WO2024049120A1 - Composition cosmétique contenant un extrait extrait au moyen d'un solvant eutectique naturel respectueux de l'environnement - Google Patents
Composition cosmétique contenant un extrait extrait au moyen d'un solvant eutectique naturel respectueux de l'environnement Download PDFInfo
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- WO2024049120A1 WO2024049120A1 PCT/KR2023/012660 KR2023012660W WO2024049120A1 WO 2024049120 A1 WO2024049120 A1 WO 2024049120A1 KR 2023012660 W KR2023012660 W KR 2023012660W WO 2024049120 A1 WO2024049120 A1 WO 2024049120A1
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- Prior art keywords
- acid
- eutectic solvent
- natural
- skin
- natural eutectic
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- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
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- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
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- 229960001790 sodium citrate Drugs 0.000 description 1
- 235000019983 sodium metaphosphate Nutrition 0.000 description 1
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- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000019830 sodium polyphosphate Nutrition 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
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- 239000003549 soybean oil Substances 0.000 description 1
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- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/60—Moraceae (Mulberry family), e.g. breadfruit or fig
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/889—Arecaceae, Palmae or Palmaceae (Palm family), e.g. date or coconut palm or palmetto
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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]
- A61K8/9789—Magnoliopsida [dicotyledons]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- 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
-
- 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
Definitions
- organic solvents are used for liquid extraction.
- Organic solvents have the advantage of being cheap and having good extraction efficiency, but they have the problem of being harmful to the user's health or causing environmental pollution problems. Accordingly, interest in sustainable development is increasing, and research related to extraction solvents that can replace organic solvents is actively underway.
- a eutectic solvent is a eutectic mixture of two components that have a lower melting point than each component.
- ionic liquids were used as an alternative to organic solvents, but they were found to be unsuitable as environmentally friendly solvents due to low biodegradability, toxicity, and the amount of pollutants emitted during the manufacturing process. There is a report. Since then, research has been conducted on deep eutectic solvents and natural eutectic solvents that complement the shortcomings of conventional ionic liquids.
- One aspect is to provide a composition for improving skin condition containing as an active ingredient a natural product extract extracted with an eco-friendly natural eutectic solvent.
- Another aspect is to provide a method for producing an environmentally friendly natural eutectic solvent.
- Another aspect provides the use of a natural product extract extracted with a natural eutectic solvent for the production of a cosmetic composition for improving skin condition, wherein the natural eutectic solvent includes an amino acid or a derivative thereof, and an organic acid. .
- Another aspect is the use of a natural product extract extracted with a natural eutectic solvent for the production of a skin external composition for improving skin condition, wherein the natural eutectic solvent includes an amino acid or a derivative thereof, and an organic acid.
- the natural eutectic solvent includes an amino acid or a derivative thereof, and an organic acid.
- Another aspect is the use of a natural product extract extracted with a natural eutectic solvent for the production of a pharmaceutical composition for the prevention or treatment of skin inflammatory diseases, wherein the natural eutectic solvent includes an amino acid or a derivative thereof, and an organic acid. is to provide.
- Another aspect is the use of a natural product extract extracted with a natural eutectic solvent for the production of a pharmaceutical composition for preventing or treating hair loss, or promoting hair growth or hair growth, wherein the natural eutectic solvent includes an amino acid or a derivative thereof, and an organic acid. It provides a purpose.
- Another aspect provides a method of preventing, ameliorating, or treating a condition in a subject comprising treating or administering an effective amount of the composition described above to the subject in need thereof.
- One aspect provides a composition for improving skin condition containing as an active ingredient a natural product extract extracted with an eco-friendly natural eutectic solvent.
- the natural eutectic solvent may be one or more selected from the group consisting of amino acids or derivatives thereof, and organic acids.
- amino acids or their derivatives include, for example, betaine, alanine, cysteine, aspartic acid, glutamine, phenylalanine, glycine, histidine, isoleucine, lysine, leucine, methionine, asparagine, proline, glutamine, arginine, serine, threonine, and valine. , tryptophan, tyrosine, etc.
- the organic acids include, for example, citric acid, lactic acid, malic acid, maleic acid, pyruvic acid, fumaric acid, succinic acid, acetic acid, aconitic acid, tartaric acid, ascorbic acid, malonic acid, oxalic acid, glucuronic acid, neuraminic acid, It may be sialic acid, shikimic acid, phytic acid, galacturonic acid, iduronic acid, hyaluronic acid, hydroxycitric acid, lactone derivative, etc.
- the natural eutectic solvent may be a mixture of betaine and citric acid.
- the betaine and citric acid may be mixed at a weight ratio of 1:0.001 to 10.
- the betaine and citric acid are, for example, 1:0.001 to 10, 1:001 to 8, 1:0.05 to 7, 1:0.05 to 5, 1:0.01 to 10, 1:0.01 to 6, 1:0.1 to It can be mixed at a weight ratio of 4, 1:0.1 to 3, 1:1 to 10, 1:1 to 4, or 1:1 to 2.
- the mixing weight ratio of betaine and citric acid is less than or exceeds the above range, there is a problem in that the betaine and citric acid precipitate, the eutectic solvent becomes suspended, or the eutectic solvent becomes discolored.
- the natural eutectic solvent may have pH 2.5 to pH 8.
- an acidic solution with a pH of less than 2.5 is prepared. Because extracts extracted with acidic solvents have low acidity, they are more likely to cause irritation or skin damage when applied to the skin. Therefore, the pH of the natural eutectic solvent can be adjusted to 2.5 to 8 by adding a pH adjuster to the mixture of betaine and citric acid.
- the natural eutectic solvent is, for example, pH 2.5 to pH 8, pH 2.5 to pH 7.5, pH 3 to pH 7, pH 3 to pH 6.5, pH 3.5 to pH 6, pH 4 to pH 6, or pH 4.5 to pH 5.5. It can be.
- the pH adjusting agent may be a base or a buffering agent, for example, sodium citrate, sodium hydroxide, potassium hydroxide, sodium bicarbonate, arginine, catalytic acid, etc.
- a base or a buffering agent for example, sodium citrate, sodium hydroxide, potassium hydroxide, sodium bicarbonate, arginine, catalytic acid, etc.
- Tromethamine triethanol amine, aminomethyl propanol, dipotassium phosphate, potassium phosphate, sodium anisate, sodium lactate , sodium carbonate, urea, etc.
- the above-mentioned natural products include figs, black bean sprouts, black rice, Hyeolgal, black beans, Japanese jacaranda, snow lotus, mountain ash, pollen, duckweed, juniper, sagebrush, bleeding heart, mistletoe, sedum, goldenrod, sage mushrooms, tomatoes, Houttuynia cordata, dermis, peonies, and chestnut flowers. It may be selected from the group consisting of , kudzu, and walnut.
- the natural product extract may be extracted by chopping the dried natural product and adding 2 to 20 times the weight of the natural product with a natural eutectic solvent.
- the extraction temperature may be performed at 30°C to 100°C.
- Extraction time may be performed for 1 hour to 10 hours.
- Extraction methods may include cold immersion, ultrasonic extraction, or reflux cooling extraction. The number of extractions may be repeated 1 to 5 times.
- a natural product extract extracted with a natural eutectic solvent prepared by mixing betaine and citric acid not only has improved safety and stability compared to a natural product extract extracted with an organic solvent, but also has excellent reactive oxygen and free radical scavenging ability and ultraviolet rays. It was confirmed that the protective effect against cell damage was excellent.
- the natural product extract extracted with the natural eutectic solvent significantly inhibits the expression of hyaluronidase, inflammatory cytokines, and/or inflammatory mediators compared to the natural product extract extracted with an organic solvent, and inhibits tyrosinase activity and melanin synthesis. It was confirmed that it not only inhibits but also increases the expression of factors related to skin barrier, moisture, and elasticity, and suppresses the expression of factors related to acne, sebum, or hair loss.
- the improvement of skin condition or skin beauty may include suppressing or improving skin aging, wrinkles, elasticity, strengthening the skin barrier, skin moisturizing, and suppressing or improving skin acne or sebum. Additionally, it may be for preventing, improving or treating hair loss, or promoting hair growth or hair growth.
- skin aging refers to both tangible and intangible changes that occur in the skin as one ages, such as thinning of the epidermis, number of cells or blood vessels in the dermis, DNA damage repair ability, cell replacement cycle, It refers to a decrease in wound recovery, skin barrier function, epidermal moisture retention, sweat secretion, sebum secretion, vitamin D production, physical damage defense, chemical removal ability, immune response, sensory function, and temperature regulation.
- the composition may be used to improve skin aging caused by extrinsic or intrinsic 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.
- 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.
- wrinkles include stimulation caused by changes in internal and external factors that change the components that make up skin tissue, causing wrinkles.
- the aging may be aging caused by active oxygen or photoaging.
- the “active oxygen radicals” are generated by normal metabolic processes, ultraviolet rays, harmful toxins such as pesticides, cigarette smoke, air pollution, etc. Free radicals lead to skin cell and tissue damage, destroying the skin's antioxidant defense network, leading to lipid peroxidation, protein oxidation, activation of proteolytic enzymes that destroy interstitial components, chain cutting and abnormal cross-linking of elastic fibers collagen and elastin, and hyaluronidase. It causes damage to biological components such as cleavage of the ronic acid chain, acceleration of melanin production reaction, and oxidation of DNA.
- the “photoaging” is a phenomenon caused by external environmental factors, the most representative factor being ultraviolet rays.
- Ultraviolet rays cause damage to biological components such as activation of proteolytic enzymes, chain cutting of matrix proteins, and abnormal cross-linking, and repetition of this mechanism causes skin aging that is evident in appearance.
- wrinkle refers to a state in which the skin loses its elasticity and becomes loose, for example, the skin may be folded.
- prevention or improvement of skin wrinkles may refer to any action that prevents or improves wrinkles by suppressing the expression of factors related to wrinkles, or increases the total amount of collagen.
- skin barrier strengthening may refer to any action that improves the function of the skin barrier, which is located on the outermost layer of the skin and prevents moisture and nutrition loss.
- skin moisturizing may refer to any action that maintains skin moisture or prevents moisture loss.
- the “skin disease” may be a disease caused by damage to the skin barrier function, skin aging, skin wound, skin scar, or skin inflammation.
- prevention includes suppressing the occurrence of a disease.
- treatment includes inhibiting, alleviating, or eliminating the development of a disease.
- the damage to the skin barrier function may mean any change that appears in the skin due to decreased or damaged skin barrier function. For example, it may include increased skin wrinkles, dryness, dermatitis, atopic dermatitis, allergic dermatitis, acne, etc.
- the skin inflammatory disease may be any one selected from the group consisting of skin wounds, dermatitis, atopic dermatitis, pruritus, eczematous skin disease, dry eczema, erythema, urticaria, psoriasis, drug rash, and acne.
- lopecia refers to a phenomenon in which hair falls out from the scalp or a condition in which hair becomes sparse or thin, and "prevention or improvement of hair loss” not only promotes the creation of new hair, but also reduces existing hair. It means growing healthy.
- the hair loss is, for example, Androgenic Alopecia, Alopecia Areata, Androgenetic Alopecia, Telogen Effluvium, Traumatic Alopecia, Trichotillomania, Pressure Alopecia ( Pressure Alopecia), anagen alopecia, alopecia pityroides, Alopecia Syphlltiac, Alopecia Seborrhecia, symptomatic alopecia, cicatricial alopecia, congenital alopecia, etc.
- hair growth refers to hair growing from the scalp
- hair growth refers to lengthening of hair (i.e., hair growth)
- hair growth is another term used in the art. It is used with the same meaning.
- the composition is effective in improving hair loss caused by exogenous or endogenous factors.
- the exogenous factors include various external factors, such as ultraviolet rays, and the endogenous factors are factors that occur over time and include cell death of dermal papilla cells caused by telomeres and oxidative stress due to cell function decline. can do.
- hair growth or hair growth promotion means promoting the production and growth of hair and ultimately increasing the proportion of growth-phase hair in total hair.
- promotion of hair growth or hair growth means suppressing hair loss caused by a decrease in the specific gravity of hair in the growth phase.
- the composition is 0.001% 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, 0.05% 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, 0.1% to 60% by weight, 0.1% to 40% by weight, 0.1% to 30% by weight, 0.1% to 20% by weight, 0.1% by weight % to 10% by weight, or 0.1% to 5% by weight of natural eutectic solvent extract.
- the skin condition improvement effect for example, skin aging inhibition, wound improvement, skin barrier strengthening, skin wrinkle inhibition, or skin moisturizing effect is not sufficiently exerted.
- the term "included as an active ingredient” means that the natural product extract of the present specification is added to the extent that it can exhibit the effects mentioned above, and various ingredients are added as sub-ingredients for drug delivery and stabilization, etc. to form various forms. This means that it includes being formulated.
- the composition may be a cosmetic composition.
- 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 composition may be a composition for external application to the skin.
- 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 external skin agents include scalp tonic, scalp lotion, scalp cream, scalp serum, scalp essence, scalp ampoule, scalp treatment, scalp conditioner, scalp shampoo, scalp pack, hair tonic, hair lotion, hair cream, hair spray, and hair. Mousse, hair gel, hair conditioner, hair shampoo, hair rinse, hair pack, hair treatment, eyebrow hair growth agent, eyelash growth medicine, eyelash nutrition, pet shampoo, pet rinse, hand sanitizer, detergent soap, soap, disinfectant cleanser, It may be a wet tissue, mask, ointment, patch, or filter filler.
- 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 pharmaceutical composition.
- 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 as an oral or parenteral dosage form.
- Oral dosage forms may be granules, powders, solutions, tablets, capsules, dry syrup, or combinations thereof.
- Parenteral dosage forms may be injectable.
- 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).
- the composition of the present specification may be added in an amount of 15 parts by weight or less based on the raw materials.
- 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.
- 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.
- Another aspect provides the use of a natural product extract extracted with a natural eutectic solvent for the production of a cosmetic composition for improving skin condition, wherein the natural eutectic solvent includes an amino acid or a derivative thereof, and an organic acid.
- the natural eutectic solvent includes an amino acid or a derivative thereof, and an organic acid.
- Another aspect provides the use of a natural product extract extracted with a natural eutectic solvent for the production of a skin external composition for improving skin condition, wherein the natural eutectic solvent includes an amino acid or a derivative thereof, and an organic acid.
- the natural eutectic solvent includes an amino acid or a derivative thereof, and an organic acid.
- Another aspect is the use of a natural product extract extracted with a natural eutectic solvent for the production of a pharmaceutical composition for the prevention or treatment of skin inflammatory diseases, wherein the natural eutectic solvent includes an amino acid or a derivative thereof, and an organic acid. to provide.
- the natural eutectic solvent includes an amino acid or a derivative thereof, and an organic acid.
- Another aspect is the use of a natural product extract extracted with a natural eutectic solvent for the production of a pharmaceutical composition for preventing or treating hair loss, or promoting hair growth or hair growth, wherein the natural eutectic solvent includes an amino acid or a derivative thereof, and an organic acid. It provides a useful purpose.
- specific details regarding hair loss, prevention, treatment, hair growth, hair growth, pharmaceutical compositions, natural eutectic solvents, extractions, natural products, amino acids, derivatives, organic acids, etc. are as described above.
- Another aspect provides a method of preventing, ameliorating, or treating a condition of a subject comprising treating or administering an effective amount of the composition described above to the subject in need thereof.
- the condition of the subject may be a skin-related condition or an inflammation-related condition.
- administering 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.
- 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.
- 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.
- another aspect includes mixing betaine and citric acid to prepare a mixture;
- aminomethyl propanol, dipotassium phosphate, potassium phosphate, sodium anisate, sodium lactate, sodium carbonate, and urea is provided, comprising the step of adjusting pH by adding any one selected from the group consisting of.
- another aspect provides a method for producing a natural product extract extracted with a natural eutectic solvent, comprising the step of preparing the extract by extracting the natural product with an amino acid, an organic acid, or a mixture thereof. Details of the natural product, natural eutectic solvent, etc. are as described above.
- the natural product extract prepared according to the above method has an excellent oxygen and free radical scavenging rate, inhibits melanin synthesis, increases the expression of SPT, AQP3, and RNase7, thereby strengthening the skin barrier, improving skin moisturization, elasticity, and skin aging. It can be useful in improving skin conditions such as: Additionally, it can be usefully used to prevent, improve, or treat skin inflammatory diseases by reducing the expression of inflammatory cytokines.
- the cosmetic composition according to one aspect not only has lower cytotoxicity compared to organic solvent extracts by extracting natural products using an eutectic solvent of betaine and citric acid, but also improves safety and stability by preventing discoloration of the extract, thereby improving skin condition. It can be usefully used in improving cosmetics and external skin preparations.
- a natural eutectic solvent containing betaine as an amino acid and citric acid as an organic acid was prepared. Specifically, betaine and citric acid were mixed in equal amounts and stirred at 60100°C at 150 rpm for 2 hours to prepare a natural eutectic solvent with pH 2. .
- a natural eutectic solvent with adjusted pH was prepared. Specifically, 1, 5, and 10 kg of 1M sodium citrate aqueous solution were added to the natural eutectic solvent of Preparation Example 1, respectively, to pH 3 (Preparation Example 2), pH 5 (Preparation Example 3), and pH 7 ( The natural eutectic solvent of Preparation Example 4) was prepared.
- a natural eutectic solvent extract of Ficus carica fruit was prepared. Specifically, 1 kg of dried and ground fig fruit was extracted with the natural eutectic solvent of Preparation Example 1 for 6 hours. Afterwards, the fig fruit eutectic solvent extract was prepared by filtering with Whatman #5 filter paper.
- a eutectic solvent extract of Selaginella tamariscine was prepared in the same manner as in Example 1, except that Selaginella tamariscine was used.
- a eutectic solvent extract of germinated black rice was prepared in the same manner as in Example 1, except that germinated black rice (Oryza sativa) was used.
- a Daemonorops draco eutectic solvent extract was prepared in the same manner as in Example 1, except that Daemonorops draco was used.
- Example 5 Preparation of eutectic solvent extract of fig fruit, Kwonbaek, germinated black rice, and Hyeolgal mixture
- a eutectic solvent extract of the fig fruit, Kwonbaek, germinated black rice, and blood stem mixture was prepared in the same manner as in Example 1, except that the same amounts of fig fruit, Kwonbaek, germinated black rice, and blood stem were used.
- a pH-adjustable fig fruit natural eutectic solvent extract was prepared in the same manner as Example 1, except that the natural eutectic solvent of Preparation Examples 2 to 4 was used.
- a pH-adjustable Kwonbaek natural eutectic solvent extract was prepared in the same manner as Example 1, except that the natural eutectic solvent of Preparation Examples 2 to 4 was used.
- a pH-adjusted germinated black rice eutectic solvent extract was used in the same manner as Example 1, except that the natural eutectic solvent of Preparation Examples 2 to 4 was used.
- a pH-adjustable Hyegal natural eutectic solvent extract was prepared in the same manner as Example 1, except that the natural eutectic solvent of Preparation Examples 2 to 4 was used.
- a eutectic solvent extract of fig fruit, kimchi, germinated black rice, and blood stem mixture was prepared in the same manner as Example 1, except that the natural eutectic solvent of Preparation Examples 2 to 4 was used.
- a fig fruit ethanol extract was prepared in the same manner as in Example 1, except that 70% (v/v) ethanol was used.
- An ethanol extract of Kwonbaek was prepared in the same manner as in Example 1, except that 70% (v/v) ethanol was used.
- An ethanol extract of germinated black rice was prepared in the same manner as in Example 1, except that 70% (v/v) ethanol was used.
- the content of phenol and flavonoid contained in the natural eutectic solvent extract according to one embodiment was confirmed. Specifically, 1 ml each of Examples 1 to 20 and Comparative Examples 1 to 4 were added to 10 ml of distilled water, and then 2 ml of Folin-Ciocalteu phenol reagent (Sigma) was added and mixed. After reacting at room temperature for 5 minutes, 2 ml of 20% sodium carbonate was added and reacted at room temperature for an additional hour. The total phenol content was determined by measuring absorbance at 680 nm. Gallic acid was used as an indicator material.
- Example 1 148.9 59.1
- Example 2 212.5 73.8
- Example 3 163.5 51.5
- Example 4 184.1 53.7
- Example 6 204.4 49.7
- Example 7 221.4 71.6
- Example 8 220.1 57.2
- Example 9 241.8 64.7
- Example 10 254.6 88.4
- Example 11 245.4 88.2
- Example 12 254.7 63.4
- Example 13 268.9 73.5
- Example 14 264.1 68.9
- Example 15 210.4 74.1
- Example 17 229.5 87.1
- Example 18 213.5 63.2
- Example 19 253.6 72.5
- Comparative Example 3 279.4 103.8 Comparative Example 4 234.5 99.4
- the natural eutectic solvent according to one embodiment can maximize the active ingredient to be extracted at a specific pH.
- the cytotoxicity of the natural eutectic solvent extract according to one embodiment to skin cells was confirmed. Specifically, 1x10 5 cells/mL of fibroblasts diluted in cell culture medium containing 10% FBS in DMEM were added to a 96-well plate and allowed to attach for 24 hours. Thereafter, Examples 1 to 20 and Comparative Examples 1 to 4 were diluted to an appropriate concentration, applied to each well, and cultured for 24 hours. After 24 hours, the medium was removed, and cell culture medium containing MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) solution (2.5 mg/ml) was added to each well.
- MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
- Example 1 0.25%
- Example 2 0.25%
- Example 3 0.25%
- Example 4 0.25%
- Example 5 0.25%
- Example 6 One%
- Example 7 2%
- Example 8 One%
- Example 9 One%
- Example 10 2%
- Example 11 2%
- Example 12 One%
- Example 13 2%
- Example 14 2%
- Example 15 One%
- Example 16 2%
- Example 17 2%
- Example 18 One%
- Example 19 2%
- Example 20 2% Comparative Example 1 0.05% Comparative Example 2 0.05% Comparative Example 3 0.05% Comparative Example 4 0.05%
- the natural eutectic solvent according to one embodiment has a low possibility of causing skin irritation and has a wide useful concentration range, so it can be used as a safe and efficient solvent.
- the room temperature stability of the natural eutectic solvent extract according to one embodiment was confirmed. Specifically, samples were prepared by mixing 60% by weight of dipropylene glycol with Examples 1 to 20 and Comparative Examples 1 to 4. Thereafter, the samples were each placed in a straw container and stored in a thermostat maintained at a constant temperature of 45°C for 4 weeks to measure the degree of discoloration. The color change ( ⁇ E) of the sample was measured using a chromatometer (Minolta CR300), stability was evaluated, and the results are shown in Table 3 below.
- Example 1 19.84 Example 2 28.16 Example 3 22.98 Example 4 25.47 Example 5 25.81 Example 6 15.34 Example 7 8.32 Example 8 9.11 Example 9 23.47 Example 10 8.05 Example 11 11.36 Example 12 15.54 Example 13 9.51 Example 14 9.17 Example 15 19.57 Example 16 8.97 Example 17 9.24 Example 18 18.47 Example 19 8.16 Example 20 8.03 Comparative Example 1 18.35 Comparative Example 2 13.84 Comparative Example 3 9.44 Comparative Example 4 15.21
- Comparative Examples 1 to 4 had excellent extraction efficiency compared to Examples 1 to 20, but had problems with cytotoxicity and poor room temperature stability.
- the natural eutectic solvent according to one embodiment can be usefully used as a solvent for the production of cosmetics and external skin preparations in that it improves problems of cytotoxicity and room temperature stability that may occur due to organic solvent extraction.
- the antioxidant activity of the natural eutectic solvent extract according to one embodiment was confirmed using the NBT (Nitro Blue Tetrazolium) method. Specifically, 2.4 ml of 0.05M Na2CO3, 0.1 ml of 3mM xanthine solution, 0.1 ml of 3mM EDTA solution, 0.1 ml of BSA solution, and 0.1 ml of 0.72mM NBT solution were added to the Bayer bottle, and Examples 7, 10, and 13 above were added. , 16 and 19 and Comparative Examples 1 to 4 were added at 0.1% by weight, respectively, and left at 25°C for 10 minutes.
- NBT Niro Blue Tetrazolium
- the natural eutectic solvent extract according to one embodiment has excellent antioxidant activity and can be usefully used to prevent or improve aging.
- the antioxidant activity of a natural eutectic solvent extract according to one embodiment was confirmed using the DPPH method [2,2-Di(4-tert-octylphenyl)-1-picrylhydrazyl free radical].
- DPPH 2,2-Di(4-tert-octylphenyl)-1-picrylhydrazyl free radical.
- Examples 7, 10, 13, 16, and 19 and Comparative Examples 1 to 4 were diluted to a concentration of 0.1% and placed in a 96-well plate. Afterwards, DPPH prepared from 100 ⁇ l methanol solution was added to bring the total volume of the solution to 200 ⁇ l, left at 37°C for 30 minutes, and absorbance was measured at 560 nm. Free radical scavenging activity (%) was calculated using Equation 3 below, and the results are shown in Table 5 below.
- BHT Butylated hydroxytoluene
- the natural eutectic solvent extract according to one embodiment has excellent antioxidant activity and can be usefully used to prevent or improve aging.
- the effect of a natural eutectic solvent extract on alleviating cytotoxicity caused by ultraviolet rays was confirmed. Specifically, 1x10 5 cells/ml of fibroblasts were placed in a 96-well plate and allowed to attach for 24 hours. After 24 hours, Examples 7, 10, 13, 16, and 19 and Comparative Examples 1 to 4 were treated and cultured for an additional 24 hours under the same culture conditions. Afterwards, the medium was removed, each well was washed once with PBS, and 100 ⁇ l of PBS was added to each well.
- UVB ultraviolet B
- Bo Cell viability in wells without UV irradiation and sample treatment.
- St Cell viability of wells irradiated with ultraviolet rays and treated with samples.
- the natural eutectic solvent extract according to one embodiment has excellent activity in protecting against cell damage caused by ultraviolet rays, and can be usefully used to prevent or improve aging.
- the inflammation prevention, improvement, or treatment effect of the natural eutectic solvent extract according to one embodiment was confirmed.
- 50 ⁇ l of hyaluronidase solution (type Kygigma, 400 U/ml) was added to each well of Examples 7, 10, 13, 16, and 19 and 100 ⁇ l of Comparative Examples 1 to 4 at 37°C.
- 100 ⁇ l of enzyme activation solution (compound 48/80 CaCl 2 2H 2 O, Sigma, 0.1 mg/ml) was added and reacted at 37°C for an additional 20 minutes.
- the natural eutectic solvent extract according to one embodiment can be usefully used for preventing, improving, or treating inflammatory diseases.
- the effectiveness of the natural eutectic solvent extract according to one embodiment to prevent, improve, or treat inflammation caused by ultraviolet rays was confirmed. Specifically, 3 ml of the keratinocyte cell line diluted to 3X10 5 cells/ml was dispensed onto a 35 ⁇ dish in medium supplemented with 10% FBS and cultured for 24 hours. Thereafter, irradiated with UVB 15 mJ/cm 2 and Examples 7, 10, 13, 16, and 19 and Comparative Examples 1 to 4 were diluted in a medium containing 2% FBS to a concentration that did not cause cytotoxicity, and then incubated for 24 hours. Additional culture was carried out during the period.
- the product generated by PCR was electrophoresed on a 2% agarose gel to confirm gene expression using an image analyzer, and the density of each band was determined using the Image J program (NIH Image software, Maryland, USA). Madecassoside was used as a positive control.
- the inhibition rate of expression of inflammatory cytokines and inflammatory mediators was calculated according to Equation 7 below, and the results are shown in Table 8 below.
- Bo Production amount of inflammatory cytokines or inflammatory mediators in wells without UV irradiation or sample treatment.
- Bt Production amount of inflammatory cytokines or inflammatory mediators in wells irradiated with ultraviolet rays and without sample treatment.
- St Production amount of inflammatory cytokines or inflammatory mediators in wells irradiated with ultraviolet rays and treated with samples.
- Examples 7, 10, 13, 16, and 19 had a significant inhibition rate of expression of inflammatory cytokines and inflammatory mediators compared to Comparative Examples 1 to 4 in which the same extraction target was extracted with an organic solvent. I was able to confirm that it was quite high.
- the natural eutectic solvent extract inhibits the expression of inflammatory cytokines and/or inflammatory mediators, and can be usefully used in the prevention, improvement or treatment of inflammatory diseases caused by ultraviolet rays.
- the whitening improving activity of the natural eutectic solvent extract according to one embodiment was confirmed. Specifically, L-tyrosine (Sigma) was dissolved in 0.05M sodium phosphate buffer solution (pH 6.8) to prepare a 0.1 mg/ml solution, and then 0.5 ml of the prepared solution was placed in a test tube. Here, 0.5 ml each of Examples 7, 10, 13, 16, and 19 and Comparative Examples 1 to 4 dissolved in 0.05M sodium phosphate buffer solution (pH 6.8) adjusted to an appropriate concentration were added and incubated for 10 minutes in a thermostat at 37°C. It was left for a minute.
- the natural eutectic solvent extract according to one embodiment can be usefully used to improve skin whitening.
- melanoma cells B16F10 (accession number: ATCC 6323) were dispensed into a 6 -well plate at a concentration of 2 10, 13, 16, and 19 and Comparative Examples 1 to 4 were treated and cultured for 72 hours. Afterwards, the cells were removed with trypsin-EDTA, the number of cells was measured, and the cells were recovered by centrifugation. Quantification of intracellular melanin was performed by slightly modifying the method of Lotan [Lotan: Cancer Res., 40, 3345-3350 (1980)].
- the natural eutectic solvent extract according to one embodiment can be usefully used to improve skin whitening.
- HaCaT cells a human keratinocyte cell line
- DMEM medium Dulbecco's modified Eagle's Medium, Gibco 11965-092
- fetal bovine serum 10% fetal bovine serum
- primers and cDNA for the target genes SPT (serine palmitoyl transferase), AQP3, a factor related to skin barrier strengthening and moisturization, and RNase7, an antibacterial peptide, and cDNA were added and used in a real-time PCR machine (Mic qPCR, Real-time polymerase chain reaction was performed on a biomolecular system (Australia). The expression level of the gene was finally analyzed through correction for the GAPDH gene, and the results are shown in Table 11 below.
- Examples 7, 10, 13, 16, and 19 have ceramide synthase SPT, skin moisturizing, barrier strengthening, and It was confirmed that the expression of RNase7, a related AQP and skin antibacterial peptide, was significantly high.
- the natural eutectic solvent extract according to one embodiment can be usefully used to strengthen the skin barrier.
- the skin wrinkle and moisturizing improvement activity of the natural eutectic solvent extract was confirmed. Specifically, 10% fetal bovine serum (FBS) was added to DMEM/F-12 (3:1) medium, and human dermal fibroblasts (Modern Tissue Technology, Korea) were cultured at a concentration of 1 ⁇ 10 4 cell/cm 2 . When the cells grew to about 70-80%, they were divided and sub-cultured at a ratio of 1:3, and the 3rd-4th subcultured cells were used for experiments.
- FBS fetal bovine serum
- human dermal fibroblasts Modern Tissue Technology, Korea
- the fibroblasts were cultured at a concentration of 90% or more in a 48 well plate, and then Examples 7, 10, 13, 16, and 19 and Comparative Examples 1 to 4 were added at a concentration that did not cause cytotoxicity, and after 24 hours, The amount of procollagen released in the medium was measured using a procollagen type-1 C-peptide EIA kit (MK101, Takara, Japan). Ascorbic acid was used as a positive control.
- the natural eutectic solvent extract according to one embodiment can be usefully used to prevent or improve skin wrinkles and moisturization.
- the effectiveness of the natural eutectic solvent extract according to one embodiment to prevent or improve acne, sebum, or hair loss was confirmed. Specifically, after adding 0.1 ⁇ Ci of testosterone radiolabeled with 3H (tritium) to each microplate hole, Examples 7, 10, 13, 16, and 19, and Comparative Examples 1 to 4. Fibroblasts were inoculated and cultured to contain 10,000 cells. After culturing for 24 hours, the supernatant was obtained, and steroids were obtained with 1 ml of ethyl acetate-cyclohexane (1:1) extraction solvent. The steroid was placed on a thin layer chromatography plate and developed with a chloroform/methanol mixture (98/2 (v/v)).
- the radioactivity of the points corresponding to testosterone and dihydrotestosterone (DHT) was measured using a densitometer to calculate the conversion rate, and the results were compared with the negative control group to obtain 5-alpha-reductase enzyme by Equation 10 below. The inhibition rate was evaluated.
- the natural eutectic solvent extract inhibits the conversion of dihydrotestosterone by 5-alpha-reductase, and not only prevents or improves acne and sebum, but also prevents, improves or treats hair loss, or hair growth or hair growth. It can be useful for promotion.
- a cream-type cosmetic composition containing the ingredients and contents shown in Table 14 below was prepared. Specifically, phase B of Table 14 below was heated and stored at 70°C, and then phase A was added and pre-emulsified. Afterwards, the mixture was uniformly emulsified using a homomixer and then slowly cooled to prepare a cosmetic composition. Unless otherwise stated herein, content is in weight percent.
- the natural eutectic solvent natural product extract according to one embodiment can be usefully used to improve skin elasticity.
- the skin wrinkle improvement effect of a cosmetic composition containing a natural eutectic solvent extract according to one embodiment was confirmed.
- Formulation Examples 1, 5, and Comparative Formulation Example 1 of Experimental Example 14 were used in the same manner on the same subject. After producing a replica of silicone material, the formulation example 1, The skin wrinkle condition was measured after using 5 and Comparative Formulation Example 1. The measured values were expressed as an average after subtracting the parameter values before use from the values of each parameter after two months of use. The more negative the measured value, the higher the wrinkle improvement effect.
- R4 Average value of the wrinkle contour's baseline minus the values of each peak and valley.
- the natural eutectic solvent natural product extract according to one embodiment can be usefully used to improve skin wrinkles.
- Formulations Examples 1 and 5 showed a significant increase in skin color brightness compared to Comparative Formulation Example 1. Specifically, in Formulation Example 5, in which the acidity of the natural eutectic solvent was adjusted to pH 5, it was confirmed that the change in skin color brightness significantly increased.
- the natural eutectic solvent natural product extract according to one embodiment can be usefully used to improve skin whitening.
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Abstract
La présente invention concerne une composition cosmétique, qui présente une cytotoxicité inférieure par rapport à des extraits de solvant organique, en utilisant un solvant eutectique de bétaïne et d'acide citrique dans l'extraction d'un produit naturel, et présente une sécurité et une stabilité améliorées en raison de l'effet de prévention de la décoloration d'un extrait, et peut ainsi être utilisée en tant que produit cosmétique pour améliorer la peau et en tant qu'agent topique de la peau.
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KR20180016352A (ko) * | 2015-04-10 | 2018-02-14 | 나투렉스 에스아 | 공융 추출 용매, 상기 용매를 사용한 공융생성에 의한 추출 방법, 및 상기 추출 방법으로부터 유래된 추출물 |
KR101901451B1 (ko) * | 2018-01-23 | 2018-09-27 | (주)해피엘앤비 | 천연 공융 용매로 추출한 꽃 혼합추출물을 함유하는 화장료 조성물 |
US20200360457A1 (en) * | 2017-10-06 | 2020-11-19 | Plant Advanced Technologies Pat | Root extracts from plants of the morus genus and uses of same |
KR20210157614A (ko) * | 2020-06-22 | 2021-12-29 | 충북대학교 산학협력단 | 천연공융용매를 이용한 녹차추출물의 제조방법 및 이의 용도 |
KR102493443B1 (ko) * | 2022-08-29 | 2023-01-31 | 주식회사 잇츠한불 | 친환경 천연 공융 용매로 추출한 추출물을 포함하는 화장료 조성물 |
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2022
- 2022-08-29 KR KR1020220108583A patent/KR102493443B1/ko active IP Right Grant
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2023
- 2023-08-25 WO PCT/KR2023/012660 patent/WO2024049120A1/fr unknown
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KR20180016352A (ko) * | 2015-04-10 | 2018-02-14 | 나투렉스 에스아 | 공융 추출 용매, 상기 용매를 사용한 공융생성에 의한 추출 방법, 및 상기 추출 방법으로부터 유래된 추출물 |
US20200360457A1 (en) * | 2017-10-06 | 2020-11-19 | Plant Advanced Technologies Pat | Root extracts from plants of the morus genus and uses of same |
KR101901451B1 (ko) * | 2018-01-23 | 2018-09-27 | (주)해피엘앤비 | 천연 공융 용매로 추출한 꽃 혼합추출물을 함유하는 화장료 조성물 |
KR20210157614A (ko) * | 2020-06-22 | 2021-12-29 | 충북대학교 산학협력단 | 천연공융용매를 이용한 녹차추출물의 제조방법 및 이의 용도 |
KR102493443B1 (ko) * | 2022-08-29 | 2023-01-31 | 주식회사 잇츠한불 | 친환경 천연 공융 용매로 추출한 추출물을 포함하는 화장료 조성물 |
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