Compositions for delaying aging or extending lifespan containing amino aromatic compounds as active ingredients

Abstract

The present invention provides a pharmaceutical composition for the prevention or treatment of aging-related diseases or disorders, a composition for delaying aging or extending lifespan, and a health functional food composition for the prevention or improvement of aging-related diseases, all containing an amino-aromatic compound or a pharmaceutically acceptable salt thereof as an active ingredient.

Description

[Technical Field]

[0001] The present invention relates to a composition for delaying aging or extending lifespan, comprising an amino aromatic compound as an active ingredient. [Background technology]

[0002] Living organisms have a limited lifespan and, as time passes, they naturally go through a process of being born, growing, and aging, which eventually leads to death. Aging is one of the most complex biological pathways that occurs in all living organisms.

[0003] Numerous studies have been conducted to clarify the causes and processes of aging, and these are broadly explained by two mechanisms: the aging clock and cellular senescence. The aging clock is a theory that explains aging through telomere replication loss at the ends of DNA, arguing that the depletion of telomeres, which are repetitive sequences found at both ends of each chromosome, can lead to cellular senescence and organismal aging. Cellular senescence views the accumulation of intracellular damage due to oxidative damage, mitochondrial dysfunction, etc., as the main cause of aging, and among these, the mitochondrial reduction theory emphasizes the importance of mitochondrial function in healthy cellular metabolism and bioenergy. The decline in mitochondrial function associated with aging includes decreased ATP production, increased ROS production, decreased mitochondrial number, and changes in mitochondrial permeability.

[0004] As we age, the activity of pathways related to fat metabolism is inhibited. That is, fat breakdown decreases, and the absorption of low-density cholesterol (LDL) by cells decreases, leading to an increase in LDL concentration in the blood, which can cause cardiovascular disease. In addition, aging increases the incidence of neurological diseases such as Alzheimer's and Parkinson's disease, which lead to a decline in cognitive and motor function and reduce the quality of life.

[0005] During the aging process, various physiological changes occur, such as a decrease in body and bone mass, an increase in blood pressure and blood sugar, and a decrease in exercise volume and cardiac output. At the molecular level, aging is characterized by the accumulation of DNA mutations, protein oxidation, and lipid peroxidation. However, the fundamental mechanisms that can explain the changes associated with aging and the increase in mortality have not yet been fully elucidated.

[0006] In addition to research focusing on understanding the aging process, numerous studies on delaying aging and extending lifespan are also underway. The most successful method to date is dietary restriction. The effect of dietary restriction was first reported in rats, and subsequently, a lifespan phenotype due to dietary restriction has been observed in yeast, nematodes, Drosophila, and rats. However, the beneficial effects of dietary restriction as described above are only observed when dietary restriction is continuously maintained, and it is difficult to apply to all living organisms.

[0007] To date, many studies and efforts have been made to fulfill the dream of immortality and longevity, but the mechanism of aging has not yet been fully elucidated.

[0008] On the other hand, amino aromatic compounds are reported to be effective in treating neurodegenerative diseases by scavenging hydrogen peroxide in the blood as a blood hydrogen peroxide scavenger, reducing the relatively high levels of hydrogen peroxide present in pathological conditions such as neurodegenerative diseases, especially Alzheimer's disease, to an appropriate concentration. However, this is to treat neurodegenerative diseases by scavenging excess hydrogen peroxide in the blood, and there has been no research on delaying biological aging or extending lifespan. SUMMARY OF THE INVENTION PROBLEMS TO BE SOLVED BY THE INVENTION

[0009] Therefore, the inventors have confirmed that amino aromatic compounds, known as blood hydrogen peroxide scavengers, can delay biological aging and extend lifespan, and have focused on their applicability as uses related to delaying aging or extending lifespan, thus completing the present invention.

[0010] The present invention provides a pharmaceutical composition for preventing or treating an aging-related disease or disorder, containing an amino aromatic compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0011] The present invention also provides a composition for delaying aging or extending lifespan, containing an amino aromatic compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0012] The present invention also provides a health functional food composition for preventing or improving an aging-related disease, containing an amino aromatic compound or a food-acceptable salt thereof as an active ingredient.

Means for Solving the Problems

[0013] To achieve the above object, One aspect of the present invention provides a pharmaceutical composition for preventing or treating an aging-related disease or disorder, containing an amino aromatic compound represented by the following Chemical Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. [Chemical Formula 1] JPEG2026522513000002.jpg38170In the above Chemical Formula 1, Ar is C6-C 20 arylene, and the arylene of the Ar may be further substituted with one or more selected from C1-C 10 alkyl, C1-C 10 alkoxy, amino, mono- or di-C1-C 10 alkylamino, halo C1-C 10 alkyl, halo C1-C 10 alkoxy and hydroxy, and may be further substituted, R 1 and R 2 are each independently hydrogen or C1-C 10 alkyl, R 3 is halogen, C1-C 10 alkoxy, halo C1-C 10 alkyl or halo C1-C 10 alkoxy, n is an integer, either 1 or 2. However, R 3 If n is a halogen, then n is an integer of 1.

[0014] Another aspect of the present invention provides a composition for delaying aging or extending lifespan, comprising an amino-aromatic compound represented by chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0015] Another aspect of the present invention provides a health functional food composition for the prevention or improvement of aging-related diseases, comprising an amino-aromatic compound represented by chemical formula 1 or a food-grade salt thereof as an active ingredient. [Effects of the Invention]

[0016] A composition according to one embodiment can significantly suppress the death of nerve cells due to aging, delay age-related nerve degeneration, improve the survival rate of dopamine-secreting nerve cells, and significantly improve the degree of decline in motor function associated with aging.

[0017] Furthermore, while the size and number of branches of astrocytes tend to decrease and shrink with age, this can be delayed by treatment or administration of the composition according to one embodiment. In addition, as aging progresses, astrocytes overproduce reactive oxygen species and GABA, which cause memory loss and cognitive impairment due to the overproduction of MAOB, but the overproduction of reactive oxygen species and GABA can be suppressed by treatment or administration of the composition according to one embodiment.

[0018] In other words, a composition according to one embodiment can delay the aging of an individual and extend their lifespan, and can prevent or treat age-related diseases or disorders. Furthermore, it can exhibit preventive or restorative effects against age-related decline in motor function. [Brief explanation of the drawing]

[0019] [Figure 1]This figure shows the survival rate of C57BL / 6 female rats in Example 1, depending on whether or not an amino-aromatic compound was administered and for how long (*p=0.0126, KDS12025 0.1mpk compared to the control group, #p=0.0142, KDS12025 1mpk compared to the control group, #p=0.0306, Mantel-Cox test). [Figure 2] This figure shows the results of the open-field (OF) test in Example 2. [Figure 3] This figure shows the results of a new spatial cognition (NPR) test in Example 2. [Figure 4] This figure shows the results of the Y-maze test in Example 2. [Figure 5] This figure shows the results of the elevated cross maze (EPM) in Example 2. [Figure 6] This figure shows immunohistochemical staining images and results of the hippocampus of 18 and 30-month-old rats, showing the results of neuronal cell death and suppression. [Figure 7] This figure shows an immunohistochemical staining image and results of the substantia nigra of a 30-month-old rat, showing the results of suppression of dopamine-mediated neuronal cell death. [Figure 8] This figure shows immunohistochemical staining images of the hippocampus of 18 and 30-month-old rats. [Figure 9] This figure shows the results of immunohistochemical staining and the senescence index 1 for astrocytes. [Figure 10] This figure shows morphological analysis and photographs of astrocytes in the hippocampus of 18 and 30-month-old rats. [Figure 11] This figure shows the results of immunohistochemical staining and the 2-point scale for measuring the degree of senescence in astrocytes. [Figure 12] This figure shows the results of immunohistochemical staining and the senescence index 3 for astrocytes. [Figure 13] The image shows immunohistochemical staining images and results from the hippocampus of 18 and 30-month-old rats, along with the measurement of MAOB protein, one of the pathological indicators of astrocytes. [Modes for carrying out the invention]

[0020] The present invention will now be described in detail. In this description, unless otherwise defined, the technical and scientific terms used have the meaning that a person with ordinary skill in the art to which the present invention belongs would ordinarily understand, and descriptions of known functions and configurations that could obscure the gist of the present invention in the following description will be omitted.

[0021] The following terms used herein are defined as follows, but are merely illustrative and not intended to limit the invention, application, or use.

[0022] The terms "substituent," "radical," "group," and "moiety" can be used interchangeably.

[0023] The term “C A -C B " means "a carbon atom with a number of carbon atoms between A and B".

[0024] The term "alkyl" refers to a monovalent linear or branched saturated hydrocarbon radical consisting only of carbon and hydrogen atoms. Such alkyls may have 1 to 10 carbon atoms, 1 to 7 carbon atoms, or 1 to 4 carbon atoms. Lower alkyls refer to linear or branched alkyls having 1 to 4 carbon atoms. Examples of such alkyls include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, and ethylhexyl.

[0025] The term "alylene" refers to an aromatic ring-divalent organic radical derived from aromatic hydrocarbons by the removal of two hydrogen atoms, and includes monocyclic or fused ring systems, each containing 4 to 7, preferably 5 or 6, ring atoms, and encompassing forms in which numerous aryls are linked by single bonds. Specific examples include, but are not limited to, phenylene, naphthylene, biphenylene, and anthrylene.

[0026] The term "alkoxy" refers to an -O-alkyl radical, where alkyl is defined as described above. Specific examples include, but are not limited to, methoxy, ethoxy, isopropoxy, butoxy, isobutoxy, and t-butoxy.

[0027] The term "halo" or "halogen" refers to the halogen group elements, including, for example, fluoro, chloro, bromo, and iodine.

[0028] The terms "haloalkyl" and "haloalkoxy" refer to alkyl or alkoxy groups in which one or more hydrogen atoms are substituted with halogen atoms, respectively, where alkyl and halogen are as defined above. For example, haloalkyls include fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, and perfluoroethyl, while haloalkoxys include fluoromethoxy, difluoromethoxy, trifluoromethoxy, fluoroethoxy, difluoroethoxy, and perfluoroethoxy.

[0029] The term "amino" means -NH2, and "hydroxy" means -OH.

[0030] The term "alkylamino" refers to an amino radical in which one or two alkyl groups are substituted. Specific examples include, but are not limited to, methylamino (-NHMe), dimethylamino (-NMe2), ethylamino (-NHEt), and diethylamino (-NEt2).

[0031] The term "pharmaceutically acceptable" means that the composition is non-toxic to cells or individuals such as humans that are exposed to it, is suitable for use as a pharmaceutical preparation, is generally considered safe for such use, and is officially approved for such use by a national regulatory body or is listed in the Korean Pharmacopoeia or the United States Pharmacopoeia.

[0032] The term "pharmaceutically acceptable salt" means any organic or inorganic addition salt of the compound of the present invention that is relatively non-toxic to patients and has a harmless, effective effect, such that the side effects caused by the salt do not diminish the beneficial efficacy of the compound itself.

[0033] The terms "pharmaceutically acceptable excipient" and "pharmaceutically acceptable carrier" refer to substances that facilitate the administration of an activator and its absorption by the target organism.

[0034] The term "prevention" refers to all actions that suppress or delay the onset, spread, and recurrence of age-related diseases or disorders.

[0035] The term "improvement" refers to all actions that reduce, at least the severity of, the parameters related to the condition being treated, such as the symptoms.

[0036] The term "treatment" refers to any action that improves or alters the symptoms of an age-related disease or disorder.

[0037] The term “individual” means all animals, including humans, that have or are at risk of developing age-related diseases or disorders, or that require aging delay or life extension. Such animals may include, but are not limited to, humans, mammals such as cattle, horses, sheep, pigs, goats, camels, antelopes, dogs, and cats that require treatment for similar conditions.

[0038] The term "administration" means introducing the pharmaceutical composition of the present invention into an individual by any appropriate method, and the administration route of the composition of the present invention can be via various oral or parenteral routes, insofar as it can reach the target tissue.

[0039] The term "pharmaceutically effective dose" means a quantity sufficient to treat a disease in a reasonable benefit / risk ratio applicable to medical treatment without causing side effects. The level of the effective dose can be readily determined by those skilled in the art, depending on factors including the patient's sex, age, weight, health status, type and severity of the disease, drug activity, sensitivity to the drug, method of administration, time of administration, route of administration, and elimination ratio, duration of treatment, drugs used in combination or concurrently, and other factors well known in the medical field.

[0040] The term "food" includes all foods in the ordinary sense, such as meat, sausages, bread, chocolate, candy, snacks, sweets, pizza, ramen, other noodle products, gum, dairy products including ice cream, various soups, beverages, tea, energy drinks, alcoholic beverages, vitamin complexes, health functional foods, and health foods.

[0041] The term "health functional food" refers to foods manufactured and processed using raw materials or ingredients that have beneficial functional properties for the human body, as defined in the Act on Health Functional Foods No. 6727. "Functionality" means that the food is consumed with the purpose of regulating nutrients in relation to the structure and function of the human body, or obtaining beneficial effects for health purposes, such as physiological effects.

[0042] The term "food-grade salt" refers to a dosage form of a compound that does not cause serious irritation to the organism to which the compound is administered and does not impair the compound's biological activity or physical properties.

[0043] The present invention provides a pharmaceutical composition for the prevention or treatment of aging-related diseases or disorders, comprising an amino-aromatic compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0044] [Chemical formula 1] JPEG2026522513000003.jpg38170 In the above chemical formula 1, Ar is C6-C 20 It is allylene, and the allylene of Ar is C1-C 10 Alkyl, C1-C10 Alkoxy, amino, mono- or di-C1-C 10 Alkylamino, Halo C1-C 10 Alkyl, Halo C1-C 10 They may be further substituted with one or more selected from alkoxy and hydroxyl groups. R 1 and R 2 Each of these is independently hydrogen or C1-C 10 It is alkyl, R 3 Halogen, C1-C 10 Alkoxy, Halo C1-C 10 Alkyl or Halo C1-C 10 It is an alkoxy, n is an integer, either 1 or 2. However, R 3 If n is a halogen, then n is an integer of 1.

[0045] Furthermore, the present invention provides a composition for delaying aging or extending lifespan, comprising an amino-aromatic compound represented by the chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0046] The aforementioned amino-aromatic compound is a compound described in the Korean registered patent KR10-2643653 B1 held by the present applicant, and is known to act as a scavenger that removes hydrogen peroxide, a type of reactive oxygen species, and is useful for the prevention, improvement, or treatment of neurodegenerative diseases.

[0047] According to one embodiment of the present invention, the amino aromatic compound can extend lifespan by effectively delaying the aging of an individual and can be usefully used for the prevention or treatment of aging-related diseases.

[0048] The term "aging" refers to the phenomenon that occurs after an individual's birth, as time passes, involving various physiological changes such as a decrease in cell differentiation and proliferation, a decline in function, a decrease in homeostasis of organs and tissue systems, and an increase in susceptibility to external stress and disease. The term "aging-related diseases" refers to diseases that occur more frequently with aging.

[0049] In the present invention, delaying the aging of an individual means reducing the rate of aging that occurs over time compared to a control group, i.e., an individual that has not been treated or administered with the composition or compound according to one embodiment, resulting in a slower aging process. Furthermore, in the present invention, extending the lifespan of an individual means allowing it to survive for a longer period of time compared to a negative control group, i.e., an individual that has not been treated or administered with the composition or compound according to one embodiment.

[0050] In one embodiment, the age-related disease may be one or more diseases selected from the group consisting of Alzheimer's disease, diabetes, Parkinson's disease, Huntington's disease, degenerative joint disease, stroke, angina pectoris, osteoporosis, myocardial infarction, muscular dystrophy, amyotrophic lateral sclerosis, sarcopenia, cirrhosis of the liver, and chronic kidney disease.

[0051] In one embodiment, the aging-related disease may be a cognitive impairment disease caused by aging, and the cognitive function may be one or more selected from the group consisting of perception, memory, attention, speech comprehension, speech generation, reading comprehension, creation of imagery, learning, and reasoning.

[0052] A composition according to one embodiment can significantly suppress the death of nerve cells due to aging, delay age-related neuronal degeneration, improve the survival rate of dopamine-secreting nerve cells, and significantly improve the degree of decline in motor function associated with aging.

[0053] Furthermore, while the size and number of branches of astrocytes tend to decrease and shrink with age, this can be delayed by treatment or administration of the composition according to one embodiment. Also, as aging progresses, astrocytes overproduce GABA, which causes memory loss and cognitive impairment due to the overproduction of MAOB, but the overproduction of GABA can be suppressed by treatment or administration of the composition according to one embodiment.

[0054] In other words, a composition according to one embodiment can delay aging and extend the lifespan of an individual, and can prevent or treat age-related diseases or disabilities. Furthermore, it can exhibit preventive or restorative effects against age-related decline in motor function.

[0055] In the chemical formula 1, Ar is C6-C 12 It may be allylene, preferably phenylene or biphenylene, and the Ar may be further substituted with one or more selected from C1-C7 alkyl, C1-C7 alkoxy, amino, and hydroxy.

[0056] In the above chemical formula 1, Ar may be phenylene, and it is preferable that nitrogen atoms are introduced at the 1st and 4th positions of the phenylene, respectively.

[0057] The aforementioned amino-aromatic compound can specifically be represented by the following chemical formula 2 or 3.

[0058] [Chemical formula 2] JPEG2026522513000004.jpg45170

[0059] [Chemical formula 3] JPEG2026522513000005.jpg45170

[0060] In the aforementioned chemical formulas 2 and 3, R 1 and R 2 Each of these is independently either hydrogen or a C1-C7 alkyl group. Hal is a halogen, R 3 These are C1-C7 alkoxy or halo-C1-C7 alkyl, R' is a C1-C7 alkyl, C1-C7 alkoxy, amino, or hydroxy. a is an integer between 0 and 4. n is an integer, either 1 or 2.

[0061] In the above chemical formulas 2 and 3, the R 1 and R 2 Each is independently hydrogen or a C1-C4 alkyl group, where Hal is a halogen and R 3 a is a C1-C4 alkoxy or a halo-C1-C4 alkyl, a is an integer of 0, and n may be an integer of 1 or 2.

[0062] The aforementioned chemical formula 2 can be represented by the following chemical formula 4.

[0063] [Chemical formula 4] JPEG2026522513000006.jpg45170

[0064] In chemical formula 4, R 1 and R 2 Each of these is independently either hydrogen or a C1-C4 alkyl group. Hal is a halogen.

[0065] Specifically, in the chemical formula 4, the R 1 and R 2 Each of these is independently a C1-C4 alkyl group, and Hal may be a halogen.

[0066] Specifically, in the chemical formula 4, the R 1 is hydrogen, and R 2 is a C1-C4 alkyl group, and Hal may be a halogen.

[0067] Specifically, in the chemical formula 4, the R 1 and R 2 Each of these is independently hydrogen, and Hal may be a halogen.

[0068] The aforementioned chemical formula 3 can be represented by the following chemical formula 5.

[0069] [Chemical formula 5] JPEG2026522513000007.jpg46170

[0070] In chemical formula 5, R 1 and R 2 Each of these is independently either hydrogen or a C1-C4 alkyl group. R 3 These are C1-C4 alkoxy or halo-C1-C4 alkyl, n is an integer, either 1 or 2.

[0071] Specifically, in the chemical formula 5, the R 1 and R 2 Each of them is independently a C1-C4 alkyl, and R 3 is a C1-C4 alkoxy or halo-C1-C4 alkyl, and n is an integer of 1 or 2.

[0072] Specifically, in the above chemical formula 5, R 1 is hydrogen, and R 2 It is a C1-C4 alkyl, and R 3 is a C1-C4 alkoxy or halo-C1-C4 alkyl, and n is an integer of 1 or 2.

[0073] Specifically, in the chemical formula 5, the R 1 and R 2Each of them is independently hydrogen, and R 3 is a halo-C1-C4 alkyl group, and n is an integer of 1 or 2.

[0074] In any of the compounds described herein, the halogen or halo may be fluorine.

[0075] The aforementioned amino-aromatic compound may be any one selected from the following group of compounds, but is not limited thereto.

[0076] JPEG2026522513000008.jpg224170

[0077] The aforementioned amino-aromatic compounds are available in the form of pharmaceutically acceptable salts, which are salts produced by conventional methods in the art, and the methods of producing them are known to those skilled in the art. Specifically, the pharmaceutically acceptable salts include, but are not limited to, salts derived from the following pharmacologically or physiologically acceptable free acids and bases.

[0078] Acid addition salts formed from pharmaceutically acceptable free acids can be obtained from inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrite, and phosphorous acid, and organic acids such as methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carboxylic acid, vanillic acid, and hydroiodic acid. Examples of pharmaceutically non-toxic salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, nitrates, phosphates, monohydrogen phosphates, dihydrogen phosphates, metaphosphates, pyrophosphate chlorides, bromides, iodides, fluorides, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, caprates, heptanoates, propioates, oxalates, malonates, succinates, sverate, sebacate, fumarate, maleate, butane-1,4-dioate, and hexagonal salts. This includes sun-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybutyrate, glycolate, malate, tartarate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, mandelate, and others.

[0079] Acid addition salts can be produced by conventional methods. For example, they can be produced by dissolving the amino-aromatic compound in a water-miscible organic solvent such as methanol, ethanol, acetone, dichloromethane, or acetonitrile, adding an organic or inorganic acid, filtering and drying the resulting precipitate, or by vacuum distillation of the solvent and excess acid, followed by drying and crystallization under an organic solvent.

[0080] Furthermore, pharmaceutically acceptable metal salts can be produced using bases. Alkali metal salts or alkaline earth metal salts can be obtained, for example, by dissolving the amino aromatic compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering out the insoluble amino aromatic compound salt, and then evaporating and drying the filtrate. Here, sodium, potassium, or calcium salts are pharmaceutically suitable as metal salts, but are not limited to these. Corresponding silver salts can be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (e.g., silver nitrate).

[0081] Preferably, the pharmaceutically acceptable salt of the amino aromatic compound may be a hydrochloride salt.

[0082] In other words, the amino-aromatic compound may be a hydrochloride salt form selected from the following structures.

[0083] JPEG2026522513000009.jpg223170

[0084] A composition according to one embodiment further comprises, in addition to the active ingredient, a conventional non-toxic, pharmacoagulably acceptable carrier and / or excipient, and can be formulated into a conventional pharmaceutical formulation, i.e., an oral or parenteral formulation. It may also further contain diluents such as fillers, bulking agents, binders, wetting agents, disintegrants, and surfactants.

[0085] Examples of pharmaceutically acceptable carriers, excipients, or diluents include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, amorphous cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, or mineral oil.

[0086] A composition according to one embodiment can be prepared in various forms by conventional methods, depending on the intended use, such as oral dosage forms like powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, as well as sterile injection solutions. It can be administered orally or via various routes, including intravenous, intraperitoneal, subcutaneous, rectal, and local administration.

[0087] A composition according to one embodiment may further contain fillers, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers, preservatives, and the like.

[0088] Oral dosage forms include, for example, tablets, pills, hard / soft capsules, liquids, suspensions, emulsifiers, syrups, granules, and elixirs. These dosage forms may use one or more diluents or excipients, such as fillers, bulking agents, wetting agents, disintegrants, lubricants, binders, and surfactants, in addition to the active ingredient. Disintegrants can include agar, starch, alginic acid or its sodium salt, and anhydrous calcium monohydrogen phosphate. Lubricants can include silica, talc, stearic acid or its magnesium or calcium salt, and polyethylene glycol. Binders can include magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium capoxymethylcellulose, polyvinyl pyrrolidine, and low-substituted hydroxypropylcellulose. In addition, lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, and glycine can be used as diluents, and in some cases, commonly known effervescent mixtures, absorbents, colorants, flavorings, and sweeteners can be used together.

[0089] Examples of formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, and suppositories. Examples of non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Examples of suppository bases include witepsol, macrogol, Twin 61, cocoa butter, lauric acid butter, glycerol, and gelatin. On the other hand, injectable formulations may contain conventional additives such as solvents, isotonic agents, suspending agents, emulsifiers, stabilizers, and preservatives. To formulate an injectable formulation, the amino-aromatic compound of the present invention or a pharmaceutically acceptable salt thereof may be mixed with water along with a stabilizer or buffer to produce a solution or suspension, which can then be manufactured in ampoules or vials for unit administration.

[0090] A composition according to one embodiment may be sterilized or further contain auxiliary agents such as preservatives, stabilizers, viscosity enhancers, hydrates or emulsifiers, salts and / or buffers for osmotic pressure adjustment, and other therapeutically useful substances, and may be formulated by conventional methods such as dissolution, dispersion, mixing, granulation, gelation or coating.

[0091] The pharmaceutically effective amount of the amino-aromatic compound can be determined by the patient's health condition, the type and severity of the disease, the activity of the drug, the patient's sensitivity to the drug, the method of administration, the time of administration, the route of administration and the ratio of excretion, the duration of treatment, factors including drugs that are compounded or used concurrently, and other factors well known in the medical field. Specifically, in a composition according to one embodiment, the effective amount of the amino-aromatic compound can vary depending on the patient's age, sex, and weight, and is generally about 0.01 to 500 mg / kg / day, preferably 0.1 to 100 mg / kg / day, and can be administered daily, every other day, or in one to several divided doses per day. However, the dose can be increased or decreased depending on the route of administration, the severity of the disease, sex, weight, age, etc., and the aforementioned dose does not limit the scope of the present invention in any way.

[0092] A composition according to one embodiment can be administered orally or parenterally, with parenteral administration such as subcutaneous injection, intravenous injection, intramuscular injection, or intraperitoneal injection being preferred.

[0093] A composition according to one embodiment can be administered as a standalone therapeutic agent or in combination with other therapeutic agents, can be administered sequentially or simultaneously with conventional therapeutic agents, and can be administered single or multiple times. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect with the minimum amount without side effects, which can be easily determined by those skilled in the art.

[0094] Furthermore, the present invention provides a method for preventing or treating age-related diseases or disorders, or a method for delaying aging or extending lifespan, which includes the step of administering the composition to an individual who has developed or is likely to develop an age-related disease or disorder, or who needs aging delay or life extension.

[0095] Furthermore, the present invention provides a health functional food composition for the prevention or improvement of aging-related diseases, comprising an amino aromatic compound represented by the chemical formula 1 or a food-grade salt thereof as an active ingredient.

[0096] The aforementioned food-grade salts can be obtained by reacting the amino-aromatic compound with an inorganic acid such as hydrochloric acid, bromate, sulfuric acid, nitric acid, or phosphoric acid; a sulfonic acid such as methanesulfonic acid, ethanesulfonic acid, or p-toluenesulfonic acid; or an organic carboxylic acid such as tartaric acid, formic acid, citric acid, acetic acid, trichloroacetic acid, trifluoroacetic acid, capric acid, isobutanoic acid, malonic acid, succinic acid, phthalic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, maleic acid, or salicylic acid. Alternatively, the amino-aromatic compound can also be obtained by reacting it with a base to form salts such as ammonium salts, alkali metal salts such as sodium or potassium salts, alkali metal salts such as calcium or magnesium salts, salts of organic bases such as dicyclohexylamine, N-methyl-D-glucamine, or tris(hydroxymethyl)methylamine, and amino acid salts such as arginine or lysine.

[0097] The aforementioned health functional food composition may be provided in the form of a powder, granules, tablets, capsules, syrup, or beverage, and the health functional food may be used in combination with other foods or food additives in addition to the amino aromatic compound which is the active ingredient, and may be used appropriately in accordance with conventional methods. The amount of active ingredient mixed may be suitably determined by its intended use, for example, prevention, health, or therapeutic treatment.

[0098] The aforementioned health functional food composition may contain various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavoring agents, coloring agents and fillers (for cheese, chocolate, etc.), pectin acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, and carbonating agents used in carbonated beverages. It may also contain fruit pulp for the production of natural fruit juices, fruit juice beverages, and vegetable beverages. These components can be used independently or in combination.

[0099] Furthermore, the aforementioned health functional foods may contain additional food additives. Unless otherwise specified, the suitability of a food additive shall be determined according to the standards and criteria for that item, such as the general provisions and general test methods of the Food Additives Code approved by the Ministry of Food and Drug Safety.

[0100] Examples of items listed in the aforementioned "Food Additives Codex" include chemically synthesized products such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid; natural additives such as oyster pigment, licorice extract, crystalline cellulose, and guar gum; and mixed preparations such as L-sodium glutamate preparations, alkaline agents added to noodles, preservative preparations, and tar dye preparations.

[0101] The amino aromatic compound contained in the health functional food composition can be used in accordance with the effective volume of the pharmaceutical composition. However, in the case of long-term intake for health and hygiene purposes or for health regulation purposes, the amount may be less than the aforementioned range. It goes without saying that the active ingredient can be used in amounts exceeding the aforementioned range, as there are no safety concerns with the active ingredient.

[0102] The aforementioned health functional food composition can be formulated into various dosage forms, including meats, sausages, bread, chocolates, candies, snacks, sweets, pizzas, ramen noodles, other noodle products, gums, dairy products including ice cream, various soups, beverages, teas, drinks, alcoholic beverages, and vitamin complexes.

[0103] The present invention will be described in more detail below with reference to preferred embodiments. However, these are presented as examples of the present invention and do not limit the scope of the present invention in any way, and the scope of the present invention is defined solely by the claims described below.

[0104] [Manufacturing Example 1] Production of amino aromatic compounds JPEG2026522513000010.jpg46170

[0105] An amino-aromatic compound was prepared with reference to Korean registered patent KR10-2643653 B1. The specific preparation process is as follows: Potassium carbonate (3.0 equivalents), potassium iodide (0.1 equivalent), and phenylalkyl bromide compound (b, 1.0 equivalent) were added to an acetonitrile solution containing p-phenylenediamine compound (a, 1.2 equivalents), and the mixture was stirred at 110°C for 36 hours. Next, it was cooled to room temperature, diluted with ethyl acetate, and washed with brine. The remaining organic layer was dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was purified via column chromatography to obtain compound P1. The purified compound P1 was dissolved in dichloromethane (DCM), and then a 4.0 M hydrogen chloride solution was added. Next, it was stirred at room temperature for 48 hours, and the resulting precipitate was filtered to obtain compound P2 in hydrochloride form.

[0106] Using the method described above, an amino aromatic compound in hydrochloride form was produced, and its structure is shown in Table 1 below.

[0107] [Table 1] JPEG2026522513000012.jpg227170

[0108] Animal Husbandry One-year-old C57BL / 6J experimental rats were purchased from Janvier Labs (France) and isolated at the Institute for Basic Science's animal facility for two weeks prior to the experiment. The rats' body weight was measured, and their water intake (in grams) was monitored for three days to calculate the optimal drug concentration for each group. The experimental rats were randomly assigned to drug / control and dosage groups. After drug administration, water intake was observed for one week to ensure there were no changes in daily intake. Drug concentrations were adjusted every three months according to changes in the animals' body weight and water intake. The temperature and humidity in the animal housing room were set to 23±1℃ and 50±5%, maintained on a 12-hour day-night cycle (lights off at 8pm), and samples and water were freely accessible. Basal body temperature and body weight were monitored every two weeks. Animal management and handling followed the guidelines of the Institute for Basic Science's Institutional Animal Management and Use Committee.

[0109] Quantification and statistical analysis All analyses were performed in a blinded manner. Data representation and statistical analysis were performed using GraphPad Prism (Graphpad Software). Image analysis was performed using ImageJ (NIH). Here, p-values ​​less than 0.05 were considered statistically significant (*P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, NS, not significant).

[0110] [Example 1] Confirmation of life extension by amino aromatic compounds We conducted an experiment using 14-month-old female C57BL / 6 rats to confirm the extent to which amino aromatic compounds extend lifespan.

[0111] Fourteen-month-old C57BL / 6 female rats were divided into four groups of 15 rats each for the experiment. All four groups were given the same sample, but the control group was supplied with untreated general drinking water, while the remaining three groups were supplied with water containing the amino aromatic compound KDS12025, with daily intake levels of 0.1 mpk, 1 mpk, and 10 mpk, respectively. The rats' body weight and water intake during the first three days were measured to determine the amount of KDS12025 dissolved in the water. The amount of KDS12025 dissolved in the water was then checked for any abnormalities over the course of one week. Subsequently, the rats' water intake was measured every three months to adjust the drug concentration. In addition, the rats' body weight and body temperature were measured every two weeks, and the number of surviving rats was counted. The experiment was conducted for 24 months.

[0112] The survival rates of C57BL / 6 female rats during the experimental period are shown in Figure 1. From this, it was confirmed that the survival rate increased in the group treated with the amino aromatic compound KDS12025 compared to the control group. In particular, a statistically significant increase in survival time was confirmed in the groups treated with 0.1 mpk and 1 mpk of the amino aromatic compound KDS12025.

[0113] In other words, we confirmed that prolonged treatment with amino aromatic compounds delayed aging in rats, improved their survival rate, and consequently extended their lifespan.

[0114] [Example 2] Animal behavior experiment The animals were allowed one hour to acclimate to the laboratory environment before the experiment, and the experiment was conducted under ambient lighting and white noise. On the day of the experiment, all experimental equipment was cleaned with 10% bleach and 70% ethanol, and then washed with distilled water. Behavioral experiments were conducted at the same time each day. All behavioral recordings were made using the Ethovision XT (Noldus) program.

[0115] In an open field test (OFT), animals were placed in a 40cm x 40cm box and allowed to explore freely for 10 minutes. The total distance traveled and speed were measured during the last 8 minutes of the recording.

[0116] In the Novel Place Recognition Test (NPRT), two identical objects were placed in a 40cm x 40cm box, and animals were allowed to explore them freely. After exploring the objects for 8 minutes, the animals were returned to their cages. 60 minutes later, one of the objects was moved to a different, distant location, and the animals were placed back into the experimental box. The animals' exploration time for each object was recorded for 8 minutes. The recorded videos were analyzed by experimenters who were unaware of the experimental conditions. Exploration was considered to consist of the animals smelling the objects without crawling over them. The discrimination ratio was calculated as follows: (time spent smelling the moved object) / (total time spent smelling both objects).

[0117] In the Y-maze test, animals were placed in the center of a symmetrical Y-shaped maze with three identical "arms" (30 cm long, 15 cm high, and 6 cm wide) and allowed to explore freely for 8 minutes, which was recorded. The number of times the animals entered an "arm" was recorded. An entry was considered only when all four of the animal's feet were inside an "arm". The alternation rate (%) was calculated as follows: Alternation rate (%) = [(Total number of alternations) / (Number of "arm" entries - 2)] × 100.

[0118] In the Elevated Plus Maze (EPMT) test, animals were placed in an open area of ​​a symmetrical cross-shaped maze 60 cm above the ground and observed for 8 minutes to freely explore the maze, which had two "open arms" and two "walled arms" (30 cm long, 6 cm wide, 15 cm high). The total distance traveled, the number of times each "arm" was entered, and the time spent in each "arm" were recorded. An entry was considered successful when the animal's center point was within the area. Time spent in the center area was not included in the time spent in individual "arms".

[0119] Open Field Test (OFT) Results Fourteen-month-old C57BL / 6 female rats were divided into four groups of 15 rats each for the experiment. All four groups were given the same sample, but the control group was supplied with untreated general drinking water, while the remaining three groups were supplied with water containing the amino aromatic compound KDS12025, with daily intakes of 0.1 mpk, 1 mpk, and 10 mpk, respectively. An open-field test (OFT) was performed on C57BL / 6 female rats at 26 months of age after being supplied with water containing KDS12025 for 12 months. The aim was to confirm whether it could prevent age-related decline in behavioral ability beyond simple life extension. A comparison group of 12-month-old C57BL / 6 female rats, representing a time when they were healthy and energetic, was used.

[0120] The overall degree of movement was confirmed by the open-field test results illustrated in Figure 2. From Figure 2, it was confirmed that the average speed (left side of Figure 2) and total distance traveled (right side of Figure 2) of 26-month-old animals (1 year after drug administration) treated with the amino-aromatic compound KDS12025 for an extended period were statistically significantly increased in the KDS12025 1mpk treatment group compared to the control group, indicating improved mobility. The KDS12025 0.1 and 10mpk treatment groups showed a tendency towards increase compared to the 26-month-old control group, but there was no statistically significant difference compared to the 12-month-old comparison group. Average speed and total distance traveled indicate the degree of movement and activity. In other words, it was confirmed that the experimental groups treated with the amino-aromatic compound for an extended period, despite their age, showed a level of mobility equivalent to that of the 12-month-old comparison group.

[0121] Results of the Novel Place Recognition Test (NPRT) Fourteen-month-old C57BL / 6 female rats were divided into four groups of 15 rats each for the experiment. All four groups were given the same sample, but the control group was supplied with untreated general drinking water, while the remaining three groups were supplied with water containing the amino aromatic compound KDS12025, with daily intakes of 0.1 mpk, 1 mpk, and 10 mpk, respectively. A novel spatial cognition test (NPRT) was performed on 26-month-old C57BL / 6 female rats that had been supplied with KDS12025-containing water for 12 months. A comparison group consisted of 12-month-old C57BL / 6 female rats, representing a time when they were healthy and energetic.

[0122] Figure 3 shows the results of a novel spatial recognition test (NPRT) that examined memory, particularly spatial memory. Figure 3 shows that the 26-month-old animal group (1 year after drug administration) treated with the amino-aromatic compound KDS12025 10mpk for an extended period showed a statistically significant improvement in the discrimination index for moving objects compared to the control group, confirming improved spatial memory. The amino-aromatic compounds KDS12025 0.1 and 1mpk showed a tendency to increase the discrimination index, but this was not statistically significant compared to 12-month-old rats. In other words, the group treated with the amino-aromatic compound for an extended period showed spatial memory at a level equivalent to or higher than the 12-month-old control group, despite their age.

[0123] Results of the Y-maze test Fourteen-month-old C57BL / 6 female rats were divided into two groups of 15 rats each for the experiment. Both groups were given the same sample, but the control group was supplied with untreated general drinking water, while the remaining groups were supplied with water containing the amino aromatic compound KDS12025, with a daily intake of 1 mpk. A Y-maze test was performed on 24-month-old C57BL / 6 female rats that had been supplied with water containing KDS12025 for 10 months.

[0124] Spatial memory was evaluated using the Y-maze test, and the results are shown in Figure 4. From Figure 4, it was confirmed that the 24-month-old animal group (1 year after drug administration) treated with the amino aromatic compound KDS12025 for an extended period showed a statistically significantly higher switching ratio compared to the control group, indicating a considerable improvement in memory.

[0125] Results of the Elevated Plus Maze (EPM) test Fourteen-month-old C57BL / 6 female rats were divided into two groups of 15 rats each for the experiment. Both groups were given the same sample, but the control group was supplied with untreated general drinking water, while the remaining groups were supplied with water containing the amino aromatic compound KDS12025, with a daily intake of 1 mpk. An elevated plus maze (EPM) test was performed on C57BL / 6 female rats at 24 months of age after being supplied with water containing KDS12025 for 10 months.

[0126] Anxiety levels were assessed using the Elevated Plus Maze (EPM) test, and the results are shown in Figure 5. From Figure 5, it was confirmed that the 24-month-old animal group (1 year after drug administration) treated with the amino-aromatic compound KDS12025 for an extended period spent in the open arm of the Elevated Plus Maze had a greater total time spent in the open arm compared to the control group, resulting in a significant improvement in anxiety.

[0127] [Example 3] Immunohistochemical staining (IHC) and Scholl analysis (morphological analysis) of brain tissue C57BL / 6 female rats were used as the experimental group, and those drank water containing the amino aromatic compound KDS12025 in a daily intake of 1 mpk from 12 months to 30 months of age. C57BL / 6 female rats that drank regular drinking water were used as the control group. C57BL / 6 female rats aged 18 months were used as the comparison group.

[0128] Immunohistochemical staining After anesthetizing the experimental animals in each group with isoflurane, they were washed with 0.9% saline and administered cold 4% paraformaldehyde (PFA). The brains were excised, fixed by immersion in 4% PFA at 4°C for one day, and dehydrated in 30% sucrose solution for 48 hours. Tissues 30 μm thick were prepared using a freeze-cutting machine and stored in a glycerol-based storage solution until before the experiment. Before staining, brain sections were washed three times with 0.1 M phosphate buffer (PBS) and incubated for 1 hour in staining solution (4% serum, 0.3% Triton X-100 in 0.1 M PBS). Primary antibodies were added to the staining solution at the desired dilution ratio and incubated overnight at 4°C. To remove unbound antibodies, the sections were washed three times with 0.1 M PBS, the corresponding secondary antibodies were added, and the sections were incubated at room temperature for 2 hours. To remove unbound secondary antibodies, the tissue sections were washed three times with 0.1M PBS, the first wash containing DAPI (1:1000) for nuclear staining. The tissue sections were mounted using fluorescent mounting medium (Dako) and dried. Fluorescence images were obtained using a Zeiss LSM900 microscope. For visualization, ZEN Digital Imaging for Light Microscopy blue system (Zeiss, ver.3.2) and ImageJ (NIH, ver.1.54b) software were used.

[0129] The antibodies used in the experiment are as follows: rabbit-anti-AOC1 (aviva #ARP41908_P0050, 1:200), chicken-anti-GFAP (Millipore #AB5541, 1:500), x-anti-NeuN (1:250), rabbit-anti-TH (Pelfreez #p40101-0, 1:500), guinea pig-anti-GABA (Millipore #ab175, 1:200), mouse-anti-MAOB (SantaCruz sc-515354, 1:200), donkey-anti-chicken-647 (1:500), donkey-anti-rabbit-488 (1:200), donkey-anti-rabbit-594 (1:200), donkey-anti-guinea pig-488(1:200), donkey-anti-mouse-594(1:200).

[0130] Sholl analysis (morphological analysis) Sholl analysis was performed using confocal microscopy images, following the reference [Nature Neuroscience volume 23, pages 1555-1566 (2020)]. Images of brain sections immunostained with GFAP antibody were used for Sholl analysis. Using a Sholl analysis plugin applied to the Imagej program (NIH Image, Bethesda, MD), a series of circles were constructed at 5 μm intervals from the center to the end of the GFAP signal. The number of GFAP intersections and the radius of the largest circle crossing the star pattern were measured and analyzed within each circle.

[0131] The hippocampus is a crucial brain region involved in learning and memory. As we age, neurogenesis decreases, axonal degeneration increases, and the volume of the hippocampus is known to decrease. Figure 6 shows the results of measuring the degree of age-related neuronal cell (NeuN) death in the hippocampal region of experimental animals' brains. Figure 6 shows the degree of age-related neuronal cell death and the degree of suppression of death by the amino-aromatic compound KDS12025 using tissue staining. NeuN refers to neuronal cell staining, DAPI refers to cell nucleus staining, and GFAP refers to astrocyte staining. In Figure 6, we confirmed that the 30-month-old control group showed a sharp decrease in hippocampal CA1 pyramidal neurons compared to the 18-month-old comparison group. On the other hand, we confirmed that the 30-month-old experimental group showed statistically significant suppression of age-related neuronal cell death by long-term treatment with the amino-aromatic compound KDS12025. In particular, the experimental group treated with amino aromatic compounds for an extended period expressed neurons at a level equivalent to or higher than the 18-month-old control group, despite aging, confirming that aging-related neuronal degeneration was delayed.

[0132] Previous studies have shown that dopamine neurons are lost in the ventral tegmental area, which is associated with decreased motor function in aged animals. Therefore, we measured the degree of age-related dopamine neuron loss and the results are shown in Figure 7. Figure 7 shows tissue staining that restored age-related dopamine neuron death with the amino-aromatic compound KDS12025. TH indicates dopamine neuron staining, and DAPI indicates cell nucleus staining. From Figure 7, we confirmed that the experimental group treated with the amino-aromatic compound KDS12025 for a long period of time had significantly more viable dopamine neurons expressing tyrosine hydroxylase (TH). On the other hand, the control group of the same age as the experimental group had fewer TH-positive dopamine neurons in the ventral tegmental area and substantia nigra. From this, we confirmed that the experimental group treated with amino aromatic compounds for a long period of time showed a significantly improved survival rate of dopamine neurons compared to the control group of the same age, despite aging.

[0133] Previous studies have shown that with age, the astrocyte area significantly decreases due to atrophy of astrocytes (or star cells), resulting in a reduction in the number of branches and the volume ratio of astrocytes. The pathological phenomena of astrocytes (star cells) were analyzed using immunohistochemistry and Scholl analysis, and the results of this analysis are shown in Figures 8-12. Figure 8 shows the degree of neuronal cell death due to aging and the morphological characteristics of astrocytes using the amino-aromatic compound KDS12025, as shown by tissue staining. NeuN indicates neuronal cell staining, DAPI indicates cell nucleus staining, and GFAP indicates astrocyte staining. Figure 9 shows the measurement of astrocyte size (GFAP area). Figure 10 is a morphological analysis photograph of astrocytes. Figures 11 and 12 show some of the Scholl analysis results. Figure 11 shows the number of intersections between each circle and a cell, starting from the center of the circle (or the center of the cell), during Scholl analysis. In normal cells, the length is long and there are many intersections (degree of differentiation), but in aged cells, the length is atrophied, the length is short, and there are fewer intersections. Figure 12 shows the sum of the number of points where astrocytes intersect the circles in Scholl analysis, in order to examine whether they exhibit morphological characteristics. A higher number of intersections indicates more branching or branching.

[0134] The 30-month-old control group showed a decrease in the astrocyte region due to aging compared to the 18-month-old comparison group. Furthermore, not only was the size of individual astrocytes smaller as measured by Scholl analysis, but the number of branched astrocytes was also significantly reduced. Surprisingly, while the control group showed significant atrophy of astrocytes due to aging, the experimental group of the same age treated with the amino-aromatic compound KDS12025 for an extended period recovered to levels equivalent to or better than the 18-month-old comparison group, despite the progression of aging (Figures 9-12). This suggests that while the size and number of branches of astrocytes tend to decrease with aging, administration of amino-aromatic compounds can delay this process.

[0135] Furthermore, Figure 13 shows the results of an analysis of the expression pattern of MAOB protein, one of the mechanisms of pathological phenomena in astrocytes. GFAP refers to astrocyte staining, and MAOB refers to MAOB protein staining. From this, it was confirmed that in the 30-month-old control group, MAOB was overproduced in astrocytes due to aging, while in the experimental group of the same age that received long-term administration of the amino-aromatic compound KDS12025, MAOB levels decreased. Therefore, it was confirmed that long-term administration of the amino-aromatic compound reduced MAOB production in astrocytes and suppressed the overproduction of reactive oxygen species and GABA, which cause memory decline and cognitive impairment, even as the animals aged.

Claims

1. A pharmaceutical composition for the prevention or treatment of age-related diseases or disorders, comprising an amino-aromatic compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. [Chemical formula 1] In the aforementioned chemical formula 1, Ar is C ６ -C ２０ arylene, and the arylene of the Ar is C １ -C １０ alkyl, C １ -C １０ alkoxy, amino, mono- or di-C １ -C １０ alkylamino, halo C １ -C １０ alkyl, halo C １ -C １０ substituted with one or more selected from alkoxy and hydroxy and may be further substituted. R １ and R ２ Each of them is independently of hydrogen or C １ -C １０ It is alkyl, R ３ is halogen, C １ -C １０ Alkoxy, Halo C １ -C １０ Alkyl or Halo C １ -C １０ It is an alkoxy, n is an integer of 1 or 2, However, R ３ If the element is a halogen, then n is an integer of 1.

2. The Ar is phenylene or biphenylene, and the Ar is C １ -C ７ Alkyl, C １ -C ７ The pharmaceutical composition according to claim 1, which may be further substituted with one or more selected from alkoxy, amino, and hydroxy.

3. The aforementioned amino-aromatic compound is represented by the following chemical formula 2, the pharmaceutical composition according to claim 1. [Chemical formula 2] In the aforementioned chemical formula 2, R １ and R ２ Each of them is independently of hydrogen or C １ -C ７ It is alkyl, Haal is a halogen, R' is C １ -C ７ Alkyl, C １ -C ７ It is alkoxy, amino, or hydroxy, a is an integer between 0 and 4.

4. The aforementioned amino-aromatic compound is represented by the following chemical formula 3, the pharmaceutical composition according to claim 1. [Chemical formula 3] In the aforementioned chemical formula 3, R １ and R ２ Each of them is independently of hydrogen or C １ -C ７ It is alkyl, R ３ C １ -C ７ Alkoxy or Halo C １ -C ７ It is alkyl, R' is C １ -C ７ Alkyl, C １ -C ７ It is alkoxy, amino, or hydroxy, a is an integer between 0 and 4. n is an integer, either 1 or 2.

5. The aforementioned R １ and R ２ Each of them is independently of hydrogen or C １ -C ４ The pharmaceutical composition according to claim 3, wherein Hal is an alkyl, a is a halogen, and a is an integer of 0.

6. The aforementioned R １ and R ２ Each of them is independently of hydrogen or C １ -C ４ It is alkyl, R ３ C １ -C ４ Alkoxy or Halo C １ -C ４ The pharmaceutical composition according to claim 4, wherein the alkyl group is an integer of 0, and n is an integer of 1 or 2.

7. The pharmaceutical composition according to claim 3, wherein the amino aromatic compound is one selected from the following group of compounds.

8. The pharmaceutical composition according to claim 4, wherein the amino aromatic compound is one selected from the following group of compounds.

9. The pharmaceutical composition according to claim 1, wherein the pharmaceutically acceptable salt is a hydrochloride salt.

10. The pharmaceutical composition according to claim 1, wherein the aging-related disease is one or more diseases selected from the group consisting of Alzheimer's disease, diabetes, Parkinson's disease, Huntington's disease, degenerative joint disease, stroke, angina pectoris, osteoporosis, myocardial infarction, muscular dystrophy, amyotrophic lateral sclerosis, sarcopenia, cirrhosis of the liver, and chronic kidney disease.

11. The pharmaceutical composition according to claim 1, wherein the aging-related disease is a cognitive impairment disease caused by aging.

12. The pharmaceutical composition according to claim 11, wherein the cognitive function is one or more selected from the group consisting of perception, memory, attention, speech comprehension, speech generation, reading comprehension, creation of imagery, learning, and reasoning.

13. A composition for delaying aging or extending lifespan, comprising an amino-aromatic compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. [Chemical formula 1] In the aforementioned chemical formula 1, Ar is C ６ -C ２０ It is allylene, and the allylene of Ar is C １ -C １０ Alkyl, C １ -C １０ Alkoxy, amino, mono- or di-C １ -C １０ Alkylamino, Halo C １ -C １０ Alkyl, Halo C １ -C １０ They may be further substituted with one or more selected from alkoxy and hydroxyl groups. R １ and R ２ Each of them is independently of hydrogen or C １ -C １０ It is alkyl, R ３ is halogen, C １ -C １０ Alkoxy, Halo C １ -C １０ Alkyl or Halo C １ -C １０ It is an alkoxy, n is an integer of 1 or 2, However, R ３ If the element is a halogen, then n is an integer of 1.

14. A health functional food composition for the prevention or improvement of aging-related diseases, comprising an amino aromatic compound represented by the following chemical formula 1 or a food-grade salt thereof as an active ingredient. [Chemical formula 1] In the aforementioned chemical formula 1, Ar is C ６ -C ２０ arylene, and the arylene of the Ar is C １ -C １０ alkyl, C １ -C １０ alkoxy, amino, mono- or di-C １ -C １０ alkylamino, halo C １ -C １０ alkyl, halo C １ -C １０ alkoxy and hydroxy, and may be further substituted with one or more selected therefrom R １ and R ２ Each of them is independently of hydrogen or C １ -C １０ It is alkyl, R ３ is halogen, C １ -C １０ Alkoxy, Halo C １ -C １０ Alkyl or Halo C １ -C １０ It is an alkoxy, n is an integer of 1 or 2, However, R ３ If the element is a halogen, then n is an integer of 1.

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