WO2017082144A1 - Nouvel acide aminé de type mycosporine - Google Patents

Nouvel acide aminé de type mycosporine Download PDF

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Publication number
WO2017082144A1
WO2017082144A1 PCT/JP2016/082661 JP2016082661W WO2017082144A1 WO 2017082144 A1 WO2017082144 A1 WO 2017082144A1 JP 2016082661 W JP2016082661 W JP 2016082661W WO 2017082144 A1 WO2017082144 A1 WO 2017082144A1
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amino acid
compound
acid residue
pharmaceutically acceptable
prodrug
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PCT/JP2016/082661
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English (en)
Japanese (ja)
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恵介 松山
山本　省吾
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長瀬産業株式会社
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Publication of WO2017082144A1 publication Critical patent/WO2017082144A1/fr

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    • 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
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
    • C07C225/20—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/02—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups
    • C07C251/20—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups being part of rings other than six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K3/00—Materials not provided for elsewhere
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P13/00—Preparation of nitrogen-containing organic compounds

Definitions

  • the present invention relates to novel mycosporine-like amino acids, pharmaceutically acceptable salts and prodrugs thereof, and compositions containing them.
  • UV-A and UV-B have an influence on the living body, and UV-C does not normally cause problems because it cannot pass through the atmosphere.
  • UV-B is a main cause of sunburn outdoors, and it is known that energy is relatively large compared to UV-A. When absorbed by the skin layer, it reaches the stratum corneum and epidermis, causing acute skin pigmentation such as spots and freckles. It is also known to cause immunosuppression, which is involved in the development of aging and skin cancer.
  • UV-A has a longer wavelength and lower energy than UV-B, but is known to penetrate deeper into the skin than UV-B and reach the dermis. As a result, it causes not only acute skin pigmentation such as spots and freckles but also a decrease in elasticity of the dermis (photoelastic fibrosis), and causes early skin aging such as wrinkles and sagging. More recently, UV-A has also been shown to cause immunosuppression and participate in the development of precancerous skin lesions and skin cancer.
  • UV-B The amount of UV-B varies depending on the season, weather, latitude, etc., while UV-A reaches a certain amount on the surface throughout the year. Therefore, it is also important to protect the skin from UV-A.
  • the ultraviolet absorber is an agent that converts ultraviolet energy into heat energy and releases it, and examples thereof include synthetic organic compounds such as 4-tert-butyl-4′-methoxydibenzomethane.
  • the ultraviolet scattering agent contains inorganic particles such as titanium oxide (TiO 2 ) and zinc oxide (ZnO), and when applied to the skin, the inorganic particles present on the skin surface function as a barrier that reflects ultraviolet rays.
  • UV absorbers are (1) easily decomposed by light and have poor stability, (2) cause molecular excitation and promote melanin production, causing itching and allergies, and (3) chemical synthesis substances There is a problem that the image given to the user is bad.
  • UV scattering agents (1) When applied to the skin, it tends to whiten and give a heavy feeling to the skin. (2) Causes the generation of active oxygen. (3) Blocks skin pores and inhibits skin respiration There is a problem that there are concerns. Due to such problems, expectations for safe UV-absorbing substances derived from nature are increasing.
  • Mycosporine-like amino acid (Mycosporine-like Amino Acid, hereinafter referred to as “MAA”) is a natural UV-absorbing substance known to exist widely in aquatic organisms such as corals, red algae, fish internal organs, and microalgae. is there.
  • Known MAAs include sinoline and porphyra-334.
  • Patent Document 1 describes that synoline and other compounds belonging to MAA were obtained from cultures of microorganisms belonging to the genus Micrococcus. However, the specific structures of these other compounds are not specified.
  • Non-Patent Document 1 describes that synoline and porphyra-334 and mycosporin-glycine-alanine were obtained as novel MAA from actinomycete cultures.
  • Patent Documents 2 to 4 also disclose structural formulas of compounds belonging to MAA, but only known MAAs are specifically determined compounds.
  • the problem to be solved by the present invention is to provide a naturally occurring novel compound having an ultraviolet absorbing action.
  • the solution of the present invention includes providing novel mycosporine-like amino acids, pharmaceutically acceptable salts and prodrugs thereof, and compositions containing them.
  • novel compounds belonging to mycosporin-like amino acids are contained in the culture of actinomycetes, and that these compounds have an ultraviolet-absorbing action. Completed.
  • the present invention provides the following: [1] Formula (I): Wherein (I), Q 1 represents an oxygen atom, an amino acid residue or amino alcohol, if Q 1 is an amino acid residue or amino alcohol, in the amino acid residue or amino alcohol via a nitrogen atom ring Q 2 is an oxygen atom, an amino acid residue or an amino alcohol, and when Q 2 is an amino acid residue or an amino alcohol, the amino acid residue or amino alcohol is cyclized through the nitrogen atom. It is something that is bound to.
  • Q 1 is an oxygen atom, glycine, alanine, valine, serine, threonine, leucine, isoleucine, asparagine, aspartic acid, glutamine, glutamic acid, homoserine, .gamma.-aminobutyric acid (GABA), consisting of serinol, and Gurutaminoru is selected from the group
  • Q 2 is oxygen atom, valine, asparagine, aspartic acid, threonine, leucine, isoleucine, alanine, is selected from glycine, serine, glutamine, glutamic acid, homoserine, GABA, serinol, and from the group consisting of Gurutaminoru
  • the compound of [1] or [2], or a pharmaceutically acceptable salt or prodrug thereof is selected from the group consisting of Gurutaminoru
  • novel mycosporine-like amino acid of the present invention has an ultraviolet absorbing action, it is useful as an active ingredient for cosmetics, quasi drugs and pharmaceuticals. It is also useful for protecting various industrial products from deterioration due to ultraviolet rays.
  • the present invention provides compounds of formula (I): [In Formula (I), Q 1 is an oxygen atom, an amino acid residue or an amino alcohol, and when Q 1 is an amino acid residue or an amino alcohol, the amino acid residue or amino alcohol is bonded to the ring via a nitrogen atom. it is those that are bonded to; Q 2 represents an oxygen atom, an amino acid residue or amino alcohol, if Q 2 is an amino acid residue or amino alcohol, the amino acid residue or amino alcohol via a nitrogen atom ring It is something that is bound to. ] Or a pharmaceutically acceptable salt or prodrug thereof.
  • amino acid is a general term for organic compounds having both an amino group and a carboxyl group.
  • the amino acid residues contained in formula (I) are 20 kinds of amino acids (ie, glycine, alanine, valine, serine, threonine, leucine, isoleucine, asparagine, aspartic acid, glutamine, glutamic acid contained in naturally occurring proteins) Arginine, histidine, lysine, methionine, phenylalanine, tryptophan, tyrosine, proline, cysteine), other naturally occurring amino acid residues (eg homoserine, ⁇ -aminobutyric acid (GABA) ), Ornithine, and citrulline residues, but are not limited thereto.
  • GABA ⁇ -aminobutyric acid
  • aminoalcohol means a derivative of an amino acid in which a carboxylic acid group has been reduced to an alcohol.
  • amino alcohols contained in the formula (I) include amino alcohols derived from the above amino acids, such as glycinol (ethanolamine), alaninol, barinol, serinol, threoninol, leucinol, isoleucinol, asparaginol, 3-amino-4 -Hydroxybutyric acid, glutaminol, 4-amino-5-hydroxyvaleric acid, argininol, histidinol, ricinol, methioninol, phenylalaninol, tryptophanol, tyrosinol, prolinol, cysteinol, homoselinol, 4-amino-1-butanol, etc. However, it is not limited to these.
  • compound refers to a compound of formula (I), as well as pharmaceutically acceptable salts, prodrugs, oxides, ethers, esters, glycosides, or conjugates thereof. means.
  • “pharmaceutically acceptable salts” include inorganic acids such as sulfuric acid, hydrochloric acid, hydrofluoric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, nitric acid, perchloric acid, and carbonic acid.
  • Prodrug means any derivative of a compound of the present invention that, when administered to a subject, can directly or indirectly obtain a compound of the present invention or an active metabolite thereof or residue thereof.
  • Prodrugs may have the following advantages: improved bioavailability of the compound; reduced side effects and / or toxicity of the compound; facilitated delivery of the compound to the biological area; halved of the compound of the invention Prolongation of period; Stabilization of compound; Improvement of taste and smell of compound.
  • Prodrugs include, for example, the ester forms of the compounds of the invention. Examples of ester prodrugs include formate, acetate, propionate, butyrate, acrylate, farnesylate and ethyl succinate derivatives.
  • “Compound” further includes isomers such as structural isomers (eg, chain isomers, positional isomers), stereoisomers (eg, rotational isomers), and tautomers of compounds.
  • the “compound” includes any one isomer and a mixture of isomers. Each of these isomers can be obtained as a single product by a conventionally known synthesis method or separation method (concentration, solvent extraction, column chromatography, recrystallization, etc.).
  • “compound” includes all possible resonance forms.
  • “compound” includes all possible isotope-labeled compounds.
  • Structural isomers refers to molecules having the same compositional formula but different bond relationships between atoms. Structural isomers include “chain isomers” composed of straight and branched chains, “positional isomers” depending on the bonding position of substituents, and the like.
  • the amino acid residue or amino alcohol contained in formula (I) includes any amino acid or structural isomer of amino alcohol.
  • the amino acid residue contained in formula (I) when the amino acid residue contained in formula (I) is alanine, the amino acid residue may be ⁇ -alanine or ⁇ -alanine.
  • the amino acid residue contained in the formula (I) is lysine, the amino acid residue may be ⁇ -lysine or ⁇ -lysine.
  • the amino acid residue contained in formula (I) is leucine or isoleucine, the amino acid residue may be norleucine.
  • the amino acid residue contained in the formula (I) is valine, the amino acid residue may be norvaline or isovaline.
  • Homoserin is a structural isomer of threonine and is also called isothreonine.
  • Stereoisomers refer to molecules that differ in the chirality of one or more stereocenters. Stereoisomers include enantiomers, diastereomers, and racemates. Stereoisomers also include “rotamers”. “Rotational isomers” refers to molecules having different conformations that can be separated due to a large rotation barrier around a single bond due to large steric hindrance or the like.
  • the amino acid residue or amino alcohol contained in the formula (I) includes any amino acid or amino alcohol stereoisomer. That is, the amino acid residue contained in formula (I) may be an L-amino acid residue or a D-amino acid residue.
  • the amino acid residue contained in the formula (I) is an arbitrary amino acid having two or more asymmetric carbon atoms
  • the amino acid residue contained in the formula (I) is a diastereomer of the arbitrary amino acid. Is also included.
  • the amino acid residue contained in the formula (I) is isoleucine
  • the amino acid residue may be L-isoleucine or D-isoleucine.
  • the amino acid residue may also be L-alloisoleucine or D-alloisoleucine.
  • the amino acid residue contained in the formula (I) is threonine
  • the amino acid residue may be L-threonine or D-threonine.
  • the amino acid residue may also be L-alosleonine or D-alosle
  • a carbon atom marked with an asterisk (*) in the following formula (I ′) is an asymmetric carbon atom.
  • the steric configuration may be either S configuration or R configuration.
  • Tautomers refer to those that have a high isomerization rate in which isomers convert to each other and can reach an equilibrium state in which both isomers coexist.
  • Tautomerism includes, for example, proton tautomerism due to 1,3-rearrangement of protons.
  • the present invention relates to the above formula (I), wherein Q 1 is an oxygen atom, glycine, alanine, valine, serine, threonine, leucine, isoleucine, asparagine, aspartic acid, glutamine, glutamic acid, homoserine, ⁇ - aminobutyric acid (GABA), are selected from the group consisting of serinol, and Gurutaminoru, Q 2 is oxygen atom, valine, asparagine, aspartic acid, threonine, leucine, isoleucine, alanine, glycine, serine, glutamine, glutamic acid, homoserine , GABA, serinol, and glutaminol, as described above, or a pharmaceutically acceptable salt or prodrug thereof.
  • the combination of Q 1 and Q 2 includes all possible combinations.
  • the present invention provides the aforementioned compound, or a pharmaceutically acceptable salt or prodrug thereof, wherein in formula (I), at least one of Q 1 and Q 2 is homoserine.
  • Q 1 is homoserine and Q 2 is an oxygen atom, an amino acid residue or an amino alcohol.
  • Q 1 is an oxygen atom, an amino acid residue or an amino alcohol, and Q 2 is homoserine.
  • Q 1 is homoserine
  • Q 2 is an oxygen atom, glycine, alanine, valine, serine, threonine, leucine, isoleucine, asparagine, aspartic acid, glutamine, glutamic acid, homoserine, ⁇ -aminobutyric acid (GABA), Selected from the group consisting of serinol and glutaminol.
  • GABA ⁇ -aminobutyric acid
  • Q 1 is selected from the group consisting of an oxygen atom, glycine, alanine, valine, serine, threonine, leucine, isoleucine, asparagine, aspartic acid, glutamine, glutamic acid, homoserine, ⁇ -aminobutyric acid (GABA), serinol, and glutaminol.
  • Q 2 is a homoserine.
  • the combination of Q 1 and Q 2 includes all possible combinations.
  • both Q 1 and Q 2 may be homoserine.
  • the present invention provides the above compound, or a pharmaceutically acceptable salt thereof, wherein in the above formula (I), the combination of Q 1 and Q 2 is any one combination of the following tables: Prodrug is provided.
  • the present invention provides the above compound, or a pharmaceutically acceptable salt thereof, wherein in the above formula (I), the combination of Q 1 and Q 2 is any one combination of the following tables: Prodrug is provided.
  • the present invention provides a compound as described above, or a pharmaceutically acceptable salt or prodrug thereof, wherein in formula (I) above, Q 1 is glycine and Q 2 is homoserine. .
  • the compound of the present invention may be obtained from a microorganism that produces the compound of the present invention.
  • Microorganism refers to, for example, actinomycetes, bacteria such as Escherichia coli and Bacillus subtilis, fungi such as mold and yeast, microalgae such as Cyanobacteria, and Labyrinthula ), But is not limited thereto.
  • Actinomycetes refers to gram-positive eubacteria belonging to Actinobacteria. Examples of “actinomycetes” include Streptomyces lividans, Streptomyces violaceoruber, Streptomyces cerimitostomyctostomyctostomycto, Stomyces vivocaceto, S.
  • Streptomyces such as Streptomyces griseius, Actinocinema pletisum and Actinosinumineum Pseudonocardia bacterium, Pseudonocardia thermophila and Pseudonocardia genus Pseudonocardia
  • the genus Corynebacterium is included. Actinomycetes can be isolated from soil, for example, or can be obtained from a microorganism depository distribution agency.
  • yeast includes asynocystospore yeast, basidiospore-forming yeast, and yeast belonging to imperfect fungi.
  • Saccharomyces Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Saccharomyces cerevisiae
  • Saccharomyces pombe Saccharomyces pombe
  • Xanthophyllomyces, Kluyveromyces marxianus and other Kluyveromyces genus Yarrowia lipolytica, etc.
  • Yeast can be isolated, for example, from plants, animals, soil, and the like, and can also be obtained from microorganism depository distribution agencies.
  • Microalgae refers to algae having a microscopic structure obtained by removing seaweeds that are multicellular organisms from algae.
  • Algae refers to all of the organisms that perform oxygen-generating photosynthesis, excluding moss plants, fern plants, and seed plants that mainly live on the ground. Algae include a variety of unicellular and multicellular organisms. Examples include seaweeds, prokaryotes, Cyanobacteria, eukaryotes, Gray plant phyto (Glaucophyta), red plant phylum (Rhodophyta), green plant phylum (Chlorophyta), and the like.
  • the microalgae includes those in which a plurality of cells form a colony.
  • Cyanobacteria includes, for example, Anabena variabilis, Nostoc punctiforme, Nostoc linckia, Nostoc commune (mm). Nostoc verrucosum) and Nostoc muscorum are included. Cyanobacteria can be isolated, for example, from the natural world, or can be obtained from a microbial deposit agency.
  • Labyrinthula is an amoeba-like eukaryote contained in Stramenopiles.
  • Labyrinthula includes, for example, the genus Aurantiochytrium, the genus Schizochytrium, the genus Thraustochytrium, and the genus Ulkenia.
  • Labyrinthulas can be isolated from the natural world such as seaweeds and land plants, and can also be obtained from microbial deposit agencies.
  • the microorganism that produces the compound of the present invention is, for example, a microorganism that produces MAA.
  • “Microorganism producing MAA” refers to a microorganism having the ability to biosynthesize MAA, for example, a microorganism having a MAA biosynthetic enzyme gene.
  • These “microorganisms producing MAA” may be wild strains or strains artificially subjected to mutation treatment. Examples of the artificial mutation treatment include gene recombination, UV irradiation, X-ray irradiation, treatment with a mutation agent, and the like.
  • the “microorganism producing MAA” may be a naturally occurring mutant strain.
  • the “microorganism producing MAA” includes a microorganism having a MAA biosynthetic enzyme gene derived from the same species or a different species.
  • a microorganism into which a heterologous MAA biosynthetic enzyme gene has been introduced by genetic recombination may be used.
  • a method widely known in the art can be used.
  • a promoter, 5 ′ untranslated region (UTR), a transformant selection marker gene, 3 ′ untranslated region (UTR) or A part of them may be introduced together with the gene.
  • a promoter widely known to those skilled in the art as used in each microorganism may be used.
  • the codon of the gene may be appropriately modified according to the codon usage frequency of the microorganism into which the MAA biosynthetic enzyme gene is introduced.
  • codon usage frequency of a certain microorganism using, for example, Kazusa DNA Research Institute database Codon Usage Database (http://www.kazusa.or.jp/codon/). Can do.
  • the codon usage frequency can be investigated using a geneart design program GeneOptimizer (registered trademark) of GENEART.
  • GeneOptimizer registered trademark of GENEART.
  • the codons of the gene of interest can be optimized using conventional means.
  • mycosporin-like amino acid biosynthetic enzyme gene examples include, for example, amir_4256 (SEQ ID NO: 1), amir_4257 (SEQ ID NO: 2), amir_4258 (SEQ ID NO: 3) and amir_4259 (SEQ ID NO: 4) derived from Actinocinema mirum DSM43827. Genes, Pseudocardia sp.
  • Labyrinthula as a mycosporin-like amino acid biosynthetic enzyme gene, codon-modified amir_4256 (SEQ ID NO: 9), codon-modified amir_4257 (SEQ ID NO: 10), codon-modified Amir_4258 (SEQ ID NO: 11) and codon-modified amir_4259 (SEQ ID NO: 12) genes are used.
  • the compound represented by the above formula (I) may be synthesized by chemical synthesis according to a conventionally known method. See for example WO 02/39974.
  • a conventionally known method can be used as the compound identification method.
  • HPLC-TOFMS high performance liquid chromatography-time-of-flight mass spectrometry
  • a novel compound may be identified by a combination of high resolution mass spectrometry (HR-MS), nuclear magnetic resonance (NMR), and nuclear magnetic resonance (NMR).
  • HR-MS high resolution mass spectrometry
  • NMR nuclear magnetic resonance
  • NMR nuclear magnetic resonance
  • you may identify a novel compound from the result of retention time and UV spectrum using HPLC.
  • the novel compound may be identified by measuring the ultraviolet absorption spectrum and the accurate mass using HPLC equipped with a photodiode array detector and an HR-MS detector.
  • the present invention provides a composition comprising a compound of the present invention as described above, or a pharmaceutically acceptable salt or prodrug thereof.
  • the composition of the present invention may further comprise at least one of sinoline or porphyra-334.
  • the composition of the present invention is an ultraviolet absorbing composition.
  • Such a composition can be used as a coating composition or other coating agent in the cosmetics and pharmaceutical fields.
  • the ultraviolet ray absorbing composition of the present invention when applied to human skin, contains about 0.05 to 10% by weight of the compound of the present invention, about 5 to 40% by weight of an oil phase medium, and emulsifier. About 1-10% by weight, may contain trace amounts of adjuvants and aqueous phase media such as water.
  • the composition of the present invention is a pharmaceutical, quasi-drug, or cosmetic composition.
  • the composition of the present invention is a cosmetic composition.
  • the present invention provides a pharmaceutical, quasi-drug, or cosmetic comprising the composition of the present invention described above.
  • the present invention provides a cosmetic comprising the above-described composition of the present invention.
  • cosmetics, quasi drugs, and pharmaceuticals include, but are not limited to, dermatological agents.
  • the “dermatological agent” may be used externally. Alternatively, it may be used by other methods such as internal use, injection and infusion.
  • cosmetics and “quasi-drugs” include, but are not limited to, those for skin, hair, eyes, and nails.
  • lotion, milky lotion, gel, serum, cream, sunscreen cream, sunscreen spray, pack, mask, foundation, funny, nail polish (base coat, color polish, top coat, etc.), bath preparation, antiperspirant, vitamin Examples include, but are not limited to, agents, body lotions, shampoos, rinses, hair treatments, hair conditioners, hair colors, hair styling agents, hair tonics, and hair restorers.
  • “pharmaceuticals” include, but are not limited to, those for skin, hair, eyes, and nails.
  • pharmaceuticals for preventing or treating acute skin reactions include, but are not limited to, those for skin, hair, eyes, and nails.
  • pharmaceuticals for preventing or treating acute skin reactions include, but are not limited to, those for skin, hair, eyes, and nails.
  • pharmaceuticals for preventing or treating acute skin reactions include, but are not limited to, those for skin, hair, eyes, and nails.
  • pharmaceuticals for preventing or treating acute skin reactions include, but are not limited to, those for skin, hair, eyes, and nails.
  • pharmaceuticals for preventing or treating acute skin reactions include, but are not limited to, those for skin, hair, eyes, and nails.
  • pharmaceuticals for preventing or treating acute skin reactions include, but are not limited to, pharmaceuticals for preventing or improving skin aging, pharmaceuticals for preventing or treating skin cancer, pharmaceuticals for hair growth, for preventing or treating eye diseases
  • examples include, but are not limited to, pharmaceuticals and pharmaceuticals for preventing or
  • compositions include liquid, cream, lotion, paste, ointment, emulsion (oil-in-water emulsion, water-in-oil emulsion, multiple emulsion, microemulsion, PET -Emulsions, pickering emulsions), gels (hydrogels, alcohol gels), suspensions, foams, sprays, tablets, powders, eye drops, eye ointments or patches etc., but are not limited to these.
  • Cosmetics “quasi-drugs”, or “pharmaceuticals” refer to adjuvants such as humectants, surfactants, pigments, fragrances, preservatives, bactericides, and antioxidants that are commonly used in these. An additive may be included.
  • the above-described composition of the present invention is used in an ultraviolet absorbing composition such as a coating composition or other coating agent.
  • the coating composition and other coating agents are prepared by using a method known to those skilled in the art such as a spray method, a dipping method, a roller coating method, a flow coater method, a flow coating method, and the like (metal, plastic, wood, ceramic, Glass, fiber, paper, etc.).
  • a spray method a dipping method, a roller coating method, a flow coater method, a flow coating method, and the like
  • Such an ultraviolet absorbing composition can be applied to industrial use and medical equipment.
  • the ultraviolet absorbing composition may be applied to contact lenses and spectacle lenses.
  • the invention provides a compound of the invention as described above, or a pharmaceutically acceptable thereof, for preventing one or more symptoms or diseases selected from the group consisting of acute skin reaction, skin aging and skin cancer.
  • a composition comprising a salt or prodrug thereof.
  • the composition comprises as an active ingredient an effective amount of a compound of the invention, or a pharmaceutically acceptable salt or prodrug thereof.
  • compositions of the present invention described above can be used in creams, lotions, pastes, ointments, emulsions (oil-in-water emulsions, water-in-oil emulsions, multiple emulsions, microemulsions, PET-emulsions, pickering emulsions), gels ( Hydrogel, alcohol gel), suspension, foam, spray, tablet or powder.
  • emulsions oil-in-water emulsions, water-in-oil emulsions, multiple emulsions, microemulsions, PET-emulsions, pickering emulsions
  • gels Hydrogel, alcohol gel
  • suspension foam
  • spray tablet or powder.
  • composition of the present invention described above may further include other components acceptable for cosmetics, quasi drugs or pharmaceuticals.
  • examples of such components include benzalkonium chloride, benzethonium chloride, hexamethonium chloride, butyl alcohol, benzyl alcohol, alkyl parabens such as methyl paraben or propyl paraben, catechol, resorcinol, cyclohexanol, and m-cresol.
  • Antioxidants such as ascorbic acid and methionine; buffers such as phosphoric acid, citric acid and other organic acids; emulsifiers such as sorbitan esters, Tween®, silicon polyols, potassium stearate and ethoxylated fatty acid esters; emulsification Stabilizers; anionic, cationic, nonionic or amphoteric polymers; chelating agents such as EDTA; oil phase media (hydrocarbon oils such as mineral oil, paraffin wax, natural oils) Fatty acid esters such as oil, silicone oil and isopropyl palmitate, fatty acid alcohols such as stearyl alcohol); thickeners; moisturizers; emollients; surfactants such as polyethylene glycol (PEG); acidifying or basifying agents; Perfumes; fragrances; dyes; colorants; or may include conventional cosmetic, quasi-drug or pharmaceutical auxiliaries and additives such as cosmetics, quasi-drugs, or other ingredients that are usually incorporated into
  • composition of the present invention may be, for example, a crude extract itself of a culture of a microorganism that produces the above-described compound of the present invention, or may contain a crude extract.
  • compositions of the invention may be prepared by isolating or synthesizing the compounds of the invention and mixing them.
  • the invention provides a compound of the invention for the manufacture of a medicament for preventing one or more symptoms or diseases selected from the group consisting of acute skin reaction, skin aging and skin cancer, or Use of the pharmaceutically acceptable salt or prodrug is provided.
  • the invention provides a compound of the invention, or a pharmaceutically acceptable salt thereof, for use in a method of preventing one or more symptoms or diseases selected from the group consisting of acute skin reaction, skin aging and skin cancer.
  • a pharmaceutically acceptable salt thereof for use in a method of preventing one or more symptoms or diseases selected from the group consisting of acute skin reaction, skin aging and skin cancer.
  • the invention provides an acute skin reaction, skin aging and skin cancer comprising applying to a subject's skin a composition comprising a compound of the invention, or a pharmaceutically acceptable salt or prodrug thereof.
  • a 0.1% pre-culture of the Streptomyces lividans main culture was added to 20 100 mL TSBt media (see table below) in a 500 mL baffled flask. Glucose was further added to the TSBt medium at the start of the culture so that the initial glucose concentration was 50 g / L. The culture was shaken at 28 ° C. and 160 rpm for 2 weeks.
  • the structure was determined by measuring ⁇ max , retention time, accurate mass, and 1 H-NMR spectrum of the MAA-related compound contained in the sample culture medium.
  • Compounds 1, 5-8, 13, and 16-18 were known compounds. Specifically, compound 1 is sinoline, compound 5 is porphyra-334, compound 6 is mycosporin-serine, compound 7 is mycosporin-glycine, compound 8 is mycosporin-glycine-alanine, compound 13 is mycosporin-alanine, compound 16 is Mycosporin-GABA, compound 17 was mycosporin-glycine-valine, and compound 18 was mycosporin-valine.
  • compounds 2 to 4, 9 to 12, 14, 15, and 19 were newly identified compounds.
  • compound 2 is mycosporin-alanine-serine
  • compound 3 is mycosporin-glycine-homoserine
  • compound 4 is mycosporin-glycine-glutamine
  • compound 9 is mycosporin-alanine-glutamine
  • compound 10 is mycosporin-alanine-threonine
  • compound 11 was mycosporin-homoserine
  • compound 12 was mycosporin-alanine-alanine
  • compound 14 was mycosporin-glycine-GABA
  • compound 15 was mycosporin-serine-valine
  • compound 19 was mycosporin-alanine-valine.
  • a naturally occurring novel compound having an ultraviolet absorbing action can be obtained.
  • the obtained compound, its pharmaceutically acceptable salt and prodrug can be used as an active ingredient of an ultraviolet absorbing composition. Therefore, the present invention can be used in fields such as protection of various industrial products from deterioration due to ultraviolet rays and cosmetics and pharmaceuticals.
  • SEQ ID NO: 9 Codon-optimized amir_4256 for SAM2179
  • SEQ ID NO: 10 Codon-optimized amir_4257 for SAM2179
  • SEQ ID NO: 11 Codon-optimized amir_4258 for SAM2179
  • SEQ ID NO: 12 Codon-optimized amir_4259 for SAM2179

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Abstract

La présente invention concerne un composé représenté par la formule (I) ou un sel ou un promédicament pharmaceutiquement acceptables correspondants. La présente invention concerne également : une composition qui comprend le composé représenté par la formule (I) ou le sel ou le promédicament pharmaceutiquement acceptables correspondants; et un produit cosmétique comprenant ladite composition. (Dans la formule (I) : Q1 représente oxygène, un résidu d'acide aminé ou un aminoalcool et, lorsque Q1 représente un résidu d'acide aminé ou un aminoalcool, le résidu d'acide aminé ou l'aminoalcool est lié au cycle par un atome d'azote; et Q2 représente oxygène, un résidu d'acide aminé ou un aminoalcool et, lorsque Q2 représente un résidu d'acide aminé ou un aminoalcool, le résidu d'acide aminé ou l'aminoalcool est lié au cycle par un atome d'azote.)
PCT/JP2016/082661 2015-11-11 2016-11-02 Nouvel acide aminé de type mycosporine WO2017082144A1 (fr)

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WO2020094954A3 (fr) * 2018-11-06 2020-07-16 Societe D'exploitation De Produits Pour Les Industries Chimiques Seppic Procédé pour évaluer la capacité d'une substance ou d'une composition à prévenir, ralentir ou éliminer les signes du vieillissement de la peau ou des lèvres
CN112969920A (zh) * 2018-11-06 2021-06-15 化工产品开发公司Seppic 评估物质或组合物预防、减缓或消除皮肤或嘴唇老化迹象的能力的方法

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