WO2023167367A1 - 수용화 커큐민과 밀겨 추출물을 이용한 피부 미백 및 피부 주름 개선용 조성물 - Google Patents
수용화 커큐민과 밀겨 추출물을 이용한 피부 미백 및 피부 주름 개선용 조성물 Download PDFInfo
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- WO2023167367A1 WO2023167367A1 PCT/KR2022/006928 KR2022006928W WO2023167367A1 WO 2023167367 A1 WO2023167367 A1 WO 2023167367A1 KR 2022006928 W KR2022006928 W KR 2022006928W WO 2023167367 A1 WO2023167367 A1 WO 2023167367A1
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- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9794—Liliopsida [monocotyledons]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/30—Other Organic compounds
- A23V2250/31—Glutathione
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/59—Mixtures
- A61K2800/591—Mixtures of compounds not provided for by any of the codes A61K2800/592 - A61K2800/596
Definitions
- the present invention relates to a composition for skin whitening and wrinkle improvement using water-soluble curcumin and wheat bran extract.
- the skin occupies about 16% of the human body, and it is in direct contact with the external environment and plays an important role in protecting the human body from external harmful factors such as temperature, humidity and ultraviolet rays.
- the skin is composed of epidermis, dermis, and subcutaneous tissue under the keratin.
- the epidermis is a thin protective layer composed mainly of keratinocytes, melanocytes that produce and secrete melanin, immune cells such as Langerhans cells, and Merkel's copuscles. It prevents the invasion of external stimuli and pathogens, regulates body temperature, and maintains moisture and lipid components.
- Melanin is a phenolic polymeric natural pigment widely present in living organisms. In the human body, it is synthesized in melanosomes in melanocytes in the basal layer of the epidermis, and is transferred to surrounding keratinocytes to show human skin color. When melanin is abnormally low, skin lesions such as vitiligo are induced, and on the contrary, when it is produced in excess, acquired hyperpigmentation such as melasma, postinflammatory melanoderma, and solar lentigo It can cause various skin diseases, including
- melanin production uses tyrosine, one of the amino acids, as a substrate, and DOPA (3,4- After conversion to DOPA quinone through dihydroxyphenylalanine), melanin is synthesized by polymerization with amino acids or proteins after undergoing a non-enzymatic reaction and spontaneous oxidation process (Korean J. FOOD SCI. TECHNOL., 2000. 32(3):736;Journal of Life Science, 2013.
- cAMP/PKA cyclic monophosphate/protein kinase A pathway.
- cAMP promotes the expression of MITF via PKA and CREB1 (cAMP responsive element binding protein 1), and MITF plays an important role in melanin synthesis.
- PKA cyclic monophosphate/protein kinase A pathway.
- CREB1 cAMP responsive element binding protein 1
- MITF plays an important role in melanin synthesis.
- As a transcriptional regulator it promotes the transcription of tyrosinase, TRP-1 and TRP-2 (Pharmazie. 2015 Oct;70(10):646-9.; Int J Mol Sci. 2015 Oct 13;16(10):24219- 42; Curr Pharm Biotechnol. 2015;16(12):1111-9.).
- the skin occupies about 16% of the human body and is in direct contact with the external environment, so it plays an important role in protecting the human body from external harmful factors such as temperature, humidity and ultraviolet rays.
- the skin is composed of epidermis, dermis, and subcutaneous tissue under the keratin.
- the epidermis is a thin protective layer composed mainly of keratinocytes, melanocytes that produce and secrete melanin, immune cells such as Langerhans cells, and Merkel's copuscles. It prevents the invasion of external stimuli and pathogens, regulates body temperature, and maintains moisture and lipid components.
- the dermis is a connective tissue beneath the epidermis and is mostly composed of a network structure of macromolecules called the extracellular matrix. This extracellular matrix is made from fibroblasts and is composed of fibrous proteins such as collagen and elastin and polysaccharides such as hyaluronic acid.
- Collagen is the most important protein for maintaining skin moisture and maintaining skin flexibility and elasticity. It accounts for 90% of the dermal layer (J Am Acad Dermatol, 17(4):610-613. 2001) and provides strength and tension to the skin. It serves to protect the skin from external stimuli.
- elastin in the dermis layer accounts for about 2%, which is less than collagen, but plays a role in supporting collagen fibers, and many recent studies have reported that the deficiency, aggregation, and loss of elastin fibers play an important role in the mechanism of skin wrinkle formation. (Weihermann AC et al., Int J Cosmet Sci. 2017 Jun; 39(3): 241-247; Mora Huertas AC et al., Biochimie. 2016 Sep-Oct; 128-129: 163-73).
- Collagen and elastin are synthesized in fibroblasts and degraded by collagenase or elastase. As people age or are exposed to ultraviolet light, the activity and cell number of fibroblasts decrease, the amount of synthesis of collagen or elastin decreases, and the activity of collagenase or elastase that decomposes them increases. Once the elasticity of the skin by collagen and elastin is reduced, it is very difficult to recover.
- the present invention discloses tyrosinase inhibitory activity and collagen biosynthesis inhibitory activity of water-soluble curcumin and wheat bran extract.
- An object of the present invention is to provide a composition for skin whitening using water-soluble curcumin and wheat bran extract.
- Another object of the present invention is to provide a composition for improving skin wrinkles using water-soluble curcumin and wheat bran extract.
- the present invention found that water-soluble curcumin, wheat bran extract, and mixtures thereof inhibited the activity of tyronisase in a concentration-dependent manner and also inhibited the biosynthesis of collagen in human fibroblasts in a concentration-dependent manner. It is completed by confirming suppression.
- the present invention can be understood as a skin whitening composition containing water-soluble curcumin, wheat bran extract, or a mixture thereof as an active ingredient in one aspect, and water-soluble curcumin, wheat bran extract, or a mixture thereof in another aspect. It can be identified as a composition for improving skin wrinkles using the mixture as an active ingredient.
- water-soluble curcumin refers to a product obtained by suspending water-insoluble curcumin in water as a solvent (that is, maintained in a dispersed state without aggregation or precipitation in water as a solvent). At this time, in order to stabilize the dispersed particles and prevent their aggregation and precipitation, suspending agents may be added in appropriate amounts before and after mixing curcumin with water.
- suspending agent known in the art may be used, such as gum arabic, tragacanth gum, agar, karaya gum, locust bean gum, guar gum ( guar gum), xanthan gum, ghatti gum, water-soluble polymers such as pectin, cyclodextrin, glycerin or its fatty acid ester derivatives, methylcellulose or hydroxymethylcellulose, etc. Modified cellulose, various surfactants, and the like can be used. These suspending agents may be used alone or in combination of two or more, and may be used in an appropriate amount for suspending, specifically in the range of 2 to 100 parts by weight based on 100 parts by weight of curcumin.
- wheat bran extract refers to wheat bran to be extracted, water, lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, butanol, etc.), methylene chloride, ethylene, acetone, hexane, ether, chloroform, ethyl acetate, butyl acetate , N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), 1,3-butylene glycol, propylene glycol, or an extract obtained by leaching using a mixed solvent thereof, carbon dioxide, supercritical extraction solvents such as pentane It refers to an extract obtained by using or a fraction obtained by fractionating the extract, and the extraction method is any method such as cooling, reflux, heating, ultrasonic radiation, supercritical extraction, etc., in consideration of the polarity, extraction degree, and preservation degree of the active substance.
- the extraction method is any method such as cooling, reflux, heating, ultrasonic radiation, supercritical extraction, etc., in consideration of the polarity
- the fractionated extract after suspending the extract in a specific solvent, the fraction obtained by mixing and standing with a solvent of different polarity, and the crude extract are adsorbed on a column filled with silica gel, etc., and then a hydrophobic solvent, a hydrophilic solvent, or a mixed solvent thereof It is meant to include fractions obtained as a mobile phase.
- the meaning of the extract includes a concentrated liquid extract or solid extract from which the extraction solvent is removed by lyophilization, vacuum drying, hot air drying, spray drying, or the like.
- it refers to an extract obtained by using water, ethanol or a mixed solvent thereof as an extraction solvent, and more preferably a water (hot water) extract as an extraction solvent.
- the "wheat bran” means a by-product obtained in the process of milling wheat. These by-products usually consist of pericarp and germ, except for the endosperm, which becomes flour.
- the meaning of the "active ingredient” means a component that exhibits the desired activity alone or can exhibit activity in combination with a carrier having no activity itself.
- the composition of the present invention may contain the active ingredient in any amount (effective amount) as long as it can exhibit skin whitening effect, wrinkle improvement effect, etc. depending on the use, formulation, blending purpose, etc. It will be determined within the range of 0.001% by weight to 15% by weight as a reference.
- effective amount means intended medical and cosmetic effects such as skin whitening effect and wrinkle improvement effect when the composition of the present invention is administered to a mammal, preferably a human, to which the composition is applied, during the administration period according to the advice of medical experts, etc. It refers to the amount of the active ingredient included in the composition of the present invention, which can represent the like. Such an effective amount can be determined empirically within the ordinary skill of the skilled artisan.
- composition of the present invention has similar activities, such as skin whitening effect or skin wrinkle improvement effect, skin hypersensitivity reaction inhibitory activity, skin protection activity (suppression of skin damage by ultraviolet rays, skin moisturizing, etc.)
- skin whitening effect or skin wrinkle improvement effect skin hypersensitivity reaction inhibitory activity
- skin protection activity suppression of skin damage by ultraviolet rays, skin moisturizing, etc.
- any compound or natural extract known to have a corresponding activity and whose safety has already been verified in the art may be further included.
- ingredients include, for example, arbutin, niacinamide, ascorbyl glucoside, alpha-bisabolol, which are recognized as skin whitening ingredients in the Cosmetics Codex (Korean Ministry of Food and Drug Safety Notice, "Standards and Test Methods for Functional Cosmetics") in accordance with the Korean Cosmetics Act.
- Licorice extract Oil Soluble Licorice (Glycyrrhiza) Extract
- retinol retinyl palmitate
- adenosine polyethoxylated amide
- composition of the present invention can be regarded as a food composition.
- the food composition of the present invention can be prepared in any form, for example, beverages such as tea, juice, carbonated beverages, and ionic beverages, processed oils such as milk and yogurt, chewing gum, rice cakes, traditional Korean snacks, bread, snacks, noodles, etc. It can be manufactured into health functional food preparations such as foods, tablets, capsules, pills, granules, liquid, powder, flakes, pastes, syrups, gels, jellies, and bars.
- the food composition of the present invention may take any product classification as long as it conforms to the enforcement regulations at the time of manufacture and distribution in legal and functional classification.
- health functional food according to the Korean ⁇ Health Functional Food Act ⁇ , or snacks, legumes, teas, beverages according to each food type according to the Food Code (MFDS notification ⁇ Food Standards and Specifications ⁇ ) of the Korea ⁇ Food Sanitation Act ⁇ , special purpose foods, etc.
- MFDS notification ⁇ Food Standards and Specifications ⁇
- special purpose foods etc.
- the food composition of the present invention may include food additives in addition to the active ingredient.
- Food additives may generally be understood as substances that are added to, mixed with, or infiltrated into food in manufacturing, processing, or preserving food. Since food is consumed daily and for a long period of time, its safety must be guaranteed.
- Food Additives Code under the laws of each country governing the manufacture and distribution of food (in Korea, it is the ⁇ Food Sanitation Act ⁇ ), safety-guaranteed food additives are limitedly regulated in terms of ingredients or functions.
- Korean Food Additives Codex MFDS notification ⁇ Standards and Specifications for Food Additives ⁇
- food additives are classified into chemical synthetic products, natural additives and mixed preparations in terms of ingredients and are regulated. It is divided into additives, preservatives, emulsifiers, acidulants, and thickeners.
- Sweeteners are used to impart appropriate sweetness to foods, and both natural and synthetic sweeteners can be used in the composition of the present invention.
- a natural sweetener is used, and examples of the natural sweetener include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose, and maltose.
- Flavors may be used to improve taste or aroma, and both natural and synthetic flavors may be used. Preferably, it is the case of using a natural one. In case of using natural ones, in addition to flavor, the purpose of enhancing nutrition can also be combined.
- a natural flavoring agent it may be obtained from apples, lemons, tangerines, grapes, strawberries, peaches, etc., or obtained from green tea leaves, roundworms, bamboo leaves, cinnamon, chrysanthemum leaves, jasmine, and the like.
- those obtained from ginseng (red ginseng), bamboo shoots, aloe vera, ginkgo, etc. can be used.
- Natural flavors can be liquid concentrates or solid extracts. In some cases, synthetic flavors may be used, and synthetic flavors may include esters, alcohols, aldehydes, terpenes, and the like.
- sodium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate, EDTA (ethylenediaminetetraacetic acid), etc. may be used, and as emulsifiers, acacia gum, carboxymethylcellulose, xanthan gum, pectin and the like, and examples of the acidulant include acid salt, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid, and the like. Acidulants may be added to the food composition to have an appropriate acidity for the purpose of inhibiting the growth of microorganisms in addition to improving taste.
- a suspending agent As the thickening agent, a suspending agent, a sedimentation agent, a gel forming agent, a swelling agent, and the like may be used.
- the food composition of the present invention may include physiologically active substances or minerals known in the art and whose stability is guaranteed as food additives for the purpose of supplementing or reinforcing functionality and nutrition.
- physiologically active substances include catechins contained in green tea, vitamins such as vitamin B1, vitamin C, vitamin E, and vitamin B12, tocopherol, dibenzoylthiamine, and the like.
- minerals include calcium preparations such as calcium citrate and magnesium stearate. magnesium preparations such as the like, iron preparations such as iron citrate, chromium chloride, potassium iodine, selenium, germanium, vanadium, zinc, and the like.
- the food composition of the present invention may include the above-mentioned food additives in an appropriate amount to achieve the purpose of addition according to the type of product.
- composition of the present invention can be understood as a pharmaceutical composition in another specific aspect.
- composition for skin whitening of the present invention is understood as a pharmaceutical composition
- its use may be understood as a composition for improving skin hyperpigmentation.
- the pharmaceutical composition of the present invention may be formulated into an oral formulation or a parenteral formulation according to the route of administration by a conventional method known in the art, including a pharmaceutically acceptable carrier in addition to the active ingredient.
- the route of administration herein may be any appropriate route including topical route, oral route, intravenous route, intramuscular route, and direct absorption through mucosal tissue, and two or more routes may be used in combination.
- An example of a combination of two or more routes is a case in which two or more formulations of drugs are combined according to the route of administration, for example, one drug is firstly administered intravenously and the other drug is secondly administered through a topical route.
- Pharmaceutically acceptable carriers are well known in the art depending on the route of administration or dosage form, and specifically, reference may be made to the pharmacopoeia of each country including the "Korean Pharmacopoeia”.
- the pharmaceutical composition of the present invention is prepared as an oral dosage form, powder, granule, tablet, pill, dragee, capsule, liquid, gel, syrup, suspension, wafer according to a method known in the art together with a suitable carrier.
- suitable carriers include sugars such as lactose, glucose, sucrose, dextrose, sorbitol, mannitol, and xylitol, starches such as corn starch, potato starch, and wheat starch, cellulose, methylcellulose, ethylcellulose, sodium carboxymethylcellulose, Celluloses such as hydroxypropylmethylcellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, mineral oil, malt, gelatin, talc, polyol, vegetable oil, ethanol, glycerol etc.
- binders include starch, magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, glucose, corn sweetener, sodium alginate, polyethylene glycol, wax, and the like, and sodium oleate as a lubricant , sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, silica, talcum, stearic acid, magnesium salts and calcium salts thereof, polyethylene glycol, etc.
- disintegrants starch, methyl cellulose, agar, bentonite, xanthan gum, starch, alginic acid or its sodium salt, and the like.
- diluent examples include lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, and glycine.
- the pharmaceutical composition of the present invention when prepared as a parenteral formulation, it may be formulated in the form of an injection, transdermal administration, nasal inhalation, and suppository along with a suitable carrier according to a method known in the art.
- a suitable carrier such as phosphate buffered saline (PBS) containing triethanolamine, sterile water for injection, or 5% dextrose may be used.
- PBS phosphate buffered saline
- a transdermal formulation it may be formulated in the form of ointments, creams, lotions, gels, external solutions, pastas, liniments, air rolls, and the like.
- nasal inhalation it can be formulated in the form of an aerosol spray using a suitable propellant such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, etc., and when formulated as a suppository, the carrier is Witepsol ( witepsol), tween 61, polyethylene glycols, cacao fat, laurin fat, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, sorbitan fatty acid esters, and the like can be used.
- Witepsol witepsol
- tween 61 polyethylene glycols, cacao fat, laurin fat, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, sorbitan fatty acid esters, and the like can be used.
- the preferred dosage of the pharmaceutical composition of the present invention is in the range of 0.001 mg/kg to 10 g/kg per day, preferably 0.001 mg/kg to 1 g, depending on the patient's condition, weight, sex, age, severity of the patient, and route of administration. /kg range. Administration can be done once a day or divided into several times. These dosages should not be construed as limiting the scope of the present invention in any respect.
- composition of the present invention can be identified as a cosmetic composition.
- the cosmetic composition may be classified as an arbitrary product in terms of its use and law, and specifically, functional cosmetics and non-functional cosmetics with uses such as improving skin troubles and atopic dermatitis. It may be a general cosmetic or the like.
- product form it may take any product form, specifically, solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax It may take the form of a product such as foundation or spray.
- it may be a softening lotion, nutrient lotion, nutrient cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray or powder formulation.
- the cosmetic composition of the present invention may include, in addition to the active ingredient, ingredients commonly used in cosmetic compositions, for example, stabilizers, solubilizers, surfactants, vitamins, conventional adjuvants such as pigments and fragrances, and carriers.
- ingredients commonly used in cosmetic compositions for example, stabilizers, solubilizers, surfactants, vitamins, conventional adjuvants such as pigments and fragrances, and carriers.
- the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component.
- lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and in particular, in the case of a spray, additional chlorofluorohydrocarbon, propane / May contain a propellant such as butane or dimethyl ether.
- a solvent, solubilizing agent or emulsifying agent is used as a carrier component, specifically water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic esters, polyethylene glycol, fatty acid esters of sorbitan, and the like may be used.
- the formulation of the present invention is a suspension
- a liquid diluent such as water, ethanol or propylene glycol
- a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, or polyoxyethylene sorbitan ester, microcrystals Star cellulose, aluminum metahydroxide, bentonite, agar, and the like can be used.
- the formulation of the present invention is surfactant-containing cleansing
- carrier components aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.
- the cosmetic composition of the present invention may be prepared according to a method for preparing a cosmetic composition conventionally performed in the art, except for including an active ingredient exhibiting skin whitening activity.
- composition for skin whitening or wrinkle improvement using water-soluble curcumin and wheat bran extract can be provided.
- the composition for skin whitening and the composition for improving skin wrinkles of the present invention can be commercialized as pharmaceuticals, functional foods, and the like.
- 1 to 3 are evaluation results of tyrosinase inhibitory activity.
- Water-soluble curcumin was prepared using the method disclosed in Korean Patent Registration No. 10-2177749 (Name: Method for preparing turmeric extract powder (curcumin) using turmeric and curcumin colloidal dispersion prepared thereby). Specifically, 100 parts by weight of curcumin powder extracted from turmeric was added to 3,000 parts by weight of purified water (based on 100 parts by weight of curcumin powder), followed by 0.3 parts by weight of xanthan gum (based on 100 parts by weight of curcumin powder) and 3.0 parts by weight of glycerin (based on 100 parts by weight of curcumin powder). parts by weight) was added and dispersed at a stirring speed of 4,500 rpm for 20 hours to prepare water-soluble curcumin as a curcumin dispersion. A mixture of water-soluble curcumin and wheat bran extract was prepared by dissolving 5 parts by weight of wheat bran extract powder based on 100 parts by weight of the dispersion in the thus prepared curcumin dispersion.
- the wheat bran extract is obtained by adding 20 times the weight of water to wheat bran powder, extracting by heating at a temperature of 80 to 100 ° C. for 6 hours, and then concentrating and freeze-drying under reduced pressure to prepare a powder.
- the whitening activity test was performed by measuring the tyrosinase inhibitory activity. Specifically, 20 uL of the sample for each concentration of the embodiment and 20 uL of mushroom tyrosinase (125 U) were added to 60 uL of potassium phosphate buffer (pH 6.8) containing 10 mM L-DOPA as a substrate and reacted at 37 ° C. for 10 minutes Absorbance was measured at 492 nm using an absorbance photometer. The tyrosinase inhibitory activity results were obtained as a percentage compared to the sample untreated group, and the results are shown in FIGS. 1 to 3.
- HDFn cells human dermal fibroblast neonatal cells
- DMEM medium Dulbeco's modified eagle's medium
- FBS fetal bovine serum
- penicillin/streptomycin 100 U/ mL
- each of the samples in Examples promoted collagen biosynthesis in a concentration-dependent manner, and in particular, the mixture of water-soluble curcumin and wheat bran extract had a high collagen biosynthesis promoting effect.
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Abstract
본 발명은, 티로니사아제의 활성을 농도 의존적으로 저해하고, 또한 인간섬유아세포에서 콜라겐의 생합성을 농도 의존적으로 억제 활성을 가진 수용화 커큐민, 밀겨 추출물 또는 이들의 혼합물을 이용한 피부 미백 및 피부 주름 개선용 조성물을 개시한다.
Description
본 발명은 수용화 커큐민과 밀겨 추출물을 이용한 피부 미백 및 피부 주름 개선용 조성물에 관한 것이다.
의학기술의 발달과 생활수준의 향상으로 사람들의 아름다움에 대한 욕구가 강해지고 외모 자체가 하나의 사회적 경쟁력이라는 인식도 증가하고 있어 피부 미백, 피부 주름 개선 등에 대한 선호도가 높아지고 화장품 시장이 확대되고 있다(J. Korean Soc. Food Sci. Nutr., 42(3):355 (2013)).
피부는 인체의 약 16%를 차지하고 있으며, 외부환경과 직접적으로 접해 있어 온도, 습도 및 자외선 등과 같은 외부 유해인자들로부터 인체를 보호하는 중요한 역할을 하고 있다. 피부는 각질 아래 표피, 진피, 피하조직으로 구성되어 있다. 표피는 주로 케라틴으로 되어 있는 케라티노사이트(keratinocytes), 멜라닌을 생성하고 분비하는 멜라닌 세포(melanocytes), 랑게르한스 세포(langerhans cells) 등의 면역세포 그리고 지각관련세포 (Merkel's copuscles)로 구성되는 얇은 보호층으로 외부자극과 병원균의 침입을 방지하고 체온조절, 수분과 지질 성분 유지 작용을 한다.
멜라닌은 생물체에 널리 존재하는 페놀류 고분자 천연 색소로 인체에서는 표피 기저층에 있는 멜라린 세포(melanocyte) 내의 멜라노솜(melanosome)에서 합성되며 주변 각질 세포로 전이되어 사람의 피부색을 나타낸다. 멜라닌이 비정상적으로 적게 되면 백반증과 같은 피부 병변이 유발되며, 반대로 과잉으로 생산될 경우에는 흑피증(melasma), 염증후흑피증(postinflammatory melanoderma), 일광흑색점(solar lentigo) 등과 같은 후천성 과다색소침착증을 포함하는 다양한 피부질환을 유발할 수 있다.
멜라닌의 합성은 피부의 기저층에 존재하는 멜라노사이트(melanocyte)에서 멜라닌소체(melanosome)를 만들어 이루어지며 멜라닌이 합성되는 일련의 과정을 총칭하여 멜라닌 생성 경로(melanogenesis)라 한다. 멜라닌 생성은 아미노산의 하나인 티로신(tyrosine)을 기질로 하며, 티로시나제(tyrosinase), TRP-1(tyrosinase related protein-1), TRP-2(tyrosinase related protein-2)에 의해 DOPA(3,4-dihydroxyphenylalanine)를 거쳐 도파 퀴논(DOPA quinone)으로 전환된 후 비효소적 반응, 자발적 산화 과정을 거친 후 아미노산 혹은 단백질과의 중합 반응에 의해 멜라닌이 합성된다(Korean J. FOOD SCI. TECHNOL., 2000. 32(3):736; Journal of Life Science, 2013. 23(12):1445; Pigment Cell Res.1999. 12(1):4-12.). 최근에는 티로시나제, TRP-1, TRP-2뿐만 아니라 MITF(microphtalmia associated transcription factor) 등과 같은 단백질을 이용하여 멜라닌 합성 억제에 대한 연구도 이루어지고 있다. 주요한 세포 내 신호전달 경로는 cAMP/PKA(cyclic monophosphate/protein kinase A) 경로로서, cAMP는 PKA, CREB1(cAMP responsive element binding protein 1)을 경유하여 MITF의 발현을 촉진하며 MITF는 멜라닌 합성 과정에서 중요한 전사 조절 인자로 티로시나제, TRP-1, TRP-2의 전사를 촉진한다(Pharmazie. 2015 Oct;70(10):646-9.; Int J Mol Sci. 2015 Oct 13;16(10):24219-42; Curr Pharm Biotechnol. 2015;16(12):1111-9.).
멜라닌을 생성하는 첫 단계로 티로시나아제가 가장 중요한 역할을 하기 때문에 미백제에 대한 연구는 주로 티로시나아제(tyrosinase) 활성을 조절하기 위하여 티로시나아제 활성 저해 물질이나 티로시나아제의 기질에 대한 길항물질을 개발하는 방향으로 연구가 진행되어 왔다(Kor. J. Pharmacogn., 44(3):220, 2013).
피부는 인체의 약 16 %를 차지하고 있으며, 외부환경과 직접적으로 접해 있어 온도, 습도 및 자외선 등과 같은 외부 유해인자들로부터 인체를 보호하는 중요한 역할을 하고 있다. 피부는 각질 아래 표피, 진피, 피하조직으로 구성되어 있다. 표피는 주로 케라틴으로 되어 있는 케라티노사이트(keratinocytes), 멜라닌을 생성하고 분비하는 멜라닌 세포(melanocytes), 랑게르한스 세포(langerhans cells) 등의 면역세포 그리고 지각관련세포 (Merkel's copuscles)로 구성되는 얇은 보호층으로 외부자극과 병원균의 침입을 방지하고 체온조절, 수분과 지질 성분 유지 작용을 한다. 진피는 표피 아래에 있는 결합조직으로 대부분 세포외 간질(extracellular matrix)이라 불리는 거대 분자의 망상 구조로 구성되어 있다. 이 세포외 간질은 섬유아세포에서 만들어지며, 콜라겐, 엘라스틴 등의 섬유상 단백질과 히알루론산 등의 다당체로 이루어져 있다.
나이가 들어감에 따라 각종 오염물질, 강한 자외선, 스트레스 및 영양결핍 등으로 인해 피부 세포들이 손상을 입게 되고, 세포 증식이 원활하게 되지 않아 피부에 주름, 탄력 손실, 색소 침착 및 각질화 등이 발생한다(Gilchrest B.A., J. Am. Acad. Dermatol, 21, 610. 1989).
콜라겐은 피부 수분을 유지하고 피부 유연성과 탄력을 유지하는 데 가장 중요한 단백질로 진피층의 90%를 차지하고 있으며(J Am Acad Dermatol, 17(4):610-613. 2001) 피부의 강도와 장력을 부여하여 외부의 자극으로부터 피부를 보호하는 역할을 한다. 또한 진피층의 엘라스틴은 2% 정도를 차지하고 있어 콜라겐보다는 적은 양이지만, 콜라겐 섬유를 지탱하는 역할을 하고 있으며 엘라스틴 섬유의 결핍과 응집, 소실이 피부 주름 형성 기전에서 중요한 역할을 하는 것으로 최근 많은 연구에서 보고되고 있다(Weihermann AC et al., Int J Cosmet Sci. 2017 Jun;39(3):241-247; Mora Huertas AC et al., Biochimie. 2016 Sep-Oct;128-129:163-73).
콜라겐과 엘라스틴은 섬유아세포에서 합성되며 콜라겐나아제(collagenase) 또는 엘라스타아제(elastase)에 의해 분해된다. 나이가 들거나 자외선 등에 노출되면 섬유아세포의 작용과 세포 수가 감소하여 콜라겐 또는 엘라스틴의 합성량이 줄어들고 이들을 분해하는 콜라겐나아제 또는 엘라스타아제의 작용이 증가하게 된다. 콜라겐과 엘라스틴에 의한 피부의 탄력성은 한번 감소하고 난 후 회복하기가 매우 어렵다.
현재 피부 주름형성을 억제하는 물질로는 레티노익산과 레티놀(Simon C et al., J Invest Dermatol 98: 248-260. 1992; Elaine S et al., J Invest Dermatol 96: 975-978. 1991)의 효과가 입증되어 있고, dehydroepiandrosterone(Shin MH et al., J Invest Dermatol 124: 315-323.2005), 인삼에서 추출한 ginsenoside Rg3(Kim SW et al., J Soc Cosmet Scientists Korea 30: 221-225.2004), 플라보노이드(Francesco B et al., Int J Pharm 145: 87-94.1996), 팥배나무 추출물(한국등록특허 제 101008833호), 연교 추출물(한국등록특허 제 100825450호)등 다양한 물질의 주름 개선 및 피부 보호효과가 탐색되었다. 그러나 일부 물질들은 안정성이 낮거나 피부 자극을 일으켜 안전성에 문제가 있기 때문에 사용에 제한이 있다. 이에 따라 우수한 주름개선 활성 효과와 안전성 및 안정성을 지닌 물질의 탐색이 지속되고 있다.
본 발명은 수용화 커큐민과 밀겨 추출물의 티로시나아제 저해 활성과 콜라겐 생합성 저해 활성을 개시한다.
본 발명의 목적은 수용화 커큐민과 밀겨 추출물을 이용한 피부 미백용 조성물을 제공하는 데 있다.
본 발명의 다른 목적은 수용화 커큐민과 밀겨 추출물을 이용한 피부 주름 개선용 조성물을 제공하는 데 있다.
본 발명의 또 다른 목적이나 구체적인 목적은 이하에서 제시될 것이다.
본 발명은 아래의 실시예 및 실험예에서 확인되는 바와 같이 수용화 커큐민과 밀겨 추출물 그리고 이들의 혼합물이 티로니사아제의 활성을 농도 의존적으로 저해하고, 또한 인간섬유아세포에서 콜라겐의 생합성을 농도 의존적으로 억제함을 확인함으로써 완성된 것이다.
전술한 바를 고려할 때, 본 발명은 일 측면에 있어서 수용화 커큐민, 밀겨 추출물 또는 이들의 혼합물을 유효성분으로 하는 피부 미백용 조성물로 파악할 수 있고, 다른 측면에 있어서는 수용화 커큐민, 밀겨 추출물 또는 이들의 혼합물을 유효성분으로 하는 피부 주름 개선용 조성물로 파악할 수 있다.
본 명세서에서, 수용화 커큐민은 수불용성인 커큐민을 용매인 물에 현탁시켜 얻어진 것(즉 용매인 물에서 응집·침전하지 않고 분산된 상태가 유지되도록 한 것)을 말한다. 이때 분산된 입자를 안정화시켜 그 응집·침전을 방지하기 위하여 현탁화제(suspending agents)가 커큐민의 물과의 혼합 전후 적량으로 첨가될 수 있다. 현탁화제는 당업계에 공지된 임의의 것을 사용할 수 있는데, 예컨대 아라비아 검, 트라가칸트 검(tragacanth gum), 한천, 카라야 검(karaya gum), 로커스트빈 검(locust bean gum), 구아검(guar gum), 잔탄검(xanthan gum), 가티검(ghatti gum), 펙틴(pectin) 등의 수용성 고분자, 사이클로덱스트린(cyclodextrin), 글리세린이나 그것의 지방산 에스테르 유도체, 메칠셀룰로오스나 히드록시메칠셀룰로오스 등의 변형된 셀룰로오스(modified cellulose), 각종 계면활성제 등을 사용할 수 있다. 이들 현탁화제는 단독으로 또는 2종 이상 혼합하여 사용할 수 있으며, 현탁화를 위한 적량으로, 구체적으로 커큐민 100 중량 기준 2 내지 100 중량부의 범위로 사용할 수 있다.
또 본 명세서에서, "밀겨 추출물"이란 추출 대상인 밀겨를 물, 탄소수 1 내지 4의 저급 알콜(메탄올, 에탄올, 부탄올 등), 메틸렌클로라이드, 에틸렌, 아세톤, 헥산, 에테르, 클로로포름, 에틸아세테이트, 부틸아세테이트, N,N-디메틸포름아미드(DMF), 디메틸설폭사이드(DMSO), 1,3-부틸렌글리콜, 프로필렌글리콜 또는 이들의 혼합 용매를 사용하여 침출하여 얻어진 추출물, 이산화탄소, 펜탄 등 초임계 추출 용매를 사용하여 얻어진 추출물 또는 그 추출물을 분획하여 얻어진 분획물을 의미하며, 추출 방법은 활성물질의 극성, 추출 정도, 보존 정도를 고려하여 냉침, 환류, 가온, 초음파 방사, 초임계 추출 등 임의의 방법을 적용할 수 있다. 분획된 추출물의 경우 추출물을 특정 용매에 현탁시킨 후 극성이 다른 용매와 혼합·정치시켜 얻은 분획물, 상기 조추출물을 실리카겔 등이 충진된 칼럼에 흡착시킨 후 소수성 용매, 친수성 용매 또는 이들의 혼합 용매를 이동상으로 하여 얻은 분획물을 포함하는 의미이다. 또한 상기 추출물의 의미에는 동결건조, 진공건조, 열풍건조, 분무건조 등의 방식으로 추출 용매가 제거된 농축된 액상의 추출물 또는 고형상의 추출물이 포함된다. 바람직하게는 추출용매로서 물, 에탄올 또는 이들의 혼합 용매를 사용하여 얻어진 추출물, 더 바람직하게는 추출용매로서 물(열수) 추출물을 의미한다.
또 본 명세서에서, 상기 "밀겨"는 밀(wheat)을 도정하는 과정에서 얻어지는 부산물을 의미한다. 이러한 부산물은 통상 밀가루가 되는 배유를 제외하고 과피와 배아로 구성되게 된다.
또 본 명세서에서, 상기 "유효성분"의 의미는 단독으로 목적하는 활성을 나타내거나 또는 그 자체는 활성이 없는 담체와 함께 활성을 나타낼 수 있는 성분을 의미한다.
본 발명의 조성물은 그 유효성분을 용도, 제형, 배합 목적 등에 따라 피부 미백 효과, 주름 개선 효과 등을 나타낼 수 있는 한 임의의 양(유효량)으로 포함할 수 있는데, 통상적인 유효량은 조성물 전체 중량을 기준으로 할 때 0.001 중량 % 내지 15 중량 % 범위 내에서 결정될 것이다. 여기서 "유효량"이란 그 적용 대상인 포유동물 바람직하게는 사람에게 의료 전문가 등의 제언에 의한 투여 기간 동안 본 발명의 조성물이 투여될 때, 피부 미백 효과, 주름 개선 효과 등 의도한 의료적·화장품학적 효과 등을 나타낼 수 있는, 본 발명의 조성물에 포함되는 유효성분의 양을 말한다. 이러한 유효량은 당업자의 통상의 능력 범위 내에서 실험적으로 결정될 수 있다.
본 발명의 조성물은 유효성분 이외에, 피부 미백 효과 또는 피부 주름 개선 효과의 상승·보강 등을 위하여 또는 피부 과민 반응 억제 활성, 피부 보호 활성(자외선에 의한 피부 손상 억제, 피부 보습 등) 등 유사활성의 부가를 통한 복용이나 섭취, 사용의 편리성 증진을 위하여, 당업계에서 이미 안전성이 검증되고 해당 활성을 갖는 것으로 공지된 임의의 화합물이나 천연 추출물을 추가로 포함할 수 있다.
이러한 화합물 또는 추출물에는 각국 약전(한국에서는 "대한민국약전"), 각국 건강기능식품공전(한국에서는 식약처 고시인 "건강기능식품 기준 및 규격"), 각국 기능성화장품공전(한국에서는 식약처 고시인 "기능성화장품 기준 및 시험방법") 등의 공정서에 실려 있는 화합물 또는 추출물, 의약품의 제조·판매를 규율하는 각국의 법률(한국에서는 "약사법")에 따라 품목 허가를 받은 화합물 또는 추출물, 건강기능식품의 제조·판매를 규율하는 각국 법률(한국에서는 "건강기능식품에관한법률")에 따라 기능성이 인정된 화합물 또는 추출물, 기능성 화장품의 제조·판매를 규율하는 각국 법률(한국에서는 "화장품법")에 따라 기능성이 인정된 화합물 또는 추출물이 포함된다.
이러한 성분들로서는 예컨대 한국 화장품법에 따른 화장품공전(한국 식약처 고시, "기능성화장품의 기준 및 시험방법")에서 피부 미백 성분으로 인정된 알부틴, 나이아신아마이드, 아스코빌글루코사이드, 알파-비사보롤, 유용성 감초 추출물(Oil Soluble Licorice(Glycyrrhiza) Extract) 등과, 또 같은 한국 화장품공전에서 피부 주름 개선 성분으로 인정된 레티놀, 레티닐팔미테이트, 아데노신, 폴리에톡실레이티드아마이드 등과, 또 같은 한국 화장품공전에서 자외선 보호 성분으로 인정된 드로메트리졸, 드로메트리졸트리실록산, 디갈로일트리올리에이트, 디메치코디에칠벤잘말로네이트, 디에칠헥실부타미도트리아존 등과, 한국 "건강기능식품에관한법률"에 따라 자외선 보호 성분으로 인정된 소나무 껍질 추출물 등의 복합물, 포스파티딜세린, 핑거루트 추출 분말, 홍삼과 산수유 등의 복합 추출물 등을 들 수 있고, 또한 한국 "건강기능식품에관한법률"에 따라 과민피부상태 개선 기능성 성분으로 인정된 L. sakei Probio 65, 감마리놀렌산 함유 유지, 과채 유래 유산균인 L.plantarum CJLP133, 프로바이오틱스 ATP 등을 들 수 있다. 이러한 화합물 또는 천연 추출물은 본 발명의 조성물에 그 유효성분과 함께 하나 이상 포함될 수 있다.
본 발명의 조성물은 구체적인 양태에 있어서, 식품 조성물로서 파악할 수 있다.
본 발명의 식품 조성물은 어떠한 형태로도 제조될 수 있으며, 예컨대 차, 쥬스, 탄산음료, 이온음료 등의 음료류, 우유, 요구르트 등의 가공 유류, 껌류, 떡, 한과, 빵, 과자, 면 등의 식품류, 정제, 캡슐, 환, 과립, 액상, 분말, 편상, 페이스트상, 시럽, 겔, 젤리, 바 등의 건강기능식품 제제류 등으로 제조될 수 있다.
또 본 발명의 식품 조성물은 법률상·기능상의 구분에 있어서 제조·유통 시점의 시행 법규에 부합하는 한 임의의 제품 구분을 띨 수 있다. 예컨대 한국 「건강기능식품에관한법률」에 따른 건강기능식품이거나, 한국 「식품위생법」의 식품공전(식약처 고시 「식품의 기준 및 규격」)상 각 식품유형에 따른 과자류, 두류, 다류, 음료류, 특수용도식품 등일 수 있다.
본 발명의 식품 조성물에는 그 유효성분 이외에 식품첨가물이 포함될 수 있다. 식품첨가물은 일반적으로 식품을 제조, 가공 또는 보존함에 있어 식품에 첨가되어 혼합되거나 침윤되는 물질로서 이해될 수 있는데, 식품과 함께 매일 그리고 장기간 섭취되므로 그 안전성이 보장되어야 한다. 식품의 제조·유통을 규율하는 각국 법률(한국에서는 「식품위생법」임)에 따른 식품첨가물공전에는 안전성이 보장된 식품첨가물이 성분 면에서 또는 기능 면에서 한정적으로 규정되어 있다. 한국 식품첨가물공전(식약처 고시 「식품첨가물 기준 및 규격」)에서는 식품첨가물이 성분 면에서 화학적 합성품, 천연 첨가물 및 혼합 제제류로 구분되어 규정되어 있는데, 이러한 식품첨가물은 기능 면에 있어서는 감미제, 풍미제, 보존제, 유화제, 산미료, 점증제 등으로 구분된다.
감미제는 식품에 적당한 단맛을 부여하기 위하여 사용되는 것으로, 천연의 것이거나 합성된 것 모두 본 발명의 조성물에 사용할 수 있다. 바람직하게는 천연 감미제를 사용하는 경우인데, 천연 감미제로서는 옥수수 시럽 고형물, 꿀, 수크로오스, 프룩토오스, 락토오스, 말토오스 등의 당 감미제를 들 수 있다.
풍미제는 맛이나 향을 좋게 하기 위하여 사용될 수 있는데, 천연의 것과 합성된 것 모두 사용될 수 있다. 바람직하게는 천연의 것을 사용하는 경우이다. 천연의 것을 사용할 경우에 풍미 이외에 영양 강화의 목적도 병행할 수 있다. 천연 풍미제로서는 사과, 레몬, 감귤, 포도, 딸기, 복숭아 등에서 얻어진 것이거나 녹차잎, 둥굴레, 댓잎, 계피, 국화 잎, 자스민 등에서 얻어진 것일 수 있다. 또 인삼(홍삼), 죽순, 알로에 베라, 은행 등에서 얻어진 것을 사용할 수 있다. 천연 풍미제는 액상의 농축액이나 고형상의 추출물일 수 있다. 경우에 따라서 합성 풍미제가 사용될 수 있는데, 합성 풍미제는 에스테르, 알콜, 알데하이드, 테르펜 등이 이용될 수 있다.
보존제로서는 소듐 소르브산칼슘, 소르브산나트륨, 소르브산칼륨, 벤조산칼슘, 벤조산나트륨, 벤조산칼륨, EDTA(에틸렌디아민테트라아세트산) 등이 사용될 수 있고, 또 유화제로서는 아카시아검, 카르복시메틸셀룰로스, 잔탄검, 펙틴 등을 들 수 있으며, 산미료로서는 연산, 말산, 푸마르산, 아디프산, 인산, 글루콘산, 타르타르산, 아스코르브산, 아세트산, 인산 등이 사용될 수 있다. 산미료는 맛을 증진시키는 목적 이외에 미생물의 증식을 억제할 목적으로 식품 조성물이 적정 산도로 되도록 첨가될 수 있다.
점증제로서는 현탁화 구현제, 침강제, 겔 형성제, 팽화제 등이 사용될 수 있다.
본 발명의 식품 조성물은 전술한 바의 식품첨가물 이외에, 기능성과 영양성을 보충, 보강할 목적으로 당업계에 공지되고 식품첨가물로서 안정성이 보장된 생리활성 물질이나 미네랄류를 포함할 수 있다.
그러한 생리활성 물질로서는 녹차 등에 포함된 카테킨류, 비타민 B1, 비타민 C, 비타민 E, 비타민 B12 등의 비타민류, 토코페롤, 디벤조일티아민 등을 들 수 있으며, 미네랄류로서는 구연산 칼슘 등의 칼슘 제제, 스테아린산마그네슘 등의 마그네슘 제제, 구연산철 등의 철 제제, 염화 크롬, 요오드칼륨, 셀레늄, 게르마늄, 바나듐, 아연 등을 들 수 있다.
본 발명의 식품 조성물에는 전술한 바의 식품첨가물이 제품 유형에 따라 그 첨가 목적을 달성할 수 있는 적량으로 포함될 수 있다.
본 발명의 식품 조성물에 포함될 수 있는 기타의 식품첨가물과 관련하여서는 각국 식품공전이나 식품첨가물 공전을 참조할 수 있다.
본 발명의 조성물은 다른 구체적인 양태에 있어서는 약제학적 조성물로 파악될 수 있다. 본 발명의 피부 미백용 조성물이 약제학적 조성물로 파악될 경우, 그 용도는 피부 과색소 침착증 개선용 조성물로 이해될 수 있다.
본 발명의 약제학적 조성물은 유효성분 이외에 약제학적으로 허용되는 담체를 포함하여 당업계에 공지된 통상의 방법으로 투여 경로에 따라 경구용 제형 또는 비경구용 제형으로 제조될 수 있다. 여기서 투여 경로는 국소 경로, 경구 경로, 정맥 내 경로, 근육 내 경로, 및 점막 조직을 통한 직접 흡수를 포함하는 임의의 적절한 경로일 수 있으며, 두 가지 이상의 경로를 조합하여 사용할 수도 있다. 두 가지 이상 경로의 조합의 예는 투여 경로에 따른 두 가지 이상의 제형의 약물이 조합된 경우로서 예컨대 1차로 어느 한 약물은 정맥 내 경로로 투여하고 2차로 다른 약물은 국소 경로로 투여하는 경우이다.
약학적으로 허용되는 담체는 투여 경로나 제형에 따라 당업계에 주지되어 있으며, 구체적으로는 "대한민국약전"을 포함한 각국의 약전을 참조할 수 있다.
본 발명의 약제학적 조성물이 경구용 제형으로 제조될 경우, 적합한 담체와 함께 당업계에 공지된 방법에 따라 분말, 과립, 정제, 환제, 당의정제, 캡슐제, 액제, 겔제, 시럽제, 현탁액, 웨이퍼 등의 제형으로 제조될 수 있다. 이때 적합한 담체의 예로서는 락토스, 글루코스, 슈크로스, 덱스트로스, 솔비톨, 만니톨, 자일리톨 등의 당류, 옥수수 전분, 감자 전분, 밀 전분 등의 전분류, 셀룰로오스, 메틸셀룰로오스, 에틸셀룰로오스, 나트륨 카르복시메틸셀룰로오스, 하이드록시프로필메틸셀룰로오스 등의 셀룰로오스류, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 마그네슘 스테아레이트, 광물유, 맥아, 젤라틴, 탈크, 폴리올, 식물성유, 에탄올, 글리세롤 등을 들 수 있다. 제제화할 경우 필요에 따라적절한 결합제, 윤활제, 붕해제, 착색제, 희석제 등을 포함시킬 수 있다. 적절한 결합제로서는 전분, 마그네슘 알루미늄 실리케이트, 전분 페이스트, 젤라틴, 메틸셀룰로스, 소듐 카복시메틸셀룰로스, 폴리비닐피롤리돈, 글루코스, 옥수수 감미제, 소듐 알지네이트, 폴리에틸렌 글리콜, 왁스 등을 들 수 있고, 윤활제로서는 올레산나트륨, 스테아르산나트륨, 스테아르산마그네슘, 벤조산나트륨, 초산나트륨, 염화나트륨, 실리카, 탈쿰, 스테아르산, 그것의 마그네슘염과 칼슘염, 폴리데틸렌글리콜 등을 들 수 있으며, 붕해제로서는 전분, 메틸 셀룰로스, 아가(agar), 벤토나이트, 잔탄검, 전분, 알긴산 또는 그것의 소듐 염 등을 들 수 있다. 또 희석제로서는 락토즈, 덱스트로즈, 수크로즈, 만니톨, 소비톨, 셀룰로스, 글라이신 등을 들 수 있다.
본 발명의 약제학적 조성물이 비경구용 제형으로 제조될 경우, 적합한 담체와 함께 당업계에 공지된 방법에 따라 주사제, 경피 투여제, 비강 흡입제 및 좌제의 형태로 제제화될 수 있다. 주사제로 제제화할 경우 적합한 담체로서는 수성 등장 용액 또는 현탁액을 사용할 수 있으며, 구체적으로는 트리에탄올 아민이 함유된 PBS(phosphate buffered saline)나 주사용 멸균수, 5% 덱스트로스 같은 등장 용액 등을 사용할 수 있다. 경피 투여제로 제제화할 경우 연고제, 크림제, 로션제, 겔제, 외용액제, 파스타제, 리니멘트제, 에어롤제 등의 형태로 제제화할 수 있다. 비강 흡입제의 경우 디클로로플루오로메탄, 트리클로로플루오로메탄, 디클로로테트라플루오로에탄, 이산화탄소 등의 적합한 추진제를 사용하여 에어로졸 스프레이 형태로 제제화할 수 있으며, 좌제로 제제화할 경우 그 담체로는 위텝솔(witepsol), 트윈(tween) 61, 폴리에틸렌글리콜류, 카카오지, 라우린지, 폴리옥시에틸렌 소르비탄 지방산 에스테르류, 폴리옥시에틸렌 스테아레이트류, 소르비탄 지방산 에스테르류 등을 사용할 수 있다.
약제학적 조성물의 구체적인 제제화와 관련하여서는 당업계에 공지되어 있으며, 예컨대 문헌[Remington's Pharmaceutical Sciences(19th ed., 1995)] 등을 참조할 수 있다. 상기 문헌은 본 명세서의 일부로서 간주 된다.
본 발명의 약제학적 조성물의 바람직한 투여량은 환자의 상태, 체중, 성별, 연령, 환자의 중증도, 투여 경로에 따라 1일 0.001mg/kg ~ 10g/kg 범위, 바람직하게는 0.001mg/kg ~ 1g/kg 범위일 수 있다. 투여는 1일 1회 또는 수회로 나누어 이루어질 수 있다. 이러한 투여량은 어떠한 측면으로든 본 발명의 범위를 제한하는 것으로 해석되어서는 아니 된다.
본 발명의 조성물은 또 다른 구체적인 양태에 있어서, 화장료 조성물로 파악할 수 있다.
본 발명의 조성물이 화장료 조성물로 파악될 경우에도 그 화장료 조성물은 그 용도상, 법률상 임의의 제품 구분을 띨 수 있으며, 구체적으로 피부 트러블 개선, 아토피 피부염 개선 등의 용도를 가진 기능성 화장품, 비기능성 일반 화장품 등일 수 있다. 제품 형태에 있어서도 임의의 제품 형태를 띨 수 있는데, 구체적으로 용액, 현탁액, 유탁액, 페이스트, 젤, 크림, 로션, 파우더, 비누, 계면활성제-함유 클렌징, 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션, 스프레이 등의 제품 형태를 띨 수 있다. 구체적인 제품 형태에 있어서는 유연 화장수, 영양 화장수, 영양 크림, 마사지 크림, 에센스, 아이 크림, 클렌징 크림, 클렌징 포옴, 클렌징 워터, 팩, 스프레이 또는 파우더의 제형 등일 수 있다.
본 발명의 화장료 조성물은 그 유효성분 이외에 화장료 조성물에 통상적으로 이용되는 성분들, 예컨대, 안정화제, 용해화제, 계면활성제, 비타민, 색소 및 항료와 같은 통상적인 보조제, 및 담체를 포함할 수 있다.
본 발명의 제형이 페이스트, 크림 또는 젤인 경우에는 담체 성분으로서 동물성유, 식물성유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있다.
본 발명의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다.
본 발명의 제형이 용액 또는 유탁액인 경우에는 담체 성분으로서 용매, 용해화제 또는 유탁화제가 이용되는데, 구체적으로 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌 글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜, 소르비탄의 지방산 에스테르 등이 이용될 수 있다.
본 발명의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상의 희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르, 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 등이 이용될 수 있다.
본 발명의 제형이 계면-활성제 함유 클렌징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성 유, 라놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.
본 발명의 화장료 조성물은 피부 미백 활성 등을 나타내는 그 유효성분을 포함하는 것을 제외하고는 당업계에 통상적으로 행하여지는 화장료 조성물의 제조방법에 따라 제조할 수 있다.
전술한 바와 같이, 본 발명에 따르면 수용화 커큐민과 밀겨 추출물을 이용한 피부 미백용 또는 피부 주름 개선용 조성물을 제공할 수 있다. 본 발명의 피부 미백용 조성물과 피부 주름 개선용 조성물은 약품, 기능성 식품 등으로 제품화될 수 있다.
도 1 내지 도 3은 티로시나아제 저해 활성 평가 결과이다.
도 4 내지 6은 콜라겐 생합성 정도의 평가 결과이다.
도 7은 세포독성 평가 결과이다.
이하 본 발명을 실시예 및 실험예를 참조하여 설명한다. 그러나 본 발명의 범위가 이러한 실시예 및 실험예에 한정되는 것은 아니다.
<실시예> 수용화 커큐민과 밀겨 추출물의 혼합물 제조
수용화 커큐민은 한국 등록특허 제10-2177749호(명칭: 강황을 이용한 강황 추출물 분말(커큐민)의 제조방법 및 이에 의해 제조된 커큐민 콜로이드 분산액)에 개시된 방법을 이용하여 제조하였다. 구체적으로 강황에서 추출하여 얻은 커큐민 분말 100 중량부를, 정제수 3,000 중량부(커큐민 분말 100 중량부 기준)에 넣은 후 잔탄검 0.3 중량부(커큐민 분말 100 중량부 기준) 및 글리세린 3.0 중량부(커큐민 분말 100 중량부 기준)를 첨가하고 20시간 동안 4,500rpm의 교반 속도로 분산시켜 커큐민 분산액으로 수용화 커큐민을 제조하였다. 이렇게 제조된 커큐민 분산액에 그 분산액 100 중량부 기준 5 중량부의 밀겨 추출물 분말을 용해시켜 수용화 커큐민과 밀겨 추출물의 혼합물을 제조하였다.
아래의 실험에서는 상기 수용화 커큐민, 상기 혼합물을 감압농축 및 동결건조하여 분말상으로 제조하여 이용하였다.
상기 밀겨 추출물은 밀겨 분말에 20배 중량의 물을 가하고 80~100℃의 온도로 6시간 동안 가열하여 추출한 후 감압농축 및 동결건조하여 분말상으로 제조하여 얻은 것이다.
<실험예> 미백 활성 및 주름 개선 활성 실험
<실험예 1> 미백 활성 실험
미백 활성 실험은 티로시나아제 저해 활성을 측정하여 수행하였다. 구체적으로 기질 10 mM L-DOPA가 포함된 potassium phosphate buffer (pH 6.8) 60 uL에 20 uL의 실시예의 농도별 시료와 20 uL의 버섯 티로시나아제(125 U)를 가하고 37℃에서 10분간 반응시킨 후 흡광광도계를 이용하여 492 nm에서 흡광도를 측정하였다. 티로시나아제 저해 활성 결과는 시료 무처리군 대비 백분율로 구하였으며, 결과를 도 1 내지 도 3에 나타내었다.
<실험예 2> 주름 개선 활성 실험
실험에는 인간섬유아세포인 HDFn 세포(human dermal fibroblast neonatal cell)를 구입하여 사용하였으며, 세포를 DMEM 배지(Dulbeco's modified eagle's medium)에 10% FBS(fetal bovine serum)와 1% 페니실린/스트렙토마이신(100U/mL)을 첨가하여 5% CO2, 37℃ 조건 하에서 배양하였다.
24 웰 플레이트에 HDFn 세포를 5 ×104개로 분주한 후 5% CO2, 37℃하에서 24 시간 배양하고, 이후 FBS가 포함되지 않은 DMEM 배지로 교체하고, 시료를 첨가하여 24시간 동안 배양하였다. 배양액을 모아서 프로콜라겐 타입 I(procollagen type Ⅰ) 측정 키트(procollagen type I protein synthesis kit, Takara, Japan)를 이용하여 생성된 콜라겐 전구체의 양을 측정하였다. 결과를 시료 무처리군 대비 백분율로 도 4 내지 도 6에 나타내었다.
도 4 내지 도 6을 참조하여 보면, 실시예의 각 시료는 모두 농도 의존적으로 콜라겐의 생합성을 촉진하였으며, 특히 수용화 커큐민과 밀겨 추출물의 혼합물의 콜라겐 생합성 촉진 효과가 높았다.
한편 각 실시예 시료의 MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay(Br J Cancer 60, 206-210, 1989)에 의한 세포독성 평가 결과를 도 7에 나타내었다. 도 7를 참조하여 보면 100㎍/mL 처리 농도에서 각 실시예의 시료는 모두 특별한 세포독성을 보이지 않음을 알 수 있다.
Claims (6)
- 수용화 커큐민, 밀겨 추출물 또는 이들의 혼합물을 유효성분으로 포함하는 피부 미백용 조성물.
- 제1항에 있어서,상기 조성물은 식품 조성물인 것을 특징으로 하는 조성물.
- 제1항에 있어서,상기 조성물은 화장품 조성물인 것을 특징으로 하는 조성물.
- 수용화 커큐민, 밀겨 추출물 또는 이들의 혼합물을 유효성분으로 포함하는 피부 주름 개선용 조성물.
- 제4항에 있어서,상기 조성물은 식품 조성물인 것을 특징으로 하는 조성물.
- 제4항에 있어서,상기 조성물은 화장품 조성물인 것을 특징으로 하는 조성물.
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JPH07206669A (ja) * | 1994-01-14 | 1995-08-08 | Nikken Food Kk | チロシナーゼ阻害活性剤 |
KR20100082880A (ko) * | 2009-01-12 | 2010-07-21 | (주)씨네이처 | 폴리사카라이드를 담체로 이용한 울금 추출물과 탄닌을 포함하는 주름 개선용 비누 조성물 및 그 제조방법 |
KR20160014562A (ko) * | 2014-07-29 | 2016-02-11 | 신일제약주식회사 | 피부노화 개선효과를 가지는 밀 추출물, 이의 제조방법 및 이를 함유한 피부노화 개선용 조성물 |
KR20170128098A (ko) * | 2016-05-11 | 2017-11-22 | 씨제이제일제당 (주) | 밀배아 발효물의 추출물을 유효성분으로 함유하는 피부 미백용 외용제 조성물 |
KR20180134232A (ko) * | 2017-06-08 | 2018-12-18 | 동덕여자대학교 산학협력단 | 밀 껍질 추출물을 포함하는 화장료 조성물 |
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2022
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- 2022-05-13 WO PCT/KR2022/006928 patent/WO2023167367A1/ko unknown
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
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JPH07206669A (ja) * | 1994-01-14 | 1995-08-08 | Nikken Food Kk | チロシナーゼ阻害活性剤 |
KR20100082880A (ko) * | 2009-01-12 | 2010-07-21 | (주)씨네이처 | 폴리사카라이드를 담체로 이용한 울금 추출물과 탄닌을 포함하는 주름 개선용 비누 조성물 및 그 제조방법 |
KR20160014562A (ko) * | 2014-07-29 | 2016-02-11 | 신일제약주식회사 | 피부노화 개선효과를 가지는 밀 추출물, 이의 제조방법 및 이를 함유한 피부노화 개선용 조성물 |
KR20170128098A (ko) * | 2016-05-11 | 2017-11-22 | 씨제이제일제당 (주) | 밀배아 발효물의 추출물을 유효성분으로 함유하는 피부 미백용 외용제 조성물 |
KR20180134232A (ko) * | 2017-06-08 | 2018-12-18 | 동덕여자대학교 산학협력단 | 밀 껍질 추출물을 포함하는 화장료 조성물 |
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