Ages-degrading agent
A novel AGE decomposer using specific plant extracts addresses the inefficiency of existing technologies by effectively decomposing AGEs, providing anti-glycation effects for disease prevention and tissue health.
Patent Information
- Application Number
- JP2025010658
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-01-24
- Filing Date
- 2025-01-24
- Publication Date
- 2025-08-05
AI Technical Summary
Existing technologies lack effective agents to efficiently decompose advanced glycation end products (AGEs), which contribute to diseases such as diabetic complications, Alzheimer's disease, cataracts, and arteriosclerosis, and tissue aging, as the activity of proteolytic enzymes declines with age.
A novel AGE decomposer containing extracts from rose (Rose rugosa cv. Plena), N-acetylneuraminic acid, tea plant (Camellia sinensis) flower, saffron (Crocus sativus), Daiyohana (Citrus aurantium) powder, nicotinamide mononucleotide, Dendrobium (Dendrobium officinale) flower, Saccharomyces lysate, carcinine, camellia (Camellia japonica) seed, Bupleurum falcatum, and iris (Iris Florentina) root, which have been discovered to possess AGE-degrading activity.
These agents effectively decompose AGEs, offering anti-glycation effects and potential therapeutic benefits for diseases and tissue aging, and can be used in cosmetics and foods.
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Abstract
Description
[Technical Field]
[0001] The present invention relates to a novel agent for decomposing AGEs, and to cosmetics and / or foods having anti-glycation effects that contain this novel agent for decomposing AGEs. [Background technology]
[0002] Oxidation and glycation reactions in vivo are known to have adverse effects on cells and tissues. In particular, the production and accumulation of proteins that have undergone oxidation or glycation, i.e., oxidized proteins or glycated proteins, is a cause of diseases such as diabetic complications, Alzheimer's disease, cataracts, and arteriosclerosis, as well as aging and functional decline in tissues such as the skin. For this reason, these oxidized and glycated proteins are called damaged proteins. In particular, the accumulation of AGEs (advanced glycation end products), end products resulting from nonenzymatic addition reactions of sugars to proteins, is considered problematic.
[0003] Normally, these damaged proteins are degraded and removed by proteolytic enzymes such as proteases and oxidized protein hydrolases (hereinafter referred to as "OPHs"). However, the activity of these enzymes declines with age. Therefore, enhancing the activity of these enzymes is expected to be useful in treating and preventing the diseases, tissue aging, and tissue functional decline.
[0004] Prior art has disclosed that substances that activate the protease include soybean saponin, kale extract, silybin, Bletilla striata compounds, and iris extract (Patent Documents 1 to 5). On the other hand, OPH is a type of serine protease, and substances that activate it are known to be Roman chamomile, Houttuynia cordata, hawthorn, grapes, and the like (Patent Document 6). However, in recent years, there has been a need for new decomposing agents that can efficiently decompose AGEs.
[0005] Prior art literature Patent documents Patent Document 1: Japanese Patent Application Laid-Open No. 2002-179592 Patent document 2: Patent No. 4255432 Patent Document 3: Japanese Patent Application Laid-Open No. 2008-308505 Patent Document 4: Japanese Patent Application Laid-Open No. 2004-91398 Patent Document 5: Japanese Patent Application Laid-Open No. 2007-99650 Patent Document 6: WO2011 / 004733 Summary of the Invention [Problem to be solved by the invention]
[0006] One object of the present invention is to provide a novel agent for degrading AGEs, and a second object is to provide cosmetics and / or foods having anti-glycation effects that contain this novel agent for degrading AGEs. [Means for solving the problem]
[0007] The present inventors conducted a large number of tests in search of a novel AGE decomposing agent having an AGE decomposing activity. As a result, the present inventors discovered that at least one selected from the group consisting of rose (Rose rugosa cv. Plena) extract, N-acetylneuraminic acid (NANA), tea plant (Camellia sinensis (L.) O. Kuntze) flower extract, saffron (Crocus sativus L.) extract, Daiyohana (Citrus aurantium L.) powder, nicotinamide mononucleotide (NMN), Dendrobium (Dendrobium officinale Kimura et Migo) flower extract, Saccharomyces lysate extract, carcinine, camellia (Camellia japonica) seed extract, Bupleurum falcatum extract, and Iris (Iris Florentina L.) root extract has an AGE-degrading activity and can function as an AGE-degrading agent, and therefore can be used in cosmetics and / or foods having anti-glycation activity, thus completing the present invention.
[0008] The present invention provides the following technical solutions:
[0009] Technical proposal 1: An AGE decomposer containing at least one ingredient selected from the group consisting of rose (Rose rugosa cv. Plena) extract, N-acetylneuraminic acid (NANA), tea plant (Camellia sinensis (L.) O. Kuntze) flower extract, saffron (Crocus sativus L.) extract, Daiyohana (Citrus aurantium L.) powder, nicotinamide mononucleotide (NMN), Dendrobium (Dendrobium officinale Kimura et Migo) flower extract, Saccharomyces lysate extract, carcinin, camellia (Camellia japonica) seed extract, Bupleurum falcatum extract, and iris (Iris Florentina L.) root extract.
[0010] Technical proposal 2: In terms of mass %, when rose (Rose rugosa cv. Plena) extract is used as the active ingredient, its concentration is 0.005-1.0%, when N-acetylneuraminic acid (NANA) is used as the active ingredient, its concentration is 0.1-1.0%, when tea tree (Camellia sinensis (L.) O. Kuntze) flower extract is used as the active ingredient, its concentration is 0.005-1.0%, when saffron (Crocus sativus L.) extract is used as the active ingredient, its concentration is 0.005-1.0%, when Daiyoi flower (Citrus aurantium L.) powder is used as the active ingredient, its concentration is 0.005-1.0%, when nicotinamide mononucleotide (NMN) is used as the active ingredient, its concentration is 0.1-1.0%, and when Dendrobium (Dendrobium officinale The AGE decomposer described in Technical Proposal 1 has a concentration of 0.005 to 1.0% when Kimura et Migo flower extract is used as the active ingredient, a concentration of 0.01 to 1.0% when Saccharomyces lysate extract liquid is used as the active ingredient, a concentration of 0.5 to 1.0% when carboxycarnosine is used as the active ingredient, a concentration of 0.005 to 1.0% when camellia (Camellia japonica) seed extract is used as the active ingredient, a concentration of 0.2 to 1.0% when Bupleurum falcatum extract is used as the active ingredient, and a concentration of 0.1 to 1.0% when Iris (Iris Florentina L.) root extract is used as the active ingredient.
[0011] Technical proposal 3: Use of the AGE decomposer described in Technical proposal 1 to produce cosmetics or foods with anti-glycation effects.
[0012] Technical proposal 4: Use of at least one agent selected from the group consisting of rose (Rose rugosa cv. Plena) extract, N-acetylneuraminic acid (NANA), tea plant (Camellia sinensis (L.) O. Kuntze) flower extract, saffron (Crocus sativus L.) extract, Daiyohana (Citrus aurantium L.) powder, nicotinamide mononucleotide (NMN), Dendrobium (Dendrobium officinale Kimura et Migo) flower extract, Saccharomyces lysate extract, carcinin, camellia (Camellia japonica) seed extract, Bupleurum falcatum extract, and iris (Iris Florentina L.) root extract as an AGE decomposition agent.
[0013] Technical proposal 5: Use of at least one AGE decomposer selected from the group consisting of rose (Rose rugosa cv. Plena) extract, N-acetylneuraminic acid (NANA), tea plant (Camellia sinensis (L.) O. Kuntze) flower extract, saffron (Crocus sativus L.) extract, Daiyohana (Citrus aurantium L.) powder, nicotinamide mononucleotide (NMN), Dendrobium (Dendrobium officinale Kimura et Migo) flower extract, Saccharomyces lysate extract, carcinine, camellia (Camellia japonica) seed extract, Bupleurum falcatum extract, and iris (Iris Florentina L.) root extract in the production of cosmetics or foods with anti-glycation activity.
[0014] Technical proposal 6: A cosmetic product with anti-glycation properties, characterized by containing an AGE decomposer described in technical proposal 1 or 2.
[0015] Technical proposal 7: A food product with anti-glycation effects, characterized by containing an AGE decomposing agent described in technical proposal 1 or 2. [Effects of the Invention]
[0016] The present inventors have discovered for the first time that at least one selected from the group consisting of rose (Rose rugosa cv. Plena) extract, N-acetylneuraminic acid (NANA), tea plant (Camellia sinensis (L.) O. Kuntze) flower extract, saffron (Crocus sativus L.) extract, Daiyohana (Citrus aurantium L.) powder, nicotinamide mononucleotide (NMN), Dendrobium (Dendrobium officinale Kimura et Migo) flower extract, Saccharomyces lysate extract, carcinine (Carboxycarnosine), camellia (Camellia japonica) seed extract, Bupleurum falcatum extract, and iris (Iris Florentina L.) root extract is capable of decomposing AGEs and can be used as an AGE decomposer. Furthermore, the present invention can provide novel cosmetics and / or foods having anti-glycation effects, which contain as an active ingredient at least one selected from the group consisting of rose (Rose rugosa cv. Plena) extract, N-acetylneuraminic acid (NANA), tea plant (Camellia sinensis (L.) O. Kuntze) flower extract, saffron (Crocus sativus L.) extract, Daiyohana (Citrus aurantium L.) powder, nicotinamide mononucleotide (NMN), Dendrobium (Dendrobium officinale Kimura et Migo) flower extract, Saccharomyces lysate extract, carcinine (Carboxycarnosine), camellia (Camellia japonica) seed extract, Bupleurum falcatum extract, and Iris (Iris Florentina L.) root extract. DETAILED DESCRIPTION OF THE INVENTION
[0017] The AGE decomposer of the present invention is characterized by containing at least one ingredient selected from the group consisting of rose (Rose rugosa cv. Plena) extract, N-acetylneuraminic acid (NANA), tea plant (Camellia sinensis (L.) O. Kuntze) flower extract, saffron (Crocus sativus L.) extract, Daiyohana (Citrus aurantium L.) powder, nicotinamide mononucleotide (NMN), Dendrobium (Dendrobium officinale Kimura et Migo) flower extract, Saccharomyces lysate extract, carcinin, camellia (Camellia japonica) seed extract, Bupleurum falcatum extract, and iris (Iris Florentina L.) root extract.
[0018] The rose (Rose rugosa cv. Plena) extract described in the present invention refers to an extract of rose (Rose rugosa cv. Plena). Dried bud extracts include mainly rose powder, while distilled extracts include mainly rose extract and rose essential oil. Rose rugosa extract is made from Rose rugosa cv. Plena and processed through processes such as crushing, boiling extraction, filtration, concentration, with or without maltodextrin, spray drying, and packaging. The rose extract described in the present invention may also be commercially available rose extract products such as dried instant rose powder and freeze-dried rose powder.
[0019] When the AGE decomposer of the present invention is a rose (Rose rugosa cv. Plena) extract, its concentration is 0.005 to 1.0% by mass. This concentration is the effective concentration for verifying that the rose extract has AGE-decomposing activity, and is preferably 0.01 to 1.0% by mass, and more preferably 0.02 to 1.0% by mass. In other words, when the rose (Rose rugosa cv. Plena) extract, which is the AGE decomposer of the present invention, is applied to cosmetics or foods in the hope of exerting its AGE-decomposing effect, the active concentration that should be achieved in the cosmetics or foods is also within the above-mentioned range.
[0020] N-acetylneuraminic acid (NANA) described in the present invention is also known as sialic acid, N-acetylneuraminic acid, aceneuramic acid, N-acetylsialic acid, o-sialic acid, or N-acetyl-neuraminid (sugar) acid. It is a sialic acid monosaccharide widely present in glycoproteins of cell membranes and glycolipids of mammalian cell gangliosides, and is known to exert biological effects in neurotransmission, leukocyte extravasation, and viral or bacterial infection. The present inventors were the first to discover that N-acetylneuraminic acid has the ability to degrade AGEs and can be used as an AGE decomposer. Various commercially available N-acetylneuraminic acid products can be used.
[0021] When the AGE decomposer of the present invention is N-acetylneuraminic acid (NANA), its concentration is 0.1 to 1.0% by mass. This concentration is the effective concentration for verifying that N-acetylneuraminic acid has AGE-decomposing activity, and is preferably 0.25 to 1.0% by mass, and more preferably 0.5 to 1.0% by mass. When N-acetylneuraminic acid, the AGE decomposer of the present invention, is applied to cosmetics or foods in the hope of exerting its AGE-decomposing effect, the active concentration that should be achieved in the cosmetics or foods is also within the above-mentioned range.
[0022] The tea plant (Camellia sinensis (L.) O. Kuntze) flower extract described in the present invention refers to an extract obtained from the flower of the tea plant. The tea plant refers to the tea plant (Camellia sinensis (L.) O. Kuntze) of the genus Camellia in the family Theaceae, and its flowers are the edible part. The tea plant flower extract is obtained by processing the tea plant flowers, including crushing, extraction with water or ethanol, concentration, filtration, drying, with or without the addition of maltodextrin, and packaging. Preferably, the pure water extract is centrifuged, membrane separated, concentrated, sterilized, freeze-dried, and subjected to metal detection, followed by packaging to obtain the product. The tea plant flower extract used in the present invention may be any extract from the flower of the tea plant, and various commercially available products can be used, such as Hua Luo Yuen's Tea Plant Flower Freeze-Dried Instant Powder, product number GFTB01.
[0023] When the AGE decomposer of the present invention is tea blossom (Camellia sinensis (L.) O. Kuntze) flower extract, its concentration is 0.005 to 1.0% by mass. This concentration is the effective concentration for verifying that the tea blossom extract has AGE-decomposing activity, and is preferably 0.25 to 1.0% by mass, and more preferably 0.5 to 1.0% by mass. When the tea blossom extract, which is the AGE decomposer of the present invention, is applied to cosmetics or foods in the hope of exerting its AGE-decomposing effect, the active concentration that should be achieved in the cosmetics or foods is also within the above-mentioned range.
[0024] The saffron (Crocus sativus L.) extract described in the present invention is a product extracted from the upper part of the style and stigma of the saffron (Crocus sativus L.), a plant of the Iridaceae family, through processing steps such as crushing, water or ethanol extraction, concentration, filtration, drying, with or without the addition of maltodextrin, and packaging. Various commercially available products can be used as the saffron extract in the present invention, including saffron extract manufactured by Shanghai Kaida Biotechnology Co., Ltd. Saffron extract is a powerful scavenger of hydroxyl radicals and superoxide radicals, and can prevent oxidation reactions, improve mitochondrial function, and inhibit optic nerve cell apoptosis. It is also known to have beneficial effects such as improving microcirculation, enhancing immunity, preventing arteriosclerosis, acting as an antioxidant, lowering blood lipids, promoting cholestasis and liver protection, preventing and treating osteoporosis, and protecting the kidneys. The present inventors were the first to discover that saffron extract has the ability to decompose AGEs and can be used as an AGE decomposer.
[0025] When the AGE decomposer of the present invention is a saffron (Crocus sativus L.) extract, its concentration is 0.005 to 1.0% by mass. This concentration is the effective concentration for verifying that the saffron (Crocus sativus L.) extract has AGE-decomposing activity, and is preferably 0.25 to 1.0% by mass, and more preferably 0.5 to 1.0% by mass. When the saffron (Crocus sativus L.) extract, which is the AGE decomposer of the present invention, is applied to cosmetics or foods in the hope of exerting its AGE-decomposing effect, the active concentration that should be achieved in the cosmetics or foods is also within the above-mentioned range.
[0026] The daidaihana (Citrus aurantium L.) powder extract described in the present invention is an extract obtained from the buds of the dicotyledonous plant, the Rutaceae family, specifically an aqueous extract. Other names for daidaihana include kajuka (a kind of citrus), sour orange, and tangerine. Commercially available daidaihana extracts are available in various specifications, such as 50:1, 20:1, and 10:1, and any of these can be used. For example, daidaihana pollen manufactured by Seiunzan Pharmaceutical Co., Ltd. is an example. The whole daidaihana plant is known to contain multiple cardiac glycoside and non-cardiac glycoside components and is found in medicinal diets in many countries. In traditional Chinese medicine, it is known as adonis grass (Adonis ramosa) and has cardiotonic, diuretic, sedative, and heart rate-slowing functions, reducing nervous system excitability and spinal cord hypertonic reflexes. It is used for acute diseases and chronic heart failure, primarily to treat congestive heart failure, cardiac edema, and atrial fibrillation. When combined with silver bromide, it can enhance the therapeutic effect on epilepsy. The present inventors have discovered for the first time that pollen has the ability to decompose AGEs for many generations and can be used as an AGE decomposing agent.
[0027] When the AGE decomposer of the present invention is Daiyohana (Citrus aurantium L.) powder, its concentration is 0.005 to 1.0% by mass. This concentration is the effective concentration for verifying that Daiyohana (Citrus aurantium L.) powder has AGE-decomposing activity, and is preferably 0.25 to 1.0% by mass, and more preferably 0.5 to 1.0% by mass. When the Daiyohana (Citrus aurantium L.) powder extract, which is the AGE decomposer of the present invention, is applied to cosmetics or foods in the hope of exerting its AGE-decomposing effect, the active concentration that should be achieved in the cosmetics or foods is also within the above-mentioned range.
[0028] Nicotinamide mononucleotide (NMN) described in the present invention, officially named β-nicotinamide mononucleotide, has the chemical formula C 11 H 15N2O8P is a naturally occurring, biologically active nucleotide. Its molecule is structurally composed of a nicotinamide group, ribose, and a phosphate group. NMN is a substance endemic to the human body and is known to be found in large quantities in some fruits and vegetables. Because nicotinamide belongs to vitamin B3, NMN belongs to the category of vitamin B derivatives, which widely participate in multiple biochemical reactions in the human body and are closely related to immunity and metabolism. The present inventors have discovered for the first time that nicotinamide mononucleotide (NMN) has AGE-degrading activity and can be used as an AGE-degrading agent. Various commercially available nicotinamide mononucleotides (NMN) can be used in the present invention.
[0029] When the agent for degrading AGEs of the present invention is nicotinamide mononucleotide (NMN), its concentration is 0.1 to 1.0% by mass. This concentration is the effective concentration for verifying that nicotinamide mononucleotide has AGE-degrading activity, and is preferably 0.25 to 1.0% by mass, and more preferably 0.5 to 1.0% by mass. When nicotinamide mononucleotide, the agent for degrading AGEs of the present invention, is applied to cosmetics or foods in the hope of exerting its AGE-degrading effect, the active concentration that should be achieved in the cosmetics or foods is also within the above-mentioned range.
[0030] The Dendrobium (Dendrobium officinale Kimura et Migo) flower extract described in the present invention refers to a product obtained by processing Dendrobium flowers, such as crushing, water or ethanol extraction, concentration, filtration, drying, with or without the addition of maltodextrin, and packaging, and is preferably a water extract. Various commercially available Dendrobium flower extracts can be used in the present invention, including Dendrobium pollen manufactured by Seiunzan Pharmaceutical. Prior art has already reported that Dendrobium has the effects of nourishing yin and stimulating energy, antitumor and antimutagenicity, blood sugar reduction, immune enhancement, and antioxidant properties. The present inventors have discovered for the first time that Dendrobium (Dendrobium officinale Kimura et Migo) flower extract has the ability to decompose AGEs and can be used as an AGE decomposer.
[0031] When the AGE decomposer of the present invention is a Dendrobium (Dendrobium officinale Kimura et Migo) flower extract, its concentration is 1.0% by mass. This concentration is the effective concentration for verifying that the Dendrobium (Dendrobium officinale Kimura et Migo) flower extract has AGE-decomposing activity, and is preferably 0.25 to 1.0% by mass, and more preferably 0.5 to 1.0% by mass. When the Dendrobium (Dendrobium officinale Kimura et Migo) flower extract, which is the AGE decomposer of the present invention, is applied to cosmetics or foods in the hope of exerting its AGE-decomposing effect, the active concentration that should be achieved in the cosmetics or foods is also within the above-mentioned range.
[0032] The Saccharomyces lysate extract liquid described in the present invention refers to a liquid obtained by subjecting a lysate produced by yeast fermentation to microfiltration. Various commercially available Saccharomyces lysate extract products can be used as the Saccharomyces lysate extract liquid in the present invention, for example, Saccharomyces lysate extract liquid manufactured by AC Dermal Respiratory Factor ECM JP, which consists solely of Saccharomyces lysate extract liquid, phenoxyethanol, and water. The liquid contains multiple types of bioactive ingredients, such as polysaccharides, proteins, and nucleic acids. In the pharmaceutical field, Saccharomyces lysate extract liquid has already been reported in the prior art to be useful in immunomodulation, antitumor, antiviral, and other areas. In the food field, Saccharomyces lysate extract liquid serves as a natural immune enhancer, enhancing human immunity and preventing disease. It also serves as a natural antioxidant, reducing the generation of free radicals and protecting cells from oxidative damage. In the cosmetics field, it serves as a natural moisturizer, increasing skin moisture and alleviating problems such as dryness and flaking. It also serves as a natural antibacterial agent, reducing the proliferation of skin bacteria and preventing skin infections. The present inventors have discovered for the first time that Saccharomyces lysate extract liquid has the ability to decompose AGEs and can be used as an AGE decomposer.
[0033] When the AGE decomposer of the present invention is a Saccharomyces lysate extract liquid, its concentration is 0.01 to 1.0% by mass. This concentration is the effective concentration for verifying that the Saccharomyces lysate extract liquid has AGE-decomposing activity, and is preferably 0.25 to 1.0% by mass, and more preferably 0.5 to 1.0% by mass. When the Saccharomyces lysate extract liquid, which is the AGE decomposer of the present invention, is applied to cosmetics or foods in the hope of exerting its AGE-decomposing effect, the active concentration that should be achieved in the cosmetics or foods is also within the above-mentioned range.
[0034] Carboxycarnosine, scientific name β-alanyl histamine, described in this invention is an imidazole dipeptide composed of β-alanyl and L-histidine. Carboxycarnosine was first discovered in crustaceans in 1975 and later in the hearts of some mammals. This compound is structurally similar to carnosine and possesses antioxidant and anti-glycation properties. Its activity is not impaired by enzymes in the body, resulting in better stability. Carboxycarnosine is known to be effective in scavenging hydroxyl radicals, elementary oxygen, and hydrogen peroxide radicals, inhibiting lipid oxidation caused by nonmetallic ions, and providing stable cell membrane protection. The present inventors were the first to discover that carboxycarnosine has AGE-degrading properties and can be used as an AGE-degrading agent. Various commercially available carcinines can be used as the carcinine used in this invention.
[0035] When the AGE decomposer of the present invention is carcinine (carboxycarnosine), its concentration is 0.01 to 1.0% by mass. This concentration is the effective concentration for verifying that carcinine (carboxycarnosine) has AGE-decomposing activity, and is preferably 0.25 to 1.0% by mass, and more preferably 0.5 to 1.0% by mass. When carboxycarnosine, the AGE decomposer of the present invention, is applied to cosmetics or foods in the hope of exerting its AGE-decomposing effect, the active concentration that should be achieved in the cosmetics or foods is also within the above-mentioned range.
[0036] The camellia (Camellia japonica) seed extract described in this invention refers to the camellia (Camellia japonica) seed extract listed in the "List of Names of Used Cosmetic Ingredients," and various commercially available products can be used. For example, CAMELLIA SEED EXTRACT BG-S, manufactured by NOF Corporation, is a product consisting entirely of camellia seed extract, butylene glycol, and water. Camellia (Camellia japonica) seed extract is known to have multiple skin care benefits, including anti-aging, anti-pollution, anti-allergic and anti-inflammatory properties, whitening and moisturizing properties, and oil secretion suppression. The present inventors were the first to discover that camellia (Camellia japonica) seed extract has AGE-degrading properties and can be used as an AGE-degrading agent.
[0037] When the AGE decomposer of the present invention is camellia (Camellia japonica) seed extract, its concentration is 1.0% by mass. This concentration is the effective concentration for verifying that the camellia (Camellia japonica) seed extract has AGE-decomposing activity, and is preferably 0.25 to 1.0% by mass, and more preferably 0.5 to 1.0% by mass. When the camellia (Camellia japonica) seed extract, which is the AGE decomposer of the present invention, is applied to cosmetics or foods in the hope of exerting its AGE-decomposing effect, the active concentration that should be achieved in the cosmetics or foods is also within the above-mentioned range.
[0038] The Bupleurum falcatum extract described in this invention refers to the root extract of Bupleurum falcatum. Bupleurum falcatum root extract contains multiple substances, including volatile oil, bupleurumol, oleic acid, linolenic acid, palmitic acid, stearic acid, lignocerin, glucose, and saponin, and is known to be a natural plant extract with anti-inflammatory and antiviral properties. The main active ingredient, saikosaponin, has a potentiating effect on the immune system of human cells, improves skin metabolic function, increases capillary permeability, and promotes cortical cell proliferation. Tranexamic acid, glycyrrhizic acid, and urea can all enhance the efficacy of saikosaponin, synergistically promoting wound healing, smoothing rough skin, and preventing skin aging. Saikosaponin can absorb UV rays and, in vitro, has been shown to inhibit melanin pigmentation. Saikosaponin has good transdermal permeability and can accelerate the transdermal penetration of other ingredients. It has strong antioxidant, anti-inflammatory, and antiviral properties, and the uridine it contains can accelerate skin cell metabolism and the regeneration of the stratum corneum. The present inventors were the first to discover that Bupleurum falcatum extract has the ability to degrade AGEs and can be used as an AGE decomposer. Various commercially available Bupleurum falcatum extracts can be used as the Bupleurum extract in the present invention, including, for example, Bupleurum falcatum extract manufactured by Maruzen Pharmaceutical Co., Ltd., which consists entirely of Altais Bupleurum Root Extract, butylene glycol, and water.
[0039] When the AGE decomposer of the present invention is a Bupleurum falcatum extract, its concentration is 0.2 to 1.0% by mass. This concentration is the effective concentration for verifying that the Bupleurum falcatum extract has AGE-decomposing activity, and is preferably 0.25 to 1.0% by mass, and more preferably 0.5 to 1.0% by mass. When the Bupleurum falcatum extract, which is the AGE decomposer of the present invention, is applied to cosmetics or foods in the hope of exerting its AGE-decomposing effect, the active concentration that should be achieved in the cosmetics or foods is also within the above-mentioned range.
[0040] The iris (Iris Florentina L.) root extract described in the present invention is an extract obtained from the root of Iris florentina L. (Iris florentina L.). Iris florentina L. is an ornamental plant that blooms white flowers and is found primarily in temperate regions. Its roots contain a large amount of isoflavones, which promote skin metabolism, prevent the degradation of skin structural proteins (collagen and elastin), act as antioxidants, improve skin moisture retention, restore elasticity, and brighten skin tone. The present inventors have discovered for the first time that Iris (Iris florentina L.) root extract has the ability to decompose AGEs and can be used as an AGE decomposer. Various commercially available Iris (Iris florentina L.) root extracts can be used in the present invention, including, for example, the Iris root extract manufactured by Koei Kogyo Co., Ltd., which is composed entirely of Iris root extract, butylene glycol, and water.
[0041] When the AGE decomposer of the present invention is iris (Iris Florentina L.) root extract, its concentration is 0.1 to 1.0% by mass. This concentration is the effective concentration for verifying that the iris (Iris Florentina L.) root extract has AGE-decomposing activity, and is preferably 0.25 to 1.0% by mass, and more preferably 0.5 to 1.0% by mass. When the iris (Iris Florentina L.) root extract, which is the AGE decomposer of the present invention, is applied to cosmetics or foods in the hope of exerting its AGE-decomposing effect, the active concentration that should be achieved in the cosmetics or foods is also within the above-mentioned range.
[0042] The agent for decomposing AGEs of the present invention may contain one of the above active ingredients, or may contain two or more of them in combination.
[0043] In the present invention, the extract can be obtained by extracting a part or the whole of each plant. The extraction method is not particularly limited, and examples thereof include known methods such as solvent extraction, pressing, enzyme extraction, microwave-assisted extraction, and ultrasonic-assisted extraction.
[0044] The solvent used in the solvent extraction method is not particularly limited, and examples thereof include aqueous solvents and organic solvents. The aqueous solvent is not particularly limited, and examples thereof include purified water, ion-exchanged water, tap water, and other waters. The organic solvent is not particularly limited, and examples thereof include lower alcohols, polyhydric alcohols, ketones, esters, ethers, nitriles, aromatic compounds, and alkyl chlorides. Examples of the lower alcohol include methanol, ethanol, and absolute ethanol. Examples of the polyhydric alcohol include propylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, pentylene glycol, and hexylene glycol. Examples of the ketone include acetone and methyl ethyl ketone. Examples of the ester include ethyl acetate. Examples of the ether include ethyl methyl ether and diethyl ether. Examples of the nitrile include acetonitrile. Examples of the aromatic compound include benzene, toluene, and xylene. Examples of the alkyl chloride include chloroform.
[0045] The extraction solvent may be used alone or in combination of two or more. The solvent may also be a mixed solvent of an aqueous solvent and an organic solvent. The mixed solvent is not particularly limited, but examples thereof include aqueous solutions of lower alcohols such as aqueous ethanol solutions. The proportion of the organic solvent in the mixed solvent is not particularly limited, but may be, for example, 1 to 99% by volume.
[0046] The solvent extraction method can be carried out, for example, by immersing the extraction part or the entire plant as the raw material in the extraction solvent. The raw material may be subjected to processes such as washing, drying, and crushing before the immersion. When two or more types of raw materials are used, each raw material may be extracted separately, or a mixture of two raw materials may be extracted. When each raw material is extracted separately, the resulting extracts may be mixed to prepare a mixed extract. The amount of each extract in the mixed extract is not particularly limited, but may be equal (by weight). When raw materials are mixed and then extracted, the ratio of each raw material is not particularly limited, but may be equal (by weight), for example.
[0047] The ratio of the raw material to the extraction solvent used for extraction is not particularly limited, but may be, for example, 1 to 1000 L of the extraction solvent per 100 g (dry weight) of the raw material, and preferably 1 to 100 L. The immersion time can be appropriately set depending on the type and amount of the raw material and the extraction solvent, and is not particularly limited. Specifically, when 100 g of the raw material is immersed in 10 L of the extraction solvent, the immersion time is, for example, 0.5 hours or more, and preferably 0.5 to 24 hours.
[0048] The temperature of the extraction solvent during the extraction may be room temperature, or may be above or below room temperature, and is not particularly limited. When the extraction solvent is an aqueous solvent, the extraction process is preferably hot water extraction. When extracting with hot water, the temperature of the aqueous solvent is not particularly limited, but is, for example, 30°C or higher, preferably 50 to 100°C. The processing time for the hot water extraction can be appropriately set depending on the type and amount of the raw material, the amount of the aqueous solvent, and the like, and is not particularly limited. Specifically, when 100 g (dry weight) of the raw material is immersed in 10 L of the aqueous solvent, the immersion time is, for example, 0.5 hours or more, preferably 0.5 to 24 hours.
[0049] After extraction, the extract may be subjected to, for example, a purification treatment. The purification treatment is not particularly limited, and examples thereof include known methods such as distillation, filtration, chromatography, and drying.
[0050] The form of the extract is not particularly limited, and examples thereof include liquid, paste, and powder, and can be appropriately selected depending on the form of the AGE decomposer.
[0051] The AGE decomposer may contain only the extract or a combination of the extract and other components. The other components may include various additives such as the OPH activity enhancer, excipients, binders, lubricants, disintegrants, absorption enhancers, emulsifiers, stabilizers, and preservatives. The blending ratio of the various additives in the AGE decomposer is not particularly limited and can be set appropriately.
[0052] The form of the AGE decomposer is not particularly limited and may be, for example, a solid, gel, or liquid. Specific examples of the form include powders, fine granules, granules, tablets, coated tablets, capsules, lozenges, eye drops, liquids, patches, lotions, and ointments.
[0053] The AGE decomposer of the present invention may be added to cosmetics or foods to be used in the production of cosmetics or foods having anti-glycation effects. [Example]
[0054] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.
[0055] Example 1. Detection test of degradation of AGEs-protein crosslinks
[0056] (A) Test principle Advanced glycation end products (AGEs) form cross-links with collagen, affecting the normal physiological function of proteins and leading to skin aging, loss of elasticity and luster. Peroxidase (HRP) is a commonly used enzyme in enzyme immunoassays, and 3,3',5,5'-tetramethylbenzidine (TMB) has higher sensitivity than other chromogens in the HRP color reaction system, is non-carcinogenic, and is widely used.
[0057] AGEs-HRP, formed by labeling AGEs with HRP, can react with collagen to form collagen-AGEs-HRP crosslinks. Based on the color reaction between HRP and TMB, TMB can react with collagen-AGEs-HRP crosslinks to produce a dark blue substance. After adding different AGE crosslink-cleaving agents, the collagen-AGEs-HRP crosslinks in the system can be decomposed into collagen and AGEs-HRP. Because collagen covers the bottom of the 96-well plate, the free AGEs-HRP is removed by washing the plate, leaving only collagen-AGEs-HRP bound to collagen in the system. Therefore, the addition of AGE crosslink-cleaving agents leads to a change in the number of HRP molecules, further revealing the color difference between TMB and HRP. The color depth of TMB and HRP was observed and the absorbance at 450 nm was measured. A control group was set up, and the cleavage ability of different AGE crosslink-cleaving agents could be quantified based on the percentage change in absorbance.
[0058] Cross-link cleavage ability (%) = (blank control group OD value - sample group OD value) / blank control group OD value × 100%
[0059] (B) Test sample: control Blank control: Water Test sample: See each sample in Table 1 below, sample concentration 0.5 to 1% by mass
[0060] (C) Operation flow 1. Purified AGEs were labeled with HRP (GLu-BSA ELISA kit) according to the technical manual. The operating procedure in the technical manual is as follows: (1) Add 100 μl of washing buffer and a sample solution containing 50 to 200 μg of AGEs to a filtration tube. (2) Centrifuge at 8,000 to 10,000 g for 10 minutes, then add 100 μl of wash buffer and centrifuge again. (3) Add 10 μl of reaction buffer to the NH2-reactive peroxidase and dissolve it by blowing with a pipette. (4) The NH2-reactive peroxidase-containing solution is transferred to the filter membrane of the filter tube where AGEs are concentrated. (5) Suck up the solution with a pipette and blow the filter membrane completely clean. Then, place the filter tube in an incubator and culture it at 37°C for 2 hours. (6) Add 100 μl of washing buffer to the filter tube. If the volume of the filtrate exceeds 300 μl, the filtrate must be discarded before proceeding to step (7). (7) Centrifuge at 8,000 to 10,000 g for 10 minutes. (8) Add 200 μl of storage buffer and spray with a pipette 10 to 15 times to recover the labeled product. Transfer the solution to a 0.5 ml test tube and store at 0 to 5°C.
[0061] 2. The AGEs-HRP labeled product obtained in 1 above was used as reaction substrate S1, and this reaction substrate S1 was added to a 96-well plate. Collagen was added to reaction substrate S1 to form reaction substrate S2, and after 4 hours of reaction at 37°C, washing was performed to obtain an AGEs-HRP-collagen crosslinked product. Water (blank control, designated BC) and various test samples were then added to this crosslinked product, and after 16 hours of reaction at 37°C, washing was performed. TMB was then added to detect HRP, and its OD value was measured at 450 nm. AGEs-induced collagen crosslink degradation rate = (absorption OD value of BC - OD value of sample absorption) / absorption OD value of BC x 100
[0062] [Table 1]
[0063] As can be seen from the above test results, rose (Rose rugosa cv. Plena) extract, N-acetylneuraminic acid (NANA), tea plant (Camellia sinensis (L.) O. Kuntze) flower extract, saffron (Crocus sativus L.) extract, Daiyohana (Citrus aurantium L.) powder, nicotinamide mononucleotide (NMN), Dendrobium (Dendrobium officinale Kimura et Migo) flower extract, Saccharomyces lysate extract, carcinine, camellia (Camellia japonica) seed extract, Bupleurum falcatum extract, and iris (Iris Florentina L.) root extract all have the ability to degrade AGEs and can be used as AGE decomposers. Therefore, one or more of these can be used in the production of cosmetics or foods with anti-glycation properties.
[0064] Industrial Applicability The present inventors have discovered for the first time that at least one selected from the group consisting of rose (Rose rugosa cv. Plena) extract, N-acetylneuraminic acid (NANA), tea plant (Camellia sinensis (L.) O. Kuntze) flower extract, saffron (Crocus sativus L.) extract, Daiyohana (Citrus aurantium L.) powder, nicotinamide mononucleotide (NMN), Dendrobium (Dendrobium officinale Kimura et Migo) flower extract, Saccharomyces lysate extract, carcinine, camellia (Camellia japonica) seed extract, Bupleurum falcatum extract, and iris (Iris Florentina L.) root extract has an AGE-degrading effect and can be used as an AGE-degrading agent, and have verified this effect. Therefore, one or more of these can be used to produce cosmetics or foods with anti-glycation activity.
Claims
1. Rose (Rose rugosa cv. Plena) extract, N-acetylneuraminic acid, Tea plant (Camellia sinensis (L.) O. Kuntze) flower extract, Saffron (Crocus sativus L.) extract, Daiyohana (Citrus aurantium L.) powder, Nicotinamide mononucleotide, Dendrobium (Dendrobium officinale Kimura et Migo) flower extract, Saccharomyces lysate extract, Carcinine, Camellia japonica (Camellia japonica) seed extract, Bupleurum falcatum (Bupleurum falcatum) extract, Iris (Iris Florentina) An AGEs decomposing agent characterized by containing at least one selected from the group consisting of L.) root extracts.
2. In terms of mass %, when rose (Rose rugosa cv. Plena) extract is used as the active ingredient, its concentration is 0.005 to 1.0%, when N-acetylneuraminic acid is used as the active ingredient, its concentration is 0.1 to 1.0%, when tea tree (Camellia sinensis (L.) O. Kuntze) flower extract is used as the active ingredient, its concentration is 0.005 to 1.0%, when saffron (Crocus sativus L.) extract is used as the active ingredient, its concentration is 0.005 to 1.0%, and when Daiyo-ka (Citrus aurantium) extract is used as the active ingredient, its concentration is 0.005 to 1.0%. When Dendrobium (Dendrobium officinale Kimura et Migo) flower extract is used as the active ingredient, its concentration is 0.005 to 1.0%, when nicotinamide mononucleotide is used as the active ingredient, its concentration is 0.1 to 1.0%, when Saccharomyces lysate extract liquid is used as the active ingredient, its concentration is 0.01 to 1.0%, when carcinine is used as the active ingredient, its concentration is 0.5 to 1.0%, when Camellia japonica seed extract is used as the active ingredient, its concentration is 0.005 to 1.0%, when Bupleurum 2. The AGEs decomposing agent according to claim 1, wherein when an Iris (Iris florentina L.) root extract is used as an active ingredient, the concentration of the active ingredient is 0.2 to 1.0%, and when an Iris (Iris florentina L.) root extract is used as an active ingredient, the concentration of the active ingredient is 0.1 to 1.0%.
3. Use of the AGEs decomposing agent according to claim 1 for producing cosmetics or foods having anti-glycation activity.
4. Rose (Rose rugosa cv. Plena) extract, N-acetylneuraminic acid, Tea plant (Camellia sinensis (L.) O. Kuntze) flower extract, Saffron (Crocus sativus L.) extract, Daiyohana (Citrus aurantium L.) powder, Nicotinamide mononucleotide, Dendrobium (Dendrobium officinale Kimura et Migo) flower extract, Saccharomyces lysate extract, Carcinine, Camellia japonica (Camellia japonica) seed extract, Bupleurum falcatum (Bupleurum falcatum) extract, Iris (Iris Florentina) Use of at least one selected from the group consisting of L.) root extracts as an AGEs decomposing agent.
5. Rose (Rose rugosa cv. Plena) extract, N-acetylneuraminic acid, Tea plant (Camellia sinensis (L.) O. Kuntze) flower extract, Saffron (Crocus sativus L.) extract, Daiyohana (Citrus aurantium L.) powder, Nicotinamide mononucleotide, Dendrobium (Dendrobium officinale Kimura et Migo) flower extract, Saccharomyces lysate extract, Carcinine, Camellia japonica (Camellia japonica) seed extract, Bupleurum falcatum (Bupleurum falcatum) extract, Iris (Iris Florentina) 1. Use of at least one extract selected from the group consisting of L.) root extracts as an AGEs decomposing agent in the production of cosmetics or foods having anti-glycation activity.
6. A cosmetic having an anti-glycation effect, characterized by containing the AGEs decomposing agent according to claim 1 or 2.
7. A food having an anti-glycation effect, characterized by containing the AGEs decomposing agent according to claim 1 or 2.