[go: up one dir, main page]

WO2025192761A1 - Composés pour induire un nicotinamide adénine dinucléotide, composition le comprenant, et agent topique dermatologique - Google Patents

Composés pour induire un nicotinamide adénine dinucléotide, composition le comprenant, et agent topique dermatologique

Info

Publication number
WO2025192761A1
WO2025192761A1 PCT/KR2024/003132 KR2024003132W WO2025192761A1 WO 2025192761 A1 WO2025192761 A1 WO 2025192761A1 KR 2024003132 W KR2024003132 W KR 2024003132W WO 2025192761 A1 WO2025192761 A1 WO 2025192761A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
compound
chemical formula
hydrogen atom
alkyl group
Prior art date
Legal status (The legal status 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 status listed.)
Pending
Application number
PCT/KR2024/003132
Other languages
English (en)
Korean (ko)
Inventor
이동희
정진
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Remybio Corp
Original Assignee
Remybio Corp
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 Remybio Corp filed Critical Remybio Corp
Priority to PCT/KR2024/003132 priority Critical patent/WO2025192761A1/fr
Publication of WO2025192761A1 publication Critical patent/WO2025192761A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/13—Nucleic acids or 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • 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
    • A61K8/60—Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • 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
    • A61Q19/08—Anti-ageing preparations
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/048—Pyridine radicals

Definitions

  • This patent application is related to the results of the project “Development of anti-aging (NMN derivative) using skin permeability promotion platform technology” (Main institution: Remi Bio Co., Ltd., Project number: S3223332) as part of the “New product development project with purchase conditions for small and medium-sized enterprises technology development support project” of the Ministry of SMEs and Startups of the Republic of Korea government.
  • the present disclosure relates to a compound for inducing nicotinamide adenine nucleotide, and more particularly, to a compound for inducing nicotinamide adenine nucleotide with improved stability and cell permeability, and a functional composition and a skin external preparation containing the compound as an active ingredient.
  • Oxidative stress which generates reactive oxygen species (ROS)
  • ROS reactive oxygen species
  • NAD + nicotinamide adenine dinucleotide
  • NAD + is a key coenzyme found in cells and plays a key role in regulating the epigenome. NAD + plays a variety of roles related to aging, including facilitating the proper functioning of the anti-aging protein sirtuin and assisting in the repair of damaged DNA. Low levels of NAD + in living tissues and cells can lead to metabolic slowdowns, increased risk of dementia, fatigue, deteriorating vascular health, age-related muscle loss, cognitive decline, vision and hearing impairment, and a shortened lifespan.
  • NAD + levels within living cells and tissues decline, contributing to the development of various age-related diseases. Therefore, promoting NAD + synthesis, or restoring or increasing NAD + levels within living tissues and cells, can delay or inhibit biological aging.
  • NAD + is composed of two nucleotides linked by a phosphate group. Therefore, it is a relatively large molecule compared to its precursor and is a phosphorylated molecule. NAD + , which exists outside the cell, has difficulty passing through cell membranes or mitochondrial membranes. NAD + precursors that can be converted to NAD + in vivo are attracting attention to delay biological aging by restoring reduced NAD + levels in living tissues and cells.
  • NAD + precursors include nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), nicotinic acid mononucleotide (NAMN), and nicotinic acid adenine dinucleotide (NAAD).
  • NR is converted to NMN in vivo by the nicotinamide riboside kinase (NRK) enzyme
  • NMN can be converted to NAD + in vivo by the nicotinamide mononucleotide adenylyltransferase (NMNAT) enzyme.
  • NRK nicotinamide riboside kinase
  • NMNAT nicotinamide mononucleotide adenylyltransferase
  • Precursors such as NR and NMN have a mononucleoside structure in which a 5-carbon sugar, ribose, is linked to a base, nicotinamide or nicotinic acid, via an N-glycosidic bond, or a mononucleotide structure in which a phosphate group is further linked to ribose.
  • NAD + precursors such as NR and NMM
  • NAD + precursors are relatively small molecules compared to NAD + , which has a dinucleotide structure, and thus can more easily penetrate cell membranes and mitochondrial membranes than NAD + . Therefore, when these NAD + precursors are transferred from the outside of a living cell to the inside of the cell, they can increase NAD + levels within the cell, effectively preventing and delaying the aging process.
  • NAD + precursors such as NR and NMN
  • NR and NMN are unstable due to heat and other factors, and have been shown to have disadvantages such as low skin (tissue) permeability and low intracellular delivery. Therefore, interest is growing in substances that exhibit high stability, skin (tissue) permeability, and intracellular delivery, and that can induce and promote NAD + synthesis in vivo.
  • the purpose of the present disclosure is to provide a nicotinamide adenine dinucleotide derivative having excellent stability, cell permeability and intracellular delivery properties, a physiologically acceptable salt thereof and/or a stereoisomer thereof.
  • Another object of the present disclosure is to provide a composition for inducing the synthesis of nicotinamide adenine dinucleotide in a cell, an anti-inflammatory composition, an anti-aging composition and/or an anti-aging skin topical agent, comprising a compound for inducing nicotinamide adenine dinucleotide, a physiologically acceptable salt thereof and/or a stereoisomer thereof as an active ingredient.
  • R 1 , R 2 and R 3 each independently have a hydroxyl group, a C 1 to C 20 alkoxy group or a structure represented by the following chemical formula 2, and at least one of R 1 , R 2 and R 3 has a structure represented by the following chemical formula 2,
  • R 4 is a hydroxy group, a C 1 -C 20 alkoxy group, or an amino group.
  • R a is a hydrogen atom, a C 1 ⁇ C 20 alkyl group, a hydroxy group, or a C 1 ⁇ C 20 alkoxy group,
  • n is an integer from 0 to 4,
  • R 13 is a hydrogen atom
  • m is an integer from 1 to 4
  • at least one R 14 is not a hydrogen atom
  • R a may be a C 1 to C 10 alkyl group or a C 1 to C 20 alkoxy group.
  • at least one of R 13 and R 14 is selected from the group consisting of a C 1 to C 20 alkyl group, a C 2 to C 20 alkenyl group, and a C 2 to C 20 alkynyl group
  • R 13 is a hydrogen atom
  • m is an integer of 1 to 4
  • at least one R 14 is not a hydrogen atom
  • R a may be a C 1 to C 10 alkyl group.
  • R 1 , R 2 and R 3 of the above chemical formula 1 one has the structure of the above chemical formula 2, and among R 1 , R 2 and R 3 , the remaining are each independently a hydroxy group or a C 1 to C 20 alkoxy group, and R 4 may be a hydroxy group or an amino group.
  • the above compound may have a structure represented by the following chemical formula 3.
  • R 21 has the structure of chemical formula 4 below,
  • R 22 and R 23 are each independently a hydroxy group or a C 1 ⁇ C 20 alkoxy group
  • R 24 is a hydroxyl group or an amino group.
  • R b is a C 1 ⁇ C 20 alkyl group
  • the present disclosure provides a composition for inducing the synthesis of nicotinamide adenine dinucleotide (NAD + ) in a cell, comprising the above-described compound, a physiologically acceptable salt thereof, or a stereoisomer thereof as an active ingredient.
  • NAD + nicotinamide adenine dinucleotide
  • the present disclosure provides an anti-inflammatory composition, or a composition for alleviating or improving inflammation, comprising the compound, a physiologically acceptable salt thereof, or a stereoisomer thereof as an active ingredient.
  • the present disclosure provides an anti-aging composition
  • an anti-aging composition comprising the compound, a physiologically acceptable salt thereof, or a stereoisomer thereof as an active ingredient.
  • the composition that induces the synthesis of NAD + , the anti-inflammatory composition and/or the anti-aging composition may each be a pharmaceutical composition, a functional food composition and/or a cosmetic composition.
  • the present disclosure provides an anti-aging skin topical composition
  • an anti-aging skin topical composition comprising the compound, a physiologically acceptable salt thereof, or a stereoisomer thereof as an active ingredient.
  • the present disclosure provides a method of inducing the synthesis of nicotinamide adenine dinucleotide (NAD+) in a subject, for example, in a cell of the subject, comprising administering to the subject a physiologically effective amount of the compound, a physiologically acceptable salt thereof, or a stereoisomer thereof.
  • NAD+ nicotinamide adenine dinucleotide
  • the present disclosure provides a method of delaying, preventing and/or inhibiting senescence of a subject, e.g., a cell of the subject, comprising administering to the subject a physiologically effective amount of the compound, a physiologically acceptable salt thereof or a stereoisomer thereof.
  • Nicotinic acid/nicotinamide riboside derivative compounds that can be synthesized or converted into nicotinamide adenine nucleotide (NAD + ) have excellent stability, cell permeability, and intracellular delivery characteristics.
  • NAD + nicotinamide adenine nucleotide
  • Nicotinic acid/nicotinamide riboside derivative compounds, physiologically acceptable salts thereof, and/or stereoisomers thereof can be used as active ingredients in pharmaceuticals, health functional foods, and/or functional cosmetics.
  • nicotinic acid/nicotinamide riboside derivative compounds, physiologically acceptable salts thereof, and/or stereoisomers thereof can be used as active ingredients or ingredients in compositions that induce the synthesis of nicotinamide adenine dinucleotide in cells, anti-inflammatory compositions, anti-aging compositions, and/or anti-aging skin topical agents.
  • FIG. 1 is a graph showing the results of measuring the thermal stability of a nicotinamide adenine dinucleotide derivative compound synthesized according to an exemplary embodiment of the present disclosure.
  • FIG. 2 is a graph showing the results of measuring the NAD + induction effect of a nicotinamide adenine dinucleotide derivative compound synthesized according to an exemplary embodiment of the present disclosure.
  • FIG. 3 is a graph showing the results of measuring the TNF-alpha biosynthesis inhibitory effect of a nicotinamide adenine dinucleotide derivative synthesized according to an exemplary embodiment of the present disclosure.
  • FIG. 4 is a graph showing the results of measuring the NAD + induction effect of a nicotinamide adenine dinucleotide-derived compound synthesized according to an exemplary embodiment of the present disclosure in inflammation-inducing cells.
  • FIG. 5 is a graph measuring the inhibitory effect of a nicotinamide adenine dinucleotide-derived compound synthesized according to an exemplary embodiment of the present disclosure on ROS production in senescence-inducing cells.
  • FIG. 6 is a graph showing the results of measuring the SIRT1 induction effect in senescence-inducing cells of a nicotinamide adenine dinucleotide-inducing compound synthesized according to an exemplary embodiment of the present disclosure.
  • FIG. 7 is a graph showing the measurement results according to the SA- ⁇ -Gal assay of a nicotinamide adenine dinucleotide derivative synthesized according to an exemplary embodiment of the present disclosure.
  • FIG. 8 is a graph showing the results of measuring the skin permeability of a compound for inducing nicotinamide adenine dinucleotide synthesized according to an exemplary embodiment of the present disclosure.
  • FIG. 9 is a graph showing the results of measuring the thermal stability of a nicotinamide adenine dinucleotide derivative compound synthesized according to an exemplary embodiment of the present disclosure.
  • FIG. 10 is a graph showing the results of measuring the NAD + induction effect of a nicotinamide adenine dinucleotide derivative synthesized according to an exemplary embodiment of the present disclosure.
  • the present disclosure relates to a nicotinic acid/nicotinamide riboside derivative compound that can increase the level or content of nicotinamide adenine dinucleotide (NAD + ), a coenzyme that performs various functions in a living body, by inducing the synthesis of NAD + .
  • the compound according to the present disclosure has excellent stability, exhibits good cell permeability and cell delivery characteristics, and is converted into NAD + within a cell. Therefore, it can delay the aging phenomenon associated with a decrease in NAD + levels, and can be expected to have an effect in preventing and treating aging-related diseases.
  • the nicotinic acid/nicotinamide riboside derivative compound can have a structure represented by the following chemical formula 1.
  • R 1 , R 2 and R 3 each independently have a hydroxyl group, a C 1 to C 20 alkoxy group or a structure represented by the following chemical formula 2, and at least one of R 1 , R 2 and R 3 has a structure represented by the following chemical formula 2,
  • R 4 is a hydroxy group, a C 1 -C 20 alkoxy group, or an amino group.
  • R a is a hydrogen atom, a C 1 ⁇ C 20 alkyl group, a hydroxy group, or a C 1 ⁇ C 20 alkoxy group,
  • n is an integer from 0 to 4,
  • alkyl group, alkenyl group, alkynyl group and alkoxy group are saturated or unsaturated chain-like aliphatic substituents, including both linear and branched groups.
  • Cycloalkyl group, heterocycloalkyl group, cycloalkenyl group and heterocycloalkenyl group are saturated or unsaturated cyclic aliphatic substituents.
  • Aryl group and heteroaryl group may correspond to aromatic substituent or heteroaromatic substituent, respectively.
  • a cycloalkyl group may include a monovalent functional group corresponding to cyclopropane, cyclobutane, cyclopentane, cyclohexane, or cycloheptane
  • a heterocycloalkyl group may include a monovalent functional group corresponding to piperazine, piperidine, or homo-piperazine, but is not limited thereto.
  • the aryl group can be an unfused or fused aryl group such as, but not limited to, phenyl, biphenyl, terphenyl, naphthyl, anthracenyl, pentanlenyl, indenyl, indenoindenyl, heptalenyl, biphenylenyl, indacenyl, phenalenyl, phenanthrenyl, benzophenanthrenyl, dibenzophenanthrenyl, azulenyl, pyrenyl, fluoranthenyl, triphenylenyl, chrysenyl, tetraphenyl, tetracenyl, plydaenyl, pycenyl, pentaphenyl, pentacenyl, fluorenyl, indenofluorenyl, or fluorenyl having a spiro structure.
  • aryl group such as, but
  • heteroaryl groups include pyrrolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, tetrazinyl, imidazolyl, pyrazolyl, indolyl, isoindolyl, indazolyl, indolizinyl, pyrrolizinyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl, indenocarbazolyl, benzofurocarbazolyl, benzothienocarbazolyl, quinolinyl, isoquinolinyl, phthalazinyl, quinoxalinyl, cinolinyl, quinazolinyl, quinozolinyl, quinolizinyl, purinyl, benzoquinolinyl, benzoisoquinolinyl, benzoquinazolinyl, be
  • At least one of R 11 and R 12 of Formula 2 may not be a hydrogen atom, and/or at least one, at least two, or at least three of R 13 and R 14 may not be hydrogen atoms.
  • the amino moiety may have at least one substituent, and/or the indole moiety may have at least one, at least two, or at least three substituents.
  • At least one of R 11 and R 12 of formula 2 may be an aliphatic substituent, and at least one, at least two, or at least three of R 13 and R 14 may be an aliphatic substituent.
  • R 13 is a hydrogen atom
  • m is an integer from 1 to 4
  • at least one R 14 is not a hydrogen atom
  • R a may be a C 1 to C 10 alkyl group or a C 1 to C 20 alkoxy group.
  • at least one of R 13 and R 14 is selected from the group consisting of a C 1 to C 20 alkyl group, a C 2 to C 20 alkenyl group and a C 2 to C 20 alkynyl group
  • R 13 is a hydrogen atom
  • m is an integer from 1 to 4
  • at least one R 14 is not a hydrogen atom
  • R a may be a C 1 to C 10 alkyl group or a C 1 to C 20 alkoxy group.
  • one of R 1 , R 2 and R 3 of formula 1 has the structure of formula 2, the remaining of R 1 , R 2 and R 3 are each independently a hydroxy group or a C 1 -C 20 alkoxy group, and R 4 may be a hydroxy group or an amino group.
  • R 1 of Formula 1 may have the structure of Formula 2, and R 2 and R 3 may be a hydroxy group or a C 1 -C 20 alkoxy group.
  • R 2 and R 3 may be a hydroxy group or a C 1 -C 20 alkoxy group.
  • a nicotinic acid/nicotinamide riboside derivative compound that may have the structure of Formula 1 may have the structure of Formula 3 below.
  • R 21 has the structure of chemical formula 4 below,
  • R 22 and R 23 are each independently a hydroxy group or a C 1 ⁇ C 20 alkoxy group
  • R 24 is a hydroxyl group or an amino group.
  • R b is a C 1 ⁇ C 20 alkyl group or a C 1 ⁇ C 20 alkoxy group
  • one of R 31 and R 32 in Chemical Formula 4 may be a hydrogen atom
  • the other of R 31 and R 32 may be an alkyl carbonyl group
  • at least one of R 33 to R 35 may be a substituent that is an aliphatic hydrocarbon.
  • R 31 and R 32 in Chemical Formula 4 may be a hydrogen atom
  • R b may be a C 1 to C 10 alkyl group or a C 1 to C 20 alkoxy group
  • at least one of R 33 to R 35 may be a C 1 to C 10 alkyl group, a C 2 to C 20 alkenyl group, or a C 2 to C 20 alkynyl group.
  • one of R 31 and R 32 in formula 4 is a hydrogen atom
  • the other of R 31 and R 32 is an alkyl group such as a methyl group or a tert-butyl group, an acetyl group, or a tert-butoxycarbonyl group
  • at least one of R 33 to R 35 may be an alkyl group (e.g., a tert-butyl group).
  • R 31 and R 32 in chemical formula 4 is a hydrogen atom
  • R b is a methyl group, a tert-butyl group, or a tert-butoxy group
  • at least one of R 33 to R 35 may be a C 1 to C 10 alkyl group (e.g., a tert-butyl group).
  • the compound according to the present disclosure is a moiety having a structure of chemical formula 1 or chemical formula 3 having a nucleoside structure in which nicotinic acid/nicotinamide and a pentose sugar, ribose, are linked via an N-glycosidic bond, and a moiety having a structure of chemical formula 2 or chemical formula 4 including a substituted or unsubstituted amino group and a hydrophobic substituted or unsubstituted indole ring, which are conjugated via an ester bond.
  • Nicotinic acid/nicotinamide riboside derivative compounds having structures represented by Chemical Formulas 1 to 4 have excellent cell penetration properties. Under physiological conditions, the ester bond, which is a condensed moiety connecting a nicotinic acid/nicotinamide riboside moiety having a structure represented by Chemical Formula 1 or 3 and a moiety having a structure represented by Chemical Formula 2 or 4, is broken.
  • the generated nicotinamide riboside can be converted into nicotinamide mononucleotide (NMN) in vivo by the enzyme nicotinamide riboside kinase (NRK).
  • the nicotinamide (NAM) compound can be converted into NMN by the enzyme nicotinamide phophoribosyltransferase (NAMPT).
  • NAMPT nicotinamide phophoribosyltransferase
  • NMN converted from NR or NAM can be converted into nicotinamide adenine dinucleotide (NAD + ) in vivo by the enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT).
  • NA nicotinic acid
  • NAPRT nicotinic acid phosphoribosyltransferase
  • the moiety represented by chemical formula 2 or chemical formula 4 can be converted into quinolinic acid (QA) in vivo, and the converted quinolinic acid can be converted into NAMN by quinolinate phosphoribosyl transferase (QPRT).
  • NAMN is converted into nicotinic acid adenine dinucleotide (NAAD), and NAAD can be finally synthesized into NAD + by nicotinamide adenine dinucleotide synthase (NADS).
  • NAAD nicotinic acid adenine dinucleotide
  • NADS nicotinamide adenine dinucleotide synthase
  • nicotinic acid/nicotinamide riboside derivative compounds having structures of chemical formulas 1 to 4 can efficiently induce conversion to NAD + or NAD + synthesis in senescent cells.
  • the nicotinic acid/nicotinamide riboside derivative compound according to the present disclosure has superior thermostability, cell permeability, skin permeability, and cell delivery characteristics compared to conventional NAD + precursors such as NMN.
  • NAD + precursors such as NMN.
  • induction or biosynthesis of NAD+ occurs efficiently from the nicotinic acid/nicotinamide riboside derivative compound having a structure represented by Chemical Formulas 1 to 4.
  • the nicotinic acid/nicotinamide riboside derivative compound according to the present disclosure has superior anti-inflammatory effects and efficiently promotes induction or biosynthesis of NAD+ in cells induced by inflammation and aging.
  • the nicotinic acid/nicotinamide riboside derivative compound having a structure of Chemical Formula 1 to Chemical Formula 4 reduces the level of reactive oxygen species (ROS) that cause cellular aging.
  • the nicotinic acid/nicotinamide riboside derivative compound according to the present disclosure promotes the expression of SIRT1 (silent information regulator transcript-1, NAD-dependent deacetylase sirtuin-1), which is involved in metabolism, aging inhibition, anticancer, neural differentiation, rRNA synthesis, etc., and reduces the expression of senescence-associated- ⁇ -galatosidase (SA- ⁇ -gal), an enzyme associated with aging.
  • SIRT1 sirtuin-1
  • SA- ⁇ -gal senescence-associated- ⁇ -galatosidase
  • the present disclosure relates to a functional composition and an anti-aging skin topical agent comprising a compound having a structure represented by Chemical Formulas 1 to 4, a physiologically acceptable salt thereof, and/or a stereoisomer thereof as an active ingredient.
  • the functional composition promotes the synthesis of nicotinamide adenine dinucleotide (NAD + ) or its conversion into NAD + within a cell, and induces anti-inflammation, inflammation relief, and/or anti-aging of the cell.
  • NAD + nicotinamide adenine dinucleotide
  • the active ingredient and/or physiologically acceptable salt of the functional composition and/or anti-aging skin topical preparation may include any salt that can be converted into the compound according to the present disclosure in vivo.
  • the physiologically acceptable salt may include a pharmaceutically acceptable salt, a food engineering acceptable salt, and/or a cosmetic engineering acceptable salt.
  • the stereoisomer of the nicotinic acid/nicotinamide riboside derivative compound according to the present disclosure may be an enantiomer or a diastereomer of the compound.
  • a physiologically acceptable salt is understood to mean any salt that can be converted into the original compound under in vivo conditions and/or ex vivo conditions, or that can exhibit the same or similar performance as the original compound.
  • a physiologically acceptable salt may include a pharmaceutically acceptable salt, a food- and/or cosmetically acceptable salt.
  • physiologically acceptable salts may include, but are not limited to, acid addition salts or basic salts formed by pharmaceutically acceptable free acids, food- and/or cosmetically acceptable free acids.
  • acid addition salts can be prepared by conventional methods, for example, dissolving the active ingredient, a nicotinic acid/nicotinamide riboside derivative compound, in an excess of an aqueous acid solution and precipitating the salt using a water-miscible organic solvent, for example, methanol, ethanol, acetone, or acetonitrile.
  • Equimolar amounts of the compound and an acid or alcohol (e.g., glycol monomethyl ether) in water can be heated, and the mixture can then be evaporated to dryness, or the precipitated salt can be filtered off with suction.
  • Acid addition salts are obtained from inorganic acids such as hydrochloric, nitric, phosphoric, sulfuric, hydrobromic, hydroiodic, nitrous or phosphorous acids and from non-toxic organic acids such as aliphatic mono- and dicarboxylates, phenyl-substituted alkanoates, hydroxyalkanoates and alkanedioates, aromatic acids, aliphatic and aromatic sulfonic acids.
  • inorganic acids such as hydrochloric, nitric, phosphoric, sulfuric, hydrobromic, hydroiodic, nitrous or phosphorous acids
  • non-toxic organic acids such as aliphatic mono- and dicarboxylates, phenyl-substituted alkanoates, hydroxyalkanoates and alkanedioates, aromatic acids, aliphatic and aromatic sulfonic acids.
  • Pharmaceutically/food engineeringly and/or cosmetically non-toxic salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, nitrates, phosphates, monohydrogen phosphates, dihydrogen phosphates, metaphosphates, pyrophosphate chlorides, bromides, iodides, fluorides, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, caprates, heptanoates, propiolates, oxalates, malonates, succinates, suberates, sebacates, fumarates, maleates, butyn-1,4-dioate, hexane-1,6-dioate, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, hydroxybenzoates, Contains methoxybenzoate, phthalate, terephthalate, benz
  • a base can be used to prepare a pharmaceutically/food engineering- and/or cosmetically acceptable metal salt.
  • the alkali metal or alkaline earth metal salt is obtained, for example, by dissolving the active ingredient, a nicotinic acid/nicotinamide derivative compound, in an excess of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering off the undissolved compound salt, and evaporating and drying the filtrate.
  • sodium, potassium, or calcium salts are pharmaceutically suitable as the metal salt.
  • the corresponding silver salt is obtained by reacting the alkali metal or alkaline earth metal salt with a suitable silver salt (e.g., silver nitrate).
  • the present disclosure relates to a method of inducing the synthesis of nicotinamide adenine dinucleotide (NAD+) in a subject, for example, in a cell of the subject, comprising administering to the subject a physiologically effective amount of the compound, a physiologically acceptable salt thereof, or a stereoisomer thereof, and/or a method of delaying, preventing, and/or inhibiting aging of a subject, for example, a cell of the subject, comprising administering to the subject a physiologically effective amount of the compound, a physiologically acceptable salt thereof, or a stereoisomer thereof.
  • NAD+ nicotinamide adenine dinucleotide
  • physiologically effective amount means an amount sufficient to achieve a biological and/or biochemical effect or activity (e.g., promoting or inducing NAD + synthesis or conversion within a cell, anti-aging, and/or anti-inflammation).
  • a physiologically effective amount may include a 'pharmaceutically effective amount,' a 'food engineering effective amount,' and/or a 'cosmetologically effective amount.
  • nicotinic acid/nicotinamide riboside derivative compounds having structures of chemical formulas 1 to 4, which are active ingredients of pharmaceutical compositions, cosmetic compositions, food compositions and/or external skin preparations, physiologically acceptable salts thereof and/or stereoisomers thereof, may be included in the functional compositions and/or external skin preparations in a concentration of 0.001 to 0.5 mM, for example, 0.001 to 0.1 mM or 0.0075 to 0.06 mM, but are not limited thereto.
  • Functional compositions and external skin preparations in which the derivative compounds according to the present disclosure, physiologically acceptable salts thereof and/or stereoisomers thereof may be included as active ingredients and/or active ingredients will be described in more detail.
  • the present disclosure relates to an anti-inflammatory or anti-inflammatory composition
  • a pharmaceutical composition related to anti-inflammation and/or anti-aging may contain, as an active ingredient, a nicotinic acid/nicotinamide riboside derivative compound having a structure of Chemical Formula 1 to Chemical Formula 4, a pharmaceutically acceptable salt thereof and/or a stereoisomer thereof.
  • the pharmaceutical composition may further contain, in addition to the active ingredient and/or active component, additional components, i.e., a pharmaceutically acceptable or nutritionally acceptable carrier, excipient, diluent and/or auxiliary component, depending on the formulation, method of use and intended use of the pharmaceutical composition.
  • an anti-inflammatory and/or anti-aging pharmaceutical composition comprising a nicotinic acid/nicotinamide riboside derivative compound, a pharmaceutically acceptable salt thereof and/or a stereoisomer thereof can be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injectable solutions according to conventional methods.
  • nicotinic acid/nicotinamide riboside derivative compounds, pharmaceutically acceptable salts thereof, and/or stereoisomers thereof can be administered in various oral or parenteral dosage forms for clinical administration.
  • they may further include diluents or excipients such as commonly used fillers, bulking agents, binders, humectants, surfactants, anticoagulants, lubricants, wetting agents, flavoring agents, emulsifiers, or preservatives, and can be used either orally or parenterally.
  • carriers, excipients and diluents that can be included in a pharmaceutical composition comprising a nicotinic acid/nicotinamide riboside derivative compound, a pharmaceutically acceptable salt thereof and/or a stereoisomer thereof may include, but are not limited to, at least one selected from the group consisting of lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, dextrin, calcium carbonate, propylene glycol, liquid paraffin and saline solution, and any conventional carrier, excipient or diluent may be used.
  • solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations are prepared by mixing nicotinic acid/nicotinamide riboside derivative compounds, pharmaceutically acceptable salts thereof, and/or stereoisomers thereof with one or more excipients, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc.
  • excipients such as starch, calcium carbonate, sucrose or lactose, gelatin, etc.
  • lubricants such as magnesium stearate and talc are also used.
  • Liquid preparations for oral administration include suspensions, oral solutions, emulsions, and syrups, and in addition to commonly used simple diluents such as water and liquid paraffin, various excipients, such as wetting agents, sweeteners, flavoring agents, and preservatives, may be included.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories.
  • Non-aqueous solutions and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.
  • Suppository bases may include witepsol, macrogol, Tween 61, cacao butter, laurin butter, glycerol, gelatin, and glycerogelatin.
  • the pharmaceutical composition of the present disclosure may be administered parenterally via subcutaneous injection, intravenous injection, or intramuscular injection.
  • Forms for parenteral administration include toothpaste, mouthwash, topical preparations (creams, ointments, dressing solutions, sprays, other applications, etc.).
  • An example of the formulation of the topical preparation may be a pharmaceutical composition containing an active ingredient impregnated into a carrier such as gauze made of natural or synthetic fibers.
  • a cream or ointment it may be suitable for direct application to a lesion or inflamed area related to dermatitis (e.g., atopic dermatitis).
  • a spray it may be manufactured by a conventional spray manufacturing method, except that it contains an active ingredient, and may be filled and packaged in a pressurized container or other spray container and sprayed on a lesion or inflamed area from time to time to prevent or treat inflammatory diseases or diseases caused by bacteria.
  • a dressing solution it may be manufactured by a conventional dressing solution manufacturing method, except that it contains an active ingredient, and may be used for dressing a lesion or dressing other bacterially infected areas to prevent or treat inflammatory diseases or diseases caused by bacteria.
  • the dosage form of the pharmaceutical composition of the present disclosure may take various forms depending on the method of use.
  • the pharmaceutical composition may be formulated by adopting a method known in the art so as to provide rapid, sustained, or delayed release of the active ingredient after administration to a mammal.
  • dosage forms include ointments, granules, lotions, liniments, limonades, powders, syrups, eye ointments, solutions, aerosols, extracts, elixirs, ointments, fluid extracts, emulsions, suspensions, emulsions, infusions, eye drops, tablets, suppositories, injections, tablets, capsules, creams, pills, soft or hard gelatin capsules, and the like.
  • the anti-inflammatory and/or anti-aging pharmaceutical composition may further contain, in addition to the active ingredient, nutrients, vitamins, electrolytes, flavoring agents, coloring agents, thickeners, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc.
  • the anti-inflammatory and/or anti-aging pharmaceutical compositions of the present disclosure can be administered to mammals, such as rats, mice, livestock, and humans, via various routes. Any route of administration is contemplated, including oral, rectal, or intravenous, intramuscular, subcutaneous, intrauterine, or intracerebroventricular injection.
  • the preferred dosage of the anti-inflammatory and/or anti-aging pharmaceutical composition comprising the nicotinic acid/nicotinamide riboside derivative compound of the present disclosure, a pharmaceutically acceptable salt thereof, and/or a stereoisomer thereof varies depending on the patient's condition and body weight, the extent of the disease, the drug form, the route of administration, and the duration of the administration, but can be appropriately selected by a person skilled in the art.
  • the anti-inflammatory pharmaceutical composition comprising the nicotinic acid/nicotinamide riboside derivative compound, a pharmaceutically acceptable salt thereof, and/or a stereoisomer thereof can be administered at 0.0001 to 100 mg/kg per day, preferably 0.001 to 100 mg/kg.
  • the administration may be administered once a day or divided into several times.
  • the above dosage does not limit the scope of the present disclosure in any way.
  • the present disclosure relates to an anti-inflammatory, anti-inflammatory, and/or anti-aging food composition or health functional food comprising, as an active ingredient, a nicotinic acid/nicotinamide derivative compound having a structure represented by Formulae 1 to 4, a food-technically acceptable salt thereof, and/or a stereoisomer thereof.
  • a food composition of the present disclosure include a food, a food additive, a beverage, or a beverage additive.
  • a food may include all of a food, a food additive, a health functional food, and a beverage.
  • foods containing nicotinic acid/nicotinamide riboside derivative compounds, food engineering acceptable salts thereof and/or stereoisomers thereof include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, ice cream, various soups, beverages, tea, drinks, alcoholic beverages and vitamin complexes, and include all health functional foods in the conventional sense.
  • food includes, but is not limited to, special nutritional foods (e.g., formula milk, infant/toddler food, etc.), processed meat products, fish products, tofu, starch jelly, noodles (e.g., ramen, noodles, etc.), health supplements, seasoned foods (e.g., soy sauce, soybean paste, red pepper paste, mixed paste, etc.), sauces, confectionery (e.g., snacks), dairy products (e.g., fermented milk, cheese, etc.), other processed foods, kimchi, pickled foods (various kimchi, pickled vegetables, etc.), beverages (e.g., fruit and vegetable beverages, soy milk, fermented beverages, ice cream, etc.), natural seasonings (e.g., ramen soup, etc.), vitamin complexes, alcoholic beverages, liquors, and other health supplements.
  • special nutritional foods e.g., formula milk, infant/toddler food, etc.
  • processed meat products e.g., fish products, tofu, starch jelly
  • the food composition and/or health functional food may contain food additives acceptable in terms of food engineering, and may further contain suitable carriers, excipients, and diluents commonly used in the manufacture of functional foods.
  • the food composition or health functional food of the present disclosure may include forms such as tablets, capsules, pills, and liquids, and other than containing a nicotinic acid/nicotinamide riboside derivative compound, a food engineering-acceptable salt thereof, and/or a stereoisomer thereof as an active ingredient, there are no special limitations on other ingredients, and may contain food auxiliary additive ingredients such as flavoring agents or natural carbohydrates as additional ingredients.
  • natural carbohydrates include common sugars such as monosaccharides (single sugars) such as glucose and fructose; disaccharides (disaccharides) such as maltose and sucrose; and polysaccharides (polysaccharides) such as dextrin and cyclodextrin, as well as sugar alcohols such as xylitol, sorbitol, and erythritol.
  • natural flavorings/sweeteners such as thaumatin and stevia extracts (e.g., rebaudioside A, glycyrrhizin); and synthetic flavorings/sweeteners such as saccharin and aspartame can be used.
  • the food composition and/or health functional food may contain various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, carbonating agents used in alcoholic carbonated beverages, etc.
  • the food composition according to the present disclosure may contain fruit pulp for the production of natural fruit juices, fruit juice drinks, and vegetable drinks. These ingredients may be used independently or in combination.
  • the anti-inflammatory composition, anti-inflammatory composition, and/or anti-aging food composition of the present disclosure may include, in addition to the active ingredient, a nicotinic acid/nicotinamide riboside derivative compound, a pharmaceutically and/or food engineering-acceptable salt thereof, and/or a stereoisomer thereof, carbohydrates, proteins, lipids, vitamins, and minerals.
  • the carbohydrates, proteins, lipids, vitamins, or minerals may be appropriately selected depending on the intended use and application thereof.
  • the carbohydrate may be honey, dextrin, sucrose, palatinose, glucose, fructose, corn syrup, sugar alcohol, sorbitol, xylitol, and maltitol.
  • the protein may be casein, whey protein, and other milk-derived proteins, soy protein, and hydrolyzates of these proteins by animal-derived enzymes such as trypsin and pepsin, and neutrase and alkalase.
  • the lipid may be various plant-derived oils and fats such as sunflower oil, rapeseed oil, olive oil, safflower oil, corn oil, soybean oil, palm oil, and palm oil, containing primary saturated fatty acids and polyunsaturated fatty acids, middle-chain fatty acids, EPA, DHA, soybean-derived phospholipids, and milk-derived phospholipids.
  • Minerals may include potassium phosphate, potassium carbonate, potassium chloride, sodium chloride, calcium lactate, calcium gluconate, calcium pantothenate, calcium caseinate, magnesium chloride, ferrous sulfate, and sodium bicarbonate.
  • carbohydrates, proteins, lipids, vitamins, and minerals are not limited to the specific ingredients mentioned above.
  • the present disclosure relates to an anti-aging cosmetic composition
  • the cosmetic composition comprises a cosmetically and/or dermatologically acceptable medium, i.e., a medium suitable for the skin, mucous membranes, hair and scalp. It may be provided in any cosmetic dosage form suitable for topical application, in particular in the form of an aqueous, aqueous/alcoholic or oily solution, or an aqueous, aqueous/alcoholic or oily gel, or a solid or pasty anhydrous product, an emulsion obtained by dispersing an oil phase in an aqueous phase (O/W) or vice versa (W/O), a suspension, a microemulsion, a microcapsule, a microgranule, or an ionic (liposome) and/or non-ionic vesicular dispersion.
  • These compositions may be prepared according to methods conventional in the art.
  • the composition according to the present disclosure may also be used in the form of a foam or in the form of an aerosol composition further containing a compressed propellant.
  • a functional cosmetic composition In order to manufacture a functional cosmetic composition, at least one selected from among ethanol, glycerin, butylene glycol, propylene glycol, glycereth-26, methyl gluceth-20, isocetyl myristate, isocetyl octanoate, octyldodecyl myristate, octyldodecanol, isostearyl isostearate, cetyl octanoate, and neopentyl glycol dicaprate may be used as a solvent.
  • the solubility of the compound in the solvent slightly differs depending on the type of the compound and the mixing ratio of the solvent.
  • a person skilled in the art to which the present disclosure pertains can appropriately select the type and amount of the solvent according to the characteristics of the product.
  • the cosmetic composition according to the present disclosure may additionally include cosmetic excipients.
  • cosmetic excipients such as moisturizers, powdered ingredients, UV absorbers, antioxidants, cosmetic ingredients, glycolipids, plant extracts, preservatives, fragrances, pH adjusters, pigments, viscosity adjusters, or gelling agents, may be included as auxiliary ingredients, as long as they do not impair the effects of the present disclosure, i.e., anti-inflammatory, antibacterial, skin wrinkle improvement, skin aging prevention, skin whitening, skin antioxidant, or skin moisturizing effects.
  • Non-limiting examples of humectants may be propylene glycol, isoprene glycol, 1,2-heptanediol, 1,3-butylene glycol, dipropylene glycol, hexanediol, polyethylene glycol, glycerin, glycerin, diglycerin, triglycerin, polyglycerin, neopentyl glycol, sorbitol, erythritol, pentaerythritol, glycols such as glucose, galactose, fructose, sucrose, maltose, xylose, xylobiose, reduced oligosaccharides, proteins, mucopolysaccharides, collagen, elastin, keratin, or triethanolamine.
  • humectants may be propylene glycol, isoprene glycol, 1,2-heptanediol, 1,3-butylene glycol,
  • Non-limiting examples of powder components include white inorganic pigments such as titanium oxide, siliconized titanium oxide, zinc oxide, and barium sulfate; colored inorganic pigments such as iron oxide, carbon black, sintered titanium and titanium oxide, and ultramarine; white body powders such as talc, siliconized talc, muscovite, kaolin, silicon carbide, bentonite, smectite, anhydrous silicic acid, aluminum oxide, magnesium oxide, zirconium oxide, diatomaceous earth, calcium silicate, barium silicate, magnesium silicate, calcium carbonate, magnesium carbonate, hydroxyapatite, and boron nitride; organic polymer resin powders such as titanium dioxide-coated mica, iron oxide mica titanium, siliconized mica titanium, young gourd, polyethylene resin, fluorine resin, cellulose resin, and silicone resin; organic low molecular weight powders such as zinc stearate and N-acylysine; natural organic materials such as starch, silk powder, and cellulose powder
  • an organic pigment powder such as powder, red No. 201, red No. 202, orange No. 203, orange No. 204, blue No. 404 and yellow No. 401
  • an organic powder pigment such as zirconium, barium or aluminum lake such as red No. 3, red No. 104, red No. 106, orange No. 205, yellow No. 4, yellow No. 5, green No. 3 and blue No. 1
  • a gold leaf powder such as mica or gold powder
  • a composite powder such
  • Non-limiting examples of UV absorbers include benzophenone derivatives, para-aminobenzoic acid derivatives, methoxycinnamic acid derivatives, urocanic acid, etc.
  • Non-limiting examples of antioxidants include BHT, BHA, vitamin C, vitamin E, derivatives thereof, and salts thereof.
  • Non-limiting examples of cosmetic ingredients include vitamins including the above vitamins, derivatives thereof, and salts thereof, anti-inflammatory agents, and herbal medicines, etc.
  • Non-limiting examples of glycolipids include sphingoglycolipids, etc.
  • Non-limiting examples of plant extracts include extracts of aloe vera, witch hazel, witch hazel, cucumber, lemon, lavender, and rose, etc.
  • Non-limiting examples of preservatives include methyl parahydroxybenzoate, ethyl parahydroxybenzoate, butyl parahydroxybenzoate, propyl parahydroxybenzoate, phenoxyethanol, and ethanol, etc.
  • Non-limiting examples of fragrances include camphor oil, tangerine oil, peppermint oil, jasmine absolute, pine oil, lime oil, lavender oil, rose oil, and musk oil.
  • Non-limiting examples of pH adjusters include edetic acid, sodium edetate, sodium chloride, quenched acid, sodium quenched acid, sodium hydroxide, potassium hydroxide, and triethanolamine.
  • Non-limiting examples of colorants include Blue No. 1, Blue No. 204, Red No. 3, and Yellow No. 201.
  • Non-limiting examples of viscosity modifiers may include polyvinyl alcohol (PVA), methylcellulose (MC), ethylcellulose, hydroxypropylmethylcellulose, hydroxypropylethylcellulose, other cellulose derivatives, polyvinylpyrrolidone (PVP), carboxymethylcellulose, xanthan gum, alginic acid or a salt thereof, carrageenan, quince seed powder, alkaline polysaccharides, carboxyvinyl polymers, acrylates, acrylic acid polymers (chain-linked, cross-linked), and acrylic acid-alkyl methacrylate copolymers.
  • PVA polyvinyl alcohol
  • MC methylcellulose
  • PVP polyvinylpyrrolidone
  • carboxymethylcellulose xanthan gum
  • alginic acid or a salt thereof carrageenan
  • quince seed powder alkaline polysaccharides
  • carboxyvinyl polymers acrylates
  • acrylic acid polymers chain-linked, cross-linked
  • Non-limiting examples of gelling agents include (behenic/eicosane diacid) glyceryl and (behenic/eicosane diacid) polyglyceryl-10, fatty acid metal salts, hydroxystearic acid, dextrin fatty acid esters, inulin fatty acid esters, sugar fatty acid esters, acylated cellobiose, dibenzylidene sorbitol, amino acid gelling agents, silicic anhydride, organo-modified clay minerals, fumed silica, alumina, cross-linked organopolysiloxanes, hydrocarbon waxes such as polyethylene wax or paraffin wax, vegetable waxes such as carnauba wax or candelilla wax, agar, and gelatin.
  • fatty acid metal salts include hydroxystearic acid, dextrin fatty acid esters, inulin fatty acid esters, sugar fatty acid esters, acylated cellobiose, dibenzyliden
  • the cosmetic composition of the present disclosure may be manufactured in any formulation commonly manufactured in the relevant industry, and may be formulated as, for example, a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a soap, a surfactant-containing cleansing, an oil, a powder foundation, an emulsion foundation, a wax foundation, and a spray, but is not limited thereto. More specifically, the cosmetic composition of the present disclosure may be manufactured in the form of a flexible toner, a nourishing toner, a cream, a nourishing cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray, or a powder.
  • the cosmetic composition of the present disclosure may additionally include one or more cosmetically acceptable carriers that are incorporated into cosmetics, and may appropriately incorporate conventional ingredients such as oil, water, surfactants, moisturizers, lower alcohols, thickeners, chelating agents, pigments, preservatives, fragrances, etc., but is not limited thereto.
  • the cosmetically acceptable carriers included in the cosmetic composition of the present disclosure vary depending on the formulation.
  • the formulation of the cosmetic according to the present disclosure is a paste, cream or gel
  • animal oil, vegetable oil, wax, paraffin, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component.
  • lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and particularly in the case of a spray, a propellant such as chlorofluorohydrocarbon, propane/butane or dimethyl ether may be additionally included.
  • a solvent, a solubilizer or an emulsifier is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, and in particular, cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan.
  • the cosmetic formulation of the present disclosure is a suspension
  • a liquid diluent such as water, ethanol or propylene glycol
  • a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tragacanth, etc.
  • a carrier component such as water, ethanol or propylene glycol
  • a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester
  • microcrystalline cellulose aluminum metahydroxide
  • bentonite agar or tragacanth, etc.
  • an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, an isethionate, an imidazolinium derivative, a methyl taurate, a sarcosinate, a fatty acid amide ether sulfate, an alkyl amidobetaine, an aliphatic alcohol, a fatty acid glyceride, a fatty acid diethanolamide, a vegetable oil, a lanolin derivative or an ethoxylated glycerol fatty acid ester, etc. may be used as a carrier component.
  • the cosmetic according to the present disclosure may be formulated as a skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream, essence, nutrition essence, pack, soap, shampoo, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, milky lotion, pressed powder, loose powder, or eye shadow.
  • the present disclosure relates to an anti-aging skin topical composition
  • Topical skin preparations can be formulated in a variety of forms. Specific examples of topical skin preparations include: pastes, lotions, liniments, aromatic waters, aerosols, ointments, emulsions, cataplasmas, creams, and pastes.
  • the topical skin preparation of the present disclosure may include a pharmaceutically and/or cosmetically acceptable carrier; a carrier; an excipient; a binder including starch, gum tragacanth, gelatin, molasses, polyvinyl alcohol, polyvinyl ether, polyvinyl pyrrolidone, hydroxypropyl cellulose, methylcellulose, ethylcellulose, and carboxymethylcellulose; a grinding agent including agar, starch, gelatin powder, sodium carboxymethylcellulose, calcium carboxymethylcellulose, crystalline cellulose, calcium carbonate, sodium bicarbonate, and sodium alginate; a lubricant including magnesium stearate, talc, and hydrogenated vegetable oil; and a colorant.
  • a pharmaceutically and/or cosmetically acceptable carrier including a carrier; an excipient; a binder including starch, gum tragacanth, gelatin, molasses, polyvinyl alcohol, polyvinyl ether, polyvinyl pyrrolidone, hydroxyprop
  • the carrier and excipient include lactose, glucose, sucrose, mannitol, potato starch, corn starch, calcium carbonate, calcium phosphate, and cellulose.
  • additives such as stabilizers, solubilizers, percutaneous absorption promoters, fragrances, and preservatives may be added.
  • Oleum H 2 SO 4 (0.43 mL, 8.00 mmol) was slowly added dropwise to dried acetonitrile (25 mL) at 0°C under a nitrogen atmosphere. After stirring for about 5 minutes, 2,2-dimethoxypropane (14.40 mL, 117.53 mmol) and nicotinamide riboside chloride (NR chloride, 1 , 3.00 g, 11.75 mmol) were sequentially added. The temperature of the solution was gradually increased to room temperature and stirred for about 2 hours. After cooling the reaction mixture to 0°C, solid Na 2 CO 3 (0.64 g, 6.00 mmol) was added and stirred for about 1 hour.
  • the NAD + induction effect of nicotinamide riboside derivative compound RP-4 and NMN synthesized in Synthesis Example 1 was measured.
  • Human Dermal Fibroblast (HDF) cells which are fibroblasts, were plated in 48-well plates at a concentration of 2 x 10 4 cells/well, and then treated with DOX (doxorubicin) at a concentration of 0.5 ⁇ M for 3 days to induce cell senescence.
  • the derivative compound RP-4 and NMN were treated to the senescent cells at a concentration of 0.0075 to 0.06 mM, respectively.
  • DMEM 10% FBS
  • the cell lysate was collected, and the NAD + content in the cell lysate was measured using an NAD/NADH assay kit. The measurement results are shown in Fig. 2.
  • the NAD + level decreased in fibroblasts induced to undergo senescence by treatment with doxorubicin.
  • compound RP-4 was treated to induced senescence cells, the decreased NAD + level was confirmed to be restored in a concentration-dependent manner.
  • NMN used as a positive control substance, did not exhibit a significant NAD + induction effect in the concentration range used in the test (0.0075–0.06 mM). Therefore, it was confirmed that the nicotinamide riboside derivative compound synthesized in the synthetic example as an NAD + booster can be utilized as a biological anti-aging material.
  • RAW264.7 cells (KCLB No. 40071), a mouse monocyte cell line, were plated in 96-well plates at a density of 5 x 10 4 cells/well and treated with lipopolysaccharide (LPS) at a concentration of 10 ng/mL.
  • LPS lipopolysaccharide
  • the cells which were induced to synthesize TNF- ⁇ , a major factor in the inflammatory response, were treated with the derivative compound and NMN at a concentration of 0.0075 to 0.06 mM.
  • TNF- ⁇ produced in the conditioned media was quantified using an ELISA kit. The measurement results are shown in Fig. 3.
  • the nicotinamide riboside derivative compound RP-4 synthesized in Synthesis Example 1 effectively inhibited the biosynthesis of the anti-inflammatory cytokine TNF- ⁇ in a concentration-dependent manner at concentrations of 0.0075 to 0.06 mM.
  • compound RP-4 significantly inhibited the biosynthesis of TNF- ⁇ compared to NMN, which was used as a positive control.
  • the nicotinamide riboside derivative compound RP-4 and NMN were synthesized and measured for NAD + induction in an inflammation-induced model.
  • RAW264.7 cells KCLB No. 40071
  • LPS lipopolysaccharide
  • the nicotinamide riboside derivative compound RP-4 and NMN were treated at a concentration of 0.0075 to 0.06 mM.
  • DMEM 10% FBS
  • the cell lysate was collected and the NAD + content in the cell lysate was measured using an NAD/NADH assay kit. The measurement results are shown in Fig. 4.
  • the nicotinamide riboside derivative compound RP-4 synthesized in the Synthesis Example exhibited a reduced NAD + recovery effect in cells induced with an inflammatory response in a concentration-dependent manner in the concentration range of 0.0075–0.06 mM.
  • compound RP-4 exhibited superior NAD + induction activity compared to the positive control substance NMN.
  • ROS reactive oxygen species
  • ROS levels increased in fibroblasts induced by DOX treatment.
  • treatment with the derivative compound resulted in a concentration-dependent recovery and reduction of the increased ROS levels in the senescent cells.
  • the induction of SIRT1 by the nicotinamide riboside derivative compound RP-4 synthesized in Synthesis Example 1 and NMN was measured.
  • HDF cells which are fibroblasts, were plated in a 24-well plate at a concentration of 4x104 cells/well and treated with DOX (doxorubicin) at a concentration of 0.5 ⁇ M for 3 days.
  • DOX doxorubicin
  • the nicotinamide derivative compounds synthesized in Synthesis Example were treated at a concentration of 0.0075 to 0.06 mM, respectively.
  • DMEM, 10% FBS After culturing for 24 hours (DMEM, 10% FBS), the cell lysate was collected and the SIRT1 expression level in the cell lysate was measured using a human SIRT1 ELISA kit. The measurement results are shown in Fig. 6.
  • the SIRT1 level was reduced in fibroblasts induced by DOX treatment, but when the derivative compound was treated in the senescent cells, the reduced SIRT1 expression level was restored in a concentration-dependent manner.
  • the SIRT1 expression level was significantly increased when the derivative compound was treated in the concentration range used in the test (0.0075–0.06 mM).
  • NMN did not show any significant skin permeability for up to 24 hours
  • RP-4 showed an excellent skin permeability characteristic of approximately 27.6%.
  • NMN material has had difficulty in application to the cosmetics and pharmaceutical fields due to its poor skin permeability.
  • the nicotinamide riboside derivative compound synthesized in Synthesis Example exhibits excellent skin permeability, and therefore is expected to be applicable to various skin-related products.
  • Example 2 As in Example 1, NMN was completely decomposed from the 10th day, confirming its vulnerability to heat. In addition, H-Trp-NRH synthesized in Comparative Synthesis Example 1 was also completely decomposed from the 10th day, and no peak could be confirmed on the chromatogram. RP-4 synthesized in Synthesis Example 1 and N-methyl-Tbt-NRH synthesized in Synthesis Example 2 maintained approximately 80% of their compounds in a stable state until the 30th day.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Molecular Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Biotechnology (AREA)
  • Birds (AREA)
  • Mycology (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente divulgation concerne un composé dérivé de riboside d'acide nicotinique ou un composé dérivé de nicotinamide riboside. Le composé dérivé présente une excellente stabilité thermique et induit efficacement la biosynthèse du nicotinamide adénine dinucléotide (NAD+). Le composé dérivé, un sel physiologiquement acceptable de celui-ci et/ou un stéréoisomère de celui-ci peuvent être utilisés en tant qu'ingrédient ou principe actif d'une composition anti-inflammatoire, d'une composition pour soulager ou améliorer l'inflammation, d'une composition anti-vieillissement et/ou d'un agent topique dermatologique anti-vieillissement.
PCT/KR2024/003132 2024-03-12 2024-03-12 Composés pour induire un nicotinamide adénine dinucléotide, composition le comprenant, et agent topique dermatologique Pending WO2025192761A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/KR2024/003132 WO2025192761A1 (fr) 2024-03-12 2024-03-12 Composés pour induire un nicotinamide adénine dinucléotide, composition le comprenant, et agent topique dermatologique

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/KR2024/003132 WO2025192761A1 (fr) 2024-03-12 2024-03-12 Composés pour induire un nicotinamide adénine dinucléotide, composition le comprenant, et agent topique dermatologique

Publications (1)

Publication Number Publication Date
WO2025192761A1 true WO2025192761A1 (fr) 2025-09-18

Family

ID=97063773

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2024/003132 Pending WO2025192761A1 (fr) 2024-03-12 2024-03-12 Composés pour induire un nicotinamide adénine dinucléotide, composition le comprenant, et agent topique dermatologique

Country Status (1)

Country Link
WO (1) WO2025192761A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20170008320A (ko) * 2014-06-06 2017-01-23 글락소스미스클라인 인털렉츄얼 프로퍼티 (넘버 2) 리미티드 니코틴아미드 리보시드 유사체 및 그의 제약 조성물 및 용도
WO2017161165A1 (fr) * 2016-03-16 2017-09-21 ChromaDex Inc. Conjugués de vitamine b et d'acides aminés de ribosides de nicotinoyle et de ribosides de nicotinoyle réduits, dérivés de ceux-ci, et leurs procédés de préparation
US20200397807A1 (en) * 2019-06-18 2020-12-24 MitoPower, LLC Nicotinyl riboside compounds and their uses
KR20220017695A (ko) * 2020-08-05 2022-02-14 주식회사 레미바이오 아스코르브산 유도체 및 이를 포함하는 조성물
WO2022266322A1 (fr) * 2021-06-18 2022-12-22 Mitopower Llc Traitement de troubles liés à l'immunité, de troubles rénaux, de troubles hépatiques, de troubles hémolytiques et de troubles liés au stress oxydatif à l'aide de nrh, narh et de leurs dérivés réduits

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20170008320A (ko) * 2014-06-06 2017-01-23 글락소스미스클라인 인털렉츄얼 프로퍼티 (넘버 2) 리미티드 니코틴아미드 리보시드 유사체 및 그의 제약 조성물 및 용도
WO2017161165A1 (fr) * 2016-03-16 2017-09-21 ChromaDex Inc. Conjugués de vitamine b et d'acides aminés de ribosides de nicotinoyle et de ribosides de nicotinoyle réduits, dérivés de ceux-ci, et leurs procédés de préparation
US20200397807A1 (en) * 2019-06-18 2020-12-24 MitoPower, LLC Nicotinyl riboside compounds and their uses
KR20220017695A (ko) * 2020-08-05 2022-02-14 주식회사 레미바이오 아스코르브산 유도체 및 이를 포함하는 조성물
WO2022266322A1 (fr) * 2021-06-18 2022-12-22 Mitopower Llc Traitement de troubles liés à l'immunité, de troubles rénaux, de troubles hépatiques, de troubles hémolytiques et de troubles liés au stress oxydatif à l'aide de nrh, narh et de leurs dérivés réduits

Similar Documents

Publication Publication Date Title
WO2021137677A1 (fr) Composition contenant un extrait de plante
WO2020122360A1 (fr) Procédé de préparation d'un extrait de zizania latifolia turcz. traité avec une enzyme présentant une teneur accrue en tricine, et composition de blanchissement, réduction des rides, anti-inflammatoire, antiallergique et d'hydratation, préparée avec ce dernier
WO2014116022A1 (fr) Utilisation d'un dérivé de resvératrol pour le blanchiment de la peau
WO2018124508A1 (fr) Composition pour la prévention et le traitement de maladies musculaires ou pour l'amélioration de la fonction musculaire, contenant de l'acide 3,5-dicaféoylquinique ou de l'extrait de chrysanthème
WO2015037891A1 (fr) Agent de blanchiment de la peau contenant un nouveau composé cyclique
WO2022031044A1 (fr) Dérivé de l'acide ascorbique et composition le comprenant
WO2014003232A1 (fr) Composition comprenant un extrait de dendropanax morbifera léveille en tant que principe actif pour la favorisation de la pousse des cheveux
WO2018004141A1 (fr) Composition ayant pour effet d'améliorer l'hydratation de la peau, d'exfolier la peau, d'améliorer l'élasticité de la peau, d'inhiber l'érythème, d'atténuer les rides cutanées ou d'atténuer le photovieillissement cutané, contenant, en tant qu'ingrédient actif, un ou plusieurs composés choisis dans le groupe constitué du cimène, de l'acide béhénique, du 2-méthoxynaphtalène, du thymol et de leurs sels
WO2016080796A2 (fr) Composition pharmaceutique contenant un composé sesquiterpénique et utilisable en vue de la prévention ou du traitement de maladies à médiation par stat3, et son utilisation
WO2022250313A1 (fr) Composition d'hydratation de la peau, favorisant la régénération de la peau, et le traitement des plaies, comprenant de l'extrait de fleur d'aloe vera, ou de l'extrait de fleur d'aloe vera et des polysaccharides d'aloe vera, comme ingrédient(s) actif(s)
WO2025192761A1 (fr) Composés pour induire un nicotinamide adénine dinucléotide, composition le comprenant, et agent topique dermatologique
WO2012067316A1 (fr) Composition pour la prévention ou le traitement de maladies métaboliques ou de complications de celles-ci contenant des composés à base de ptérocarpane ou des sels pharmaceutiquement acceptables de ceux-ci comme principe actif ou composition anti-oxydation
WO2020218890A1 (fr) Composition consistant en un extrait d'actinidia polygama destiné à attenuer des lésions cutanées ou hydrater la peau
WO2014168433A2 (fr) Composition pour favoriser la croissance des cheveux, la régénération de la mélanine des cheveux gris et la régénération de la peau
WO2020085826A1 (fr) Composition pour soulager une irritation de la peau induite par des facteurs de pollution environnementaux ou pour la protection de la peau, contenant comme principe actif un extrait de noix de muscade ou du macelignane
WO2020145619A1 (fr) Composition pour la prévention des allergies, le soulagement de la dermatite atopique ou la régénération de la peau, contenant, en tant que principe actif, un undécane ou un undécanal
WO2018062820A1 (fr) Composition visant à prévenir la chute des cheveux et à en favoriser la pousse, comprenant un phytoœstrogène en tant que principe actif
WO2018186641A1 (fr) Composition pour réduire les rides de la peau, hydrater la peau, améliorer son élasticité, l'exfolier, inhiber l'érythème ou réduire le photovieillissement de la peau, contenant du pipéronal ou l'un de ses sels à titre de principe actif
WO2019083286A2 (fr) Composition contenant de l'irone comme principe actif pour prévenir la chute des cheveux ou stimuler la repousse des cheveux
WO2023113431A1 (fr) Nouvelle souche et son utilisation
WO2023219300A1 (fr) Nouvelle souche de chlorella vulgaris et son utilisation
WO2020159146A1 (fr) Composition pharmaceutique destinée à prévenir le grisonnement des cheveux et à prévenir ou à traiter le poliosis ou le vitiligo
WO2019083287A2 (fr) Composition contenant du phellandrène comme principe actif pour prévenir la chute des cheveux ou stimuler la repousse des cheveux
WO2021141439A1 (fr) Composition pour la prévention ou le traitement des maladies musculaires contenant un extrait de pellicule argentée de café, une fraction de celui-ci ou un composé isolé à partir de celui-ci
WO2021187959A1 (fr) Composé à base de glucoside de glycérol et composition le comprenant pour protection contre la lumière ultraviolette ou anti-inflammation

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: 24929823

Country of ref document: EP

Kind code of ref document: A1