Homocysteine derivative, its production method, composition, and anti-inflammatory agent

Abstract

Provided are a novel homocysteine derivative and a method for producing the same, a composition comprising the compound, and an anti-inflammatory agent comprising the compound and / or the composition.　A compound represented by formula 1.

Description

[Technical Field]

[0001] The present invention relates to a homocysteine derivative, a method for producing the same, a composition containing the same, and an anti-inflammatory agent containing the same. [Background technology]

[0002] As compositions having an anti-inflammatory effect, for example, cosmetics having an effect of inhibiting MMP-9 production have been known so far (see, for example, Patent Documents 1 and 2).

[0003] However, there are a wide variety of uses and targets for which an anti-inflammatory effect is required, and there is a need to develop new anti-inflammatory agents. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2005-298391 [Patent Document 2] Japanese Patent Application Laid-Open No. 2015-24985 Summary of the Invention [Problem to be solved by the invention]

[0005] In light of the above circumstances, an object of the present invention is to provide a novel homocysteine derivative and a method for producing the same, a composition containing the compound, and an inflammation suppressant containing the same. [Means for solving the problem]

[0006] As a result of intensive research to solve the above problems, the present inventors succeeded in creating the novel homocysteine derivative shown below, and discovered that the above object can be achieved by using the above compound, thereby completing the present invention.

[0007] That is, the present invention provides the compounds listed below.

[0008] Section 1. A compound represented by the following formula 1. [ka]

[0009] Section 2. Item 1. The compound according to item 1, which is represented by the following formula 2: [ka]

[0010] Section 3. Item 3. The compound according to item 1 or 2, which is represented by the following formula 3: [ka]

[0011] The present invention also provides the following compositions.

[0012] Section 4. A composition comprising the compound according to any one of items 1 to 3.

[0013] Section 5. Item 5. The composition according to Item 4, further comprising L-ergothioneine (hereinafter also referred to as "EGT").

[0014] Section 6. Item 6. The composition according to Item 5, wherein the content of the compound is 50 parts by mass or less per 100 parts by mass of the L-ergothioneine.

[0015] Section 7. Item 7. The composition according to Item 5 or 6, wherein the content of the compound is 0.0001 parts by mass or more per 100 parts by mass of the L-ergothioneine.

[0016] The present invention also relates to the following anti-inflammatory agents:

[0017] Section 8. Item 4. An anti-inflammatory agent comprising the compound according to any one of Items 1 to 3.

[0018] Section 9. Item 8. An anti-inflammatory agent comprising the composition according to any one of Items 4 to 7.

[0019] The present invention also relates to the following production methods.

[0020] Section 10. Item 4. A method for producing the compound according to any one of Items 1 to 3, comprising a step of reacting ribosylhomocysteine (hereinafter also referred to as "SRH") with a reducing agent.

[0021] Section 11. Item 11. The method according to Item 10, wherein the reducing agent comprises lithium borohydride, sodium borohydride, or zinc borohydride. [Effects of the Invention]

[0022] The compound of the present invention or a composition containing the compound can be suitably used, for example, as an anti-inflammatory agent.

[0023] Furthermore, by using the method for producing a compound of the present invention, the compound or composition can be easily obtained.

[0024] Furthermore, the inflammation suppressing agent of the present invention may be able to exert an inflammation suppressing effect that leads to the maintenance of retinal pigment epithelial cells, for example. [Brief explanation of the drawings]

[0025] [Figure 1] FIG. 1 is a graph showing the evaluation results of the anti-inflammatory effect in Example 2. DETAILED DESCRIPTION OF THE INVENTION

[0026] Hereinafter, embodiments of the present invention will be described in detail.

[0027] [Compound] The homocysteine derivative of the present invention is a compound represented by the following formula 1. [ka]

[0028] The homocysteine derivative is, for example, a compound represented by the following formula 2. [ka]

[0029] The homocysteine derivative is, for example, a compound represented by the following formula 3. [ka]

[0030] The homocysteine derivatives also include derivatives such as substitution products in which the structure is partially or entirely substituted, and solvates such as hydrates, as appropriate.

[0031] In the homocysteine derivatives, some or all of the hydroxyl groups may be appropriately substituted with, for example, alkyl ether groups, aryl ether groups, or ester groups.

[0032] In the homocysteine derivatives, the carboxyl group may be appropriately substituted with an ester group, an amide group, an acid anhydride, a salt, or the like.

[0033] In the homocysteine derivatives, the amino group may be appropriately substituted with an alkylated form, an amide group, a salt, or the like.

[0034] In the homocysteine derivatives, the sulfide group may be appropriately substituted with an alkylated salt, a sulfoxide, or a sulfone.

[0035] [Method for producing compounds] The homocysteine derivatives can be produced by any known method, but it is preferable to use a production method including a step of reducing ribosylhomocysteine or the like.

[0036] For example, the method for producing the compound of the present invention preferably includes a step of reacting ribosylhomocysteine with a reducing agent.

[0037] Ribosylhomocysteine (SRH) is a homocysteine derivative in which homocysteine (2-amino-4-sulfanylbutanoic acid) is S-ribosylated, and its structure is represented by the following formula.

[0038] [ka]

[0039] SRH can be obtained by known methods such as synthesis, extraction, and fermentation.

[0040] SRH may be in the free form or in the form of a salt. The salt of SRH may be a salt formed at the carboxyl group or the amino group in these structures. Ribosylhomocysteine or a ribosylhomocysteine analog may also be a solvate such as a hydrate.

[0041] The salt of SRH is not particularly limited as long as it is pharmacologically or physiologically acceptable, but specific examples include organic acid salts, inorganic acid salts, salts with organic bases, and salts with inorganic bases. Examples of organic acid salts include monocarboxylic acid salts such as acetate, trifluoroacetate, butyrate, palmitate, and stearate; polycarboxylic acid salts such as fumarate, maleate, succinate, and malonate; oxycarboxylic acid salts such as lactate, tartrate, and citrate; and organic sulfonates such as methanesulfonate, toluenesulfonate, and tosylate. Examples of inorganic acid salts include hydrochloride, sulfate, nitrate, hydrobromide, and phosphate. Examples of salts with organic bases include salts with organic amines such as methylamine, triethylamine, triethanolamine, diethanolamine, morpholine, piperazine, pyrrolidine, and ethylenediamine. Examples of salts with inorganic bases include ammonium salts; salts with alkali metals such as sodium or potassium, alkaline earth metals such as calcium or magnesium, and metals such as aluminum. These salts may be used alone or in any combination of two or more. "Pharmaceutically or physiologically acceptable salts" may include solvates or hydrates of the salts.

[0042] The reducing agent can be appropriately used as long as it can reduce ribosylhomocysteine to produce the compound. Examples of the reducing agent include lithium borohydride, sodium borohydride, and zinc borohydride. Among these, sodium borohydride is a preferred reducing agent.

[0043] The reducing agent can be used in the reduction step by any known method. For example, ribosylhomocysteine dissolved or dispersed in a solvent such as water can be reacted in the presence of 0.01 to 1000 mol % of the reducing agent in a system at a temperature of -10°C to 30°C for 10 minutes to 48 hours.

[0044] The above compound can be produced, for example, according to the following reaction scheme. [ka]

[0045] After the reaction, a step of removing salts by electrodialysis or the like may be included.

[0046] [Composition] The composition of the present invention contains the above-mentioned compound. These compounds may be contained alone or in combination of two or more.

[0047] In the composition of the present invention, the content of the above compound is adjusted appropriately depending on the use of the composition, the type and content of other components, etc., and is not limited thereto, and can be, for example, 0.000001% by mass or more, 0.000005% by mass or more, 0.00001% by mass or more, 0.00005% by mass or more, 0.0001% by mass or more, 0.0005% by mass or more, 0.001% by mass or more, etc. Furthermore, the content of the above compound can be, for example, 99.999% by mass or less, 99.9% by mass or less, 99.5% by mass or less, 99% by mass or less, 98.5% by mass or less, 98% by mass or less, 80% by mass or less, 70% by mass or less, 60% by mass or less, 50% by mass or less, 40% by mass or less, 30% by mass or less, 20% by mass or less, 10% by mass or less, 5% by mass or less, 1% by mass or less, etc. In another embodiment, for example, when prepared as a liquid composition or liquid formulation, the content of the compound can be, for example, but not limited to, 80% by mass or less, relative to the total amount of the composition, and examples include 70% by mass or less, 60% by mass or less, 50% by mass or less, 40% by mass or less, 30% by mass or less, 20% by mass or less, 10% by mass or less, 5% by mass or less, and 1% by mass or less.

[0048] Additionally, the composition may further comprise L-ergothioneine (EGT).

[0049] EGT is a histidine derivative (N,N,N-trimethyl-L-2-thiohistidine) and its structure is represented by the following formula:

[0050] [ka]

[0051] EGT can be obtained by known methods such as synthesis, extraction, and fermentation, and commercially available products can also be obtained and used.

[0052] Commercially available EGT products include Ergonine (R) (manufactured by Tetraedron Co., Ltd.), etc.

[0053] EGT may be in the free form or in the form of a salt. The salt of EGT may be a salt formed with the carboxyl group in these structures or a salt formed with the trimethylamino group. Furthermore, L-ergothioneine or an L-ergothioneine analog may be a solvate such as a hydrate.

[0054] Salts of EGT are not particularly limited as long as they are pharmacologically or physiologically acceptable, but specific examples include organic acid salts, inorganic acid salts, salts with organic bases, and salts with inorganic bases. Examples of organic acid salts include monocarboxylic acid salts such as acetate, trifluoroacetate, butyrate, palmitate, and stearate; polycarboxylic acid salts such as fumarate, maleate, succinate, and malonate; oxycarboxylic acid salts such as lactate, tartrate, and citrate; and organic sulfonates such as methanesulfonate, toluenesulfonate, and tosylate. Examples of inorganic acid salts include hydrochloride, sulfate, nitrate, hydrobromide, and phosphate. Examples of salts with organic bases include salts with organic amines such as methylamine, triethylamine, triethanolamine, diethanolamine, morpholine, piperazine, pyrrolidine, and ethylenediamine. Examples of salts with inorganic bases include various salts with alkali metals such as sodium or potassium, alkaline earth metals such as calcium or magnesium, and metals such as aluminum. These salts may be used alone or in any combination of two or more. "Pharmaceutically or physiologically acceptable salts" may include solvates or hydrates of the salts.

[0055] Furthermore, in the composition of the present invention, the EGT content is appropriately adjusted depending on the use of the composition, the types and contents of other components, etc., and is not limited thereto, and can be, for example, 0.000001% by mass or more, relative to the total amount of the composition, including 0.000005% by mass or more, 0.00001% by mass or more, 0.00005% by mass or more, 0.0001% by mass or more, 0.0005% by mass or more, 0.001% by mass or more, etc. Furthermore, the EGT content can be, for example, 99.999% by mass or less, relative to the total amount of the composition, including 99.9% by mass or less, 99.5% by mass or less, 99% by mass or less, 98.5% by mass or less, 98% by mass or less, etc. In another embodiment, when prepared as a liquid composition or liquid formulation, the EGT content can be, for example, but is not limited to, 80% by mass or less, relative to the total amount of the composition, and examples thereof include 70% by mass or less, 60% by mass or less, 50% by mass or less, 40% by mass or less, 30% by mass or less, 20% by mass or less, 10% by mass or less, 5% by mass or less, and 1% by mass or less.

[0056] When using a composition containing EGT, the daily intake (application amount) can be an effective amount that can exert the physiological activity inherent to EGT. For example, when ingested (applied) by a healthy adult, the daily intake (application amount) of EGT can be, for example, 0.005 to 4,000 mg, preferably 0.1 to 3,000 mg, or 0.5 to 2,000 mg, 1 to 1,000 mg, 2 to 500 mg, or 5 to 30 mg.

[0057] The pH of the composition of the present invention is appropriately set depending on the type and content of other formulated ingredients, the intended use, the formulation, the method of use, etc., and is not limited as long as it is within a pharmaceutically or physiologically acceptable range, but can be, for example, pH 2 to 10. From the viewpoint of stably exerting the effects of the present invention, the pH of the composition of the present invention can be, for example, pH 2 to 10, pH 2 to 9, pH 2 to 8, pH 2 to 7, pH 3 to 10, pH 3 to 9, pH 3 to 8, pH 3 to 7, pH 4 to 10, pH 4 to 9, pH 4 to 8, pH 4 to 7, pH 5 to 10, pH 5 to 9, pH 5 to 8, pH 5 to 7, pH 6 to 10, pH 6 to 9, pH 6 to 8, pH 6 to 7, etc.

[0058] [Application] The composition of the present invention can further be appropriately blended with active ingredients and additives that can be used in foods and beverages, functional foods, foods for specified health uses, quasi-drugs, pharmaceuticals, cosmetics, daily necessities, feed, etc., and can be appropriately formulated using known formulation methods used for the relevant items.

[0059] Cosmetics and daily necessities can be formulated into, for example, lotions, emulsions, gels, serums, creams, sunscreen creams, packs, masks, foundations, powders, bath additives, body lotions, shampoos, rinses, hair treatments, hair conditioners, hair styling products, hair tonics, toothpastes, mouthwashes, etc.

[0060] Furthermore, for example, when the composition contains EGT, it can be suitably used for the physiological activities that EGT inherently possesses, such as antioxidant, brain function improvement, anti-aging, eye disease treatment, skin whitening, UV absorption, melanin production inhibition, elimination of reactive oxygen species, elastase activity inhibition, wrinkle formation inhibition, skin sagging inhibition, skin blemish formation inhibition, dark circles around the eyes inhibition, UV-induced skin damage reduction (photoaging inhibition), dry skin, sensitive skin, hair improvement, and autophagy promotion.

[0061] 〔formulation〕 The compositions of the present invention can be administered orally or parenterally (including topically) in the form of solid preparations such as tablets, capsules, granules, and powders; or liquid preparations such as solutions, syrups, injections, creams, lotions, pastes, ointments, emulsions (oil-in-water emulsions, water-in-oil emulsions, multiple emulsions, microemulsions, PET emulsions, and Pickering emulsions), gels (hydrogels and alcohol gels), and suspensions. Solid preparations may contain excipients, lubricants, binders, and disintegrants; liquid preparations may contain solvents, solubilizers, emulsifiers, emulsion stabilizers, thickeners, humectants, suspending agents, isotonicity agents, buffers, and soothing agents. Additives such as preservatives, antioxidants, colorants, sweeteners, and flavorings may also be used as needed.

[0062] Examples of excipients include sugar alcohols such as sorbitol, mannitol, and xylitol; sugars such as glucose, sucrose, lactose, and fructose; crystalline cellulose, carmellose sodium, croscarmellose sodium, calcium hydrogen phosphate, wheat starch, rice starch, corn starch, potato starch, dextrin, β-cyclodextrin, light anhydrous silicic acid, titanium oxide, magnesium aluminometasilicate, talc, kaolin, and olive oil.

[0063] Examples of binders include cellulose derivatives such as methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, and hydroxypropylmethyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol, acrylic acid polymers, gelatin, gum arabic, pullulan, pregelatinized starch, agar, tragacanth, sodium alginate, and propylene glycol alginate.

[0064] Examples of disintegrants include starch, low-substituted hydroxypropyl cellulose, carboxymethyl cellulose calcium, croscarmellose sodium, hydroxypropyl starch, and partially pregelatinized starch.

[0065] Examples of the solvent include water, alcohol, propylene glycol, macrogol, sesame oil, and corn oil.

[0066] Examples of lubricants include stearic acid, magnesium stearate, calcium stearate, polyoxyl stearate, cetanol, talc, hydrogenated oil, sucrose fatty acid ester, dimethylpolysiloxane, beeswax, and white beeswax.

[0067] Examples of solubilizing agents include polyethylene glycol, propylene glycol, mannitol, benzyl benzoate, ethanol, tris(hydroxymethyl)aminomethane, cholesterol, triethanolamine, sodium carbonate, and sodium citrate.

[0068] Examples of suspending agents and emulsifying agents include surfactants such as stearylamine, triethanolamine, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, and glycerin monostearate; hydrophilic polymers such as polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, and hydroxypropylcellulose; and waxes such as shellac wax, beeswax, carnauba wax, spermaceti, lanolin, liquid lanolin, reduced lanolin, hard lanolin, cyclic lanolin, lanolin wax, candelilla wax, Japan wax, montan wax, and rice wax.

[0069] Examples of the isotonic agent include sodium chloride, glycerin, D-mannitol, and the like.

[0070] Examples of the buffering agent include buffer solutions such as phosphate, acetate, carbonate, and citrate.

[0071] Examples of preservatives include parahydroxybenzoates, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, and sorbic acid.

[0072] Examples of antioxidants include sulfites and ascorbic acid.

[0073] When the composition of the present invention is made into a solid formulation, a manufacturing method known in the art can be used. Examples include a method in which the composition is kneaded, passed through a screen to form an extrusion granule, and then pulverized and sized; and a method in which kneading water is added to the composition, and the mixture is granulated using a vertical granulator, followed by pulverization and sieving using a Comil. Another example is a method in which the formulation composition is compressed using a roller compactor, pulverized using a roll granulator, and sieved. Another example is a method in which the composition is granulated using a fluidized bed after pulverization. For example, when the composition is produced by direct compression, the composition may be mixed and then directly charged into a tablet press for tableting.

[0074] [Inflammatory suppressant] The inflammation suppressing agent of the present invention contains the above-mentioned compound. These compounds may be contained alone or in combination of two or more.

[0075] Other inflammation suppressing agents of the present invention include the above-mentioned compositions. These compositions may be contained alone or in combination of two or more.

[0076] The inflammation suppressing agent can exert, for example, an inflammation suppressing effect that leads to the maintenance of retinal pigment epithelial cells.

[0077] [Food and beverages] The composition of the present invention can also be used as a food or drink composition, and can be provided by being contained in a food or functional food. Examples of such foods or functional foods include cooked rice; various noodles including soba, udon, vermicelli, Chinese noodles, instant noodles, and cup noodles; beverages such as soft drinks, carbonated drinks, energy drinks, fruit drinks, lactic acid drinks, and sports drinks; curry roux, stews, and various soups; frozen desserts such as ice cream, ice sherbet, and shaved ice; sweets such as candy, cookies, candy, gum, chocolate, tablet candy, snacks, biscuits, jelly, jam, cream, and other baked goods; processed seafood and livestock foods such as kamaboko, hanpen, ham, and sausage; dairy products such as processed milk and fermented milk; oils and fats and oil-based processed foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressings; condiments such as sauces, dressings, miso, soy sauce, and tare sauces; soups, stews, salads, side dishes, furikake, and pickles; and various other forms of health and nutritional supplements, functional foods, and foods for specified health uses.

[0078] Furthermore, supplements (powders, granules, soft capsules, hard capsules, tablets, chewable tablets, rapidly disintegrating tablets, syrups, liquids, etc.) containing the compositions of the present invention may be prepared.

[0079] The composition of the present invention can also be added to food for animals such as pets.

[0080] Additives may be added to foods and beverages as needed, including, for example, glucose, fructose, sucrose, maltose, sorbitol, trehalose, stevioside, rubusoside, corn syrup, lactose, mannitol, dextrin, citric acid, sodium citrate, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid esters, polyglycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, gum arabic, carrageenan, casein, gelatin, pectin, agar, B vitamins, nicotinamide, calcium pantothenate, amino acids, calcium salts, surfactants, colorings, flavorings, and preservatives.

[0081] The composition of the present invention can be used for foods and beverages that are permitted to label their products as improving, preventing, or improving various symptoms or conditions. In the present invention, foods and beverages that are permitted to label their products as improving, preventing, or improving symptoms or conditions are foods and beverages that have efficacy approved or designated by a country or public organization, such as functional foods, foods with health claims such as foods for specified health uses, and foods for special dietary uses. Although names and regulations may change depending on the situation, the times, and the systems of each country, foods that are essentially the same are included in the present invention.

[0082] In the present invention, the amount of the composition of the present invention to be incorporated is not particularly limited, and is set appropriately depending on the purpose of application (such as the type of target disease or symptom), the target area to be applied, the gender and age of the recipient, the product form such as food or drink, functional food, food for specified health uses, quasi-drug, pharmaceutical, cosmetic, daily necessities or feed, the method and frequency of administration or ingestion of these, preferences, etc.

[0083] [Embodiment] The present invention is not limited to the above-described embodiment, but discloses the following embodiments.

[0084] A compound represented by the following formula 1. [ka]

[0085] The compound is represented by the following formula 2: [ka]

[0086] The compound is represented by the following formula 3. [ka]

[0087] A composition comprising the compound described above.

[0088] The above composition, further comprising L-ergothioneine.

[0089] The composition, wherein the content of the compound is 50 parts by mass or less per 100 parts by mass of the L-ergothioneine.

[0090] The composition, wherein the content of the compound is 0.0001 parts by mass or more per 100 parts by mass of the L-ergothioneine.

[0091] The composition, wherein the content of the compound is 0.0001 parts by mass or more and 50 parts by mass or less per 100 parts by mass of the L-ergothioneine.

[0092] An anti-inflammatory agent comprising the above compound.

[0093] An inflammation suppressant comprising the above composition.

[0094] Use of the compound described above for the manufacture of an anti-inflammatory agent.

[0095] Use of the above composition for the manufacture of an anti-inflammatory agent.

[0096] The compound as defined above for use in suppressing inflammation.

[0097] The composition as defined above for use in suppressing inflammation.

[0098] A method for producing the compound, comprising the step of reacting ribosylhomocysteine with a reducing agent.

[0099] The above-mentioned production method, wherein the reducing agent comprises lithium borohydride, sodium borohydride, or zinc borohydride. [Example]

[0100] Next, the present invention will be specifically explained by way of examples, but the present invention is not limited to the following examples.

[0101] Example 1 (Preparation of reduced SRH) Ribosylhomocysteine (SRH) was prepared according to the method described in Carbohydrate Research, 2014, Vol. 394, p. 32.

[0102] To 20 mL of the ribosylhomocysteine (SRH) aqueous solution prepared above (containing 123 mg of SRH, 0.46 mmol), 17.4 mg (0.46 mmol) of sodium borohydride was added and stirred for 1 hour (pH 9-10). After the reaction was monitored by HPLC, it was confirmed that most of the SRH had been converted to its reduced form. 5 mL of 10% NH4Cl and 500 μL of 1N HCl were added to the reaction solution to adjust the pH to 6.7.

[0103] The reaction solution was desalted using an electrodialysis device (manufactured by Astom Corporation) and then concentrated to prepare 10 mL of an aqueous solution of the SRH reduced product (1.08% by qNMR, containing 108 mg of the SRH reduced product).

[0104] (HPLC analysis conditions) The HPLC analysis was carried out under the following conditions. Column: YMC-Pack ODS-AQ S-5μM, 12nm, 250x4.6mm ID Flow rate: 0.5mL / min, temperature: 30℃ Detector: PDA (210 nm) Eluent: 0.1% formic acid aqueous solution Retention time: 6.2 minutes (reduced SRH), 6.6 minutes (SRH)

[0105] (High resolution mass spectrometry) The results of liquid chromatography-high resolution mass spectrometry (LC-HRMS) are shown below. [M+H] + Calculated value C9H 20 NO6S 270.1011; Actual value 270.1016 (LC-HRMS analysis conditions) Apparatus: Agilent Technologies 6224 TOF LC / MS (Agilent Technologies) Column: YMC-Pack ODS-AQ S-5μM, 12nm, 250x4.6mm ID Flow rate: 0.5mL / min, temperature: 30℃ Eluent: 0.1% formic acid aqueous solution Ionization conditions: ESI capillary voltage 3500V, fragmentor voltage 100V Retention time: 6.6 minutes (reduced SRH), 7.2 minutes (SRH)

[0106] ( 1 H-NMR measurement) Below 1 The results of H-NMR measurement are shown below. 1 H-NMR (400 MHz, D2O) DSS-d6 was set to 0 ppm. δ 3.88(m,2H),3.79(m,2H),3.67(m,2H),2.94(m,1H),2.71(m,3H),2.16(m,2H)

[0107] Example 2 (Evaluation of anti-inflammatory effect) The human retinal pigment epithelial cell line ARPE-19 was seeded onto a 6-well plate using 10% FBS-DMEM / F12 medium and cultured in a carbon dioxide incubator under conditions of 5% CO2 and 37°C for 48 hours.

[0108] After confirming that the cells had reached confluence, the medium was replaced with fresh 10% FBS-DMEM / F12 medium (control group), 10% FBS-DMEM / F12 medium containing 5 g / L of fructose (metabolic stress model group), or 10% FBS-DMEM / F12 medium containing SRH reductant (4 mM) and 5 g / L of fructose (metabolic stress, SRH reductant test group), and the cells were continued to be cultured.

[0109] After 72 hours, the medium was removed, and RNA was extracted using TRIzol (Thermo Fisher Scientific) according to the protocol. RNA was then prepared using a cDNA preparation kit (TAKARA Scientific) according to the protocol.

[0110] The results are shown in Figure 1. The primers used had the following sequences: IL-12p40: (Forward)5'-aaggaggcgaggttctaagc-3', (Reverse)5'-aagagcctctgctgcttttg-3' IL-1beta: (Forward)5'-gggcctcaaggaaaagaatc-3', (Reverse)5'-ttctgcttgagaggtgctga-3' MMP-9: (Forward)5'ttgacagcgacaagaagtgg-3', (Reverse)5'-gccattcacgtcgtccttat-3' TNFalpha: (Forward)5'-tccttcagacaccctcaacc-3', (Reverse)5'-cagggatcaaagctgtaggc-3' TBP: (Forward)5'-tataatcccaagcggtttgc-3', (Reverse)5'-gctggaaaacccaacttctg-3'

[0111] As shown in Figure 1, the elevated levels of IL-1b and TNF due to high fructose loading confirmed the occurrence of an inflammatory response. Furthermore, the elevated levels of IL-12 suggested the occurrence of a Th1-type response. In each formulation, the addition of 4 mM SRH reduced form showed an inhibitory effect on the above responses. Furthermore, the basement membrane is essential for the maintenance of retinal pigment epithelial cells, and SRH reduced form was also found to have the effect of inhibiting the increase in MMP-9, an enzyme that breaks down basement membrane. These findings confirm that SRH reduced form has the effect of suppressing inflammatory responses and may contribute to the maintenance of retinal pigment epithelial cells.

Claims

1. A compound represented by the following formula 1: 【Chemical 1】

2. The compound according to claim 1, represented by the following formula 2: 【Chemistry 2】

3. The compound according to claim 1 or 2, represented by the following formula 3: 【Chemistry 3】

4. A composition comprising the compound according to any one of claims 1 to 3.

5. The composition of claim 4, further comprising L-ergothioneine.

6. The composition according to claim 5, wherein the content of the compound is 50 parts by mass or less relative to 100 parts by mass of the L-ergothioneine.

7. The composition according to claim 5 or 6, wherein the content of the compound is 0.0001 parts by mass or more relative to 100 parts by mass of the L-ergothioneine.

8. An anti-inflammatory agent comprising the compound according to any one of claims 1 to 3.

9. An inflammation suppressant comprising the composition according to any one of claims 4 to 7.

10. A method for producing the compound according to any one of claims 1 to 3, comprising a step of reacting ribosylhomocysteine ​​with a reducing agent.

11. The method of claim 10 , wherein the reducing agent comprises lithium borohydride, sodium borohydride, or zinc borohydride.

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