KR20230150099A - A cosmetic composition for skin whitening comprising a mixed extract of Geranium kunthii and Zephyrnathes candida as an active ingredient, and a pharmaceutical composition for preventing or treating diseases of melanin hyperpigmentation - Google Patents

Abstract

The present invention provides a cosmetic composition for skin whitening comprising as an active ingredient a Geranium kunthii extract, a Zephyrnathes candida extract, or a mixed extract of Geranium kunthii and a white flower saffron, and a treatment for melanin hyperpigmentation diseases. It relates to a pharmaceutical composition for prevention or treatment. The large-leafed saffron extract, the white-flowered saffron extract, or the mixed extract of the large-leaved saffron extract and the white-flowered saffron according to the present invention has excellent efficacy in inhibiting the tyrosinase enzyme, which determines the rate of melanin synthesis, a skin pigment, and is used as a skin whitening cosmetic. It can be useful as a composition and pharmaceutical composition for preventing or treating melanin hyperpigmentation diseases.

Description

A cosmetic composition for skin whitening comprising a mixed extract of Geranium kunthii and white flower nado saffron as an active ingredient and a pharmaceutical composition for preventing or treating melanin hyperpigmentation disease {A cosmetic composition for skin whitening comprising a mixed extract of Geranium kunthii and Zephyrnathes candida as an active ingredient, and a pharmaceutical composition for preventing or treating diseases of melanin hyperpigmentation}

The present invention provides a cosmetic composition for skin whitening comprising as an active ingredient a Geranium kunthii extract, a Zephyrnathes candida extract, or a mixed extract of Geranium kunthii and a white flower saffron, and a treatment for melanin hyperpigmentation diseases. It relates to a pharmaceutical composition for prevention or treatment.

Skin is a very important tissue that protects the human body through direct contact with the external environment and has biochemical and physical functions. This tissue is largely divided into three types: epidermis, dermis, and subcutaneous tissue. Human skin color appears dark or light mainly depending on the amount and distribution of melanin formed in melanocyte cells located between the epidermis and dermis of the skin.

Melanin, a black pigment synthesized through the enzymatic reaction of tyrosinase within melanocyte cells, is delivered from melanocyte cells to surrounding epidermal cells in the form of melanosomes, and the black pigment melanin produced is The depth of black varies depending on the amount.

Melanin absorbs the light energy of ultraviolet rays in sunlight and prevents deeper cells from being damaged by ultraviolet rays. When melanin is produced in abnormally low amounts, skin erythema and skin lesions worsen, and excessive and repetitive ultraviolet rays not only damage the skin, but can also cause skin cancer.

Melanin is produced through enzymatic and non-enzymatic oxidation reactions of tyrosine in melanocyte cells. The enzymes involved in melanin synthesis are tyrosinase and tyrosinase related protein 1 (TRP). -1) and tyrosinase related protein 2 (TRP-2) are known. Additionally, the major intracellular signaling pathway is the cyclic monophosphate/protein kinase A (cAMP/PKA) pathway, where cAMP promotes the expression of Microphthalmia-associated transcription factor (MITF) via PKA and cAMP resposive element binding protein 1 (CREB1). do. MITF is an important transcriptional regulator in the melanin synthesis process and is known to promote the transcription of tyrosinase, tyrosinase-related protein 1, and tyrosinase-related protein 2. This enzyme produces dopaquinone, which acts on the amino acid called tyrosine present in tissues, and melanin, a black pigment, is produced from this dopaquinone through several stages of auto-oxidation. Therefore, a whitening composition can be prepared in various ways as follows, depending on which stage of the process inhibits melanin production.

First, it contains ingredients that can block ultraviolet rays, which are the main cause of melanin production. The composition using this method blocks the formation/activity of tyrosinase enzyme caused by ultraviolet rays by containing a light scattering agent or a light blocker. It can inhibit melanin production. The second is to inhibit the formation of melanin using substances that inhibit the function of tyrosinase, which is involved in melanin production, such as enzyme acid (kojic acid), rucinol, eric acid, or arbutin. Third, there is a method to stabilize dopachrome and prevent its progression to black melanin, Eu-Melanin. The fourth is to use substances such as vitamin C, which has a strong antioxidant effect and can produce a whitening effect while tyrosine undergoes complex oxidation and condensation reactions through dopa and dopachrome. Fifthly, there is also a method to remove and reduce the produced melanin from the stratum corneum using enzymes or AHA (Alpha Hydroxy Acid). However, sunscreens and tyrosinase inhibitors are mainly used for efficacy and performance.

In the existing cosmetics field, whitening ingredients include, for example, substances that inhibit tyrosinase enzyme activity such as kojic acid and arbutin, hydroquinone, and vitamin C (L-Ascorbic acid). and their derivatives and various plant extracts have been used. However, the substances that inhibit the tyrosinase enzyme activity have low stability in the prescription system, so their use is limited due to decomposition and discoloration, occurrence of off-flavor, unclear efficacy and effect at the biological level, etc.

Chinese Published Patent No. 10,3641,839

While the present inventor was screening 120 samples to find a material derived from natural substances that is safe for the human body and can exhibit excellent whitening effects, it was discovered that the extract of the saffron and the saffron extract had tyrosinase activity. The present invention was completed after confirming that there was significantly excellent tyrosinase inhibitory activity, especially in the case of mixed extracts of large trefoil and white flower nano saffron.

Accordingly, the purpose of the present invention is to provide a cosmetic composition for skin whitening that is stable in the human body and has excellent melanin suppressing activity, and a pharmaceutical composition for preventing or treating melanin hyperpigmentation diseases.

One example of the present invention provides a cosmetic composition for skin whitening comprising as an active ingredient an extract of the amphibian snail, a white-flowered saffron extract, or a mixed extract of the saffron and a saffron of the white flowers.

According to the cosmetic composition of the present invention, the weight ratio of the large trifoliate and white flower nano saffron in the mixed extract of the trifoliate trifoliate and white flower nano saffron may be 1:10 to 10:1. Preferably, the weight ratio of the large trefoil and white flower nano saffron may be 1:5 to 5:1.

According to the cosmetic composition of the present invention, the cosmetic composition can inhibit the activity of tyrosinase.

According to the cosmetic composition of the present invention, the extract may be an ethanol extract.

Another example of the present invention provides a pharmaceutical composition for the prevention or treatment of diseases related to melanin pigmentation, comprising as an active ingredient a large three-leafed chinensis extract, a white flowering nado saffron extract, or a mixed extract of the large three-leafed chinensis and white flowering nado saffron. .

According to the pharmaceutical composition of the present invention, the weight ratio of the large three-leafed trifoliate and white flower nano-saffron in the mixed extract of the large trifoliate and white-flowered nano-saffron may be 1:10 to 10:1. Preferably, the weight ratio of the large trefoil and white flower nano saffron may be 1:5 to 5:1.

According to the pharmaceutical composition of the present invention, the cosmetic composition can inhibit the activity of tyrosinase.

According to the pharmaceutical composition of the present invention, the extract may be an ethanol extract.

The large-leafed saffron extract, white-flowered saffron extract, or mixed extract of large-leaved saffron and white-flowered saffron according to the present invention has excellent safety and can effectively inhibit melanin production through tyrosinase inhibitory activity, so it can be used as an active ingredient. The composition of the present invention containing the composition can exhibit an excellent whitening effect by suppressing melanin pigment without irritating the skin, and is expected to be useful as a functional cosmetic composition and a pharmaceutical composition for the prevention or treatment of melanin hyperpigmentation disease.

Figure 1 is a graph showing the cytotoxicity of the extract of L. trifolia by concentration.
Figure 2 is a graph showing the cytotoxicity of white flower nado saffron extract by concentration.
Figure 3 is a graph showing the cytotoxicity of the mixed extract of Large three-leafed saffron: White flower nado saffron (5:1) by concentration.
Figure 4 is a graph showing the cytotoxicity of the mixed extract of Large three-leafed saffron: White flower nado saffron (3:1) by concentration.

Hereinafter, the present invention will be described in more detail through experimental examples and examples. However, these experimental examples and examples are for illustrative purposes only and the scope of the present invention is not limited to these experimental examples and examples. In addition, unless there is a special definition in this specification, all scientific and technical terms used in this specification may have the same meaning as commonly understood by a person skilled in the art in the technical field to which the present invention pertains.

Throughout this specification, unless otherwise specified, “include” or “contains” refers to the inclusion of a certain component (or component) without particular limitation, excluding the addition of other components (or components). cannot be interpreted as

The term “large three-leafed jwisoni” or “ Geranium kunthii ” used in this specification is a perennial herb of the dicotyledonous plant family Jwisoni of the order Geranium kunthii that grows in mountainous areas.

The term “white flower saffron” or “ Zephyrnathes candida ” used in this specification refers to a perennial plant of the monocotyledonous family of the order Narcissus family native to South America, and is also called “White amaryllis” or “Autumn Zephyrlily.”

The term “skin whitening” used herein can mean not only brightening skin tone by inhibiting the synthesis of melanin pigment, but also improving skin hyperpigmentation such as spots or freckles caused by ultraviolet rays, hormones, or genetics. there is. The “pigmentation” refers to a condition in which the amount of pigment in the body is abnormal or there is an abnormality in the area where the pigment appears, for example, blemishes and freckles.

The term “Melanin” used in this specification is a pigment component widely distributed in living organisms such as skin, hair, and eyes, and is synthesized in melanosomes within melanocytes in the epidermal layer of the human body, using tyrosinase ( Melanin is biosynthesized using tyrosine as a starting material by the enzyme Tyrosinase. Biosynthesized melanin increases resistance to skin stimulation such as ultraviolet rays, but excessive melanin synthesis causes pigmentation such as spots, freckles, and age spots, so measuring tyrosinase activity inhibition is considered an important indicator of skin whitening effect. It is being brought in.

The term “extract” used herein has the meaning commonly used in the art as a crude extract, but also includes fractions obtained by additional fractionation of the extract. Accordingly, the extract may be juice, crude extract, fraction, or a combination thereof. The crude extract is obtained by contacting the large trefoil or white flower nado saffron with an extraction solvent, and refers to a product that has not been separated as it contains specific ingredients. The fraction refers to the separation of substances containing specific components from the crude extract. The extract or a fraction thereof may include an extract of saffron or white-flowered nado saffron, a fraction thereof, or a mixture thereof in the composition, and may contain only an isolated compound, or may contain the compound as a main ingredient. It may include The small fraction may be obtained by passing through an ultrafiltration membrane having a cut-off value.

As used herein, the term "mixed extract" refers to an extract of two or more raw materials, an extract prepared by mixing individual extracts of two or more raw materials, and an extract obtained by mixing two or more raw materials and extracting them together in an extraction solvent. It may mean that it includes everything.

As used herein, the term “treatment” means improving the condition of an individual suffering from a disease or at risk of developing a disease, delaying the progression of the disease, delaying the onset of symptoms, or slowing the progression of symptoms, etc. It means any form of treatment or prevention that provides effects including. Accordingly, the term “treatment” includes prophylactic treatment of an individual, preventing the occurrence of symptoms. Additionally, the terms “treatment” and “prevention” are not intended to imply cure or complete elimination of symptoms.

As used herein, the term “improvement” may refer to any action that at least reduces the severity of a parameter, such as a symptom, associated with the alleviation or treatment of a condition.

One embodiment of the present invention provides a cosmetic composition containing an extract of saffron or white-flowered saffron.

Another embodiment of the present invention provides a cosmetic composition comprising a mixture of a large trefoil extract and a white flower nado saffron extract.

The extract may be an extract extracted with a solvent from the entire above-ground part of the large trefoil or white-flowered nado saffron, a part thereof, or materials derived therefrom. The part may be the stem, leaf, flower, petal or seed of the large trefoil. The whole of the large trefoil used for extraction, parts thereof, or materials derived from them may be ground, shredded, or dried appropriately.

The extract may be extracted using water, acetone, alcohol, for example, C1-C6 alcohol, or a mixture thereof as a solvent. The C1-C6 alcohol may be methanol, ethanol, propanol, isopropanol, 1,3-propanediol, butanol, pentanol, hexanol, or butylene glycol. The solvent may be, for example, a mixture of water and alcohol, that is, an aqueous alcohol solution. The alcohol concentration of the aqueous alcohol solution is 1 to 100 (w/w)%, for example, 1 to 99.5 (w/w)%, 10 to 100 (w/w)%, 20 to 100 (w/w)%, It may be 20 to 80 (w/w)%, 20 to 60 (w/w)%, 20 to 40 (w/w)%, or 30 (w/w)%. The alcohol aqueous solution may be an aqueous methanol, ethanol, or butanol aqueous solution. Additionally, it may be extracted with one or more solvents selected from the group consisting of hexane, ethyl acetate, acetone, and butanol.

The extraction is performed by warm liquid extraction, pressurized liquid extraction (PLE), microwave assisted extraction (MAE), subcritical extraction (SE), or a combination thereof. It can be. The subcritical extraction may be subcritical water extraction (SWE). Subcritical water extraction is also called superheated water extraction or pressurized hot water extraction (PHWE). The warm liquid extraction may be reflux extraction. The extraction is performed at 4°C to 70°C, for example, 4°C to 50°C, 4°C to 40°C, 4°C to 30°C, 10°C to 70°C, 15°C to 70°C, 20°C to 70°C, 4 It may be carried out at ℃ to 50℃, 10℃ to 50℃, 4℃ to 40℃, 4℃ to 30℃, 10℃ to 40℃, 10℃ to 35℃, or 10℃ to 30℃. If the extraction is a heated extraction, it may be performed at a temperature at which the solvent used for extraction boils or at a temperature at which the desired component is extracted from the plant, for example, 40°C or higher, 50°C or higher, 60°C or higher, or 70°C. Above, it is carried out at a temperature of 80 ℃ or higher, 90 ℃ or higher, 100 ℃ or higher, 120 ℃ or higher, 140 ℃ or higher, 160 ℃ or higher, or 200 ℃ or higher. For example, using water as a solvent, the temperature is 90 ℃ or higher. It may be performed at a temperature of 120°C.

The time required for the extraction may vary depending on the temperature selected and may range from 1 hour to 2 months, for example, 1 hour to 1 month, 1 hour to 15 days, 1 hour to 10 days, 1 hour to 5 days, 1 hour to 1 month. 3 days, 1 hour to 2 days, 1 hour to 1 day, 5 hours to 1 month, 5 hours to 15 days, 5 hours to 10 days, 5 hours to 5 days, 5 hours to 3 days, 5 hours to 2 days , 5 hours to 1 day, 10 hours to 1 month, 10 hours to 15 days, 10 hours to 10 days, 10 hours to 5 days, 10 hours to 3 days, or 10 hours to 2 days. The extraction may include mixing the entire above-ground part, parts, seeds, or materials derived from them in the solvent and leaving them for a certain period of time. The standing may include moderate agitation. The extraction may be repeated one or more times, for example, 1 to 5 times.

The extraction may further include a process of separating plant residues and extracts by known methods such as filtration. The extraction may also include removing the solvent from the obtained extract by known methods such as concentration under reduced pressure. The extraction may also include preparing a dry extract by drying the obtained extract, such as nitrogen drying or freeze-drying. The extract can be dried and then resolvated with an appropriate solvent as needed. The composition may further include a fraction of the extract. The term “fraction” refers to a substance in which the extract of the L. trifolia extract is divided into its components, i.e., a fractionated substance. The fraction may be obtained by solvent fractionation. The solvent fractionation may be performed by mixing the extract of L. trifolia with a solvent and separating substances present in the solvent. Extracts herein are not to be construed as pure extracts excluding fractions, unless explicitly stated otherwise.

The composition is 0.01% to 80% by weight, for example, 0.01% to 60% by weight, 0.01% to 40% by weight, 0.01% to 30% by weight, 0.01% to 20% by weight, based on the total weight of the composition. %, 0.01% to 10% by weight, 0.01% to 5% by weight, 0.01% to 1% by weight, %, 0.05% to 60% by weight, 0.05% to 40% by weight, 0.05% to 30% by weight %, 0.05% to 20% by weight, 0.05% to 10% by weight, 0.05% to 5% by weight, 0.05% to 1% by weight, 0.1% to 60% by weight, 0.1% to 40% by weight, 0.1% to 30% by weight, 0.1% to 20% by weight, 0.1% to 10% by weight, 0.1% to 5% by weight or 0.1% to 1% by weight, preferably at least 0.1% by weight, 0.1% by weight. It may comprise from % to 20% by weight or from 0.1% to 10% by weight, more preferably from 0.5% to 10% by weight of the extract.

The composition may contain the extract in an effective amount or as an active ingredient depending on its intended use. The effective amount can be appropriately selected depending on the individual. The severity of the disease or condition, the subject's age, weight, health, gender, the subject's sensitivity to the extract, administration time, administration route and excretion rate, administration period, factors including other compositions combined or used simultaneously with the composition, and other factors. It can be determined according to factors well known in the field of physiology or medicine.

The composition may be a cosmetic composition for skin whitening, improving skin aging, antioxidant, or anti-inflammatory.

The composition may be a cosmetic composition for skin whitening.

The composition may be used to improve skin aging. Specifically, the extract may be used to improve skin aging caused by extrinsic or endogenous factors. The exogenous factors refer to various external factors, such as ultraviolet rays (light), and the endogenous factors are also referred to as chronological factors and mainly refer to factors that occur due to the passage of time. In other words, the skin aging is not only a premature aging phenomenon induced by external stimuli such as ultraviolet rays, pollution, cigarette smoke, chemicals, etc., but also a natural aging phenomenon that occurs as the proliferation of skin cells decreases with age. It is a concept that includes wrinkles, loss of elasticity, skin sagging, and dryness. In addition, wrinkles include stimulation caused by changes in internal and external factors that change the components that make up skin tissue, causing wrinkles.

The composition may be a cosmetic composition characterized by inhibiting the activity of tyrosinase. Specifically, the composition may inhibit the production of melanin by inhibiting the activity of tyrosinase and reducing the production of dopaquinone, which acts on tyrosine present in tissues.

The mixture has a weight ratio of 1:100 to 100:1, for example, 1:50 to 50:1, 1:30 to 30:1, 1:20 to 20:1, between the extract of L. trifolia and saffron extract. , 1:10 to 10:1, 1:1 to 5:1, 1:5 to 1:1, 1:5 to 5:1, 1:3 to 3:1, or 1:2 to 2:1 1 :1, 2:1, 3:1, 5:1, 1:2, 1:3, 1:5, preferably 1:1, 2:1, 3 :1, 5:1, 1:2, 1:3, 1:5, more preferably 1:2, 1:3, 1:5, 3:1. It may be any one cosmetic composition selected from the group consisting of:

The cosmetic composition may have, for example, an softening lotion, nourishing lotion, massage cream, nourishing cream, essence, pack, gel, ampoule, or skin-adhesive type cosmetic formulation.

Ingredients included in the cosmetic composition may include ingredients commonly used in cosmetic compositions in addition to the composition as an active ingredient, for example, conventional auxiliaries and carriers such as stabilizers, solubilizers, vitamins, pigments, and fragrances. may include.

The cosmetic composition may further include a cosmetically acceptable excipient or carrier. The types of cosmetically acceptable excipients or carriers vary depending on the formulation and purpose, and common ingredients such as water, surfactants, alcohol, oil, thickeners, chelating agents, colorants, preservatives, and fragrances are appropriately mixed. It can be done, but it is not limited to this. The mixing amount of the excipient or carrier can be easily determined by a person skilled in the art within a range that does not impair the purpose and effect of the present invention.

The cosmetic composition is not particularly limited to a specific formulation, and the formulation may be appropriately selected depending on the purpose. The cosmetic composition includes lotion (skin lotion), gel, water-soluble liquid, milk lotion, nutritional cream, massage cream, essence, oil-in-water emulsion, water-in-oil emulsion, facial anhydrous product, solid anhydrous product, and aqueous product using globules. Oil dispersion on the surface, ionic lipid vesicles, non-ionic lipid vesicles, ointment, cleansing foam, cleansing water, pack, body oil, oil-in-water type makeup base, water-in-oil type makeup base, foundation, skin cover, lipstick, lip gloss , face powder, two-way cake, eye shadow, mascara, cheek color, eyebrow pencils, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream. , foundation, essence, nutritional essence, pack, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, suspension, powder, paste, mask pack, mask sheet, or aerosol composition. It is not limited. Compositions of this dosage form can be prepared according to methods conventional in the art.

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

When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder can be used as the carrier ingredient. In particular, when the formulation is a spray, chlorofluorohydrocarbon and propane may be used as carrier ingredients. /May contain propellants 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-butyl glycol, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan.

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

When the formulation of the present invention is a surfactant-containing cleansing agent, the carrier ingredients include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, and fatty acid amide. Ether sulfate, alkylamidobetaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, or ethoxylated glycerol fatty acid ester can be used.

Another embodiment of the present invention provides a pharmaceutical composition for the prevention or treatment of diseases related to melanin pigmentation, comprising extracts of Saffron or White Flower Nados Saffron.

Another embodiment of the present invention provides a pharmaceutical composition for the prevention or treatment of diseases related to melanin pigmentation, comprising a mixture of extract of L. trefoil and extract of white flower nado saffron.

The melanin pigmentation-related disease may be melasma, freckles, senile pigmentation, or solar lentigines. Specifically, the melanin pigmentation-related disease refers to a disease that occurs when the balance of melanin pigment is unbalanced and melanin is excessively deposited on the skin. In general, melanin produced by melanocytes protects skin cells from UV damage by absorbing UV rays. In particular, when melanogenesis progresses excessively, various hyperpigmentary disorders such as freckles, freckles, solar melanoma, senile pigment spots, and melanoma occur.

The pharmaceutical composition may include a peptide compound, a stereoisomer thereof, a solvate, or a pharmaceutically acceptable salt as an active ingredient. The pharmaceutical composition may further include known active ingredients with anticancer activity. The pharmaceutical composition may additionally include a pharmaceutically acceptable diluent or carrier. The diluent may be lactose, corn starch, soybean oil, microcrystalline cellulose, or mannitol, and the lubricant may be magnesium stearate, talc, or a combination thereof. The carrier may be an excipient, disintegrant, binder, lubricant, or a combination thereof. The excipient may be microcrystalline cellulose, lactose, low-substituted hydroxycellulose, or a combination thereof. The disintegrant may be calcium carboxymethylcellulose, sodium starch glycolate, calcium monohydrogen phosphate anhydride, or a combination thereof. The binder may be polyvinylpyrrolidone, low-substituted hydroxypropylcellulose, hydroxypropylcellulose, or a combination thereof. The lubricant may be magnesium stearate, silicon dioxide, talc, or a combination thereof.

The pharmaceutical composition may be formulated in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, or sterile injection solutions according to conventional methods. When formulated, it can be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

In the pharmaceutical composition, the solid preparation for oral administration may be a tablet, pill, powder, granule, or capsule. The solid preparation may further include excipients. Excipients may be, for example, starch, calcium carbonate, sucrose, lactose, or gelatin. Additionally, the solid preparation may further include a lubricant such as magnesium stearate or talc. In the pharmaceutical composition, the liquid preparation for oral administration may be a suspension, oral solution, emulsion, or syrup. The liquid formulation may contain water or liquid paraffin. The liquid formulation may contain excipients such as wetting agents, sweeteners, flavoring agents, or preservatives. In the pharmaceutical composition, preparations for parenteral administration may be sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried products, or suppositories. Non-aqueous solvents or suspensions may contain vegetable oil or ester. The vegetable oil may be, for example, propylene glycol, polyethylene glycol, or olive oil. The ester may be, for example, ethyl oleate. The base of the suppository may be witepsol, macrogol, tween 61, cacao, laurel, or glycerogelatin. The preferred dosage of the pharmaceutical composition varies depending on the individual's condition and weight, degree of disease, drug form, administration route and period, but can be appropriately selected by a person skilled in the art. However, the compound, its isomer, derivative, solvate, or pharmaceutically acceptable salt may be administered in an amount of, for example, about 0.0001 mg/kg to about 100 mg/kg, or about 0.001 mg/kg to about 100 mg/kg. The amount can be divided and administered 1 to 24 times per day, 1 to 7 times per 2 days to 1 week, or 1 to 24 times per month to 12 months. In the pharmaceutical composition, the compound, its isomer, derivative, solvate, or pharmaceutically acceptable salt is present in an amount of about 0.0001% to about 10% by weight, or about 0.001% to about 1% by weight, based on the total weight of the composition. may be included.

As used herein, the terms “administering,” “introducing,” and “implanting” are used interchangeably and are used interchangeably to introduce a composition into an individual by a method or route that results in at least partial localization to the desired site according to one embodiment. It may refer to the arrangement of the composition according to one embodiment of.

Administration can be done by methods known in the art. Administration may be administered directly to the subject by any means, such as, for example, intravenous, intramuscular, oral, transdermal, mucosal, intranasal, intratracheal or subcutaneous administration. You can. The administration may be administered systemically or locally.

The subject may be a mammal, such as a human, cow, horse, pig, dog, sheep, goat, or cat. The subject may be an individual in need of skin beauty improvement, for example, skin moisturizing, skin barrier strengthening, skin inflammation inhibition, and skin wrinkle improvement effects.

The administration of the composition according to one embodiment is 0.1 mg to 1,000 mg, for example, 0.1 mg to 500 mg, 0.1 mg to 100 mg, 0.1 mg to 50 mg, 0.1 mg to 25 mg, 1 mg to 1 mg per day. 1,000 mg, 1 mg to 500 mg, 1 mg to 100 mg, 1 mg to 50 mg, 1 mg to 25 mg, 5 mg to 1,000 mg, 5 mg to 500 mg, 5 mg to 100 mg , 5 mg to 50 mg , 5 mg to 25 mg, 10 mg to 1,000 mg, 10 mg to 500 mg, 10 mg to 100 mg, 10 mg to 50 mg, or 10 mg to 25 mg. However, the dosage may be prescribed in various ways depending on factors such as formulation method, administration method, patient's age, weight, gender, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity, and those skilled in the art will Taking these factors into consideration, the dosage can be adjusted appropriately. The frequency of administration can be once a day or two or more times within the range of clinically acceptable side effects, and can be administered at one or two or more locations, daily or at intervals of 2 to 5 days. The number of days of administration can be from 1 to 30 days per treatment. If necessary, the same treatment can be repeated after an appropriate period. For animals other than humans, the dosage per kg is the same as for humans, or the above dosage is converted into, for example, the volume ratio (e.g., average value) of the organs (heart, etc.) between the target animal and human. One dose can be administered.

Additionally, the composition may be a composition for external skin application.

In this specification, the external skin agent may be a cream, gel, ointment, skin emulsifier, skin suspension, transdermal delivery patch, drug-containing bandage, lotion, or a combination thereof. The skin external preparations include ingredients commonly used in external skin preparations such as cosmetics and medicines, such as aqueous ingredients, oil-based ingredients, powder ingredients, alcohols, moisturizers, thickeners, ultraviolet absorbers, whitening agents, preservatives, antioxidants, surfactants, and fragrances. , colorants, various skin nutrients, or a combination thereof may be appropriately mixed according to need. The skin external preparations include metal sequestrants such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid, caffeine, tannin, belafamil, licorice extract, glablidin, and calin. Hot water extract of fruit, various herbal medicines, drugs such as tocopherol acetate, glytylitinic acid, tranexamic acid and its derivatives or salts, vitamin C, magnesium ascorbate phosphate, ascorbate glucoside, arbutin, kojic acid, glucose, fructose, Sugars such as trehalose can also be appropriately mixed.

The composition may be a health functional food composition.

The health functional food composition can be used alone or with other foods or food ingredients, such as the strain or its culture medium, and can be used appropriately according to conventional methods. The mixing amount of the active ingredient can be appropriately determined depending on the purpose of use (prevention, health, or therapeutic treatment). In general, when manufacturing food or beverages, the composition of the present specification may be added in an amount of 15 parts by weight or less based on the raw materials. There are no particular restrictions on the types of health functional foods.

Among the types of health functional foods, beverage compositions may contain various flavoring agents or natural carbohydrates as additional ingredients like ordinary beverages. The natural carbohydrates include 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 a sweetener, natural sweeteners such as thaumatin and stevia extract or synthetic sweeteners such as saccharin and aspartame can be used. The health food composition also contains nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, and carbonated beverages. It may contain the carbonating agent used, or a combination thereof. The health functional food composition may also contain pulp for the production of natural fruit juice, fruit juice beverage, vegetable beverage, or a combination thereof.

The composition for health functional foods may be manufactured in general dosage forms such as powders, granules, tablets, pills, capsules, suspensions, emulsions, syrups, steeps, liquids, extracts, etc., and may be used in meat, sausages, bread, chocolate, It may be manufactured in the form of any health food such as candy, snacks, confectionery, pizza, ramen, other noodles, gum, jelly, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes. . For the formulation of the health food, any food-acceptable carrier or additive can be used, and any carrier or additive known to be usable in the art can be used to prepare the formulation to be manufactured. The above additives include various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, and carbonated beverages. It may contain a carbonating agent, etc. In addition, it may contain pulp for the production of natural fruit juice, fruit juice drinks, and vegetable drinks. These additive components can be used independently or in combination, and the proportion of additives may be 0.001 to 5% by weight, or 0.01 to 3% by weight, based on the total weight of the composition.

Hereinafter, a cosmetic composition for skin whitening containing an extract of Geranium kunthii or Zephyrnathes candida as an active ingredient according to a specific embodiment of the invention will be described in detail. However, this is presented as an example of the invention, and the scope of the invention is not limited thereby, and it is obvious to those skilled in the art that various modifications to the embodiment are possible within the scope of the invention.

<Example>

Example 1. Preparation of herbal extract

100 g each of Geranium kunthii and Zephyranthes candida were extracted by soaking them in 1000 ml of 95% ethanol for 7 days at room temperature, then filtered through Whatman No. 1 filter paper at room temperature to remove insoluble substances. has been removed. Next, the extracted filtrate was concentrated and dried under reduced pressure at 50°C in a distillation device equipped with a cooling condenser, and the individual extracts of the large three-leafed chinensis and white flowering nado saffron were mixed in the weight ratio shown in Table 1 below. A mixed extract was prepared.

sample White Flower Nado Saffron Big three-leaf mouse hand Mixed extract 1 One One Mixed extract 2 One 2 Mixed extract 3 One 3 Mixed extract 4 One 5 Mixed extract 5 2 One Mixed extract 6 3 One Mixed extract 7 5 One

Example 2. Measurement of inhibitory activity of tyrosinase

First, 50 mL of 1 M, pH 6.8 phosphate buffer (PB) was mixed with 20 mg of L-DOPA to prepare a 2 mM L-DOPA solution. Prepare a 96-well plate, 2 μl of DMSO and 160 μl of PB were added to the blank, 2 μl of DMSO and 120 μl of PB were added to the negative control, and the individual extract or mixed extract sample prepared in Example 1 was added to the remaining wells. 2 μl and 120 μl of PB were added, respectively. Next, 1 ml of tyrosinase was mixed with 9 ml of PB, and 40 μl was added to all wells except the blank. Finally, 40 μl of 2mM L-DOPA solution was dispensed into all wells and reacted at 37°C for 10 minutes. Absorbance was measured at 475 nm, and Arbutin was used as a positive control. The tyrosinase activity inhibition rate was calculated according to the equation below, and the results are shown in Table 2 below.

[formula]

Tyrosinase inhibition rate (%) = 1-(absorbance of each sample/absorbance of negative control)x100

sample IC ₅₀ (μg/ml) Large three-leafed trifoliate extract 97.8 White Flower Saffron Extract 92.0 Mixed extract 1 (large: white = 1:1) 97.9 Mixed extract 2 (large: white = 2:1) 88.9 Mixed extract 3 (large: white = 3:1) 85.3 Mixed extract 4 (large: white = 5:1) 82.6 Mixed extract 5 (large: white = 1:2) (over 100) Mixed extract 6 (large: white = 1:3) (over 100) Mixed extract 7 (large: white = 1:5) 92.2 Arbutin (over 200)

As can be seen from Table 2 above, the tyrosinase inhibitory activity of the large three-leafed chinensis extract, the white flowering nado saffron extract, and the mixed extract of the large three-leafed flowering nado saffron were all confirmed to be superior to arbutin. In particular, the tyrosinase inhibitory activity of the mixed extract of large three-leafed saffron and white-flowered nano-saffron was found to be higher than that of the individual extracts of large-leafed saffron and white-flowered nano-saffron, and among them, the tyrosinase inhibitory activity of the mixed extracts of large three-leaved saffron and white-flowered nano-saffron was found to be 3:1. The mixed extract mixed in weight ratio showed the best tyrosinase inhibitory activity with an IC ₅₀ of 52.7 μg/ml.

Example 3. Cytotoxicity evaluation

RAW 264.7 cells were seeded in a 24-well plate at a concentration of 20*10 ⁴ cells/ml, and 2.5 μl of samples diluted to 50, 25, 12.5, 6.25, and 3.125 μg/ml were added to each well, and then 37 The cells were cultured in a 5% CO ₂ incubator at ℃ for 24 to 72 hours. Next, the medium was changed to a new medium without phenol red, and 10 μl of Premix WST-1 was added per well, and the cells were cultured for 1 to 4 hours in a 37°C, 5% CO ₂ incubator. After culturing, the mixture was mixed for about 1 minute before measuring the absorbance, then transferred to a 96 well plate and the absorbance was measured at 450 nm.

As a result, cytotoxicity was not observed in the extract of Macaron saffron (CC ₅₀ > 50 μg/ml) (Figure 1), and cytotoxicity was confirmed in the extract of White Flower Nadosaffron (CC ₅₀ = 23.3 μg/ml) (Figure 2). , in the mixed extract of large trefoil and white-flowered nado saffron, the cytotoxicity shown in the white-flowered nado saffron extract appeared to disappear above 50 μg/ml (Figure 3).

Although the present invention has been described above with reference to the above examples, the present invention is not limited thereto. Those skilled in the art will recognize that modifications and changes can be made without departing from the spirit and scope of the present invention, and that such modifications and changes also fall within the scope of the present invention.

Claims (10)

A cosmetic composition for skin whitening comprising as an active ingredient a large three-leafed chinensis extract, a white flowering nado saffron extract, or a mixed extract of a large three-leafed chinensis and a white flowering nado saffron.
According to paragraph 1,
A cosmetic composition for skin whitening, characterized in that the weight ratio of the large three-leafed saffron and the white flower nano-saffron in the mixed extract of the large saffron and white flower nano-saffron is 1:10 to 10:1.
According to paragraph 2,
A cosmetic composition for skin whitening, characterized in that the weight ratio of the large trefoil and white flower nano saffron is 1:5 to 5:1.
According to paragraph 1,
A cosmetic composition for skin whitening, characterized in that the cosmetic composition inhibits the activity of tyrosinase.
According to paragraph 1,
A cosmetic composition for skin whitening, wherein the extract is an ethanol extract.
A pharmaceutical composition comprising, as an active ingredient, a large three-leafed chinensis extract, a white flowering nado saffron extract, or a mixed extract of a large three-leafed chinensis and a white flowering nado saffron.
According to clause 6,
A pharmaceutical composition, characterized in that in the mixed extract of the large three-leafed saffron and the white flower nano-saffron, the weight ratio of the large three-leafed saffron and the white flower nano-saffron is 1:10 to 10:1.
In clause 7,
A pharmaceutical composition, characterized in that the weight ratio of the large trefoil and white flower nano saffron is 1:5 to 5:1.
According to clause 6,
A pharmaceutical composition, wherein the melanin pigmentation-related disease is freckles, freckles, senile pigment spots, or solar lentigines.
According to clause 6,
A pharmaceutical composition, wherein the extract is an ethanol extract.