CN113117083A - Application of substance for improving activity of mammal Sirtuin protein family - Google Patents

Application of substance for improving activity of mammal Sirtuin protein family Download PDF

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Publication number
CN113117083A
CN113117083A CN201911415876.1A CN201911415876A CN113117083A CN 113117083 A CN113117083 A CN 113117083A CN 201911415876 A CN201911415876 A CN 201911415876A CN 113117083 A CN113117083 A CN 113117083A
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enzyme
nad
substance
pathway
activity
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刘永政
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7084—Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/45—Transferases (2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants

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  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
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  • Gastroenterology & Hepatology (AREA)
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  • Proteomics, Peptides & Aminoacids (AREA)
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  • Animal Husbandry (AREA)
  • Zoology (AREA)
  • Toxicology (AREA)
  • Food Science & Technology (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The invention discloses application of a substance for improving the activity of a mammal Sirtuin protein family, which comprises a related substance capable of improving the activity of the mammal Sirtuin protein family, application of the related substance in pharmaceutical preparations and administration forms and a food intake form added with the related substance. The invention expands the range of medicaments, administration forms and food intake forms of related substances capable of improving the activity of the Sirtuin protein family of mammals.

Description

Application of substance for improving activity of mammal Sirtuin protein family
Technical Field
The invention relates to a medicament, in particular to application of a substance for improving the activity of a mammal Sirtuin protein family.
Background
The mammalian Sirtuin family has 7 subtypes (SIRT 1-SIRT 7), and studies have shown that a number of key proteins of the DNA damage repair pathway are downstream substrates of sirtuins. The core protein of the Sirtuin protein is involved in repairing various DNA damage types including double-strand breaks by regulating pathways such as homologous recombination repair, non-homologous end repair, nucleotide excision repair and the like, thereby playing a vital role in maintaining a series of biological effects such as genome stability, life span, cell energy metabolism regulation and the like. Moreover, the mammal over-expression models of a plurality of subtypes of the Sirtuin family show a remarkable life-prolonging effect, and have a profound significance in the treatment of the occurrence and development of tumors and senile diseases caused by aging in the aspect of DNA damage repair.
NAD + is nicotinamide adenine dinucleotide. Is a transfer electron, a coenzyme for many dehydrogenases in the body, which links the tricarboxylic acid cycle and the respiratory chain and functions to transfer hydrogen removed during metabolism to flavoproteins. NADH or more precisely NADH +, H + is its reduced form. NAD + decreases with age or disease production.
Nicotinamide Mononucleotide (NMN), a key NAD + intermediate, has been shown to enhance NAD + biosynthesis and improve various pathologies in mouse disease models. And oral NMN was found to rapidly synthesize NAD + in cells. And the age-related physiological aging of the rats was effectively reduced by oral administration of NMN. And without any significant toxic or deleterious effects, NMN has also been found to inhibit age-related body weight gain, enhance energy metabolism, promote physical activity, improve insulin sensitivity and plasma lipid profiles, improve eye function and other pathophysiology. NMN can prevent the alteration of age-related gene expression in key metabolism organs and enhanced mitochondrial oxidative metabolism and ribonucleoprotein imbalance skeletal muscle. These effects of NMN highlight the preventive and therapeutic potential intermediates of NAD + as effective anti-aging interventions in humans.
The existing research is mainly focused on the production method, i.e. the treatment direction, and does not relate to the preparation and the administration form.
Disclosure of Invention
In view of the technical deficiencies, the invention aims to provide the application of substances for improving the activity of the mammalian Sirtuin family of proteins, including related substances capable of improving the activity of the mammalian Sirtuin family of proteins, the application of the related substances in pharmaceutical preparations and administration forms and food intake forms added with the related substances.
In order to solve the technical problems, the invention adopts the following technical scheme:
the invention provides application of a substance for improving the activity of a mammal Sirtuin protein family, which comprises a related substance capable of improving the activity of the mammal Sirtuin protein family, application of the related substance in pharmaceutical preparations and administration forms and a food intake form added with the related substance.
Preferably, the substance of interest is NAD, NADH, an intermediate from a new synthesis pathway for synthesizing NAD, an intermediate from a NAD salvage pathway, an intermediate from a nicotinamide riboside kinase pathway, or a combination thereof.
Preferably, the substance of interest is NAD, nicotinamide mononucleotide, nicotinic acid mononucleotide or nicotinamide riboside.
Preferably, the substance of interest comprises an enzyme of the de novo pathway, an enzyme of the NAD salvage pathway or an enzyme of the nicotinamide riboside kinase pathway for the synthesis of NAD; a nucleic acid encoding an enzyme of the de novo pathway, an enzyme of the NAD salvage pathway, or an enzyme of the nicotinamide riboside kinase pathway for synthesizing NAD; an agent that increases expression of an enzyme from the new synthesis pathway, an enzyme of the NAD salvage pathway, or an enzyme of the nicotinamide riboside kinase pathway for synthesizing NAD; or a substance that increases the catalytic activity and/or stability of an enzyme of the de novo pathway, the NAD salvage pathway, or an enzyme of the nicotinamide riboside kinase pathway for synthesizing NAD.
Preferably, the substance of interest comprises nicotinamide mononucleotide adenylyltransferase NMNAT or a nucleic acid encoding NMNAT.
Preferably, the related substance comprises an enzyme having NMNAT activity and at least 50% identity to human NMNAT1 or at least 50% identity to human NMNAT3, at least 70% identity to human NMNAT1 or at least 70% identity to human NMNAT 3.
Preferably, the related substance is a stilbene selected from the group consisting of resveratrol, piceatannol, deoxyrhapontine, trans-stilbene and rhapontine; a chalcone selected from butein, isoliquiritigen, and 3, 4, 2 ', 4 ', 6 ' -pentahydroxychalcone; a flavone selected from the group consisting of luteolin, 5, 7, 3 ', 4 ', 5 ' -pentahydroxyflavone, luteolin, 3, 6, 3 ', 4 ' -tetrahydroxyflavone, quercetin, 7, 3 ', 4 ', 5 ' -tetrahydroxyflavone, kaempferol, 6-hydroxytapigenin, apigenin, 3, 6, 2 ', 4 ' -tetrahydroxyflavone, 7, 4 ' -dihydroxyflavone, 7, 8, 3 ', 4 ' -tetrahydroxyflavone, 3, 6, 2 ', 3 ' -tetrahydroxyflavone, 4 ' -hydroxyflavone, 5, 4 ' -dihydroxyflavone, 5, 7-dihydroxyflavone, morin, flavone, and 5-hydroxyflavone; isoflavones selected from daidzein and genistein; a flavanone selected from the group consisting of naringenin, 3, 5, 7, 3 ', 4' -pentahydroxy flavanone, and flavanone; or a catechin selected from (-) -epicatechin, (-) -catechin, (-) -gallocatechin, (+) -catechin and (+) -epicatechin.
Preferably, the mammal includes all mammalian species.
Preferably, the formulation forms mainly include liquid formulations and solid formulations; the solid preparation mainly comprises granules, tablets, capsules and dropping pills; the liquid preparation mainly comprises oral liquid preparation and injection liquid preparation.
Preferably, the administration form comprises mainly oral or parenteral administration, preferably oral administration.
The invention has the beneficial effects that: expands the range of medicament, administration form and food intake form of related substances capable of improving the activity of the Sirtuin protein family of mammals.
Detailed Description
The application of the substance for improving the activity of the mammal Sirtuin protein family comprises the related substance capable of improving the activity of the mammal Sirtuin protein family, the application of the related substance in pharmaceutical preparations and administration forms and food intake forms added with the related substance.
Further, the substance of interest is NAD, NADH, an intermediate from a new synthesis pathway for synthesizing NAD, an intermediate from a NAD salvage pathway, an intermediate from a nicotinamide riboside kinase pathway, or a combination thereof.
Further, the substance of interest is NAD, nicotinamide mononucleotide, nicotinic acid mononucleotide or nicotinamide riboside.
Further, the related substances include an enzyme of a de novo pathway for synthesizing NAD, an enzyme of a NAD salvage pathway, or an enzyme of a nicotinamide riboside kinase pathway; a nucleic acid encoding an enzyme of the de novo pathway, an enzyme of the NAD salvage pathway, or an enzyme of the nicotinamide riboside kinase pathway for synthesizing NAD; an agent that increases expression of an enzyme from the new synthesis pathway, an enzyme of the NAD salvage pathway, or an enzyme of the nicotinamide riboside kinase pathway for synthesizing NAD; or a substance that increases the catalytic activity and/or stability of an enzyme of the de novo pathway, the NAD salvage pathway, or an enzyme of the nicotinamide riboside kinase pathway for synthesizing NAD.
Further, the related substance includes nicotinamide mononucleotide adenylyltransferase NMNAT or a nucleic acid encoding NMNAT.
Further, the related substances include an enzyme having NMNAT activity and at least 50% identity to human NMNAT1 or at least 50% identity to human NMNAT3, at least 70% identity to human NMNAT1 or at least 70% identity to human NMNAT 3.
Further, the related substance is a low index member selected from resveratrol, piceatannol, deoxyrhapontin, trans-stilbene and rhapontin; a chalcone selected from butein, isoliquiritigen, and 3, 4, 2 ', 4 ', 6 ' -pentahydroxychalcone; a flavone selected from the group consisting of luteolin, 5, 7, 3 ', 4 ', 5 ' -pentahydroxyflavone, luteolin, 3, 6, 3 ', 4 ' -tetrahydroxyflavone, quercetin, 7, 3 ', 4 ', 5 ' -tetrahydroxyflavone, kaempferol, 6-hydroxytapigenin, apigenin, 3, 6, 2 ', 4 ' -tetrahydroxyflavone, 7, 4 ' -dihydroxyflavone, 7, 8, 3 ', 4 ' -tetrahydroxyflavone, 3, 6, 2 ', 3 ' -tetrahydroxyflavone, 4 ' -hydroxyflavone, 5, 4 ' -dihydroxyflavone, 5, 7-dihydroxyflavone, morin, flavone, and 5-hydroxyflavone; isoflavones selected from daidzein and genistein; a flavanone selected from the group consisting of naringenin, 3, 5, 7, 3 ', 4' -pentahydroxy flavanone, and flavanone; or a catechin selected from (-) -epicatechin, (-) -catechin, (-) -gallocatechin, (+) -catechin and (+) -epicatechin.
Further, the mammal includes all mammalian species.
Further, the preparation form mainly comprises a liquid preparation and a solid preparation; the solid preparation mainly comprises granules, tablets, capsules and dropping pills; the liquid preparation mainly comprises oral liquid preparation and injection liquid preparation.
Further, the administration form mainly includes oral administration or parenteral administration, preferably oral administration.
The invention expands the range of medicaments, administration forms and food intake forms of related substances capable of improving the activity of the Sirtuin protein family of mammals.
It will be apparent to those skilled in the art that various changes and modifications may be made in the present invention without departing from the spirit and scope of the invention. Thus, if such modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include such modifications and variations.

Claims (10)

1. The application of the substance for improving the activity of the mammal Sirtuin protein family is characterized by comprising the related substance capable of improving the activity of the mammal Sirtuin protein family, the application of the related substance in pharmaceutical preparations and administration forms and food intake forms added with the related substance.
2. The use of claim 1, wherein the substance of interest is NAD, NADH, an intermediate from a new synthetic pathway for the synthesis of NAD, an intermediate of a NAD salvage pathway, an intermediate of a nicotinamide riboside kinase pathway, or a combination thereof.
3. The use of claim 1, wherein the substance of interest is NAD, nicotinamide mononucleotide, nicotinic acid mononucleotide or nicotinamide riboside.
4. The use of claim 1, wherein the substance of interest comprises an enzyme of a de novo pathway, an enzyme of a NAD salvage pathway, or an enzyme of a nicotinamide riboside kinase pathway for the synthesis of NAD; a nucleic acid encoding an enzyme of the de novo pathway, an enzyme of the NAD salvage pathway, or an enzyme of the nicotinamide riboside kinase pathway for synthesizing NAD; an agent that increases expression of an enzyme from the new synthesis pathway, an enzyme of the NAD salvage pathway, or an enzyme of the nicotinamide riboside kinase pathway for synthesizing NAD; or a substance that increases the catalytic activity and/or stability of an enzyme of the de novo pathway, the NAD salvage pathway, or an enzyme of the nicotinamide riboside kinase pathway for synthesizing NAD.
5. The use according to claim 1, wherein the substance of interest comprises nicotinamide mononucleotide adenylyltransferase NMNAT or a nucleic acid encoding NMNAT.
6. The use of claim 1, wherein the substance of interest comprises an enzyme having NMNAT activity and at least 50% identity to human NMNAT1 or at least 50% identity to human NMNAT3, at least 70% identity to human NMNAT1 or at least 70% identity to human NMNAT 3.
7. The use according to claim 1, wherein the related substance is a young member selected from the group consisting of resveratrol, piceatannol, rhapontin, tran-young and rhapontin; a chalcone selected from butein, isoliquiritigen, and 3, 4, 2 ', 4 ', 6 ' -pentahydroxychalcone; a flavone selected from the group consisting of luteolin, 5, 7, 3 ', 4 ', 5 ' -pentahydroxyflavone, luteolin, 3, 6, 3 ', 4 ' -tetrahydroxyflavone, quercetin, 7, 3 ', 4 ', 5 ' -tetrahydroxyflavone, kaempferol, 6-hydroxytapigenin, apigenin, 3, 6, 2 ', 4 ' -tetrahydroxyflavone, 7, 4 ' -dihydroxyflavone, 7, 8, 3 ', 4 ' -tetrahydroxyflavone, 3, 6, 2 ', 3 ' -tetrahydroxyflavone, 4 ' -hydroxyflavone, 5, 4 ' -dihydroxyflavone, 5, 7-dihydroxyflavone, morin, flavone, and 5-hydroxyflavone; isoflavones selected from daidzein and genistein; a flavanone selected from the group consisting of naringenin, 3, 5, 7, 3 ', 4' -pentahydroxy flavanone, and flavanone; or a catechin selected from (-) -epicatechin, (-) -catechin, (-) -gallocatechin, (+) -catechin and (+) -epicatechin.
8. The use of claim 1, wherein said mammal comprises all mammalian species.
9. The use of claim 1, wherein said dosage form consists essentially of a liquid dosage form and a solid dosage form; the solid preparation mainly comprises granules, tablets, capsules and dropping pills; the liquid preparation mainly comprises oral liquid preparation and injection liquid preparation.
10. Use according to claim 1, wherein said administration form essentially comprises oral or parenteral administration, preferably oral administration.
CN201911415876.1A 2019-12-31 2019-12-31 Application of substance for improving activity of mammal Sirtuin protein family Pending CN113117083A (en)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1964627A (en) * 2004-06-04 2007-05-16 华盛顿大学 Methods and compositions for treating neuropathy
CN101086915A (en) * 2007-04-16 2007-12-12 刘永政 Method for manufacturing C-shaped iron core of voltage transformer
CN102038702A (en) * 2010-11-02 2011-05-04 浙江大学 Anti-ageing application of hesperidin
US20110110913A1 (en) * 2008-03-03 2011-05-12 Ross Stewart Grant Pharmaceutical formulations of resveratrol and methods of use thereof for treating cell disorders
CN109045037A (en) * 2018-08-01 2018-12-21 董玲 It is a kind of to promote the anti-apolexis composition of cozymase, preparation and preparation method thereof
CN110251493A (en) * 2019-07-16 2019-09-20 刘兆麒 A kind of anti-apolexis composition and application thereof

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1964627A (en) * 2004-06-04 2007-05-16 华盛顿大学 Methods and compositions for treating neuropathy
CN101086915A (en) * 2007-04-16 2007-12-12 刘永政 Method for manufacturing C-shaped iron core of voltage transformer
US20110110913A1 (en) * 2008-03-03 2011-05-12 Ross Stewart Grant Pharmaceutical formulations of resveratrol and methods of use thereof for treating cell disorders
CN102038702A (en) * 2010-11-02 2011-05-04 浙江大学 Anti-ageing application of hesperidin
CN109045037A (en) * 2018-08-01 2018-12-21 董玲 It is a kind of to promote the anti-apolexis composition of cozymase, preparation and preparation method thereof
CN110251493A (en) * 2019-07-16 2019-09-20 刘兆麒 A kind of anti-apolexis composition and application thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
王大鹏，等: "NMNAT的结构及其对糖代谢的影响", 《NMNAT的结构及其对糖代谢的影响》 *

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Application publication date: 20210716