Anti-aging composition

Abstract

To provide a composition for improving age-related diseases or conditions by evaluating activity related to anti-aging.SOLUTION: Provided is an anti-aging composition comprising, as an active ingredient, a cyclic peptide or a salt thereof. Also provided are a composition for promoting collagen production, a composition for enhancing mitochondrial activity, a composition for promoting bone formation, and a composition for promoting energy production, each comprising the anti-aging composition.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to an anti-aging composition. The present invention also relates to a composition for promoting collagen production, mitochondrial activity, bone formation, and energy production. [Background technology]

[0002] The average life expectancy of Japanese people continues to increase, and both men and women are now over 80 years old. However, while life expectancy is increasing, the decline in quality of life (QOL) due to age-related diseases and conditions, such as decreased cognitive ability and muscle strength, locomotive syndrome, osteoporosis, and cataracts, has become a social issue.

[0003] Various functional ingredients are being explored for treating diseases and conditions associated with aging, not only in the fields of pharmaceuticals but also in the fields of food, beverages, and supplements.

[0004] For example, in Patent Document 1, the mitochondrial activity and collagen production ability of Arthrospira platensis, an alga of the genus Arthrospira, are evaluated, and its use as an anti-aging agent is proposed.

[0005] Furthermore, Patent Document 2 proposes a composition for improving brain function using a tripeptide consisting of Leu-Arg-Ala, and shows that orally administering a peptide consisting of this sequence to mice improves their object recognition functions. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] JP 2022-184634 A [Patent Document 2] Patent Publication No. 2022-007697 Summary of the Invention [Problem to be solved by the invention]

[0007] However, the search for materials to solve the social problems related to aging is still insufficient, and the discovery of new functional materials is required. In particular, there are not yet enough reports on the use of various peptides in the anti-aging field.

[0008] Therefore, an object of the present invention is to evaluate the effects of various peptides when used in the anti-aging field and to provide a composition for ameliorating diseases and conditions associated with aging. [Means for solving the problem]

[0009] Means for Solving the Problems The present inventors conducted intensive research to find that a cyclic peptide or a salt thereof has the function of improving diseases and conditions associated with aging, and thus completed the present invention.

[0010] That is, the present invention provides the compositions described below.

[0011] [1] An anti-aging composition comprising a cyclic peptide or a salt thereof as an active ingredient.

[0012] [2] A composition for promoting collagen production, comprising a cyclic peptide or a salt thereof as an active ingredient.

[0013] [3] A composition for promoting mitochondrial activity, comprising a cyclic peptide or a salt thereof as an active ingredient.

[0014] [4] A composition for promoting bone formation, comprising a cyclic peptide or a salt thereof as an active ingredient.

[0015] [5] A composition for promoting energy production, comprising a cyclic peptide or a salt thereof as an active ingredient.

[0016] [6] The composition according to any one of [1] to [5], wherein the cyclic peptide contains at least one amino acid selected from serine, proline, threonine, valine, and isoleucine as a constituent unit.

[0017] [7] The composition according to any one of [1] to [5], wherein the cyclic peptide contains at least proline as a constituent unit.

[0018] [8] The composition according to any one of [1] to [7], wherein the cyclic peptide is a cyclic dipeptide.

[0019] [9] The composition according to any one of [1] to [8], comprising a material containing a cyclic peptide or a salt thereof as an active ingredient.

[0020]

[10] The composition described in [9], wherein the material is a protein hydrolysate.

[0021]

[11] The composition described in [9], wherein the material is a globin peptide. Effect of the Invention

[0022] According to the present invention, it is possible to improve the anti-aging effect by using a cyclic peptide or a salt thereof. [Brief description of the drawings]

[0023] [Figure 1] FIG. 1 is a graph showing the evaluation results of mitochondrial membrane potential of senescent fibroblasts in Test Example 1. [Diagram 2] FIG. 2 is a graph showing the evaluation results of collagen production by aged fibroblasts in Test Example 2. [Diagram 3] FIG. 3 is a graph showing the evaluation results of mitochondrial membrane potential of senescent fibroblasts in Test Example 3. [Figure 4]FIG. 4 is a graph showing the evaluation results of collagen production by aged fibroblasts in Test Example 3. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0024] In one embodiment, the anti-aging composition of the present invention contains an effective amount of a cyclic peptide or a salt thereof.

[0025] [Cyclic peptide or its salt] As used herein, a cyclic peptide refers to a polypeptide chain that is linked by peptide bonds or other covalent bonds to form a cyclic structure. Cyclic peptides include, but are not limited to, those in which the -NH2 terminal group of a linear peptide reacts with the COOH terminal group to form a peptide bond to close the peptide backbone. In addition to the above, the cyclic peptide may be a peptide molecule that is partially cyclized by forming a covalent bond between the -NH2 terminal group and a side chain, between the COOH terminal group and a side chain, or between two side chains.

[0026] In one embodiment, the cyclic peptide can be, for example, 10 or less, 9 or less, 8 or less, 7 or less, 6 or less, 5 or less, 4 or less, 3 or less, or 2 or less amino acids in length, preferably 5 or less, more preferably 4 or less, even more preferably 3 or less, particularly preferably 2 or less, and most preferably 2 amino acids in length.

[0027] Cyclic peptides can be obtained, for example, from proteins derived from animals, plants, or microorganisms, or can be chemically synthesized by known biochemical methods, or obtained and isolated by enzymatic methods, microbial fermentation methods, etc.

[0028] When the protein source is derived from an animal, plant or microorganism, the animal, plant or microorganism species from which it is derived is not particularly limited, but examples thereof include milk-derived proteins, soybean-derived proteins, and globin-derived proteins. It is known that cyclic peptides are included in soybean peptides, milk peptides, globin peptides, etc., but it has not been clarified so far what kind of cyclic peptides contribute to the effects of the present invention. The cyclic peptide is not limited, but is preferably derived from globin from the viewpoint of significantly achieving the effects of the present invention.

[0029] These proteins derived from animals, plants, and microorganisms can be decomposed to obtain peptides by known methods, and although there is no limitation on the method, for example, it can be carried out using hydrolases.

[0030] In one embodiment, the hydrolysis of proteins derived from animals, plants, or microorganisms can be carried out in accordance with the method described in International Publication No. WO89 / 06970. The hydrolysis is usually carried out using one or more hydrolases selected from the group consisting of acid proteases, neutral proteases, and alkaline proteases.

[0031] For example, to hydrolyze the above protein, the above protein is first dispersed in water to a concentration of 5 to 30% by weight (as solid content), and the pH is adjusted to an optimum value for the protease using an acid or alkali. The protease is then added all at once or gradually, and the enzyme is allowed to react at a temperature of 20 to 70°C for 3 to 48 hours.

[0032] Methods for chemically synthesizing cyclic peptides include, for example, solid phase peptide synthesis using t-BOC (tert-butyloxycarbonyl) or FMOC (9-fluorenylmethyloxycarbonyl) protecting groups.

[0033] In addition, the cyclic peptide may be a commercially available product, or may be designed and synthesized using a known synthesis service.

[0034] In addition, the cyclic peptide can be cyclized by dehydration or using a known cyclization reagent after obtaining a linear peptide by the above-mentioned method, etc. Examples of the cyclization reagent include PyBOP (benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate), BOP (benzotriazol-1-yl-oxy-tris-(dimethylamino)phosphonium hexafluorophosphate), DIPEA (N,N-diisopropylethylamine), DMTMM BF4 (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium tetrafluoroborate), FDPP (pentafluorophenyl diphenylphosphinate), or any combination thereof.

[0035] Although not limited thereto, the cyclic peptide is preferably a cyclic dipeptide in which the terminal portions of two amino acids are joined via an amide bond.

[0036] Furthermore, although not limited thereto, the cyclic peptide preferably contains at least one amino acid selected from serine, proline, threonine, valine, and isoleucine as a constituent unit, and more preferably contains at least proline as a constituent unit.

[0037] In this specification, a cyclic dipeptide refers to a dipeptide having a diketopiperazine structure produced by dehydration condensation of the amino group and the carboxyl group of an amino acid. If the amino acid composition of the cyclic dipeptide is the same, the order of the descriptions may be any. For example, Cyclo(Pro-Ser) and Cyclo(Ser-Pro) indicate the same cyclic dipeptide. The amino acid composition of the cyclic dipeptide may be represented by a one-letter abbreviation of the amino acid or a three-letter abbreviation. In this specification, for example, when Cyclo(Ser-Pro) is represented by a one-letter abbreviation of the amino acid, it may be represented as "cSP".

[0038] The cyclic dipeptide preferably contains at least one amino acid selected from serine, proline, threonine, valine, and isoleucine as a constituent unit, and more preferably is at least one selected from the group consisting of cSP, cGP, cTP, cAP, cPP, cVP, cLP, cIP, cYP, cFP, cPM, cNP, cVA, cGI, cAI, cVS, cVS, cLT, cVL, cFS, cVM, cFV, cLI, and cSL.

[0039] In one embodiment, the cyclic dipeptide preferably contains at least proline as a constituent unit, and is even more preferably at least one selected from the group consisting of cSP, cGP, cTP, cAP, cPP, cVP, cLP, cIP, cYP, cFP, cPM, cDP, and cNP, and is particularly preferably at least one selected from the group consisting of cSP, cTP, cPP, cVP, cIP, and cDP.

[0040] Of the above-mentioned cyclic dipeptides, although not limited thereto, from the viewpoint of significantly achieving the effects of the present invention, it is more preferable that the cyclic dipeptide is at least one selected from the group consisting of cIP, cPP, cTP, and cSP, and it is particularly preferable that the cyclic dipeptide is at least one selected from the group consisting of cIP and cPP.

[0041] Globin peptides have been newly found to contain the cyclic dipeptides cFP, cIP, cLP, cLV, cSL, and cNP.

[0042] In one embodiment, the composition of the present invention may use a material containing a cyclic peptide or a salt thereof as an active ingredient, and the material may be, but is not limited to, for example, a protein hydrolysate. For example, the protein hydrolysate is preferably a protein hydrolysate containing an effective amount of the cyclic peptide or a salt thereof, more preferably a globin-derived protein hydrolysate, and even more preferably a globin peptide.

[0043] In the present specification, the salt of the cyclic peptide is not particularly limited as long as it is a pharmacologically or physiologically acceptable salt, and specifically includes organic acid salts, inorganic acid salts, salts with organic bases, and salts with inorganic bases. Examples of organic acid salts include monocarboxylates such as acetates, trifluoroacetates, butyrates, palmitates, and stearates; polycarboxylates such as fumarates, maleates, succinates, and malonates; oxycarboxylates such as lactates, tartrates, and citrates; and organic sulfonates such as methanesulfonates, toluenesulfonates, and tosylates. Examples of inorganic acid salts include hydrochlorides, sulfates, nitrates, hydrobromides, and phosphates. Examples of salts with organic bases include salts with organic amines such as methylamine, triethylamine, triethanolamine, diethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, and ethylenediamine. Examples of salts with inorganic bases include various salts such as ammonium salts; salts with alkali metals such as sodium or potassium, alkaline earth metals such as calcium or magnesium, and metals such as aluminum.

[0044] The total content of the cyclic peptide is appropriately adjusted depending on the type and amount of other components, dosage form, etc., and is not limited, and may be, for example, 0.0001% by mass or more, 0.001% by mass or more, 0.005% by mass or more, 0.01% by mass or more, 0.05% by mass or more, 0.1% by mass or more, 0.2% by mass or more, 0.5% by mass or more, 1% by mass or more, 3% by mass or more, 5% by mass or more, 10% by mass or more, 20% by mass or more, etc. In addition, the total content of the cyclic peptide may be, for example, 100% by mass or less, and may be 50% by mass or less, 30% by mass or less, 10% by mass or less, 5% by mass or less, 3% by mass or less, 1% by mass or less, 0.5% by mass or less, 0.2% by mass or less, 0.1% by mass or less, 0.05% by mass or less, 0.01% by mass or less, etc. The total content of the cyclic peptides can be, for example, 0.0001 to 100% by mass relative to the total amount of the composition, including 0.001 to 50% by mass, 0.001 to 10% by mass, 0.001 to 5% by mass, 0.001 to 3% by mass, 0.001 to 1% by mass, 0.001 to 0.7% by mass, 0.001 to 0.5% by mass, etc. Also, it may be 0.001 to 0.1% by mass, 0.001 to 0.05% by mass, 0.001 to 0.01% by mass, 0.01 to 1% by mass, 0.05 to 1% by mass, 0.1 to 1% by mass, etc.

[0045] [Application] In one embodiment, the composition of the present invention is used for anti-aging purposes. In this specification, anti-aging refers to improving diseases and conditions associated with aging. Diseases associated with aging include, but are not limited to, myocardial infarction, cerebral infarction, osteoporosis, dementia, mild cognitive impairment, rheumatoid arthritis, cataracts, etc. In addition, conditions associated with aging include, but are not limited to, skin conditions such as spots, wrinkles, and dullness, decreased motor function due to aging, decreased energy metabolism due to aging, decreased vascular flexibility due to aging, decreased vascular dilation due to aging, decreased bone density due to aging, decreased cognitive function (memory, judgment, attention, spatial recognition, etc.) due to aging, decreased muscle mass due to aging, decreased macular pigment density of the eye due to aging, blurred or hazy vision, dry skin due to aging, increased gray hair, decreased hair volume, etc.

[0046] In the examples (test examples) described later, it has been confirmed that the cyclic peptide or a salt thereof promotes collagen production in aged fibroblasts. Fibroblasts and collagen are present in the dermis, with type I collagen accounting for 80% of the total. In addition to type I collagen, the existence of types III, V, XII and XIV collagen is known. A decrease in type I collagen is considered to be one of the causes of wrinkles and sagging. It is considered important to keep the production and decomposition cycle of collagen, which constitutes the extracellular matrix, normal in order to keep the skin in normal condition. Therefore, by using the composition of the present invention, it is possible to promote collagen production, maintain the normality of the skin, and prevent or improve wrinkles and / or sagging.

[0047] In addition, about 90% of bone matrix is ​​made up of collagen. Osteoblasts promote the formation of collagen networks outside the cells by producing and releasing collagen fibrils, thereby promoting bone formation. Therefore, by using the composition of the present invention, it is possible to promote collagen production in bones and promote bone formation.

[0048] In addition, in the examples (test examples) described below, it has been confirmed that the cyclic peptide or its salt activates mitochondria. One of the factors that induces aging is known to be the decline in mitochondrial function. Aging can be caused by the decline in the number and / or activity of mitochondria that produce energy in cells with age.

[0049] The target mitochondria are not particularly limited, and examples thereof include skin mitochondria and muscle mitochondria. Improvement of skin mitochondrial function is involved in, for example, suppression or improvement of skin wrinkle formation. Improvement of muscle mitochondrial function is involved in, for example, improvement of motor function decline and suppression of muscle weakness. In addition to the above, activation of mitochondria is known to be involved in improvement of metabolic function, extension of life span, recovery of nervous system abnormality, improvement of cognitive function, etc. Therefore, by using the composition of the present invention, it is possible to promote mitochondrial activity and / or energy production and improve the above functions.

[0050] The composition of the present invention can be added to or mixed with food, beverage, medicine, feed, or pet food. Alternatively, it can be used as it is as food, beverage, medicine, feed, or pet food. The composition of the present invention can also be used as food or beverage that expressly or implies that it has anti-aging properties, including the above-mentioned various functionalities, that is, as health food, functional food, food for sick people, and food for specified health uses. Even if the above-mentioned functionalities are not expressly or implied, it can be used as a so-called doctor's supplement recommended or presented by a doctor in the internal medicine, orthopedics, veterinary clinic, etc. of a hospital and / or clinic.

[0051] Health foods, functional foods, foods for the sick, and foods for specified health uses can be used in various formulations such as solid preparations (tablets, orally disintegrating tablets, granules, fine granules, powders, capsules, chewable tablets, candies, etc.), liquid preparations (syrups, suspensions), and liquid foods. Foods in the form of formulations can be produced in the same manner as known pharmaceutical preparations, and can be produced by mixing an active ingredient with a carrier acceptable for food, such as a suitable excipient, and then using conventional means. The formulation form is not limited, but is preferably an orally disintegrating tablet, a chewable tablet, a candy, a granule, a powder, or a liquid, from the viewpoint of significantly exhibiting the effects of the present invention.

[0052] For example, tablets can be prepared by mixing a powdered active ingredient with a pharma- ceutically acceptable carrier component (such as an excipient) and compressing the mixture, and confectionery tablets such as candy can be prepared by pouring the mixture into a mold. Tablets can also be sugar-coated to form sugar-coated tablets. Furthermore, tablets can be single-layer tablets or laminated tablets such as double-layer tablets.

[0053] Powdered granules such as granules may be prepared by various granulation methods (such as extrusion granulation, grinding granulation, dry compaction granulation, fluidized bed granulation, rolling granulation, and high-speed stirring granulation), and tablets can be prepared by an appropriate combination of the above-mentioned granulation methods and tableting methods (wet tableting, direct tableting), etc.

[0054] Capsules can be prepared by filling a capsule (soft or hard capsule) with a powdered agent (powder, granules, etc.) by a conventional method.

[0055] The liquid preparation can be prepared by dissolving or dispersing each component in an aqueous medium (purified water, purified water containing ethanol, etc.) which is a carrier component, filtering or sterilizing the mixture as necessary, filling the mixture into a predetermined container, and sterilizing the mixture. The preferred dosage form of the solid preparation of the present invention is a capsule or tablet, and a soft capsule (soft capsule) is more preferred.

[0056] Soft capsules have a smooth surface and are easy to swallow, and are therefore preferred by users. Typical methods for producing soft capsules include the plate method, the rotary method, and the seamless method.

[0057] In the rotary method (punching method), a sheet-like capsule shell sandwiches the flowing filling contents and forms a capsule shape along the holes of a rotating cylindrical die. On the other hand, in the seamless method (dropping method), the capsule shell composition and contents are simultaneously discharged from multiple concentric nozzles to form a seamless capsule shape.

[0058] The base material for the soft capsule shell is not particularly limited, but starch, pullulan, cellulose, polyvinyl alcohol, gelatin, succinated gelatin, etc. can be used, with starch, gelatin, and succinated gelatin being preferred, and gelatin and succinated gelatin being more preferred. These may be used alone or in combination of two or more kinds.

[0059] The composition of the present invention can also be manufactured as liquid beverages such as soups, juices, fruit juice drinks, milk, dairy drinks, whey drinks, lactic acid bacteria drinks, tea drinks, alcoholic drinks, coffee drinks, carbonated drinks, soft drinks, water drinks, cocoa drinks, jelly drinks, sports drinks, and diet drinks; semi-solid foods such as pudding and yogurt; noodles, confectioneries, spreads, and the like.

[0060] When the composition of the present invention is prepared as a food composition, various food additives may be blended therein, such as antioxidants, colorants, flavorings, seasonings, sweeteners, acidulants, pH adjusters, quality stabilizers, preservatives, etc.

[0061] When the composition of the present invention is prepared as a pharmaceutical composition, it is prepared as a formulation containing the cyclic peptide or its salt, which is an active ingredient, and preferably a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier generally refers to an inert, non-toxic, solid or liquid filler, diluent or encapsulating material that does not react with the active ingredient, such as water, ethanol, polyols, suitable mixtures thereof, vegetable oils, and other solvents or dispersion media.

[0062] The pharmaceutical composition is orally or parenterally administered, for example, into the oral cavity, into the digestive tract, or into the nasal cavity. Orally administered formulations include solid preparations (tablets, orally disintegrating tablets, granules, fine granules, powders, capsules, chewable tablets, candy, etc.) and liquid preparations (syrups, suspensions, inhalants). Parenterally administered formulations include eye drops, drops, nasal drops, injections, etc. The formulation form is not limited, but is preferably an orally disintegrating tablet, a chewable tablet, a candy, a granule, a powder, or a liquid preparation from the viewpoint of significantly exhibiting the effects of the present invention.

[0063] The pharmaceutical composition may further contain additives commonly used in the pharmaceutical field. Such additives include, for example, excipients, binders, disintegrants, lubricants, antioxidants, colorants, flavoring agents, etc., and can be used appropriately as needed. In order to achieve sustained release so as to act for a long time, the composition may also be coated with a known retardant, etc. The pharmaceutical composition may further contain other additives or drugs, such as antacids and gastric mucosa protectants, as needed.

[0064] The pharmaceutical composition can be applied in the form of an oral composition, an internally ingested composition, etc. The pharmaceutical composition may be used therapeutically or non-therapeutically.

[0065] The oral intake or dosage of a cyclic peptide or a salt thereof per day for an adult can be appropriately determined depending on the individual's condition, body weight, sex, age, activity of the material, intake or administration route, intake or administration schedule, formulation form, or other factors. The oral intake or dosage of a cyclic peptide or a salt thereof per day for an adult is, for example, preferably 1 μg or more, more preferably 50 μg or more, even more preferably 100 μg or more, particularly preferably 200 μg or more, and most preferably 300 μg or more. It may also be 350 μg or more, 400 μg or more. The oral intake or dosage of a cyclic peptide or a salt thereof per day for an adult is, for example, preferably 5000 μg or less, more preferably 4000 μg or less, even more preferably 2000 μg or less, and particularly preferably 1500 μg or less. It may also be 1400μg or less, 1300μg or less, 1000μg or less, 900μg or less, 800μg or less, 700μg or less, 600μg or less, 550μg or less, etc. The oral intake or administration amount of the cyclic peptide or its salt per day for an adult is, for example, preferably 1 to 3000μg, more preferably 50 to 2500μg, even more preferably 100 to 2000μg, even more preferably 100 to 1500μg, even more preferably 200 to 1500μg. It may also be 300 to 1500μg, 400 to 1500μg, 200 to 1300μg, 300 to 1300μg, 400 to 1300μg, etc. The content of the cyclic peptide or its salt can be the amount that results in the above intake or administration amount.

[0066] In one embodiment, when the composition of the present invention uses a material containing a cyclic peptide or a salt thereof as an active ingredient, the oral intake or dosage of the protein hydrolysate per adult per day is, for example, preferably 1 mg or more, more preferably 10 mg or more, even more preferably 100 mg or more, particularly preferably 500 mg or more, and most preferably 1000 mg or more. The oral intake or dosage of the protein hydrolysate per adult per day is, for example, preferably 5000 mg or less, more preferably 4000 mg or less, even more preferably 2000 mg or less, and particularly preferably 1500 mg or less. The oral intake or dosage of the protein hydrolysate per adult per day is, for example, preferably 1 to 5000 mg, more preferably 10 to 4000 mg, even more preferably 100 to 2000 mg, even more preferably 100 to 1500 mg, and even more preferably 200 to 1500 mg. It may be 300 to 1500 mg, 400 to 1500 mg, 200 to 1300 mg, 300 to 1300 μg, 400 to 1300 μg, etc.

[0067] The daily oral intake or dosage for an adult may be divided into 1 to 6 capsules, 1 to 4 capsules, 1 to 3 capsules, or 1 to 2 capsules depending on the dosage form.

[0068] The composition of the present invention can be ingested or administered once or several times a day, typically 1 to 6 times a day, 1 to 3 times a day, 1 to 2 times a day, or at any period and interval, but once a day is preferred.

[0069] When the present invention is used as feed, pet food, or the like, the target organism is not particularly limited, but is preferably a mammal, reptile, amphibian, bird, or fish, and more preferably a mammal other than humans, such as a platypus, echidna, opossum, quoll, kangaroo, aardvark, rock badger, elephant, armadillo, sloth, anteater, tree shrew, flying lemur, chimpanzee, rabbit, degu, dormouse, squirrel, raccoon, mouse, hedgehog, chinchilla, ferret, camel, wild boar, giraffe, deer, cow, goat, hippopotamus, whale, dolphin, horse, rhinoceros, tapir, bat, monkey, tiger, wolf, weasel, bear, seal, dog, cat, parakeet, parrot, finch, owl, owl, etc., and more preferably a dog or cat.

[0070] When the present invention is used as feed, pet food, or the like, it may be given to the pet in divided portions several times a day by adding it to the staple food, or it may be given to the pet as a snack at any time.

[0071] When the present invention is used as feed, pet food, etc., the daily oral intake or administration amount of the cyclic peptide or its salt is, for example, preferably 1 to 150 μg / day / kg body weight, more preferably 3 to 100 μg / day / kg body weight, even more preferably 5 to 80 μg / day / kg body weight, even more preferably 5 to 60 mg / day / kg body weight, and even more preferably 5 to 50 μg / day / kg body weight. The content of the cyclic peptide or its salt can be an amount that results in the above intake or administration amount. EXAMPLES

[0072] Next, the present invention will be specifically described with reference to examples, but the present invention is not limited to the following examples.

[0073] [Test Example 1. Evaluation test of mitochondrial membrane potential] Mitochondria have a double membrane structure consisting of an outer membrane and an inner membrane, and produce energy (ATP synthesis) by utilizing the potential difference between the outer and inner membranes. Healthy mitochondria have a high membrane potential and produce energy. On the other hand, mitochondria with impaired function have a low membrane potential and produce less energy.

[0074] In the following, the effect of the cyclic peptide or a salt thereof on the mitochondrial membrane potential was evaluated. Human skin fibroblasts (NB1RGB cells, RIKEN BioResource Research Center, same as in the following test examples) were cultured for 70 to 89 days in a medium (same as in the following test examples) containing 10% FBS, 100 μg / mL penicillin, and 100 μg / mL streptomycin in MEMα medium to obtain senescent cells. 0.1 μM cyclic peptide was added, and the human skin fibroblast senescent cells were further cultured at 37°C for 24 hours.

[0075] Mitochondrial activity was then measured by JC-1 (Dojindo Molecular Technologies) staining using a mitochondrial membrane potential detection kit ("JC-1 MitoMP Detection kit" Dojindo) according to the manufacturer's protocol. Fluorescence was measured with a fluorescence microplate reader ("Infinite M200" TECAN) using a 535 nm / 590 nm filter pair.

[0076] When mitochondrial activity is high, the membrane potential is maintained, the small molecule fluorescent dye JC-1 aggregates, and longer wavelength fluorescence is emitted. Therefore, mitochondrial activity can be measured as the longer wavelength measured at 535nm / 590nm.

[0077] The results are shown in Figure 1. "**" indicates a significant difference compared to the control group (0 μg / mL) at p<0.01 by two-way analysis of variance followed by Tukey's test.

[0078] As shown in FIG. 1, it was confirmed that cyclic peptides or salts thereof, such as cIP, cPP, cTP, and cSP, significantly increased JC-1 activity, which is an index of mitochondrial membrane potential.

[0079] [Test Example 2. Evaluation test of collagen production in aged fibroblasts] Next, the effect of the cyclic peptide or a salt thereof on the collagen production ability of aged fibroblasts was evaluated. Human dermal fibroblast senescent cells were further cultured at 37°C for 72 hours in a medium containing 0.1 μM of the cyclic peptide to obtain samples. Cell lysates were prepared from the obtained samples, and the amount of collagen in the cell layer per 25 μL of cell lysate containing the same protein concentration was evaluated using a collagen quantification kit (Cosmo Bio) according to the manufacturer's protocol. Fluorescence was measured using a fluorescence microplate reader ("Infinite M200" TECAN) equipped with a 380 nm / 485 nm filter pair.

[0080] The results are shown in Figure 2. "**" indicates a significant difference compared to the control group at p<0.01 according to two-way analysis of variance followed by Tukey's test.

[0081] As shown in FIG. 2, it was confirmed that cyclic peptides or salts thereof, such as cIP, cPP, cTP, cDP, and cVP, significantly increased collagen production in aged fibroblasts.

[0082] [Test Example 3. Evaluation test of anti-aging effect (mitochondrial activity, collagen production) of globin-derived protein hydrolysate] It has been newly discovered that a globin-derived protein hydrolysate (Metap (registered trademark), manufactured by MG Pharma Co., Ltd.) contains an effective amount of cIP, which has been confirmed to have anti-aging effects in Test Examples 1 and 2 above. The anti-aging effects of the globin-derived protein hydrolysates (effects on mitochondrial membrane potential and collagen production) were confirmed by the same methods as in the above Test Examples 1 and 2. However, the globin-derived protein hydrolysates were added at 100 μg / mL. The results of confirming the effect on mitochondrial membrane potential are shown in FIG. 3, and the results of confirming the effect on collagen production are shown in FIG.

[0083] As shown in Figures 3 and 4, it was confirmed that the protein hydrolysate containing an effective amount of a cyclic peptide or its salt, which was confirmed to have anti-aging effects in Test Examples 1 and 2 above, has a significant anti-aging effect (mitochondrial activity, collagen production) compared to the control group (0 μg / mL).

Claims

1. An anti-aging composition comprising a cyclic peptide or a salt thereof as an active ingredient.

2. A composition for promoting collagen production, comprising a cyclic peptide or a salt thereof as an active ingredient.

3. A composition for promoting mitochondrial activity, comprising a cyclic peptide or a salt thereof as an active ingredient.

4. A composition for promoting bone formation, comprising a cyclic peptide or a salt thereof as an active ingredient.

5. A composition for promoting energy production, comprising a cyclic peptide or a salt thereof as an active ingredient.

6. The composition according to any one of claims 1 to 5, wherein the cyclic peptide comprises at least one amino acid selected from serine, proline, threonine, valine, and isoleucine as a constituent unit.

7. The composition according to any one of claims 1 to 5, wherein the cyclic peptide contains at least proline as a constituent unit.

8. The composition according to any one of claims 1 to 5, wherein the cyclic peptide is a cyclic dipeptide.

9. The composition according to any one of claims 1 to 5, comprising a material containing a cyclic peptide or a salt thereof as an active ingredient.

10. The composition according to claim 9 , wherein the material is a proteolysate.

11. The composition of claim 9 , wherein the material is a globin peptide.

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