WO2022168650A1 - Dérivé d'homocystéine et son procédé de production, composition et agent anti-inflammatoire - Google Patents

Dérivé d'homocystéine et son procédé de production, composition et agent anti-inflammatoire Download PDF

Info

Publication number
WO2022168650A1
WO2022168650A1 PCT/JP2022/002372 JP2022002372W WO2022168650A1 WO 2022168650 A1 WO2022168650 A1 WO 2022168650A1 JP 2022002372 W JP2022002372 W JP 2022002372W WO 2022168650 A1 WO2022168650 A1 WO 2022168650A1
Authority
WO
WIPO (PCT)
Prior art keywords
mass
composition
less
compound
salts
Prior art date
Application number
PCT/JP2022/002372
Other languages
English (en)
Japanese (ja)
Inventor
淳 松本
邦男 小坂
恵介 松山
Original Assignee
長瀬産業株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 長瀬産業株式会社 filed Critical 長瀬産業株式会社
Priority to JP2022579446A priority Critical patent/JPWO2022168650A1/ja
Publication of WO2022168650A1 publication Critical patent/WO2022168650A1/fr

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4172—Imidazole-alkanecarboxylic acids, e.g. histidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
    • C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/57—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C323/58—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton

Definitions

  • the present invention relates to homocysteine derivatives, methods for producing them, compositions containing them, and anti-inflammatory agents containing them.
  • compositions having an anti-inflammatory action for example, cosmetics having an effect of suppressing MMP-9 production have been known so far (see Patent Documents 1 and 2, for example).
  • the present invention aims to provide a novel homocysteine derivative, a method for producing the same, a composition containing the compound, an anti-inflammatory agent containing them, and the like.
  • the inventors of the present invention have made intensive studies to solve the above problems, and as a result, have succeeded in creating the novel homocysteine derivatives shown below, and found that the above objects can be achieved by the above compounds, thereby completing the present invention. .
  • the present invention provides the compounds listed below.
  • the present invention provides the compositions listed below.
  • Section 4 A composition comprising the compound of any one of Items 1-3.
  • Item 5 The composition according to item 4, further comprising L-ergothioneine (hereinafter also referred to as "EGT").
  • Item 6. The composition according to item 5, wherein the content of the compound is 50 parts by mass or less with respect to 100 parts by mass of the L-ergothioneine.
  • Item 7. The composition according to item 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.
  • the present invention relates to the following anti-inflammatory agents.
  • Item 8. Item 4. An anti-inflammatory agent comprising the compound according to any one of items 1 to 3.
  • Item 9. An anti-inflammatory agent comprising the composition according to any one of Items 4 to 7.
  • the present invention relates to the manufacturing method listed below.
  • Item 10 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.
  • RSH ribosylhomocysteine
  • Item 11 The production method according to Item 10, wherein the reducing agent includes lithium borohydride, sodium borohydride, or zinc borohydride.
  • the compound of the present invention or a composition containing it can be suitably used, for example, as an anti-inflammatory agent.
  • the compound or the composition can be easily obtained.
  • the anti-inflammatory agent of the present invention can exhibit, for example, an anti-inflammatory effect leading to maintenance of retinal pigment epithelial cells.
  • FIG. 1 is a graph showing evaluation results of anti-inflammatory action in Example 2.
  • FIG. 1 is a graph showing evaluation results of anti-inflammatory action in Example 2.
  • the homocysteine derivative of the present invention is a compound represented by Formula 1 below.
  • homocysteine derivative is, for example, a compound represented by Formula 2 below.
  • homocysteine derivative is, for example, a compound represented by Formula 3 below.
  • homocysteine derivatives also include derivatives such as solvates such as hydrates and substituted products in which part or all of the structure is substituted as appropriate.
  • hydroxyl groups may be appropriately substituted with, for example, an alkyl ether group, an aryl ether group, or an ester group.
  • the carboxyl group may be appropriately substituted with an ester group, an amide group, an acid anhydride, a salt, or the like.
  • the amino group may be appropriately substituted with an alkylated product, an amide group, a salt, or the like.
  • the sulfide group may be appropriately substituted with an alkylated salt, sulfoxide, or sulfone.
  • the above homocysteine derivative can be produced by appropriately using a known technique, but it is preferable to use a production method including a step of reducing ribosylhomocysteine and the like.
  • the method for producing the compound of the present invention preferably includes a step of reacting ribosylhomocysteine with a reducing agent.
  • Ribosylhomocysteine is a homocysteine derivative in which homocysteine (2-amino-4-sulfanylbutanoic acid) is S-ribosylated, and its structure is represented by the following formula.
  • SRH can be obtained by known methods such as synthesis, extraction, and fermentation.
  • SRH may be in the form of a free form or in the form of a salt.
  • the salt of SRH may be a salt formed with a carboxyl group or a salt formed with an amino group in these structures.
  • Ribosylhomocysteine or ribosylhomocysteine analogues may also be solvates such as hydrates.
  • the salt of SRH is not particularly limited as long as it is pharmacologically or physiologically acceptable.
  • Specific examples include organic acid salts, inorganic acid salts, salts with organic bases, or salts with inorganic bases I can give you the salt of
  • organic acid salts include monocarboxylic acid salts such as acetate, trifluoroacetate, butyrate, palmitate, and stearate; Polyvalent carboxylates; oxycarboxylates such as lactate, tartrate and citrate; organic sulfonates such as methanesulfonate, toluenesulfonate and tosylate.
  • inorganic acid salts include hydrochlorides, sulfates, nitrates, hydrobromides, and phosphates.
  • salts with organic bases include salts with organic amines such as methylamine, triethylamine, triethanolamine, diethanolamine, morpholine, piperazine, pyrrolidine and ethylenediamine.
  • Salts with inorganic bases include, for example, ammonium salts; various salts such as salts with alkali metals such as sodium and potassium; alkaline earth metals such as calcium and magnesium; and salts with metals such as aluminum. These salts may be used singly or in any combination of two or more.
  • “Pharmaceutically or physiologically acceptable salts” may include solvates or hydrates of salts.
  • the above reducing agent can be used as appropriate as long as it can reduce ribosylhomocysteine to produce the above compound.
  • the reducing agent include lithium borohydride, sodium borohydride, zinc borohydride, and the like. Among them, sodium borohydride can be mentioned as a suitable reducing agent.
  • the reducing agent can be appropriately used in the reduction step using a known method.
  • a solvent such as water
  • 0.01 to 1000 mol% of a reducing agent for example, at a temperature range of -10 ° C. to 30 ° C. , for example, 10 minutes to 48 hours.
  • the above compound can be produced, for example, according to the following reaction scheme.
  • a step of removing salts by electrodialysis or the like may be included.
  • compositions of the invention include the compounds described above. These compounds may be contained singly or in combination of two or more.
  • the content of the above compound is appropriately adjusted depending on the application of the composition, the type and content of other components, etc., and is not limited, but for example, 0.000001 with respect to the total amount of the composition. 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. can be given. Further, 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% by mass or less, relative to the total amount of the composition.
  • the content of the compound is not limited, but can be, for example, 80% by mass or less with respect to the total amount of the composition, 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, or 1% by mass or less.
  • the content of the compound is not limited, but can be, for example, 80% by mass or less with respect to the total amount of the composition, 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. .
  • composition can further contain L-ergothioneine (EGT).
  • EGT L-ergothioneine
  • EGT is a histidine derivative (N,N,N-trimethyl-L-2-thiohistidine), and its structure is represented by the following formula.
  • EGT can be obtained by known methods such as synthetic methods, extraction methods, and fermentation methods, and it is also possible to obtain and use commercially available products.
  • EGT products include, for example, Ergoneine (R) (manufactured by Tetraedron).
  • EGT may be in the form of a free form or in the form of a salt.
  • the salt of EGT may be a salt formed with a carboxyl group in these structures, or a salt formed with a trimethylamino group.
  • L-ergothioneine or L-ergothioneine analogues may be solvates such as hydrates.
  • the salt of EGT is not particularly limited as long as it is a pharmacologically or physiologically acceptable salt.
  • Specific examples include organic acid salts, inorganic acid salts, salts with organic bases, or salts with inorganic bases I can give you the salt of
  • organic acid salts include monocarboxylic acid salts such as acetate, trifluoroacetate, butyrate, palmitate, and stearate; Polyvalent carboxylates; oxycarboxylates such as lactate, tartrate and citrate; organic sulfonates such as methanesulfonate, toluenesulfonate and tosylate.
  • inorganic acid salts include hydrochlorides, sulfates, nitrates, hydrobromides, and phosphates.
  • salts with organic bases include salts with organic amines such as methylamine, triethylamine, triethanolamine, diethanolamine, morpholine, piperazine, pyrrolidine and ethylenediamine.
  • Salts with inorganic bases include, for example, various salts such as salts with alkali metals such as sodium or potassium, alkaline earth metals such as calcium or magnesium, and salts with metals such as aluminum. These salts may be used singly or in any combination of two or more.
  • “Pharmaceutically or physiologically acceptable salts” may include solvates or hydrates of salts.
  • the content of EGT is appropriately adjusted depending on the application of the composition, the type and content of other components, etc., and is not limited, but for example, 0.00% relative to the total amount of the composition.
  • 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 I can give you the above.
  • the content of EGT 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, 98.9% by mass or less, based on the total amount of the composition.
  • the content of EGT is not limited, but can be, for example, 80% by mass or less, and 70% by mass, relative to the total amount of the composition. % or less, 60 mass % or less, 50 mass % or less, 40 mass % or less, 30 mass % or less, 20 mass % or less, 10 mass % or less, 5 mass % or less, 1 mass % or less, and the like.
  • the daily intake (applied amount) is, for example, 0.005 to 4,000 mg, preferably 0.1 to 3,000 mg, or 0.1 to 3,000 mg. 5 to 2,000 mg, 1 to 1,000 mg, 2 to 500 mg, 5 to 30 mg, etc. can be used.
  • the pH of the composition of the present invention is appropriately set according to the type and content of other compounding ingredients, application, formulation form, method of use, etc., and is not limited as long as it is within a pharmaceutically or physiologically acceptable range.
  • the pH of the composition of the present invention is, 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 3-7, pH 4-10, pH 4-9, pH 4-8, pH 4-7, pH 5-10, pH 5-9, pH 5-8, pH 5-7, pH 6-10, pH 6-9, pH 6-8, It is possible to set the pH to 6 to 7 or the like.
  • composition of the present invention can further contain active ingredients and additives that can be used in foods and drinks, foods with function claims, foods for specified health uses, quasi-drugs, pharmaceuticals, cosmetics, daily necessities, feeds, etc., as appropriate. Also, it can be appropriately formulated by a known formulation method used for the item.
  • cosmetics and daily necessities include lotions, milky lotions, gels, serums, creams, sunscreen creams, packs, masks, foundations, powders, bath agents, body lotions, shampoos, rinses, hair treatments, hair conditioners, and hair styling products. , hair tonic, toothpaste, mouthwash, etc.
  • EGT when the composition contains EGT, EGT has physiological activities such as antioxidant, brain function improvement, anti-aging, eye disease, whitening, ultraviolet absorption, and suppression of melanin production. Eliminates reactive oxygen species, inhibits elastase activity, suppresses wrinkle formation, suppresses skin sagging, suppresses formation of dark spots on the skin, suppresses dark circles around the eyes, reduces skin damage caused by UV rays (suppresses photoaging) ), for dry skin, for sensitive skin, for improving hair, for promoting autophagy, and the like.
  • physiological activities such as antioxidant, brain function improvement, anti-aging, eye disease, whitening, ultraviolet absorption, and suppression of melanin production. Eliminates reactive oxygen species, inhibits elastase activity, suppresses wrinkle formation, suppresses skin sagging, suppresses formation of dark spots on the skin, suppresses dark circles around the eyes, reduces skin damage caused by UV rays (suppresses photoaging) ), for dry skin, for sensitive skin, for
  • the composition of the present invention includes, for example, solid formulations such as tablets, capsules, granules, and powders; It can also be administered orally or parenterally (including external use) as a liquid preparation such as a type emulsion, multiple emulsion, microemulsion, PET-emulsion, Pickering emulsion), gel (hydrogel, alcohol gel), suspension, etc. can.
  • a liquid preparation such as a type emulsion, multiple emulsion, microemulsion, PET-emulsion, Pickering emulsion), gel (hydrogel, alcohol gel), suspension, etc.
  • a liquid preparation such as a type emulsion, multiple emulsion, microemulsion, PET-emulsion, Pickering emulsion), gel (hydrogel, alcohol gel), suspension, etc.
  • a liquid preparation such as a type emulsion, multiple emulsion, microemulsion, PET-emulsion, Pickering emulsion), gel (hydr
  • 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; Starch, corn starch, potato starch, dextrin, ⁇ -cyclodextrin, light anhydrous silicic acid, titanium oxide, magnesium aluminometasilicate, talc, kaolin, olive oil and the like can be mentioned.
  • 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
  • Binders include, for example, cellulose derivatives such as methylcellulose, ethylcellulose, hydroxypropylcellulose, and hydroxypropylmethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, acrylic polymers, gelatin, gum arabic, pullulan, pregelatinized starch, agar, tragacanth, Examples include sodium alginate and propylene glycol alginate.
  • disintegrants include starch, low-substituted hydroxypropylcellulose, carboxymethylcellulose calcium, croscarmellose sodium, hydroxypropyl starch, partially pregelatinized starch, and the like.
  • solvents examples include water, alcohol, propylene glycol, macrogol, sesame oil, corn oil, and the like.
  • lubricants include stearic acid, magnesium stearate, calcium stearate, polyoxyl stearate, cetanol, talc, hydrogenated oil, sucrose fatty acid ester, dimethylpolysiloxane, beeswax, white beeswax, and the like.
  • solubilizing agents include polyethylene glycol, propylene glycol, mannitol, benzyl benzoate, ethanol, tris(hydroxymethyl)aminomethane, cholesterol, triethanolamine, sodium carbonate, and sodium citrate.
  • Suspending agents/emulsifiers include surfactants such as stearylamine, triethanolamine, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, and glyceryl monostearate; , polyvinylpyrrolidone, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, and hydroxypropylcellulose; hydrophilic polymers such as shellac wax, beeswax, carnauba wax, spermaceti wax, lanolin, liquid lanolin, reduced lanolin, hard lanolin, cyclic lanolin , lanolin wax, candelilla wax, Japanese wax, montan wax, rice wax and the like.
  • surfactants such as stearylamine, triethanolamine, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkon
  • isotonizing agents examples include sodium chloride, glycerin, D-mannitol, and the like.
  • buffering agents include buffers such as phosphate, acetate, carbonate, and citrate.
  • antiseptics examples include paraoxybenzoic acid esters, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, sorbic acid and the like.
  • antioxidants examples include sulfites and ascorbic acid.
  • a manufacturing method known in the art can be used. For example, a method of kneading the composition and passing it through a screen to form extruded granules, pulverizing and sizing them, or adding kneading water to the composition and forming it with a vertical granulator by stirring granulation.
  • a method of pulverizing and sieving using a combill can be mentioned after the above.
  • pulverizing with a roll granulator and sieving can be mentioned after compressing the said pharmaceutical composition with a roller compactor.
  • a method of performing fluidized bed drying after stirring granulation can be mentioned.
  • the composition is produced by direct compression, the composition may be mixed and directly put into a tableting machine to be tableted.
  • the anti-inflammatory agent of the present invention contains the compounds described above. These compounds may be contained singly or in combination of two or more.
  • compositions include the above composition. These compositions may be contained singly or in combination of two or more.
  • the anti-inflammatory agent may be able to exert, for example, an anti-inflammatory action that leads to maintenance of retinal pigment epithelial cells.
  • the composition of the present invention can also be used as a food and drink composition, and can be provided by being contained in food or functional food.
  • foods or functional foods include cooked rice; various types of noodles including soba, udon, vermicelli, Chinese noodles, instant noodles, and cup noodles; soft drinks, carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks, and sports drinks.
  • Beverages such as curry roux, stew, various soups; Frozen desserts such as ice cream, ice sherbet, and shaved ice; Candies, cookies, candies, gums, chocolates, tablets, snacks, biscuits, jelly, jams, creams, and other baked goods
  • Processed fish and livestock foods such as fish paste, hampen, ham, sausage
  • Dairy products such as processed milk and fermented milk
  • Fats and oils such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressing Processed foods; seasonings such as sauces, dressings, miso, soy sauce, sauce; soups, stews, salads, side dishes, furikake, pickles; other various forms of health foods, dietary supplements, foods with function claims, foods for specified health uses, etc. are exemplified.
  • supplements powder, granule, soft capsule, hard capsule, tablet, chewable tablet, rapidly disintegrating tablet, syrup, liquid, etc.
  • composition of the present invention may be prepared.
  • composition of the present invention can also be contained in food for animals such as pets.
  • Additives are added to food and drink as needed.
  • additives include 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 ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, gum arabic, carrageenan, casein, gelatin, pectin, agar, vitamin B group, nicotinic acid amide, calcium pantothenate, amino acids, calcium salts, surfactants, pigments, fragrances, preservatives and the like can be mentioned.
  • composition of the present invention can be used for foods and drinks that are permitted to be labeled as improving, preventing, improving, etc. various symptoms and conditions.
  • food and drink that are permitted to display symptoms and conditions such as improvement, prevention, improvement, etc. are food and drinks that have efficacy permitted or designated by the country or public organizations.
  • These include foods with function claims, foods with health claims such as foods for specified health uses, and foods for special dietary uses.
  • the names and regulations change depending on the situation, the times, and the systems of each country, those that are essentially the same are included in the present invention.
  • the amount of the composition of the present invention is not particularly limited, and the purpose of application (type of target disease or symptom, etc.), target site for application, gender and age of the applicant, food and drink, food with function claims , foods for specified health uses, quasi-drugs, pharmaceuticals, cosmetics, daily necessities, feeds, and other product forms;
  • composition which further contains L-ergothioneine.
  • composition wherein the content of the compound is 50 parts by mass or less with respect to 100 parts by mass of the L-ergothioneine.
  • composition wherein the content of the compound is 0.0001 parts by mass or more with respect to 100 parts by mass of the L-ergothioneine.
  • composition wherein the content of the compound is 0.0001 parts by mass or more and 50 parts by mass or less with respect to 100 parts by mass of the L-ergothioneine.
  • An anti-inflammatory agent containing the above composition.
  • a compound as described above for use in suppressing inflammation is provided.
  • composition for use in suppressing inflammation.
  • a method for producing the above compound comprising a step of reacting ribosylhomocysteine with a reducing agent.
  • the reducing agent contains lithium borohydride, sodium borohydride, or zinc borohydride.
  • SRH ribosylhomocysteine
  • reaction solution was desalted using an electrodialyzer (manufactured by Astom) and then concentrated to prepare 10 mL of an aqueous SRH reductant solution (containing 108 mg of SRH reductant of 1.08% by qNMR).
  • HPLC analysis HPLC analysis was performed under the following conditions. Column: YMC-Pack ODS-AQ S-5 ⁇ M, 12 nm, 250 ⁇ 4.6 mm I.D. D. Flow rate: 0.5 mL/min, temperature: 30°C Detector: PDA (210 nm) Eluent: 0.1% formic acid aqueous solution Retention time: 6.2 minutes (SRH reductant), 6.6 minutes (SRH)
  • Example 2 Evaluation of anti-inflammatory effect
  • Human retinal pigment epithelial cell line ARPE-19 was seeded in a 6-well plate using 10% FBS-DMEM/F12 medium, and cultured for 48 hours in a carbon dioxide gas incubator under conditions of 5% CO 2 and 37°C. rice field.
  • the medium After confirming that it has reached confluence, the medium is replaced with fresh 10% FBS-DMEM/F12 medium (control group) or 10% FBS-DMEM/F12 medium containing 5 g/L of fructose (metabolic stress model group), Alternatively, the medium was changed to 10% FBS-DMEM/F12 medium containing SRH reductant (4 mM) and fructose 5 g/L (under metabolic stress, SRH reductant test group), and culture was continued.
  • IL-12p40 (Forward) 5′-aaggaggcgaggttctaagc-3′, (Reverse) 5′-aagagcctctgctgcttttg-3′
  • IL-1beta (Forward) 5′-gggcctcaaggaaaagaatc-3′, (Reverse) 5′-ttctgcttgagaggtgctga-3′
  • MMP-9 (Forward) 5′ ttgacagcgacaagaaagtgg-3′, (Reverse) 5′-gccattcacgtcgtcttat-3′
  • TNFalpha (Forward) 5′-tccttcagacacctcaacc-3′, (Reverse) 5′-cagggatcaaagctgtaggc-3′
  • TBP (Forward) 5′-tataatcccaagc
  • IL-1b and TNF increased due to high fructose load, and that an inflammatory reaction occurred.
  • a Th1-type reaction occurred from the increase in IL-12.
  • the system to which 4 mM of the SRH reductant was added showed an inhibitory effect on the above reaction.
  • the basement membrane is essential for the maintenance of retinal pigment epithelial cells, and the SRH reduced form was also effective in suppressing the increase in MMP-9, an enzyme that degrades the basement membrane. From the above, it was confirmed that the reduced SRH has an effect of suppressing inflammatory reactions and that it can contribute to the maintenance of retinal pigment epithelial cells.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Birds (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne un nouveau dérivé d'homocystéine et son procédé de production, une composition comprenant le composé, ainsi qu'un agent anti-inflammatoire comprenant le composé et/ou la composition.　L'invention concerne également un composé représenté par la formule 1.
PCT/JP2022/002372 2021-02-03 2022-01-24 Dérivé d'homocystéine et son procédé de production, composition et agent anti-inflammatoire WO2022168650A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2022579446A JPWO2022168650A1 (fr) 2021-02-03 2022-01-24

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2021015895 2021-02-03
JP2021-015895 2021-02-03

Publications (1)

Publication Number Publication Date
WO2022168650A1 true WO2022168650A1 (fr) 2022-08-11

Family

ID=82741722

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2022/002372 WO2022168650A1 (fr) 2021-02-03 2022-01-24 Dérivé d'homocystéine et son procédé de production, composition et agent anti-inflammatoire

Country Status (3)

Country Link
JP (1) JPWO2022168650A1 (fr)
TW (1) TW202246210A (fr)
WO (1) WO2022168650A1 (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2015528499A (ja) * 2012-09-14 2015-09-28 エリザベス アーデン インコーポレイテッド イデベノンとｎ−アセチル−ｓ−ファルネシル−ｌ−システインとエルゴチオネインとを含む調合物及びその使用法

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2015528499A (ja) * 2012-09-14 2015-09-28 エリザベス アーデン インコーポレイテッド イデベノンとｎ−アセチル−ｓ−ファルネシル−ｌ−システインとエルゴチオネインとを含む調合物及びその使用法

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
GOPISHETTY BHASKAR, ZHU JINGE, RAJAN RAKHI, SOBCZAK ADAM J., WNUK STANISLAW F., BELL CHARLES E., PEI DEHUA: "Probing the Catalytic Mechanism of S -Ribosylhomocysteinase (LuxS) with Catalytic Intermediates and Substrate Analogues", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, vol. 131, no. 3, 28 January 2009 (2009-01-28), pages 1243 - 1250, XP055955382, ISSN: 0002-7863, DOI: 10.1021/ja808206w *
HUANG WENJUAN, GHERIB RAMI, GAULD JAMES W.: "An Active Site Water Broadens Substrate Specificity in S -Ribosylhomocysteinase (LuxS): A Docking, MD, and QM/MM Study", JOURNAL OF PHYSICAL CHEMISTRY PART B, AMERICAN CHEMICAL SOCIETY, US, vol. 116, no. 30, 2 August 2012 (2012-08-02), US , pages 8916 - 8929, XP055955384, ISSN: 1520-6106, DOI: 10.1021/jp3049907 *
VENKATA L.A. MALLADI; ADAM J. SOBCZAK; TIFFANY M. MEYER; DEHUA PEI; STANISLAW F. WNUK;: "Inhibition of LuxS by-ribosylhomocysteine analogues containing a [4-aza]ribose ring", BIOORGANIC & MEDICINAL CHEMISTRY, ELSEVIER, AMSTERDAM, NL, vol. 19, no. 18, AMSTERDAM, NL, pages 5507 - 5519, XP028389416, ISSN: 0968-0896, DOI: 10.1016/j.bmc.2011.07.043 *
ZHU JINGE, HU XUBO, DIZIN ERIC, PEI DEHUA: "Catalytic Mechanism of S -Ribosylhomocysteinase (LuxS): Direct Observation of Ketone Intermediates by 13 C NMR Spectroscopy", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, vol. 125, no. 44, 1 November 2003 (2003-11-01), pages 13379 - 13381, XP055955383, ISSN: 0002-7863, DOI: 10.1021/ja0369663 *

Also Published As

Publication number Publication date
TW202246210A (zh) 2022-12-01
JPWO2022168650A1 (fr) 2022-08-11

Similar Documents

Publication Publication Date Title
KR101847013B1 (ko) 피부 탄력 증진 및 미백용 조성물
JP4828922B2 (ja) 抗アレルギー剤
US20130236472A1 (en) Compounds and mixtures for influencing inflammatory states
US9675538B2 (en) Anti-aging agent containing arctigenin derivative
US7622450B2 (en) Flavone C-glycoside derivatives and compositions containing the derivatives
JP2006306863A (ja) メラニン生成抑制剤
KR102139659B1 (ko) 피부 개선용 조성물
WO2022168650A1 (fr) Dérivé d'homocystéine et son procédé de production, composition et agent anti-inflammatoire
JP2009161475A (ja) インスリン様成長因子−１産生促進剤
JP5769387B2 (ja) メラニン産生促進剤
JP7240565B2 (ja) Ｌ－エルゴチオネイン含有組成物
JP7333751B2 (ja) ヒト抗菌ペプチド産生促進剤
KR101574765B1 (ko) 사이코사포닌 d를 포함하는 피부 미백용 화장료 또는 약학 조성물
JP6864131B1 (ja) Ｌ−エルゴチオネイン含有組成物
EP3448373B1 (fr) Dérivés de dihydrochalcone influençant des états inflammatoires
KR20150019678A (ko) 피부 미백용 조성물
KR20150019546A (ko) 피부 재생, 주름개선, 항염증 및 피부 미백용 조성물
KR102138263B1 (ko) 피부 재생 또는 주름 개선용 조성물
CN118055768A (zh) 包含聚半乳糖苷作为有效成分的用于预防或治疗癌症的组合物
WO2022138565A1 (fr) Agent anti-inflammatoire
JP2005306814A (ja) 皮膚外用剤

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22749525

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2022579446

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 22749525

Country of ref document: EP

Kind code of ref document: A1