KR102183896B1 - Composition for improving skin - Google Patents

Abstract

The present invention relates to a composition for improving skin. The mixed extract, which is a mixture of the extract of Lichenaceae and almond extract according to the present invention, exhibits a whitening effect by significantly reducing the total amount of melanin, promotes collagen synthesis of fibroblasts in the skin, inhibits elastase activity, improves wrinkles, and enhances elasticity. Enhances, suppresses the production of nitric oxide (NO), shows an anti-inflammatory effect, scaves out free radicals, has an antioxidant effect, and an anti-glycosylation effect that inhibits glycation, skin whitening, wrinkle improvement, elasticity enhancement, anti-inflammatory, antioxidant and / Or can be used in the manufacture of anti-glycation drugs, cosmetics or food.

Description

Composition for improving skin {Composition for improving skin}

The present invention relates to a composition for skin improvement showing skin whitening, elasticity enhancement, wrinkle improvement, anti-inflammatory, antioxidant, and anti-glycosylation effects.

It is a common desire to have white and fair skin. The color or brightness of the skin is genetically determined according to the concentration and distribution of melanin in a person's skin, but is also affected by environmental or physiological conditions such as solar ultraviolet rays, fatigue or stress. Melanin is produced through a non-enzymatic oxidation reaction after being sequentially converted into dopa and dopaquinone by an enzyme called tyrosinase acting as a catalyst on tyrosine, a type of amino acid. As such, the pathway by which melanin is produced is known, but the cause of the triggering of tyrosinase in the mechanism that induces melanin synthesis is still not elucidated in detail.

Meanwhile, as a commonly known whitening component, substances that inhibit tyrosinase enzyme activity such as Kojic acid or arbutin, hydroquinone, vitamin C (L-Ascorbic acid) or derivatives thereof, and various There are plant extracts. By inhibiting the synthesis of melanin pigments, they can not only realize skin whitening by brightening skin tone, but also improve skin hyperpigmentation such as spots and freckles caused by ultraviolet rays, hormones or genetics. However, when applied to the skin, there is a problem in that the amount of use is limited due to safety issues such as irritation and redness, or the effect is insignificant and thus no practical effect can be expected.

In addition, collagen is a major matrix protein produced by fibroblasts of the skin and is present in the extracellular interstitial, and its important functions include skin mechanical firmness, connective tissue resistance and tissue bonding, support for cell adhesion, cell division and differentiation ( The induction of organism growth or wound healing) is known. Such collagen is reduced by age and photoaging due to ultraviolet irradiation, which is known to be closely related to the formation of wrinkles in the skin. In addition, in recent years, with the development of extensive research on skin aging, an important function of collagen in the skin has been revealed.

Active ingredients that promote collagen synthesis to improve wrinkles are known. For example, retinoic acid, transforming growth factor (TGF) [Non-Patent Literature 1], protein derived from animal placenta [Patent Literature 1], betulinic acid [Patent Literature 2], chlorella extract [ Patent Documents 3 and 4] are known as collagen synthesis promoting substances. However, there is a problem in that the amount of the active ingredients is limited due to safety problems such as irritation and redness when applied to the skin, or the effect is insignificant, so that the effect of substantially promoting collagen synthesis in the skin and improving skin function cannot be expected.

In addition, inflammation is an immune response of the human body in response to wounds or diseases, and oxidative stress such as ultraviolet rays, free radicals, etc. activates inflammatory factors, causing various diseases and aging of the skin. Vasoactive polypeptides such as kinin, plasmin, or complement act as vasodilation, contraction, and chemotaxis, and other lymphokines such as interleukin-6 (IL-6) Phosphorus and arachidonic acid are responsible for the inflammatory response. Arachidonic acid is metabolized to prostaglandin or lukotriene, which is an inflammatory mediator, through two pathways of cyclooxygenase or lipooxygenase, mediating various inflammatory reactions.

In order to eliminate inflammation, it is called anti-inflammatory drugs that remove inflammatory sources, reduce biological reactions and symptoms. Substances used for anti-inflammatory purposes to date include flufenamic acid, ibuprofen, benzydamine, or indomethacin as non-steroids, and prednisolone as a steroid system. Or dexamethasone. In addition, allantoin, azene, hydrocortisone, etc. are known to be effective in anti-inflammatory, but these substances are limited in use due to safety issues on the skin, or the effect is insignificant, so that the effect of substantially reducing inflammation cannot be expected. There is this.

On the other hand, active oxygen introduced from outside the living body or generated in the living body causes many problems such as promoting aging in the living body or causing cancer. Therefore, many studies and developments have been made on antioxidants that inhibit oxidation by active oxygen. Antioxidants are widely distributed in animals and plants, and many phenolic compounds, flavonoids, tocopherols, vitamin C, selenium, etc. are known in fruits and vegetables. However, natural antioxidants cannot be expected to have a substantially sufficient effect when applied to the skin. Therefore, synthetic antioxidants that have excellent antioxidant power and are inexpensive are widely used, but their use is limited due to concerns about safety such as side effects on the human body.

Glycation refers to a reaction in which simple sugars such as glucose or fructose form covalent bonds to proteins or fats that generally occur without the involvement of enzymes. The accumulation of the final glycated product changes the protein to a harder and more brittle state, and glycated collagen prevents the collagen from forming an appropriate structure in the extracellular matrix of the dermal layer, thereby causing the skin to lose elasticity and promote wrinkle formation [ Non-Patent Document 2]. In addition, the final saccharification product produced by saccharification is a substance that has a brownish color, and is thought to be the causative agent that gradually turns yellow as the skin aging progresses, and the reflected light reflected from the skin decreases as the specific final saccharification product accumulates. It is known that it is [Non-Patent Document 3]. As substances that inhibit saccharification, aminoguanidine, pyridoxamine, and aspirin are known, but these substances have limited amounts of use due to safety issues on the skin, or their effects are insignificant. There is a problem that cannot be expected.

In addition, it is safe for the living body, the active ingredient is stable, and above all, skin whitening, wrinkle improvement, elasticity enhancement, anti-inflammatory, which is superior to the existing skin whitening, wrinkle improvement, elasticity enhancement, anti-inflammatory and/or antioxidant substances. And/or the development of a component having antioxidant activity is desperately desired.

On the other hand, Lycium chinense refers to the bulge of the root of Liriope platyphylla Wang et Tang or Ophiopogon japonicus Ker-Gawler.

Maekmun-dong is a representative medicine to supplement the essence, and is used for dry cough, sputum, phlegm, and seawater due to lung-eum damage, and is also used for thirst, sogal and constipation due to lack of false-eum. It is used for symptoms of tightness in the chest and inability to keep limbs still and insomnia due to minor blood loss.

Maekmundong (麥門冬) is Maekmundong (麥冬), Gyejeoncho (階前草), Yeodong (麗冬), horse chestnut (horse), pulsating movement (麥冬), immortality medicine, Aegu, and Yanggu. Also known as (羊), Yanggi (羊耆), Ugu (禹), Uyeoryang (禹餘粮), Indong (忍冬), Inneung (忍凌), Mundong (冬), Bokru (僕), and Suzy (隨脂). .

Also, Armeniacae Semen is also known as apricot tree ( Prunus armeniaca Linne var. ansu Maximowicz), Prunus mandshurica Koehne var. glabra Nakai), Siberian apricot ( Prunus) sibirica Linne) or Armenian Apricot ( Prunus Armeniaca Linne, Rosaceae) is a ripe seed, which removes phlegm, stops coughing and asthma, and moisturizes the intestine.

Japanese Patent Application No. Hei 8-231370 Japanese Patent Application No. Hei 8-208424 Japanese Patent Application No. Hei 9-40523 Japanese Patent Application Laid-Open No. Hei 10-36283

Cardinale G. et al, Adv. Enzymol., 41, p. 425, 1974 Dyer, D. G. et al, The Journal of Clinical Investigation., 9, p. 2463, 1993 Hiroshi, O. et al, Skin Research and Technology, 15, p. 496, 2009

Accordingly, the inventors of the present invention have shown that the mixed extract of the extract of lichenaceae and almond extract significantly reduces the total amount of melanin to show a whitening effect, promotes collagen synthesis of fibroblasts in the skin, inhibits elastin activity, improves wrinkles, and elasticity. The present invention was completed by confirming the anti-inflammatory effect by promoting and inhibiting the production of nitrogen oxide (NO), and confirming the antioxidant effect of scavenging free radicals and the anti-glycosylation effect of inhibiting saccharification.

Accordingly, it is an object of the present invention to provide a composition for skin whitening, wrinkle improvement, elasticity enhancement, anti-inflammatory, antioxidant and/or anti-glycosylation comprising a mixed extract of a mixture of licorice and almond extract as an active ingredient.

As a means for solving the above problems, the present invention comprises a mixed extract of a mixture of licorice extract and almond extract as an active ingredient for the manufacture of medicine, cosmetics or food, skin whitening, wrinkle improvement, elasticity enhancement, anti-inflammatory, antioxidant And/or it provides a composition for anti-glycation.

The mixed extract, which is a mixture of the extract of Lichenaceae and almond extract according to the present invention, exhibits a whitening effect by significantly reducing the total amount of melanin, promotes collagen synthesis of fibroblasts in the skin, inhibits elastase activity, improves wrinkles, and enhances elasticity. It can be used in medicine, cosmetics, or food manufacturing by enhancing and suppressing the production of nitric oxide (NO) to exhibit an anti-inflammatory effect, and by scavenging free radicals to exhibit an antioxidant effect and an anti-glycosylation effect to inhibit saccharification.

Hereinafter, the configuration of the present invention will be described in detail.

Skin whitening, wrinkle improvement, elasticity enhancement, anti-inflammatory, antioxidant and/or anti-glycosylation ingredients are highly active at low concentrations in order to exert excellent effects when applied to the skin. /Or exhibits anti-glycosylation activity, has excellent ability to penetrate and absorb the skin, and has low volatility so that it can stay for a sufficient time to exhibit skin whitening, wrinkle improvement, elasticity enhancement, anti-inflammatory, antioxidant and/or anti-glycosylation effects. , It is preferable that the composition or the active ingredient is stably maintained on the skin, and it is easy to manufacture as a medicine, cosmetic or food, and is safe for the skin. However, among known components, components that satisfy all of the above properties are not common. For example, some skin whitening, wrinkle improvement, elasticity enhancement, anti-inflammatory, antioxidant and/or anti-glycosylation ingredients, even at low concentrations when tested in vitro, have skin whitening, wrinkle improvement, elasticity enhancement, anti-inflammatory, antioxidant and/or anti-glycosylation activity. Is excellent, but it is difficult to apply to actual skin due to its poor ability to penetrate and absorb the skin. Other active ingredients have low hydrophilic properties, making it difficult to formulate into medicine, cosmetics, or food. In addition, some skin whitening, anti-wrinkle, elasticity, anti-inflammatory, antioxidant and/or anti-glycosylating ingredients are already decomposed or transformed into other compounds when exposed to heat, light, or oxygen, prior to application to the skin. In some cases, the effect disappears.

As can be seen in the following examples, the extract and almond extract are excellent in reducing the total amount of melanin at low concentration, anti-glycosylation effect, collagen synthesis promoting effect, anti-inflammatory, antioxidant and / or anti-glycation drugs, cosmetics or food It can be used as an active ingredient in the composition.

Accordingly, the present invention provides a composition for skin whitening, wrinkle improvement, elasticity enhancement, anti-inflammatory, antioxidant, and/or anti-glycosylation comprising a mixed extract of a mixture of licorice extract and almond extract as an active ingredient.

In the present invention, Liriope platyphylla is a monocotyledonous plant, Liriope platyphylla. Also, passersby are ripe seeds of the apricot tree.

The licorice extract or almond extract may be extracted by a method known in the art, and the method is not particularly limited. Alternatively, a commercially available extract can be used.

Preferably, the extract or almond extract may be an extract obtained by extracting almond or almond with water and/or an organic solvent, and the organic solvent may be a polar organic solvent, a non-polar organic solvent, or a mixed solvent thereof. . The polar organic solvent may be a lower alcohol having 1 to 5 carbon atoms, ethyl acetate or acetone, and the non-polar organic solvent may be ether, chloroform, benzene, hexane, or dichloromethane. For example, the lower alcohol having 1 to 5 carbon atoms may be methanol, ethanol, propanol, butanol or isopropanol.

In one embodiment, the extract or haengin extract may include a fraction obtained by fractionating the primary extract extracted using the above-described extraction solvent using an extraction solvent having a different polarity. For example, the extract of almond tree or almond extract may be a fraction that is extracted with an alcohol having 1 to 5 carbon atoms and then fractionated again with a solvent having a different polarity such as ether, benzene, or hexane. In the fractionation, two or more solvents may be used, and each solvent extract may be prepared by sequentially using or mixing according to the polarity of the solvent.

In the present invention, the prepared extract or the fraction obtained by performing the fractionation process may be filtered, concentrated or dried to remove the solvent, and the filtration, concentration, and drying may all be performed. Specifically, the filtration may be performed using a filter paper or a reduced pressure filter, the concentration may be concentrated under reduced pressure using a reduced pressure concentrator or the like, and the drying may be performed by a freeze drying method.

In addition, silica gel column chromatography, thin layer chromatography, or high performance liquid chromatography for the prepared extract or the fraction obtained by performing the fractionation process. Further purified fractions can be obtained by purification using various chromatography.

It is preferable that the mixed extract of the almond extract and the almond extract of the present invention are mixed in a weight ratio of 1: 1 to 5 of the almond extract and almond extract. Particularly, it is more preferable that the extract of almond and almond extract is mixed in a weight ratio of 1: 1.

The composition of the present invention can be used to prepare a pharmaceutical formulation.

The pharmaceutical formulation may be in the form of a solution, suspension, or emulsion in an oil or aqueous medium, or may be in the form of an extract, powder, granule, tablet or capsule.

In addition, the composition may further contain one or more active ingredients exhibiting the same or similar functions. For example, known skin whitening, wrinkle improvement, elasticity enhancement, anti-inflammatory, antioxidant and/or anti-glycosylation ingredients may be included. When additional skin whitening, wrinkle improvement, elasticity enhancement, anti-inflammatory, antioxidant and/or anti-glycation components are included, the skin regeneration, wrinkle improvement, elasticity enhancement, anti-inflammatory, antioxidant and/or anti-glycosylation improvement effect of the composition of the present invention is It could be further improved. When the above ingredients are added, skin safety, ease of formulation, and stability of active ingredients can be considered in combination with use. In one embodiment of the present invention, the composition is a skin regeneration component known in the art, retinoic acid, TGF, protein derived from animal placenta, betulinic acid and chlorella extract, as an antioxidant component known in the art, tocopherol, selenium , Vitamin C and phenolic compounds, as whitening components known in the art, substances that inhibit tyrosinase enzyme activity such as Kojic acid, arbutin, hydroquinone, vitamin-C (L- Ascorbic acid) and derivatives thereof, and one or two or more components selected from the group consisting of various plant extracts may be further included. Additional ingredients may be included in an amount of 0.0001% to 10% by weight based on the total weight of the composition, and the content range may be adjusted according to requirements such as skin safety and ease of formulation of the active ingredient.

In addition, the composition of the present invention may further include a pharmaceutically acceptable carrier.

The pharmaceutically acceptable carrier may contain various components such as a buffer solution, sterile water for injection, general saline or phosphate buffered saline, sucrose, histidine, salt, and polysorbate.

The composition of the present invention may be administered orally or parenterally, and may be administered in the form of a general pharmaceutical preparation, for example, in various oral and parenteral dosage forms during clinical administration. In the case of formulation, generally used fillers and extenders , A binder, a wetting agent, a disintegrant, and a diluent or excipient such as a surfactant.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and these solid preparations include at least one excipient in the pharmaceutical composition of the present invention, such as starch, calcium carbonate, water. It can be prepared by mixing sucrose, lactose, gelatin, or the like.

In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use include suspensions, liquid solutions, emulsions, syrups, etc., but may include various excipients, such as humectants, sweeteners, fragrances, and preservatives, in addition to water and liquid paraffin, which are commonly used simple diluents.

Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like may be used.

In the present invention, the term'whitening effect' refers to not only brightening skin tone by inhibiting the synthesis of melanin pigment, but also improving skin hyperpigmentation such as spots and freckles caused by ultraviolet rays, hormones or genetics.

In the present invention, the term "wrinkle improvement effect" refers to inhibiting or inhibiting the generation of wrinkles on the skin, or alleviating wrinkles that have already been generated.

In the present invention, the term'elasticity enhancing effect' refers to an increase in elasticity to the skin, suppressing or inhibiting the loss of skin elasticity, or alleviating the already reduced elasticity.

In the present invention, "anti-inflammatory effect" refers to suppressing inflammation. Inflammation is one of the defense responses of biological tissues to certain stimuli, and refers to a complex lesion that causes tissue deterioration, circulatory disorders, effusion, and tissue proliferation. More specifically, inflammation is part of innate immunity, and, as in other animals, innate immunity in humans recognizes patterns on the cell surface that are specific to pathogens. Phagocytes recognize cells with such surfaces as non-magnetic and attack pathogens. If pathogens break through the body's physical barriers, an inflammatory reaction occurs. The inflammatory reaction is a non-specific defense action that creates a hostile environment for microorganisms invading the wound. In the inflammatory reaction, when a wound or an external infectious agent enters the body, white blood cells responsible for the early stage immune response gather and express cytokines. Therefore, the amount of expression of cytokines in cells becomes an indicator of activation of the inflammatory response. Examples of skin diseases related to inflammation include atopic dermatitis, psoriasis, erythematous disease caused by radiation, chemical substances, or burns; Itching due to acid burns, bullous skin disease, lichen planus disease or allergies; Inflammatory hair loss such as seborrheic eczema, rose acne, pemphigus vulgaris, polymorphic exudative erythema, nodular erythema, balanitis, vulvitis or alopecia areata; Cutaneous T-cell lymphoma, but is not limited thereto.

In the present invention, the term'antioxidant effect' refers to a cell by free radicals or reactive oxygen species (ROS) having high reactivity depending on oxidative stress caused by intracellular metabolism or ultraviolet rays. It refers to inhibiting oxidation, and includes removing free radicals or reactive oxygen species, thereby reducing damage to cells.

In the present invention, the term'anti-glycosylation effect' means preventing or inhibiting glycation, in which glucose and protein present in cells react to reduce protein function in the body.

In the present invention, the term'effective amount' refers to a damaged whitening effect, improving wrinkles, enhancing elasticity, inhibiting inflammation, inhibiting or alleviating cell oxidation, or inhibiting the production of glycosylation. It means the amount of extract present. When the composition of the present invention contains a mixed extract of an effective amount of the extract and almond extract, it can provide desirable skin whitening effect, wrinkle improvement effect, elasticity enhancing effect, anti-inflammatory effect, antioxidant effect, and anti-glycosylation effect. . The effective amount of the mixed extract obtained by mixing the licorice extract and almond extract included in the composition of the present invention will vary depending on the form in which the composition is commercialized, the method in which the compound is applied to the skin, and the time to stay in the skin. For example, when the composition is manufactured as a pharmaceutical formulation, it may contain the active ingredient in a higher concentration than when it is manufactured as a cosmetic product that is routinely applied to the skin. Therefore, the daily dose is 0.1 to 100 mg/kg, preferably 30 to 80 mg/kg, more preferably 50 to 60 mg/kg, based on the amount of the mixed extract obtained by mixing the licorice extract and almond extract. kg, and can be administered 1 to 6 times a day.

The composition of the present invention may be used alone or in combination with surgery, radiation therapy, hormone therapy, chemotherapy, and methods using biological response modifiers.

The pharmaceutical formulation of the present invention may include a formulation for external application for skin.

When using the mixed extract obtained by mixing the extract of Almond and Almond extract as an external preparation for skin, additionally fatty substances, organic solvents, solubilizers, thickening and gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents ), fragrances, surfactants, water, ionic or nonionic emulsifiers, fillers, sequestering agents and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipids It may contain adjuvants commonly used in the field of dermatology such as vesicles or any other ingredients commonly used in external preparations for skin. In addition, the ingredients may be introduced in an amount generally used in the field of dermatology.

When the mixed extract obtained by mixing the extracts of the extract and almond extract is provided as a formulation for external use for skin, it is not limited thereto, but may have a formulation such as an ointment, patch, gel, cream, or spray.

In addition, the composition for skin whitening, wrinkle improvement, elasticity enhancement, anti-inflammatory, antioxidant and/or anti-glycosylation of the present invention may be used for preparing a cosmetic formulation.

The cosmetic formulation may be in the form of a general emulsified formulation and a solubilized formulation. For example, a lotion such as a flexible lotion or a nutrient lotion, an emulsion such as a facial lotion, a body lotion, a cream such as a nourishing cream, a moisture cream, an eye cream, an essence, a cosmetic ointment, a spray, a gel, a pack, a sunscreen, a makeup base, a liquid It may have a formulation such as a foundation such as a type, a solid type, or a spray type, a powder, a cleansing cream, a cleansing lotion, a makeup remover such as a cleansing oil, a cleansing foam, a soap, a body wash, and the like.

In addition, in addition to the mixed extract obtained by mixing the extract of Almond and Almond extract, the cosmetic includes a fatty substance, an organic solvent, a solubilizing agent, a thickening agent and a gelling agent, an emollient, an antioxidant, a suspending agent, a stabilizer, a foaming agent, and a fragrance. , Surfactants, water, ionic or nonionic emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic actives, lipid vesicles or cosmetics It may contain adjuvants commonly used in the field of cosmetics, such as any other ingredients commonly used in

The cosmetic formulation may contain a relatively high concentration of the active ingredient in the case of a wash-off type cosmetic such as a makeup remover or detergent in which the active ingredient stays on the skin within a short period of time. On the other hand, in the case of leave-on type cosmetics such as lotions, emulsions, creams, and essences, in which the active ingredient stays on the skin for a long period of time, even if the active ingredient contains a lower concentration than the wash-off type cosmetics. It would be okay. Although not limited thereto, in one embodiment of the present invention, the composition may contain the active ingredient in 0.0001% to 10% by weight (preferably 0.0001% to 1% by weight) based on the total weight of the composition. . When the composition of the present invention contains less than 0.0001% by weight of the mixed extract of the mixture of the extract and almond extract, sufficient skin whitening, wrinkle improvement, elasticity enhancement, anti-inflammatory, antioxidant and/or anti-glycosylation effect cannot be expected. If the content exceeds 10% by weight, unwanted reactions such as allergies may occur or there may be problems with skin safety, so this is to prevent this.

In addition, the composition for skin whitening, wrinkle improvement, elasticity enhancement, anti-inflammatory, antioxidant and/or anti-glycosylation of the present invention may be used for preparing food formulations.

The food formulation refers to a food prepared by adding a mixed extract obtained by mixing the licorice extract and almond extract to food materials such as beverages, teas, spices, gums, confectionery, or the like, encapsulated, powdered, or suspended.

Since the above food formulation can be consumed on a daily basis, high skin whitening, wrinkle improvement, elasticity enhancement, anti-inflammatory, antioxidant, and/or anti-glycosylation effects can be expected, which is very useful.

When the active ingredient is used as a food additive, a mixed extract obtained by mixing the extract of Lichenaceae and almond extract may be added as it is, or may be used together with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixed amount of the active ingredient may be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment). In general, in the preparation of food or beverage, the composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less based on the raw material. However, in the case of long-term intake for the purpose of health and hygiene or for health control purposes, the amount may be less than the above range, and there is no problem in terms of safety, so the active ingredient may be used in an amount above the above range. .

There is no particular limitation on the type of food. Examples of foods to which the above substances can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, There are alcoholic beverages and vitamin complexes, and all health foods in the usual sense are included.

When the food formulation is a beverage, it may contain various flavoring agents or natural carbohydrates, etc. as an additional component, like a conventional beverage. The natural carbohydrates described above are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the sweetener, natural sweeteners such as taumatin and stevia extract, and synthetic sweeteners such as saccharin and aspartame can be used. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the composition of the present invention.

In addition to the above, food formulations include various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonated beverages It may contain a carbonation agent used in the. In addition, the food formulation may contain flesh for the manufacture of natural fruit juice, fruit juice beverage and vegetable beverage. These ingredients may be used independently or in combination. The ratio of these additives is not very important, but it is generally selected from 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

Hereinafter, the present invention will be described in detail by examples. However, the following examples are only illustrative of the present invention, and the contents of the present invention are not limited to the following examples.

Manufacturing example 1: Preparation of licorice extract

After drying and slicing liquor, 100 g of dry weight was put into a flask, and extracted by cold soaking with 1000 g of extraction solvent (distilled water) for 3 days. The cold-precipitated extract was filtered through a filter having a pore size of 0.2 µm to prepare a licorice extract.

Manufacturing example 2: Preparation of almond extract

After the almonds were well dried and minced, 100 g of dry weight was put into a flask, and extracted by cold soaking with 1000 g of an extraction solvent (distilled water) for 3 days. The cold-precipitated extract was filtered through a filter having a pore size of 0.2 μm to prepare an almond extract.

Manufacturing example 3: Preparation of mixed extracts of lichens and almonds

A mixture of 10 g of the extract of almonds from Preparation Example 1 and 10 g of the extract of Almonds from Preparation Example 2 were mixed to prepare a mixed extract of almonds and almonds.

Example 1: melanin production inhibitory effect

In order to confirm the whitening effect through inhibition of melanogenesis, in the culture medium of mouse melanoma cells (B-16 mouse melanoma cells) according to the method described in Lotan R. et al. (Cancer Res. 40:3345-3350, 1980), The total amount of melanin was measured by adding the extract. At the time of the experiment, first, toxicity was evaluated for the melanoma cells of mice, and whitening evaluation was performed at a concentration without toxicity. DMSO was used as a negative control, and arbutin was used as a positive control.

Specifically, the sample was added to the medium so that the final concentration was 100 ppm, and arbutin was added to the medium so that it became 100 ppm, and then melanoma cells were cultured for 3 days. Thereafter, the cells were treated with trypsin, removed from the culture vessel, centrifuged, and melanin was extracted. The detached cells were boiled for 10 minutes by adding 1 ml of sodium hydroxide solution (1N concentration) to dissolve melanin, and the absorbance was measured at 400 nm using a spectrophotometer to measure the amount of melanin produced.

The amount of melanin was measured by a method expressed in terms of absorbance per unit cell count (1×10 ⁶ cells), and the total amount of melanin relative to the control was calculated as an inhibition rate (%), and the results were shown in Table 1 below. And expressed as an average value.

The effect of reducing the total amount of melanin at the cellular level according to the concentration (repeat number = 3) sample Melanin production (abs) Inhibition rate (%) Control (DMSO, 10ppm) 0.33 - Positive control (Arbutin, 100ppm) 0.228 30.91 Preparation Example 1 (100 ppm) 0.257 22.12 Preparation Example 2 (100 ppm) 0.290 12.12 Preparation Example 3 (100 ppm) 0.237 28.18

As can be seen from the results of Table 1, the mixed extract of Preparation Example 3 showed an excellent effect of reducing the total amount of melanin even at a low concentration, it was found that it can be used for whitening purposes.

Example 2: collagen synthesis promotion effect

The sample was added to the culture medium of human-derived fibroblasts to confirm the effect of promoting type 1 collagen synthesis at the cellular level. The synthesized collagen was measured using the PICP EIA kit (Procollagen Type I C-Peptide Enzyme ImmunoAssay KIT).

Make the sample at a final concentration of 10 ppm, add it to the fibroblast culture medium (DMEM medium), and incubate for 48 hours, then take the culture solution and use the PICP EIA kit to determine the level of type 1 collagen synthesis at each concentration at 450 nm using a spectrophotometer. It was measured at.

In order to compare the effect, the degree of collagen synthesis was measured in the same manner for the sample to which the culture medium (negative control) and vitamin C (positive control) of fibroblasts without sample treatment were added to a final concentration of 52.85 μg/ml.

The rate of increase in collagen production was calculated as the ratio of the relative collagen production amount to the negative control group, and the results are shown in Table 2 below, and the experiment was performed four times and expressed as an average value.

Collagen synthesis promotion effect (repeat number = 4) sample Type 1 collagen production (ng/ml) Collagen production increase rate (%) Negative control 150.2 - Positive control group (vitamin C) 246.8 64.3 Preparation Example 1 (10 ppm) 188.4 25.4 Preparation Example 2 (10 ppm) 200.9 33.8 Preparation Example 3 (10 ppm) 246.3 64.0

As shown in Table 2, when the mixed extract of Preparation Example 3 was treated, collagen synthesis was increased, and a collagen synthesis effect similar to that of applying vitamin C, which is well known to induce collagen synthesis, was exhibited.

Example 3: Ela Stays Inhibitory effect

The inhibitory effect of the activity of Elastase, an enzyme that degrades elastin, was confirmed as follows.

For Elastase, Elastase derived from human leukocyte cells was used, and MeOSuc-Ala-Ala-Pro-Val-pNA, a synthetic substrate, was used as a substrate for Elastase. As a buffer solution, a 100 mM Tris (pH 7.5) solution was used. Elastase was finally used as 0.2 mU using a buffer solution. In addition, for the synthetic substrate of Elastase, a 100 mM solution was prepared using DMSO and then diluted with a buffer solution so that the final concentration was 0.5 mM. At this time, the positive control was set to have a 10 ppm concentration of quercetin, known as an elastase inhibitor. Elastase inhibition candidate was added so that the final concentration became 10 ppm. The reaction was carried out in a 96-well plate, and the reaction was performed at room temperature for 20 minutes. The absorbance was measured at 405 nm at 1 minute intervals using a spectrophotometer, and the slope of the absorbance against time was determined to determine the activity of the enzyme. The elastase inhibition rate was calculated as in Equation 1 below.

[Equation 1]

Elastase activity inhibition effect (repeat number = 3) sample Enzyme activity Inhibition rate (%) Preparation Example 1 (10 ppm) 4.9 52.88 Preparation Example 2 (10 ppm) 5.3 49.03 Preparation Example 3 (10 ppm) 3.9 62.50 Positive control (Quercetin, 10ppm) 3.5 66.35 Control (DMSO, 20ppm) 10.4 -

As can be seen from Table 3, when the mixed extract of Preparation Example 3 was treated, the effect was less than that of the positive control group, but it can be seen that the inhibition of elastin activity was excellent. That is, the mixed extract exhibited an excellent effect of inhibiting elastase activity. Therefore, it was found that the mixed extract can be used for enhancing elasticity and improving wrinkles.

Example 4: anti-inflammatory effect

In order to confirm the anti-inflammatory effect and the effect of improving skin troubles, an experiment of inhibiting nitric oxide (NO) production was performed by the GRIESS method using RAW264.7 cell line (ATCC number: CRL-2278).

Specifically, the RAW264.7 cells, which are mouse macrophages, were subcultured several times, placed in a 24-well plate so as to enter 3×10 ⁵ cells in each well, and cultured for 24 hours. Subsequently, the cell medium containing the sample was replaced with a final concentration of 10 ppm. At this time, the NO-production inhibitor L-NMMA (L-NG-Monomethylarginine) was treated as a positive control and incubated for 30 minutes, and LPS (Lipopolysaccharide) was treated as a stimulator at 1 µg and cultured for 24 hours. 100 µl of the supernatant was taken and transferred to a 96-well plate, 100 µl of GRIESS solution was added at a time, reacted at room temperature for 10 minutes, and the absorbance at 540 nm was measured to determine the NO inhibition effect, and the NO production inhibition rate (%) was It was calculated using the following Equation 2 and shown in Table 4 below, and the experiment was performed three times each and expressed as an average value.

[Equation 2]

NO production inhibition rate (%)={(absorbance of negative control-absorbance of each extract)/absorbance of negative control} x 100

NO production inhibitory effect (repeat number = 3) sample NO production inhibition rate (%) Control (DMSO, 10 ppm) - L-NMMA (positive control, 10 ppm) 41.02 Preparation Example 1 (10 ppm) 31.77 Preparation Example 2 (10 ppm) 36.99 Preparation Example 3 (10 ppm) 40.07

As can be seen in Table 4, when compared with L-NMMA, which is a representative anti-inflammatory drug, the mixed extract of Preparation Example 3 has low activity, but exhibits excellent activity as a natural substance, so that the anti-inflammatory effect is assisted in improving skin problems. It can be expected to have a synergistic effect by acting as an effective role.

Example 5: antioxidant effect-free radical scavenging rate

Free radical scavenging activity was measured to confirm the antioxidant activity of the sample. Free radical scavenging activity was measured using DPPH (Blois, Nature 181, 1190, 1958).

DPPH is a relatively stable free radical. When it exists in a radical state, it shows maximum absorption at 517 nm, and when the radicals are scavenging, it loses absorbance. DPPH was used by Sigma.

First, a standard DPPH ethanol solution of 1.5 mM (0.06 mg/ml) was prepared. Then, a 1000 μg/ml (0.1%) vitamin C solution was prepared using tertiary distilled water, followed by serial dilution by 1/2 to 1000, 500, 250, 125, 62.5, 31.25, 15.63, 7.81, 3.91, 1.95, 0.98. , A vitamin C sample of 0.49 μg/ml was prepared. In addition, diluted solutions of Preparation Examples 1 to 3 were prepared at the same concentration as vitamin C. Then, the sample and the standard DPPH solution were added in the same ratio, stirred well, reacted at 37° C. for 30 minutes, and the absorbance at 517 nm was measured using a microplate reader (BioTek EL-340) to obtain IC ₅₀ . It was obtained and shown in Table 5 below.

IC ₅₀ (half maximal inhibitory concentration) is the concentration of a substance required to remove 50% of the free radicals of the non-added control (DPPH in this case), and is a general method of expressing the free radical scavenging ability.

Free radical elimination effect (number of iterations = 3) sample IC ₅₀ (%w/v) Positive control (vitamin C) 0.0005 Manufacturing Example 1 0.0022 Manufacturing Example 2 0.0013 Manufacturing Example 3 0.0009

As shown in Table 5, it was confirmed that the mixed extract of Preparation Example 3 had excellent free radical scavenging ability when compared with Preparation Example 1 and Preparation Example 2, and had an antioxidant effect similar to that of vitamin C, a positive control.

Example 6: Anti-glycosylation effect

In order to confirm the anti-glycation efficacy, glycation inhibitory activity was measured using L-arginine and glucose.

First, 1M L-arginine and 1M glucose were dissolved in 1M phosphate buffer solution (pH 7.4), and the sample was diluted to 50 ppm using 1M phosphate buffer solution. 1M L-arginine and 1M phosphate buffer were mixed in a ratio of 1 to 4, and then 80 μl of each was dispensed into a 96-well plate. A sample diluted to 50 ppm and 0.01M aminoguanidin to be used as a positive control were added to each of 100 μl. These samples were mixed well, and finally, glucose diluted with 1M phosphate buffer solution was added so that the final concentration of glucose was 0.1M, and then reacted at 70°C for 4 hours. The degree of saccharification was measured by measuring the absorbance at 420 nm in a 96-well plate using a spectrophotometer.

The Glycation experiment group of Equation 1 below is an experimental group in which 1M L-arginine and 1M glucose were added to induce saccharification, and to measure the absorbance of the sample itself, 1M L-arginine and only the sample were added without glucose to measure the absorbance at 420 nm. I did.

The glycation inhibitory activity can be obtained by Equation 3 below. The experiment was performed three times each and expressed as an average value.

[Equation 3]

Sample (number of iterations = 3) Glycation inhibition rate (%) Control (DMSO, 50 ppm) - Positive control (Aminoguanidine, 55 ppm) 54.89 Preparation Example 1 (50 ppm) 42.27 Preparation Example 2 (50 ppm) 49.99 Preparation Example 3 (50 ppm) 69.45

As can be seen from the results of Table 6, it can be seen that the mixed extract of Preparation Example 3 according to the present invention has a more excellent anti-glycosylation effect when compared with Aminoguanidine, which is known as an anti-glycosylation substance. That is, the mixed extract exhibits an excellent anti-glycation effect, so that the anti-glycation effect acts as an auxiliary role in whitening or wrinkle improvement, and a synergistic effect can be expected.

Formulation example 1: Preparation of pharmaceutical formulation

1. Preparation of tablets

0.2 mg of mixed extract of Preparation Example 3

100mg corn starch

100mg lactose

Magnesium stearate 2mg

After mixing the above ingredients, tablets were prepared by tableting according to a conventional tablet preparation method.

Formulation example 2: manufacture of cosmetics

1. Manufacture of nutrition cream

As shown in the following composition, a nutritional cream containing the mixed extract of Preparation Example 3 as an active ingredient was prepared according to a conventional method.

0.2% by weight of mixed extract of Preparation Example 3

5.0% by weight of beta-1,3-glucan

10.0 wt% beeswax

1.5% by weight of polysorbate 60

Fiji 60 hydrogenated castor oil 2.0% by weight

0.5% by weight of sorbitansquioleate

Liquid paraffin 10.0% by weight

5.0% by weight of squalane

Caprylic/Capric Triglyceride 5.0% by weight

5.0% by weight of glycerin

Butylene glycol 3.0% by weight

Propylene glycol 3.0% by weight

0.2% by weight of triethanolamine

0.05% by weight of preservative

0.05% by weight of pigment

Perfume 0.05% by weight

Purified water to 100% by weight

Formulation example 3: Preparation of external preparation for skin

1. Preparation of ointment

As shown in the following composition, an ointment containing the mixed extract of Preparation Example 3 as an active ingredient was prepared according to a conventional method.

0.5% by weight of the mixed extract of Preparation Example 3

Beta-1,3-glucan 10.0% by weight

10.0 wt% beeswax

5.0% by weight of polysorbate 60

Sebum 60 hydrogenated castor oil 2.0% by weight

0.5% by weight of sorbitansquioleate

Vaseline 5.0% by weight

Liquid paraffin 10.0% by weight

5.0% by weight of squalane

Shea butter 3.0% by weight

Caprylic/Capric Triglyceride 5.0% by weight

Glycerin 10.0% by weight

10.2% by weight of propylene glycol

0.2% by weight of triethanolamine

0.05% by weight of preservative

0.05% by weight of pigment

Perfume 0.05% by weight

Purified water to 100% by weight

Claims (22)

A cosmetic composition for skin whitening comprising as an active ingredient a mixed extract obtained by mixing a licorice extract and almond extract.
The method of claim 1,
The licorice extract is an extract obtained by extracting licorice with one or more selected from the group consisting of water and organic solvents,
Almond extract is an extract obtained by extracting almonds with one or more selected from the group consisting of water and organic solvents, a cosmetic composition for skin whitening.
The method of claim 2,
The organic solvent is a polar solvent including a lower alcohol having 1 to 5 carbon atoms, ethyl acetate, or acetone; A non-polar solvent including ether, chloroform, benzene, hexane or dichlorohexane; Or a cosmetic composition for skin whitening as a mixed solvent thereof.
A food composition for skin whitening comprising as an active ingredient a mixed extract obtained by mixing a licorice extract and almond extract.
A cosmetic composition for enhancing skin elasticity or improving wrinkles, comprising a mixed extract of a mixture of licorice and almond extract as an active ingredient.
The method of claim 5,
The licorice extract is an extract obtained by extracting licorice with one or more selected from the group consisting of water and organic solvents,
Almond extract is an extract obtained by extracting almonds with one or more selected from the group consisting of water and an organic solvent, a cosmetic composition for enhancing skin elasticity or improving wrinkles.
The method of claim 6,
The organic solvent is a polar solvent including a lower alcohol having 1 to 5 carbon atoms, ethyl acetate, or acetone; A non-polar solvent including ether, chloroform, benzene, hexane or dichlorohexane; Or a cosmetic composition for improving skin elasticity or wrinkles as a mixed solvent thereof.
A food composition for enhancing skin elasticity or improving wrinkles, comprising a mixed extract of a mixture of licorice and almond extract as an active ingredient.
An anti-inflammatory cosmetic composition comprising as an active ingredient a mixed extract obtained by mixing the extract of licorice and almond extract.
The method of claim 9,
The licorice extract is an extract obtained by extracting licorice with one or more selected from the group consisting of water and organic solvents,
Almond extract is an anti-inflammatory cosmetic composition obtained by extracting almonds from the group consisting of water and an organic solvent.
The method of claim 10,
The organic solvent is a polar solvent including a lower alcohol having 1 to 5 carbon atoms, ethyl acetate, or acetone; A non-polar solvent including ether, chloroform, benzene, hexane or dichlorohexane; Or a cosmetic composition for anti-inflammatory which is a mixed solvent thereof.
An anti-inflammatory food composition comprising a mixed extract of a mixture of licorice and almond extract as an active ingredient.
Antioxidant cosmetic composition comprising as an active ingredient a mixed extract of a mixture of licorice and almond extract.
The method of claim 13,
The licorice extract is an extract obtained by extracting licorice with one or more selected from the group consisting of water and organic solvents,
Almond extract is an antioxidant cosmetic composition obtained by extracting almonds from the group consisting of water and an organic solvent.
The method of claim 14,
The organic solvent is a polar solvent including a lower alcohol having 1 to 5 carbon atoms, ethyl acetate, or acetone; A non-polar solvent including ether, chloroform, benzene, hexane or dichlorohexane; Or a cosmetic composition for antioxidants that are mixed solvents thereof.
Antioxidant food composition comprising a mixed extract of a mixture of licorice and almond extract as an active ingredient.
A cosmetic composition for anti-glycosylation comprising as an active ingredient a mixed extract obtained by mixing the extract of licorice and almond extract.
The method of claim 17,
The licorice extract is an extract obtained by extracting licorice with one or more selected from the group consisting of water and organic solvents,
Almond extract is an extract obtained by extracting almonds with one or more selected from the group consisting of water and an organic solvent.
The method of claim 18,
The organic solvent is a polar solvent including a lower alcohol having 1 to 5 carbon atoms, ethyl acetate, or acetone; A non-polar solvent including ether, chloroform, benzene, hexane or dichlorohexane; Or a cosmetic composition for anti-glycosylation as a mixed solvent thereof.
A food composition for anti-glycosylation comprising a mixed extract of a mixture of licorice and almond extract as an active ingredient.
A skin external preparation for improving skin hyperpigmentation, comprising a mixed extract of a mixture of licorice and almond extract as an active ingredient.
A pharmaceutical composition for preventing or treating inflammatory diseases, comprising a mixed extract of a mixture of licorice and almond extract as an active ingredient.