycerol, propylene glycol, butylene glycol, ethyl acetate, methyl acetate, dichloromethane, chloroform, ethyl acetate, It may be any one selected from the group consisting of benzene and mixed solvents thereof, preferably water or ethanol.

The steamed ginseng liquid is a by-product formed on the surface when ginseng is steamed, and includes active ingredients or ginsenosides present on the surface of ginseng. Ginseng extract is ginseng leaf, young shoot, stem, stem bark, root, root bark, seed, fruit, immature fruit, mature fruit, pulp, fruit skin, flower, stamen group (androecium), pistil group (gynoecium), calyx, Any one selected from the group consisting of stamens, petals, calyx pieces, carpels, and combinations thereof can be obtained during steaming.

The ginseng extract or steamed ginseng solution itself is used in the sense of including without limitation the ginseng extract or steamed ginseng solution itself, the concentrate obtained therefrom, and the dried product and powder of the concentrate.

In addition, in order to obtain a desired irradiated saponin from the ginseng extract or steamed ginseng liquid, a fraction obtained by additionally performing a conventional fractionation process may be used. For example, a fraction obtained by passing the ginseng extract or steamed ginseng solution through an ultrafiltration membrane having a certain molecular weight cut-off value, separation by various chromatography (made for separation according to size, charge, hydrophobicity or affinity) Active fractions obtained through various purification methods additionally carried out, such as, etc., are also included in the ginseng-derived josaponin of the present invention. A desired specific active fraction can be obtained by separating a ginseng extract or steamed ginseng solution in which various components are mixed according to the nature of the active component through concentration gradient column chromatography or the like.

The chromatography may be, for example, at least one selected from the group consisting of column chromatography, high performance liquid chromatography (HPLC), ion exchange chromatography, affinity chromatography, and size exclusion chromatography.

The column chromatography is performed by column chromatography using a filler selected from the group consisting of silica gel, Sephadex, LH-20, ODS gel, RP-18, polyamide, Toyopearl and XAD resin to separate active fractions And it can be purified, column chromatography can be carried out several times by selecting an appropriate filler as necessary, but is not limited thereto. In using the chromatography, the elution solvent, elution rate, and elution time may apply solvents, rates, or times generally used in the art.

In addition, in order to obtain a desired irradiated saponin from the ginseng extract or steamed ginseng liquid, a fraction obtained by fractionating the ginseng extract or steamed ginseng liquid with an organic solvent may be used. The organic solvent is an alcohol such as methanol, ethanol, propanol, butanol, hexane (n-hexane), ether, glycerol, propylene glycol, butylene glycol, ethyl acetate, methyl acetate, dichloromethane, chloroform, ethyl acetate, benzene, acetone, It may be any one selected from the group consisting of acetonitrile and mixed solvents thereof, but is not limited thereto.

The ratio of the cochleatesome to the ginseng-derived radioponin may be 100:0.5 to 100:10, 100:1 to 100:7, or 100:3 to 100:7 by weight.

The cosmetic composition of the present invention may be prepared in liquid or solid form using bases, adjuvants and additives commonly used in the field of cosmetics. Cosmetics in liquid or solid form may include, but are not limited to, cosmetic products, creams, lotions, and bath products.

Bases, adjuvants and additives commonly used in the field of cosmetics are not particularly limited, and examples thereof include water, alcohol, propylene glycol, stearic acid, glycerol, cetyl alcohol, and liquid paraffin.

When the composition of the present invention is prepared as a cosmetic composition, the composition of the present invention may include ingredients commonly used in cosmetic compositions as well as cochleatesomes containing ginseng-derived sapaponin, such as antioxidants and stabilizers. conventional adjuvants such as agents, solubilizers, vitamins, pigments and flavors, and carriers.

The cosmetic composition of the present invention may be prepared in any formulation commonly prepared in the art, for example, solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing , It may be formulated as an oil, powder foundation, emulsion foundation, wax foundation and spray, but is not limited thereto. More specifically, softening lotion, nourishing lotion, nourishing cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray, powder, hair tonic, hair lotion, hair cream, hair spray, hair Mousse, hair gel, hair conditioner, hair shampoo, hair conditioner, hair pack, hair treatment, pet shampoo, pet conditioner, hand cream, hand sanitizer, detergent, soap, disinfectant, wet wipes, mask, ointment, patch or as a formulation of a filter filler.

When the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component. can

When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and in particular, in the case of a spray, additional chlorofluorohydrocarbon, propane / May contain a propellant such as butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizing agent or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butylene glycol oil, glycerol aliphatic esters, polyethylene glycol or fatty acid esters of sorbitan.

When the formulation of the present invention is a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystals Star cellulose, aluminum metahydroxide, bentonite, agar or tracanth and the like may be used.

When the formulation of the present invention is surfactant-containing cleansing, as carrier components, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, imidazolinium derivative, methyl taurate, sarcosinate, fatty acid amide ether sulfate, alkyl Amidobetaine, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, or ethoxylated glycerol fatty acid esters may be used.

The cosmetic composition of the present invention may be used alone or overlappingly applied, or may be used overlappingly with other cosmetic compositions other than the present invention. In addition, the cosmetic composition of the present invention can be used according to a conventional method of use, and the number of times of use can be varied according to the user's skin condition or taste.

When the cosmetic composition of the present invention is a soap, surfactant-containing cleansing or surfactant-free cleansing formulation, it may be applied to the skin and then wiped off, removed, or washed with water. As specific examples, the soap is liquid soap, powder soap, solid soap, and oil soap, the surfactant-containing cleansing formulation is a cleansing foam, cleansing water, cleansing towel, and a cleansing pack, and the surfactant-free cleansing formulation is a cleansing cream. , cleansing lotion, cleansing water and cleansing gel, but are not limited thereto.

2. Pharmaceutical composition for preventing or treating skin diseases caused by ultraviolet rays with improved permeability of ginseng-derived irradiation ponin

Another aspect of the present invention is ginseng-derived irradiation ponin; It provides a pharmaceutical composition for preventing or treating skin diseases caused by ultraviolet rays with improved skin permeability of ginseng-derived irradiation ponin, comprising; and cochleatesome containing a nonionic surfactant.

The skin disease may be induced by short-term, long-term, temporary, or continuous irradiation of ultraviolet rays, and may be, for example, photosensitivity dermatitis, ultraviolet keratosis, or skin cancer.

In the present invention, "prevention" refers to all activities that suppress or delay skin diseases induced by ultraviolet rays by administration of the composition, and "treatment" refers to all activities that improve or beneficially change skin diseases caused by ultraviolet rays by the composition. says

The pharmaceutical composition of the present invention, in addition to the cochleatesome containing ginseng-derived irradiation ponin, is preferably a cochleatesome containing ginseng-derived irradiation ponin within the scope of not impairing the desired effect of the present invention. It may further contain other ingredients that can give a synergistic effect to the effect. conventional adjuvants such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavors, or carriers.

The route of administration of the pharmaceutical composition includes oral, intravenous, intramuscular, intraarterial, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal, topical, sublingual or rectal, for example topical application by application method can be applied. The parenteral includes subcutaneous, intradermal, intravenous, intramuscular, intralesional injection or infusion techniques.

The pharmaceutical composition of the present invention can be administered in a pharmaceutically effective amount.

In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level is the type and severity of the subject, age, sex, type of disease, It may be determined according to the activity of the drug, the sensitivity to the drug, the time of administration, the route of administration and the rate of excretion, the duration of treatment, factors including drugs used concurrently, and other factors well known in the medical field. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And it can be single or multiple administrations. It is important to administer the amount that can obtain the maximum effect with the minimum amount without side effects in consideration of all of the above factors, and can be easily determined by a person skilled in the art.

The pharmaceutical composition of the present invention is not particularly limited as long as it is an individual for the purpose of preventing or treating skin diseases caused by ultraviolet rays, and any one is applicable. For example, the pharmaceutical composition of the present invention can be used not only for humans but also for non-human animals such as monkeys, dogs, cats, rabbits, guinea pigs, rats, mice, cows, sheep, pigs, goats, birds and fish. do.

The pharmaceutical composition may contain at least one active ingredient exhibiting the same or similar function in addition to the cochleatesome containing the ginseng-derived irradiation ponin. The composition may be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, external preparations, suppositories and sterile injection solutions according to conventional methods, respectively.

Solid preparations for oral administration include powders, granules, tablets, capsules, soft capsules, pills and the like. Liquid preparations for oral administration include suspensions, internal solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. there is.

Formulations for parenteral administration include powders, granules, tablets, capsules, sterilized aqueous solutions, solutions, non-aqueous solutions, suspensions, emulsions, syrups, suppositories, aerosols, etc., and sterile injection preparations according to conventional methods, respectively. It can be formulated and used in the form of a cream, gel, patch, spray, ointment, warning, lotion, liniment, pasta, or cataplasma. , but is not limited thereto. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for the suppository, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogeratin and the like may be used.

The composition may further contain adjuvants such as preservatives, stabilizers, hydration agents or emulsification accelerators, salts and/or buffers for osmotic pressure control, and other therapeutically useful substances, which are conventional methods such as mixing, granulation or It can be formulated according to the coating method.

The dose of the pharmaceutical composition may vary depending on various factors including age, body weight, general health, sex, administration time, route of administration, excretion rate, drug combination, and severity of a specific disease.

In addition, the pharmaceutical composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers. In addition, the pharmaceutical composition may be administered in a dosage within the range of 0.001 to 200 mg / kg on an adult basis, and when the pharmaceutical composition is an external agent, it is administered in an amount of 1.0 to 3.0 ml on an adult basis once a day to 5 It is recommended to apply once and continue for 1 month or longer, but the dosage is not intended to limit the scope of the present invention.

Hereinafter, the present invention will be described in detail with reference to preparation examples and examples.

However, the following Preparation Examples and Examples are only for exemplifying the present invention, and the contents of the present invention are not limited by the following Preparation Examples and Examples.

Preparation Example 1 - Preparation of ginseng-derived irradiation

After washing and drying ginseng, the steamed ginseng liquid generated during the steaming process was provided by Korea Ginseng Corporation. The steamed ginseng liquid was concentrated at 50°C until the concentrated liquid sugar content reached 56 Brix. At this time, the solid content of the obtained steamed ginseng concentrate was around 52%. The steamed ginseng concentrate was mixed with the same amount of butanol and then fractionated to obtain only the butanol layer. After repeating this process three times, filtration, concentration, and drying were conducted to prepare powdery ginseng-derived saponin.

Example 1 - Ginseng-derived radioactive ponin encapsulated in cochleatesomes

After warming and mixing the water phase and oil phase of Table 1 below, a composition containing cochleatesomes that capture ginseng-derived irradiated saponin was prepared by treating them 1 to 3 times with a high-pressure microemulsifier at 1000 bar.

Raw material Content (parts by weight) Awards Purified water To 100 glycerin 40.00 Polyglyceryl-10 Laurate 3.00 1,2-Hexanediol 2.00 Sodium Stearoyl Glutamate 0.50 calcium chloride 0.01 saponin 5.00 oil phase Stearic Acid 0.01 Caprylic/Capric Triglyceride 5.00 Phosphatidylserine 3.00 Ceramide NP 0.50

Comparative Examples 1 to 5

Cochleatesome (Comparative Example 1, Table 2) not containing a hydrophilic nonionic surfactant by the same method as in Example 1, except that the aqueous phase and the oil phase were different, respectively, as shown in Tables 2 to 6 below. , NLC (Comparative Example 2, Table 3), liposomes (Comparative Example 3, Table 4), niosomes (Comparative Example 4, Table 5), and elastosomes (Comparative Example 5, Table 6), respectively. manufactured.

Raw material Content (parts by weight) Awards Purified water To 100 glycerin 40.00 1,2-Hexanediol 2.00 Sodium Stearoyl Glutamate 0.50 calcium chloride 0.01 saponin 5.00 oil phase Stearic Acid 0.01 Caprylic/Capric Triglyceride 5.00 Phosphatidylserine 0.50 Ceramide NP 0.50

Raw material Content (parts by weight) Awards Purified water To 100 polysorbate 20 3.00 saponin 5.00 oil phase cetyl palmitate 20.00 macadamia seed oil 5.00 Polyglyceryl-3methylglucose distearate 3.00

Raw material Content (parts by weight) Awards Purified water To 100 saponin 5.00 oil phase lecithin 5.00 ethanol 20.00

Raw material Content (parts by weight) Awards Purified water To 100 1,2-Hexanediol 2.00 glycerin 7.00 sodium ascorbyl phosphate 0.20 Disodium EDT 0.01 Potassium Cetyl Phosphate 0.60 oil phase rapeseed sterol 3.00 cholesterol 3.00 Hydrogenated Lecithin 3.00 dimethicone 7.00 cyclomethicone 5.00

Raw material Content (parts by weight) Awards Purified water To 100 Alcohol 2.00 Disodium EDT 0.01 Sucrose Laurate 2.00 sodium ascorbyl phosphate 0.30 saponin 5.00 oil phase Hydrogenated Lecithin 5.00 Caprylic/Capric Triglyceride 10.00 Lysolecithin 0.50 Ceramide NP 0.50

Experimental Example 1 - Evaluation of skin permeability according to in vitro skin absorption test

In accordance with the “Guidelines for In Vitro Skin Absorption Test” of the Ministry of Food and Drug Safety, by the Franz diffusion cell method, distilled water is placed in the receiving compartment of the diffusion cell and 1.4 ml of sample is placed in the donor compartment. An artificial skin membrane (Strat-m membrane, Merck) was placed. The receiving compartment was maintained at 32° C. using a constant temperature circulating water bath. Samples of the receiving compartment were obtained after passive diffusion for 24 hours. After evaporating all the distilled water of the sample using a rotary vacuum concentrator, it was dissolved in methanol and the individual ginsenoside contents were measured using HPLC.

The sum of the contents of 11 ginsenosides (Rg1, Re, Rf, Rh1, Rg2s, Rb1, Rc, Rb2, Rd, Rg3s, Rg3r) in the donor and receiving compartment samples was measured, respectively, and the ginsenoside content in the donor compartment was measured. The skin permeability was calculated as 100, and the results are shown in Table 7. Here, the ginseng-derived irradiated saponin of Preparation Example 1, which was not captured by the cochleatesome, was used as a control for the irradiated saponin, and based on this, the multiple of skin permeability of each sample was calculated.

sample name Rg1 Re Rf Rh1 Rg2s Rb1 Rc Rb2 Rd Rg3s Rg3r Total of 11 types Drainage Example 1 2681.20 1977.20 185.15 90.52 131.87 801.85 258.41 200.51 90.14 0.00 0.00 6416.85 58.70 Comparative Example 1 1823.24 1444.14 108.91 70.46 95.19 440.77 175.57 147.02 42.89 0.00 0.00 4348.20 39.78 Comparative Example 2 (NLC) 1615.80 1051.50 58.91 50.16 85.21 435.87 152.87 97.89 38.52 0.00 0.00 3586.73 32.81 Comparative Example 3 (liposome) 414.83 756.53 83.22 55.23 71.45 662.74 302.69 259.47 128.74 52.12 26.11 2813.13 25.73 Comparative Example 4 (Niosome) 239.43 402.72 36.75 34.80 33.22 138.06 54.53 46.45 15.02 0.00 0.00 1000.97 9.16 Comparative Example 5 (Elastosome) 189.45 384.42 25.84 29.51 30.52 115.00 50.79 40.15 7.15 0.00 0.00 872.83 7.98 Isaponin control group 55.03 54.29 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 109.32 1.00

From the above results, it can be seen that the cochleatesome of Example 1 exhibits 58.7 times superior skin permeability compared to the irradiated ponin control group.

On the other hand, compared to the irradiation control group, the cochleatesome of Comparative Example 1 was 39.78 times, the NLC of Comparative Example 2 was 32.81 times, the liposome of Comparative Example 3 was 25.73 times, and the niosome of Comparative Example 4 was 9.16 times of Comparative Example 5. Elastosome showed a skin permeability of 7.98 times.

Therefore, as a result of measuring the skin permeability of ginseng-derived radioponin by the Franz diffusion cell method, it can be confirmed that the skin permeability of ginseng-derived radioponin decreases in Example 1 and Comparative Examples 1 to 5 in order.

Experimental Example 2 - Skin damage protection effect from UV rays

Human dermal fibroblasts (prepared from ATCC) were inoculated into two 96-well plates at 1×10 ⁴ cells/well and cultured for 24 hours. 24 hours after replacing the medium with a serum-free medium and treating serially diluted samples of the irradiated ponin control group and Example 1 at concentrations of 6, 3, and 1.5 μg/ml and EGCG (positive control) at a concentration of 20 μg/ml cultured for a while.

The medium was replaced with DPBS, and only one plate was irradiated with 10 mJ/cm ² of UVA. Both plates were replaced with fresh serum-free media and further incubated for 24 hours. Thereafter, after treatment with 5 mg/ml MTT, the cells were incubated for 3 hours and the OD ₅₄₀ absorbance was measured.

The group treated with medium only was the control group, the group treated with only UV light was the negative control group, the group treated with UV+EGCG was the positive control group, and the group treated with UV+sample (irradiated ponin control group, Example 1) by concentration was used as the experimental group. The absorbance was set to 100 and the absorbance of the negative control was set to 0. The cell viability (%) of the experimental group according to UV irradiation was calculated, and the results are shown in FIG. 1 .

From the results of FIG. 1, the cochleatesomes capturing ginseng-derived irradiation ponin according to Example 1 had cell viability of 92.29% at 6 μg/ml, 86.45% at 3 μg/ml, and 85.86% at 1.5 μg/ml. It can be confirmed that it exhibits excellent skin damage prevention effect. This is a more improved effect by 54.84%, 58.50%, and 81.67%, respectively, compared to the irradiation control group (37.45%, 27.95%, and 4.19%, respectively). It can be confirmed that it shows an excellent skin damage protection effect.

Experimental Example 3 - Effect of increasing the amount of pro-collagen synthesis

Fibroblasts (Human dermal fibroblast) were seeded in each 5×10 ⁵ cells/well in a 24-well plate. 24 hours after inoculation, the medium was replaced with a serum-free medium, and the serially diluted irradiation control group and the sample of Example 1 were treated at concentrations of 50, 25, and 12.5 μg/ml, and ascorbic acid (positive control) at a concentration of 20 μg/ml. did After 24 hours of treatment, the culture medium was taken and the amount of pro-collagen was detected using a pro-collagen assay kit. The group treated with only the medium was used as a control group, and the absorbance (OD ₄₅₀ ) of the control group, the experimental group (irradiated control group, Example 1), and the positive control group (ascorbic acid) was measured, and the amount of pro-collagen production in the control group was set as 100 for each group. The amounts of pro-collagen were compared, and the results are shown in FIG. 2 .

From the results of FIG. 2, the cochleatesomes in which ginseng-derived irradiated saponin was captured according to Example 1 showed a pro-collagen production of 141.35% at 50 μg/ml, 140.18% at 25 μg/ml, and 133.28 at 12.5 μg/ml. It can be confirmed that it exhibits excellent collagen biosynthesis effect as %. This is an effect that is improved by 16.34%, 21.67%, and 21.79%, respectively, compared to the irradiation control group (125.01%, 118.51%, and 111.49%, respectively). It can be confirmed that it exhibits an excellent pro-collagen synthesis effect.

Experimental Example 4 - Evaluation of Permeability to Human Skin

In order to confirm that the human skin permeability of the ginseng-derived irradiated saponin collected in the cochleatesome of Example 1 is improved compared to the irradiated ponin control sample, skin permeation amount and skin permeation depth were measured using Raman confocal microspectrocopy. was measured.

Specifically, the sample of Example 1 and the irradiated ponin control group were applied to the forearm of the subject, and the sample was applied to each 2 μm depth of the subject's skin before and 30 minutes after application using a Raman confocal microscope (River D International BV, Netherlands). The Raman spectrum of was measured. Skin permeation amount and skin penetration depth were evaluated based on the following criteria, and the results are shown in Table 8.

1) Skin permeation amount (A.U.): Quantitative value up to the deepest point in the skin where the Raman spectrum of the sample is detected

2) Skin Penetration Depth (㎛): Distance from the skin surface to the deepest point in the skin where the Raman spectrum of the sample is detected

Example 1 Isaponin control group before application 30 minutes after application before application 30 minutes after application Skin Permeation Amount (A.U.) 0.002±0.009 0.124±0.047 0.002±0.001 0.004±0.003 Change amount (△) 0.122±0.045 0.002±0.002 fold Compared to the irradiated ponin control group, the skin permeation amount of Example 1 was improved by 61 times Skin Penetration Depth (㎛) 25.200±6.261 16.000±12.083 fold Compared to the irradiated ponin control group, the skin penetration depth of Example 1 was improved by 1.57 times

From the above results, it can be confirmed that the skin permeation amount (A.U.) of the ginseng-derived irradiated saponin collected in the cochleatesome of Example 1 was improved by 61 times and the skin permeation depth (μm) by 1.86 times compared to the irradiated saponin control sample. there is. Therefore, it can be seen that the skin permeability of the ginseng-derived radioponin captured in cochleatesomes according to Example 1 of the present invention is greatly improved even in actual human skin.

Experimental Example 5 - Stability evaluation

While each sample of Examples and Comparative Examples was left at a high temperature (50 ° C.) for 1 month, changes in precipitate, color and odor were observed, and the results of photographing the appearance after 1 month are shown in FIG. 3 .

The irradiation control group produced a large amount of insoluble precipitate at high temperature, and the cochleatesome of Comparative Example 1, which did not contain a nonionic surfactant, was separated into three layers at high temperature as a result of the stability test, NLC and Comparative Example 2 of Comparative Example 2. The niosome of 4 also had a problem in stability because the color was cloudy and the layer separation was exhibited.

On the other hand, the liposomes of Comparative Example 3 and the elastosomes of Comparative Example 5 were transparent without precipitate and exhibited excellent stability, but as described in Experimental Example 1, they exhibited low skin permeability.

In contrast, the cochleatesome of Example 1 not only has excellent skin permeability and can penetrate deeply into the skin, but also has excellent stability, such as no odor/discoloration and transparent properties without layer separation. Therefore, by using the cochleatesome of the present invention, it is possible to deliver irradiation to the skin not only effectively but also stably.

Preparation Example 2 - Preparation of cosmetic composition

2-1. Preparation of Essence

Using the composition of Example 1, an essence was prepared according to the contents (parts by weight) shown in Table 9 below.

Raw material Content (parts by weight) triethanolamine 0.25 carboxyvinyl polymer 0.22 glycerin 4 Butylene Glycol 2 Composition of Example 1 1.5 beeswax 0.5 Cetostearyl Alcohol One Glyceryl Monostearate One squalene 4 Purified water Appropriate amount

2-2. Manufacture of softening lotion

Softening lotion containing the composition of Example 1 as an active ingredient was prepared as shown in Table 10 below.

Raw material Content (parts by weight) 1,3-butylene glycol 1.00 Disodium EDT 0.05 allantoin 0.10 dipotassium glycyrrhizate 0.05 Citric Acid 0.01 sodium citrate 0.02 glycereth-26 1.00 Arbutin 2.00 PEG-40 Hydrogenated Castor Oil 1.00 ethanol 30.00 Composition of Example 1 0.5 coloring agent a very small amount flavoring agent a very small amount Purified water balance

2-3. Manufacture of nourishing cream

A nourishing cream containing the composition of Example 1 as an active ingredient was prepared as shown in Table 11 below.

Raw material Content (parts by weight) 1,3-butylene glycol 7.0 glycerin 1.0 D-panthenol 0.1 Magnesium aluminum silicate 0.3 PEG-40 Stearate 1.2 Stearic Acid 2.0 polysorbate 60 1.5 Lipophilic Glyceryl Stearate 2.0 Sorbitan sesquioleate 1.5 Cetearyl Alcohol 3.0 mineral oil 4.0 squalene 3.8 Composition of Example 1 1.5 vegetable oil 1.8 dimethicone 0.4 dipotassium glycyrrhizate a very small amount allantoin a very small amount sodium hyaluronate a very small amount Tocopheryl Acetate Appropriate amount triethanolamine Appropriate amount flavoring agent Appropriate amount Purified water balance

2-4. manufacture of lotion

A lotion containing the composition of Example 1 as an active ingredient was prepared according to the composition shown in Table 12 below.

Raw material Content (parts by weight) Cetostearyl Alcohol 1.6 stearic acid 1.4 Glycerin lipophilic monostearate 1.8 PEG-100 Stearate 2.6 Sorbital Sesquioleate 0.6 squalene 4.8 macadamia oil 2 jojoba oil 2 Tocopherol Acetate 0.4 Methylpolysiloxane 0.2 Tocopherol Acetate 0.4 1,3-butylene glycol 4 xanthan gum 0.1 glycerin 4 d-pandenol 0.15 Composition of Example 1 1.0 allantoin 0.1 Carbomer (2% aq. Sol) 4 triethanolamine 0.15 ethanol 3 Purified water Appropriate amount

Claims (12)

ginseng-derived josaponin; and
A cosmetic composition for preventing skin damage and improving wrinkles with improved skin permeability of ginseng-derived irradiation, comprising: cochleatesome containing a nonionic surfactant. The method of claim 1,
Wherein the nonionic surfactant has an HLB value of 8 to 20. The method of claim 1,
The ratio of the cochleatesome to ginseng-derived saponin is 100: 1 to 100: 7 by weight. The method of claim 1,
The cochleatesome includes a solvent, a phospholipid, a saturated fatty acid, a softening agent, a nonionic surfactant, an anionic surfactant, a preservative, and a divalent cation salt,
The ginseng-derived irradiation ponin is located between the phospholipid bilayers of the cochleate some and is trapped in the cochleate some. The method of claim 4,
The cochleatesome is based on the total weight of the cochleatesome
55 to 99% by weight solvent;
Phospholipid 0.1 to 10% by weight;
0.0001 to 2% by weight of saturated fatty acids;
0.1 to 10% by weight of a softening agent;
0.1 to 10% by weight of a nonionic surfactant;
0.01 to 7% by weight of an anionic surfactant;
0.1 to 10% by weight of a preservative; and
A composition comprising 0.0001 to 2% by weight of a divalent cation salt. The method of claim 4,
Wherein the solvent comprises at least one selected from the group consisting of distilled water, glycerin, ethanol, butylene glycol, and propanediol. The method of claim 4,
The phospholipid includes at least one selected from the group consisting of phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, hydrogenated phosphatidylcholine, phosphatidylic acid, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, and hydrogenated products thereof,
The saturated fatty acid is a composition comprising at least one selected from the group consisting of palmitic acid, stearic acid, oleic acid, linoleic acid and linolenic acid. The method of claim 4,
The softening agent is a composition comprising one selected from the group consisting of caprylic capric triglyceride, cetylethylhexanoate, dicaprylyl ether, ceramide, and ceramide NP. The method of claim 1,
The nonionic surfactant is at least one selected from the group consisting of polyglyceryl-10 laurate, polyglyceryl-10 oleate, polyglyceryl-10 stearate, and polyglyceryl-10 disostearate A composition comprising The method of claim 4,
The anionic surfactant includes at least one selected from the group consisting of sodium stearoyl glutamate, disodium stearoyl glutamate, sodium lauroyl glutamate, sodium lauryl glucose carboxylate, and sodium methyl cocoyl taurate. composition. The method of claim 4,
The divalent cation salt is a composition comprising calcium chloride. ginseng-derived josaponin; and
A pharmaceutical composition for preventing or treating skin diseases caused by ultraviolet rays with improved skin permeability of ginseng-derived saponin, comprising: cochleatesome containing a nonionic surfactant.