Antioxidant cosmetic composition

Abstract

The present invention relates to a cosmetic composition having antioxidant activity. According to the present invention, a cosmetic composition is provided that has the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl radicals and exhibits excellent antioxidant effects.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority rights under Republic of Korea Patent Application No. 10-2023-0120961 dated September 12, 2023, Republic of Korea Patent Application No. 10-2024-0099303 dated July 26, 2024, and Republic of Korea Patent Application No. 10-2024-0099304 dated July 26, 2024, and all content disclosed in the literature of said Republic of Korea Patent Applications is incorporated herein by reference.

[0002] The present invention relates to a cosmetic composition having antioxidant activity. [Background technology]

[0003] Oxygen is absolutely essential for the survival of life on Earth.

[0004] However, ground-state triplet oxygen, a stable molecular state, is converted into highly reactive oxygen species such as superoxide radicals, hydroxyl radicals, hydrogen peroxide, and singlet oxygen by various factors including reductive metabolism, enzyme systems in the body, chemicals, photochemical reactions, and pollutants. Reactive oxygen species cause oxygen toxicity that can be fatal to living organisms.

[0005] Reactive oxygen species are known to cause non-selective and irreversible damage to cellular components such as proteins, lipids, sugars, and DNA, leading to aging and various diseases.

[0006] Even in normal cells, some free radicals and reactive oxygen species are generated during metabolic processes. However, the body has antioxidant enzymes such as superoxide dismutase as a defense mechanism against reactive oxygen species. In addition, substances such as vitamin C and vitamin E are known to have antioxidant effects in the body. However, if there is a malfunction in the body's defense mechanism or if the generation of reactive oxygen species exceeds the capacity of the body's defense system, oxidative stress is triggered.

[0007] The discovery of superoxide dismutase led to a serious advancement in antioxidant research. Furthermore, as it became known that reactive oxygen species contribute to aging and lifestyle-related diseases, research on antioxidants has become increasingly active.

[0008] However, various commercial antioxidants have numerous problems, including human toxicity, low activity, and limited applications, and there remains a strong demand for antioxidant compositions that are free from these issues. [Overview of the project] [Problems that the invention aims to solve]

[0009] This invention provides an antioxidant cosmetic composition.

[0010] Furthermore, the present invention provides an antioxidant pharmaceutical composition. [Means for solving the problem]

[0011] According to one embodiment of the invention, an antioxidant cosmetic composition is provided which contains 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

[0012] According to another embodiment of the invention, uses of 3-hydroxypropionic acid or its derivatives for the manufacture of antioxidant cosmetics are provided.

[0013] According to still other embodiments of the invention, there is provided a method for protecting skin from oxidative stress by using a cosmetic composition containing 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

[0014] According to still other embodiments of the invention, there is provided an antioxidant pharmaceutical composition containing 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

[0015] According to still other embodiments of the invention, there is provided the use of 3-hydroxypropionic acid or a derivative thereof for the manufacture of an antioxidant agent.

[0016] According to still other embodiments of the invention, there is provided a method for protecting the body from oxidative stress by using a pharmaceutical composition containing 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

[0017] Hereinafter, the antioxidant cosmetic composition and the antioxidant pharmaceutical composition according to the embodiments of the invention will be described in more detail.

[0018] The terms and words used in this specification and the claims should not be construed as being limited to their ordinary or dictionary meanings. In accordance with the principle that the inventor can appropriately define the concept of the terms in order to explain his invention in the best way, they should be construed in a meaning and concept consistent with the technical idea of the invention.

[0019] Unless otherwise defined herein, all technical and scientific terms have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terms used in the description of the present invention are merely for the purpose of effectively describing specific examples and are not intended to limit the present invention.

[0020] Although the present invention can be modified in various ways and can have various forms, specific embodiments will be illustrated and described in detail below. However, this is not intended to limit the present invention to a specific disclosed form, and it should be understood that it includes all modifications, equivalents, or alternatives included in the above idea and technical scope.

[0021] As used herein, the singular forms also include the plural forms unless the context clearly indicates the contrary meaning.

[0022] As used herein, the meaning of "comprising" does not exclude the presence or addition of other specific characteristics, regions, integers, steps, operations, elements, and / or components while embodying a specific characteristic, region, integer, step, operation, element, and / or component.

[0023] In this specification, for example, when temporal precedence is described by "after ~", "subsequent to ~", "next to ~", "before ~", etc., it can include non-consecutive cases as long as the expressions "immediately" or "directly" are not used.

[0024] In this specification, the term "derivative" means a compound in which the structure and properties of the parent compound of an organic compound are changed within the limit that they are not significantly changed by reactions such as introduction of a functional group, oxidation, reduction, substitution of atoms, etc.

[0025] In this specification, the term "comprising as an active ingredient" means that the composition according to an embodiment of the invention contains 3-hydroxypropionic acid or a derivative thereof in an amount sufficient to achieve an antioxidant effect.

[0026] In this specification, "antioxidant" means protecting the body (e.g., skin) from oxidative stress. Oxidative stress occurs naturally in normal metabolic processes, but if it is produced or accumulated in excess, it can damage DNA and cells, inducing aging and chronic diseases. The body has an antioxidant system that removes oxidation-inducing substances, but oxidation processes can be prevented or avoided by taking antioxidants.

[0027] In this specification, the term "prevention" means suppression of the occurrence of symptoms caused by reactive oxygen species. In this specification, the term "treatment" means reduction or elimination of symptoms caused by reactive oxygen species that have already occurred. And in this specification, the term "improvement" means reduction or mitigation of symptoms caused by reactive oxygen species.

[0028] As a result of our continued research, we have confirmed that 3-hydroxypropionic acid can exhibit excellent antioxidant effects, such as preventing, alleviating, or improving symptoms caused by reactive oxygen species.

[0029] In particular, 3-hydroxypropionic acid has the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals, and cosmetic compositions containing 3-hydroxypropionic acid or its derivatives as an active ingredient can exhibit excellent antioxidant effects.

[0030] According to one embodiment of the invention, an antioxidant cosmetic composition is provided which contains 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

[0031] The antioxidant cosmetic composition contains 3-hydroxypropionic acid or a derivative thereof as an active ingredient. Preferably, the antioxidant cosmetic composition contains 3-hydroxypropionic acid as an active ingredient.

[0032] 3-hydroxypropionic acid can be used as an active ingredient if it is synthesized by chemical or biological methods.

[0033] According to one embodiment, 3-hydroxypropionic acid obtained by a biological process such as fermenting a bacterial strain capable of producing 3-hydroxypropionic acid can preferably be used as the active ingredient. The 3-hydroxypropionic acid obtained by the above method is a radioactive carbon isotope ( 14 C) May include.

[0034] Preferably, the active ingredient may have a radioactive carbon isotope content of 20 pMC (percent modern carbon) or more as measured according to ASTM D6866-21, and a biocarbon content of 20% by weight or more. Specifically, the active ingredient may have a radioactive carbon isotope content of 20 pMC or more, or 50 pMC or more, or 90 pMC or more, or 100 pMC or more, or 90-110 pMC as measured according to ASTM D6866-21; and a biocarbon content of 20% by weight or more, or 50% by weight or more, or 80% by weight or more, or 90% by weight or more, or 95% by weight or more, or 90-100% by weight.

[0035] The radioactive carbon isotope content (pMC) is the amount of radioactive carbon isotopes contained in 3-hydroxypropionic acid ( 14 C) and radioactive carbon isotopes of modern reference materials ( 14 This refers to the ratio of C). For reference, since the effects of the 1950s nuclear test program are still in effect and have not disappeared, the radioactive carbon isotope content (pMC) may be greater than 100%.

[0036] The biocarbon content mentioned above represents the biocarbon content relative to the total carbon content of 3-hydroxypropionic acid. A higher value indicates a more environmentally friendly compound.

[0037] If the content of the radiocarbon isotope (pMC) and the content of biocarbon of the 3-hydroxypropionic acid are excessively low, the environmental consideration will decrease and it will not be regarded as a bio-derived substance.

[0038] The radiocarbon isotope ( 14 C) is about 1 per 1×10 carbon atoms in the Earth's atmosphere, has a half-life of about 5700 years, and can be abundantly present in the upper atmosphere by nuclear reactions in which cosmic rays and ordinary nitrogen ( 12 N) participate. 14 N) participate. Fossil fuels can have a substantially zero ratio of 14 C because the radiocarbon isotope has decayed over a long time. When using bio-derived substances as raw materials for 3-hydroxypropionic acid or using fossil fuels in combination with them, the content (pMC) of the radiocarbon isotope and the content of biocarbon contained in 3-hydroxypropionic acid can be measured according to ASTM D6866-21 standard.

[0039] The measurement method can be, for example, converting the carbon atoms contained in the compound to be measured into the form of graphite or carbon dioxide gas and measuring with a mass spectrometer, or measuring by liquid scintillation spectrometry. At this time, 14 C ions can 12 be separated from C ions, and an accelerator may be used. Also, the two isotopes can be separated and the content and content ratio can be measured with a mass spectrometer.

[0040] The cosmetic composition for antioxidation can exhibit the DPPH radical scavenging ability by the action of the active ingredient. The DPPH radical shows a deep purple color. The DPPH radical is reduced by the antioxidation active ingredient, and the deep purple color decolorizes. Using such characteristics, the performance of the antioxidation active ingredient can be measured.

[0041] According to one embodiment, the cosmetic composition can contain 0.5 wt% to 80 wt% of the active ingredient based on the total weight of the cosmetic composition.

[0042] Specifically, the cosmetic composition may contain the active ingredient in an amount of 0.5% or more by weight, or 1% or more by weight, and 80% or less by weight, or 75% or less by weight, or 70% or less by weight, based on the total weight of the cosmetic composition.

[0043] In order to ensure that the antioxidant effect is sufficiently achieved by the action of the active ingredient, the cosmetic composition preferably contains 0.5% or more by weight of the active ingredient, or 1% or more by weight of the active ingredient.

[0044] However, if the active ingredient is present in excess, the antioxidant effect may decrease or side effects may occur. For this reason, it is preferable that the cosmetic composition contains the active ingredient in an amount of 80% by weight or less, or 75% by weight or less, or 70% by weight or less.

[0045] Preferably, the cosmetic composition may contain the active ingredient in an amount of 0.5% to 80% by weight, or 0.5% to 75% by weight, or 1% to 75% by weight, or 1% to 70% by weight, based on the total weight of the cosmetic composition.

[0046] According to one embodiment, the cosmetic composition may have a common cosmetic dosage form in the art to which the present invention belongs. For example, the cosmetic composition may have a dosage form such as a solution, suspension, emulsion, paste, gel, cream, lotion, powder, oil, foam, pack, spray, aerosol, balm, solid soap, liquid soap, powder foundation, emulsion foundation, or wax foundation.

[0047] According to one embodiment, the cosmetic composition may contain, in addition to the active ingredient, organic solvents, fatty substances, solvents, concentrates, gelling agents, softening agents, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, emulsifiers, fillers, chelating agents, preservatives, vitamins, wetting agents, dyes, pigments, hydrophilic or lipophilic surfactants, and the like. Furthermore, the cosmetic composition may contain auxiliary agents commonly used in the fields of cosmetic science or dermatology.

[0048] The cosmetic composition may further include a physiologically acceptable medium, which is composed of water or a mixture of an organic solvent and water.

[0049] As an example, the organic solvent can be a C1-C4 lower alcohol such as acetone, ethanol, and isopropyl alcohol; an alkylene glycol such as ethylene glycol and propylene glycol; ethylene glycol monomethyl ether, monoethyl ether, monobutyl ether, or propylene glycol. The physiologically acceptable medium may be applied in an amount of 1 to 90% by weight relative to the total weight of the cosmetic composition.

[0050] The medium can be thickened using a thickening agent commonly used in cosmetics or pharmaceuticals. The thickening agent may be applied in an amount of 0.1 to 5% by weight relative to the total weight of the composition.

[0051] Furthermore, depending on the various embodiments of the cosmetic composition, an ordinary technician can select the auxiliary agents commonly required to manufacture such a composition. As an example, the auxiliary agents that can be used include preservatives, stabilizers, pH adjusters, osmotic pressure modifiers, emulsifying agents, light-blocking agents, antioxidants, fragrances, dyes, anionic surfactants, cationic surfactants, nonionic surfactants, and amphoteric surfactants.

[0052] According to one embodiment, when the dosage form of the cosmetic composition is a powder or a spray, it may contain carrier components such as lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder.

[0053] According to one embodiment, if the dosage form of the cosmetic composition is a paste, gel, or cream, it may contain carrier components such as animal oils, vegetable oils, waxes, paraffin, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicones, bentonite, silica, talc, and zinc oxide.

[0054] According to one embodiment, when the dosage form of the cosmetic composition is a solution or emulsion, it may contain carrier components such as a solvent, solubilizer, or emulsifier. For example, the solution or emulsion dosage form can include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan.

[0055] According to one embodiment, when the dosage form of the cosmetic composition is a suspension, liquid diluents such as water, ethanol, or propylene glycol; suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester; and microcrystalline cellulose, aluminum methhydroxyl, bentonite, etc. can be used.

[0056] According to one example, if the dosage form of the cosmetic composition is a cleanser containing a surfactant, it may contain carrier components such as aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinate monoester, isethionate, imidazolinium derivative, sodium methyl cocoyl taurate, sodium lauroyl sarcosinate, fatty acid amide ether sulfate, alkylamide betaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, and ethoxylated glycerol fatty acid ester.

[0057] According to another embodiment of the invention, uses of 3-hydroxypropionic acid or its derivatives for the manufacture of antioxidant cosmetics are provided.

[0058] Preferably, uses of 3-hydroxypropionic acid or its derivatives for the production of the antioxidant cosmetic compositions described above are provided.

[0059] 3-Hydroxypropionic acid has DPPH radical scavenging ability, and cosmetic compositions containing 3-hydroxypropionic acid or its derivatives as an active ingredient can be used for antioxidant purposes.

[0060] In the above-mentioned applications, the active ingredient, 3-hydroxypropionic acid or its derivative, may be used in an amount of 0.5% to 80% by weight based on the total weight of the cosmetic composition.

[0061] In order to ensure that the antioxidant effect is sufficiently achieved by the action of the active ingredient, it is preferable that the active ingredient be used in an amount of 0.5% or more by weight, or 1% or more by weight, based on the total weight of the cosmetic composition. However, if the active ingredient is used in excess, the antioxidant effect may decrease, or side effects may occur. For this reason, it is preferable that the active ingredient be used in an amount of 80% or less by weight, or 75% or less by weight, or 70% or less by weight, based on the total weight of the cosmetic composition. Preferably, the active ingredient may be used in an amount of 0.5% to 80% by weight, or 0.5% to 75% by weight, or 1% to 75% by weight, or 1% to 70% by weight, based on the total weight of the cosmetic composition.

[0062] According to yet another embodiment of the invention, a method is provided for protecting the skin from oxidative stress using a cosmetic composition comprising 3-hydroxypropionic acid or a derivative thereof as an active ingredient. Specifically, a method is provided for scavenging 2,2-diphenyl-1-picrylhydrazyl radicals using a cosmetic composition comprising 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

[0063] Preferably, the method for protecting the skin from oxidative stress may be carried out using the antioxidant cosmetic composition described above. The method may be carried out by applying the cosmetic composition to a part of the human body where antioxidant protection is required. The method may be carried out for a period of 1 to 6 months, 1 to 7 days a week, and 1 to several times a day (for example, 1 to 5 times or 1 to 3 times).

[0064] According to yet another embodiment of the invention, an antioxidant pharmaceutical composition is provided comprising 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

[0065] As a result of our continued research, we have confirmed that 3-hydroxypropionic acid can exhibit excellent antioxidant effects, such as preventing or treating symptoms caused by reactive oxygen species.

[0066] In particular, 3-hydroxypropionic acid has the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals, and pharmaceutical compositions containing 3-hydroxypropionic acid or its derivatives as an active ingredient can exhibit excellent antioxidant effects.

[0067] The antioxidant pharmaceutical composition contains 3-hydroxypropionic acid or a derivative thereof as an active ingredient. Preferably, the antioxidant pharmaceutical composition contains 3-hydroxypropionic acid as an active ingredient.

[0068] 3-hydroxypropionic acid can be used as an active ingredient if it is synthesized by chemical or biological methods.

[0069] According to one embodiment, as the active ingredient, 3-hydroxypropionic acid obtained by a biological process such as fermenting a bacterial strain capable of producing 3-hydroxypropionic acid can be preferably used. The 3-hydroxypropionic acid obtained by the above method is a radioactive carbon isotope ( 14 C) May include.

[0070] Preferably, the active ingredient may have a radioactive carbon isotope content of 20 pMC (percent modern carbon) or more as measured according to ASTM D6866-21, and a biocarbon content of 20% by weight or more. Specifically, the active ingredient may have a radioactive carbon isotope content of 20 pMC or more, or 50 pMC or more, or 90 pMC or more, or 100 pMC or more, or 90-110 pMC as measured according to ASTM D6866-21; and a biocarbon content of 20% by weight or more, or 50% by weight or more, or 80% by weight or more, or 90% by weight or more, or 95% by weight or more, or 90-100% by weight.

[0071] The aforementioned antioxidant pharmaceutical composition can exhibit the DPPH radical scavenging ability through the action of the active ingredient. The DPPH radical exhibits a deep purple color. The DPPH radical is reduced by the antioxidant active ingredient, and the deep purple color disappears. The performance of the antioxidant active ingredient can be measured by utilizing this property.

[0072] According to one embodiment, the pharmaceutical composition may contain the active ingredient in an amount of 0.5% to 80% by weight, based on the total weight of the pharmaceutical composition.

[0073] Specifically, the pharmaceutical composition may contain the active ingredient in an amount of 0.5% or more by weight, or 1% or more by weight, and 80% or less by weight, or 75% or less by weight, or 70% or less by weight, based on the total weight of the pharmaceutical composition.

[0074] In order to ensure that the antioxidant effect is sufficiently achieved by the action of the active ingredient, the pharmaceutical composition preferably contains 0.5% or more by weight of the active ingredient, or 1% or more by weight of the active ingredient.

[0075] However, if the active ingredient is present in excess, the antioxidant effect may decrease or side effects may occur. For this reason, it is preferable that the pharmaceutical composition contains the active ingredient in an amount of 80% by weight or less, or 75% by weight or less, or 70% by weight or less.

[0076] Preferably, the pharmaceutical composition may contain the active ingredient in an amount of 0.5% to 80% by weight, or 0.5% to 75% by weight, or 1% to 75% by weight, or 1% to 70% by weight, based on the total weight of the pharmaceutical composition.

[0077] The aforementioned pharmaceutical composition may further contain a pharmaceutically acceptable carrier.

[0078] The carrier can be any material commonly used in the formulation of pharmaceutical compositions, without any particular limitations. For example, the carrier may be sucrose, sorbitol, mannitol, lactose, dextrose, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, propyl 4-hydroxybenzoate, talc, magnesium stearate, mineral oil, etc. Pharmaceutically acceptable carriers and formulations are described in detail in Remington's The Science and Practice of Pharmacy (23rd Edition, 2020).

[0079] The pharmaceutical composition may be administered orally or parenterally. When administered parenterally, methods such as topical application, subcutaneous injection, intravenous injection, intramuscular injection, intraperitoneal injection, and transdermal administration are applicable.

[0080] The appropriate dosage of the pharmaceutical composition can be determined by comprehensively considering factors such as the patient's age, weight, sex, formulation method, administration method, and administration time.

[0081] The pharmaceutical composition may be formulated by applying pharmaceutically acceptable carriers and / or excipients. The dosage form of the pharmaceutical composition may be a solution in an aqueous medium or oil, a suspension, an emulsion, an ointment, a powder, granules, a tablet, or a capsule.

[0082] According to yet another embodiment of the invention, uses of 3-hydroxypropionic acid or derivatives for the manufacture of antioxidant agents are provided.

[0083] Preferably, uses of 3-hydroxypropionic acid or its derivatives for the production of the above-described antioxidant pharmaceutical compositions are provided.

[0084] 3-hydroxypropionic acid has DPPH radical scavenging ability, and pharmaceutical compositions containing 3-hydroxypropionic acid or its derivatives as an active ingredient can be used for antioxidant purposes.

[0085] In the above-mentioned applications, the active ingredient, 3-hydroxypropionic acid or its derivative, may be used in an amount of 0.5% to 80% by weight based on the total weight of the pharmaceutical composition.

[0086] In order to ensure that the antioxidant effect is sufficiently achieved by the action of the active ingredient, it is preferable that the active ingredient is used in an amount of 0.5% or more by weight, or 1% or more by weight, based on the total weight of the pharmaceutical composition. However, if the active ingredient is used in excess, the antioxidant effect may decrease, or side effects may occur. For this reason, it is preferable that the active ingredient is used in an amount of 80% or less by weight, or 75% or less by weight, or 70% or less by weight, based on the total weight of the pharmaceutical composition. Preferably, the active ingredient may be used in an amount of 0.5% to 80% by weight, or 0.5% to 75% by weight, or 1% to 75% by weight, or 1% to 70% by weight, based on the total weight of the pharmaceutical composition.

[0087] According to yet another embodiment of the invention, a method is provided for protecting the body from oxidative stress using a pharmaceutical composition comprising 3-hydroxypropionic acid or a derivative thereof as an active ingredient. Specifically, a method is provided for scavenging 2,2-diphenyl-1-picrylhydrazyl radicals using a pharmaceutical composition comprising 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

[0088] Preferably, the method for protecting the body from oxidative stress may be carried out using the antioxidant pharmaceutical compositions described above. The method may be administered orally or parenterally. The method may be administered for a period of 1 to 6 months, 1 to 7 days a week, and 1 to several times a day (for example, 1 to 5 times or 1 to 3 times). The method may be carried out in accordance with standard procedures, taking into account factors such as the patient's age, weight, sex, dosage form of 3-hydroxypropionic acid or its derivatives, method of administration, and timing of administration. [Effects of the Invention]

[0089] The present invention provides cosmetic and pharmaceutical compositions that possess 2,2-diphenyl-1-picrylhydrazyl radical scavenging ability and exhibit excellent antioxidant effects. [Brief explanation of the drawing]

[0090] [Figure 1] This image shows the results of the skin tissue cell stability experiment using Experimental Example 2. [Modes for carrying out the invention]

[0091] The function and effects of the invention will be explained in more detail below through specific embodiments of the invention. However, these are presented as examples for understanding the invention. It is not intended that the scope of the invention's rights be limited in any sense through the following embodiments, and it will be obvious to a person of the skill that various changes and modifications are possible within the scope of the invention and its technical concept.

[0092] Manufacturing Example 1 Recombinant vectors were prepared by introducing genes encoding glycerol dehydratase and aldehyde dehydrogenase, which are known to produce 3-hydroxypropionic acid using glycerol as a substrate. These recombinant vectors were introduced into E. coli W3110 strain to create a strain for 3-hydroxypropionic acid production.

[0093] Specifically, the BtuR gene encoding adenosyltransferase was cloned into a plasmid pCDF containing the genes encoding glycerol dehydratase (dhaB), aldehyde dehydrogenase (aldH), and glycerol dehydratase reactivase (gdrAB) to obtain the pCDF_J23101_dhaB_gdrAB_J23100_aldH_btuR vector. This vector was introduced into the W3110 strain (KCCM40219) using electroporation with an electroporation device (Bio-Rad, Gene Pulser Xcell) to create a strain for 3-hydroxypropionic acid production.

[0094] The aforementioned 3-hydroxypropionic acid production strain was fermented in a 5L fermenter at 35°C using unpurified glycerol as a carbon source to produce 3-hydroxypropionic acid. To prevent a decrease in pH due to the production of 3-hydroxypropionic acid, calcium hydroxide (Ca(OH)2), an alkali metal salt, was added to maintain a neutral pH during fermentation.

[0095] After fermentation culture, cells were removed by centrifugation (4000 rpm, 10 minutes, 4°C), and primary purification was carried out using activated carbon. The concentration of 3-hydroxypropionic acid in the fermentation liquid after the primary purification was at the level of 50-100 g / L, and it was concentrated to 600 g / L using a rotary evaporator (50°C, 50 mbar), and Ca(3HP)2 crystals were produced by stirring at room temperature (300 rpm).

[0096] The crystals were washed three times with ethanol, dried in an oven at 50°C, and finally recovered. The weight of the crystals was measured, and the crystals were dissolved in water to obtain 3-hydroxypropionic acid (3HP) using high-performance liquid chromatography (HPLC).

[0097] Manufacturing Example 2 3-hydroxypropionic acid (3HP) was obtained by a method substantially the same as in Production Example 1, except that Mg(OH)2 was used instead of Ca(OH)2 as the alkali metal salt.

[0098] Example 1 A lotion was prepared by mixing 1% by weight of 3-hydroxypropionic acid obtained in Production Example 1, 0.5% by weight of hydroxyethylcellulose, 2% by weight of cetostearyl alcohol, 2% by weight of stearyltriethylammonium chloride, and the remaining purified water (total 100% by weight).

[0099] Example 2 A lotion was prepared by mixing 5% by weight of 3-hydroxypropionic acid obtained in Production Example 1, 0.5% by weight of hydroxyethylcellulose, 2% by weight of cetostearyl alcohol, 2% by weight of stearyltriethylammonium chloride, and the remaining purified water (total 100% by weight).

[0100] Example 3 A toner emulsion was prepared by mixing 1% by weight of 3-hydroxypropionic acid obtained in Production Example 1, 55% by weight of ethanol, 3% by weight of glycerin, 5% by weight of castor oil, and the remaining purified water (total 100% by weight).

[0101] Example 4 A toner emulsion was prepared by mixing 5% by weight of 3-hydroxypropionic acid, 55% by weight of ethanol, 3% by weight of glycerin, 5% by weight of castor oil, and the remaining purified water (total 100% by weight) obtained in Production Example 1.

[0102] Example 5 A toner emulsion was prepared by mixing 10% by weight of 3-hydroxypropionic acid, 55% by weight of ethanol, 3% by weight of glycerin, 5% by weight of castor oil, and the remaining purified water (total 100% by weight) obtained in Production Example 1.

[0103] Example 6 A pharmaceutical composition in the form of an ointment was prepared by mixing 1% by weight of 3-hydroxypropionic acid, 0.5% by weight of hydroxyethylcellulose, 2% by weight of cetostearyl alcohol, 2% by weight of stearyltriethylammonium chloride, and the remainder of purified water (total 100% by weight) obtained in Production Example 1.

[0104] Example 7 A pharmaceutical composition in the form of an ointment was prepared by mixing 5% by weight of 3-hydroxypropionic acid, 0.5% by weight of hydroxyethylcellulose, 2% by weight of cetostearyl alcohol, 2% by weight of stearyltriethylammonium chloride, and the remainder of purified water (total 100% by weight) obtained in Production Example 1.

[0105] Example 8 A pharmaceutical composition in the form of an emulsion was prepared by mixing 1% by weight of 3-hydroxypropionic acid, 55% by weight of ethanol, 3% by weight of glycerin, 5% by weight of castor oil, and the remainder of purified water (total 100% by weight) obtained in Production Example 1.

[0106] Example 9 A pharmaceutical composition in the form of an emulsion was prepared by mixing 5% by weight of 3-hydroxypropionic acid, 55% by weight of ethanol, 3% by weight of glycerin, 5% by weight of castor oil, and the remainder of purified water (total 100% by weight) obtained in Production Example 1.

[0107] Example 10 A pharmaceutical composition in the form of an emulsion was prepared by mixing 10% by weight of 3-hydroxypropionic acid, 55% by weight of ethanol, 3% by weight of glycerin, 5% by weight of castor oil, and the remainder of purified water (total 100% by weight) obtained in Production Example 1.

[0108] Experimental Example 1 (Measurement of radioactive carbon isotope and biocarbon content) The radiocarbon isotope content (pMC) and biocarbon content of 3-hydroxypropionic acid obtained in Production Examples 1 and 2 were measured using ASTM D6866-21 (Method B).

[0109] The biocarbon content refers to the biocarbon content contained in the 3-hydroxypropionate crystals obtained in Production Examples 1 and 2, and the ratio of radiocarbon isotopes (pMC) refers to the radiocarbon isotopes contained in the 3-hydroxypropionate crystals. 14 C) and radioactive carbon isotopes of modern reference materials ( 14 This refers to the ratio of C). [Table 1]

[0110] Referring to Table 1 above, it was confirmed that both the 3HP salt crystals of production examples 1 and 2 had a radioactive carbon isotope ratio of 10¹ pMC or higher and a biocarbon content of 100% by weight.

[0111] Experimental Example 2 (Skin tissue cell stability experiment) 1) Culture of explant tissue Human skin tissue provided for research purposes (IRB No. 4-2023-0054; Yonsei University College of Medicine, Severance Medical Center Bioethics Committee) had its fat removed, and residual impurities were removed by washing it several times with PBS (phosphate buffered saline; Lonza). Each test group was then prepared in 1cm x 1cm sections, and the test composition was applied to the prepared skin tissue. The negative control group was coated with PBS. After absorption of the test composition was complete, the skin tissue was cultured in a dedicated medium at 37°C and 5% CO2.

[0112] 2) HE (Hematoxylin eosin) staining Tissue obtained 24 hours after application of the test composition was fixed with 10% formalin, and paraffin blocks and paraffin-embedded slides were prepared. The nuclei of the deparaffinized tissue were stained with hematoxylin (S3309; dako) solution and then washed with running water. After staining the cytoplasm with eosin (318906; sigma) solution and undergoing the washing process, the completely dehydrated tissue was fixed using a mounting solution, and the epidermis and dermal papillary layer of the fixed tissue were photographed at 400x magnification using an optical microscope (BX43F; OLYMPUS). As shown in Figure 1, no damage to the epidermis or separation between tissues was observed in skin tissue treated with 1%, 5%, and 10% concentrations of 3HP.

[0113] Experimental Example 3 (Control Group) The 3HP aqueous solution obtained in Production Example 1 was prepared at five concentrations (0% by weight, 1% by weight, 5% by weight, 10% by weight, and 70% by weight). 50 μl of each 3HP aqueous solution and 150 μl of methanol were dispensed into a 96-well plate and reacted at room temperature for 30 minutes. The absorbance (OD) of the reaction was then measured. 対照群 The measurement was repeated three times at a wavelength of 520 nm.

[0114] Experimental Example 4 (Negative Control Group) An aqueous solution of DPPH (free radical, 95%, Alfa Aesar) with a concentration of 0.5 mM was prepared. 50 μl of methanol and 150 μl of the DPPH aqueous solution were dispensed into a 96-well plate and reacted at room temperature for 30 minutes. The absorbance (OD) of the resulting solution was measured. 陰性対照群 The measurement was repeated three times at a wavelength of 520 nm.

[0115] Experimental Example 5 (Experimental Group) An aqueous solution of DPPH (free radicals, 95%, Alfa Aesar) with a concentration of 0.5 mM was prepared. The 3HP aqueous solution obtained in the above production example was prepared at five concentrations (0 wt%, 1 wt%, 5 wt%, 10 wt%, and 70 wt%). 50 μl of each 3HP aqueous solution and 150 μl of the DPPH aqueous solution were dispensed into a 96-well plate and reacted at room temperature for 30 minutes. The absorbance (OD) of the resulting solution was measured. 実験群 The measurement was repeated three times at a wavelength of 520 nm.

[0116] The absorbance at a wavelength of 520 nm was measured using a microreader. The DPPH radical scavenging capacity (antioxidant capacity) of 3HP was calculated using Equation 1 below, and the results are shown in the table below. [Formula 1] Antioxidant power (%)={[(OD 陰性対照群 -OD 対照群 )-(OD 実験群 -OD 対照群 )] / (OD 陰性対照群 -OD 対照群 )} × 100 [Table 2] [Table 3] [Table 4] [Table 5]

[0117] Based on the experimental results described above, it was confirmed that 3-hydroxypropionic acid exhibits significant DPPH radical scavenging ability at the treatment concentration.

[0118] Dosage Form Example 1 A softening lotion (skin lotion) is prepared by mixing 0.2% by weight of 3-hydroxypropionic acid according to the above-mentioned Production Example 1, 3.0% by weight of glycerin, 2.0% by weight of butylene glycol, 2.0% by weight of propylene glycol, 0.1% by weight of polyacrylic acid, 0.2% by weight of polyethylene glycol-12 nonylphenyl ether, 0.4% by weight of polysorbate-80, 10.0% by weight of ethanol, 0.1% by weight of triethanolamine, and the remainder of purified water.

[0119] Dosage Form Example 2 A nourishing lotion (milk lotion) is prepared by mixing 1.0% by weight of 3-hydroxypropionic acid according to the above-mentioned Production Example 1, 3.0% by weight of glycerin, 3.0% by weight of butylene glycol, 0.5% by weight of liquid paraffin, 4.0% by weight of beeswax, 5.0% by weight of caprylic / capric triglyceride, 5.0% by weight of squalene, 1.5% by weight of polysorbate-60, 1.0% by weight of cetearyl alcohol, 1.5% by weight of sorbitan sesquioleate, 0.1% by weight of polyacrylic acid, 0.2% by weight of triethanolamine, and the remainder of purified water.

[0120] Dosage Form Example 3 A nourishing cream is prepared by mixing 2.0% by weight of 3-hydroxypropionic acid according to the above-mentioned Production Example 1, 3.0% by weight of glycerin, 3.0% by weight of butylene glycol, 7.0% by weight of liquid paraffin, 7.0% by weight of beta-glucan, 3.0% by weight of caprylic / capric triglyceride, 5.0% by weight of squalene, 1.5% by weight of cetearyl glucoside, 1.2% by weight of polysorbate-60, 0.4% by weight of sorbitan stearate, 0.1% by weight of polyacrylic acid, 0.1% by weight of triethanolamine, and the remainder of purified water.

[0121] Dosage Form Example 4 8 mg of 3-hydroxypropionic acid, 9 mg of vitamin C, 9 mg of vitamin E, 200 mg of lactose, and 200 mg of galactooligosaccharide are mixed according to the above production example 1, granulated using a fluid bed dryer, and then 5 mg of sugar ester is added to produce a tablet composition. 500 mg of the tablet composition is compressed into tablets to produce tablets.

[0122] Dosage Form Example 5 A soft capsule filling solution is prepared by mixing 8 mg of 3-hydroxypropionic acid, 9 mg of vitamin C, 9 mg of vitamin E, 10 mg of hydrogenated vegetable oil, and 9 mg of lecithin according to the above-mentioned Production Example 1. Separately, a soft capsule sheet is prepared by mixing gelatin (65% by weight), glycerin (25% by weight), and sorbitol solution (10% by weight). Soft capsules are prepared by filling each capsule with 400 mg of the soft capsule filling solution.

[0123] Dosage Form Example 6 8 mg of 3-hydroxypropionic acid, 9 mg of vitamin C, 9 mg of vitamin E, 500 mg of starch, and 200 mg of anhydrous crystalline glucose are mixed according to the above-mentioned Production Example 1, formed into granules using a fluid bed granulator, and then filled into packets to produce a granular preparation.

[0124] Dosage Form Example 7 After mixing 8 mg of 3-hydroxypropionic acid, 9 mg of vitamin C, 9 mg of vitamin E, 0.7 g of citric acid, 10 g of glucose, and 25 g of liquid oligosaccharide according to the above production example 1, 300 ml of purified water is added to produce a drinkable composition. The drinkable composition is filled into bottles in 200 ml portions and sterilized at 130°C for approximately 5 seconds to produce a drinkable product.

[0125] Dosage Form Example 8 A solution is prepared by mixing 30 mg of 3-hydroxypropionic acid according to the above-mentioned Production Example 1, an appropriate amount of sterile distilled water for injection, and an appropriate amount of pH adjuster.

[0126] Although the present invention has been described above, even if only by limited embodiments, the present invention is not limited thereto, and of course, a wide range of modifications and variations are possible by persons with ordinary skill in the art to which the present invention pertains, within the equivalent scope of the technical concept of the present invention and the claims described below.

Claims

1. An antioxidant cosmetic composition comprising 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

2. The aforementioned cosmetic composition is an antioxidant cosmetic composition according to claim 1, having the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl radicals.

3. The antioxidant cosmetic composition according to claim 1, wherein the cosmetic composition contains 0.5% to 80% by weight of the active ingredient based on the total weight of the composition.

4. The antioxidant cosmetic composition according to claim 1, wherein the active ingredient has a radioactive carbon isotope content of 20 pMC (percent modern carbon) or more as measured by ASTM D6866-21 standard, and a biocarbon content of 20% by weight or more.

5. The antioxidant cosmetic composition according to claim 1, further comprising a physiologically acceptable medium.

6. The antioxidant cosmetic composition according to claim 1, wherein the cosmetic composition has a dosage form of a solution, suspension, emulsion, paste, gel, cream, lotion, powder, oil, foam, pack, spray, aerosol, balm, solid soap, liquid soap, powder foundation, emulsion foundation, or wax foundation.

7. An antioxidant pharmaceutical composition comprising 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

8. The above-mentioned pharmaceutical composition is an antioxidant pharmaceutical composition according to claim 7, having the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl radicals.

9. The antioxidant pharmaceutical composition according to claim 7, wherein the pharmaceutical composition contains 0.5% to 80% by weight of the active ingredient based on the total weight of the composition.

10. The antioxidant pharmaceutical composition according to claim 7, wherein the active ingredient has a radioactive carbon isotope content of 20 pMC (percent modern carbon) or more as measured by ASTM D6866-21 standard, and a biocarbon content of 20% by weight or more.

11. The antioxidant pharmaceutical composition according to claim 7, further comprising a pharmaceutically acceptable carrier.

12. The antioxidant pharmaceutical composition according to claim 7, wherein the pharmaceutical composition is for oral or parenteral use.

13. Uses of 3-hydroxypropionic acid or its derivatives for the manufacture of antioxidant cosmetics or antioxidant drugs.

14. A method for protecting the body from oxidative stress using a cosmetic composition or pharmaceutical composition containing 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

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