WO2023236740A1 - 5'-单磷酸核苷酸组合物在制备消脂减肥功能食品和药物中的应用 - Google Patents
5'-单磷酸核苷酸组合物在制备消脂减肥功能食品和药物中的应用 Download PDFInfo
- Publication number
- WO2023236740A1 WO2023236740A1 PCT/CN2023/094741 CN2023094741W WO2023236740A1 WO 2023236740 A1 WO2023236740 A1 WO 2023236740A1 CN 2023094741 W CN2023094741 W CN 2023094741W WO 2023236740 A1 WO2023236740 A1 WO 2023236740A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- monophosphate
- cmp
- application according
- nucleotide composition
- gmp
- Prior art date
Links
- 239000002773 nucleotide Substances 0.000 title claims abstract description 84
- 239000000203 mixture Substances 0.000 title claims abstract description 70
- 239000003814 drug Substances 0.000 title claims abstract description 22
- 229940079593 drug Drugs 0.000 title claims abstract description 17
- 235000013376 functional food Nutrition 0.000 title claims abstract description 15
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 210000003486 adipose tissue brown Anatomy 0.000 claims abstract description 40
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 claims abstract description 38
- IERHLVCPSMICTF-XVFCMESISA-N CMP group Chemical class P(=O)(O)(O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)N1C(=O)N=C(N)C=C1)O)O IERHLVCPSMICTF-XVFCMESISA-N 0.000 claims abstract description 16
- UPJKSWLLCONYMW-UHFFFAOYSA-N 5'-Adenosine monophosphate Natural products COc1cc(O)c(C(=O)C)c(OC2OC(COC3OC(C)C(O)C(O)C3O)C(O)C(O)C2O)c1 UPJKSWLLCONYMW-UHFFFAOYSA-N 0.000 claims abstract description 9
- UDMBCSSLTHHNCD-UHFFFAOYSA-N Coenzym Q(11) Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1O UDMBCSSLTHHNCD-UHFFFAOYSA-N 0.000 claims abstract description 9
- RAJMXAZJKUGYGW-POYBYMJQSA-N 2',3'-dideoxycytidine-5'-monophosphate Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP(O)(O)=O)CC1 RAJMXAZJKUGYGW-POYBYMJQSA-N 0.000 claims abstract description 8
- 239000002253 acid Substances 0.000 claims abstract description 6
- 235000013305 food Nutrition 0.000 claims abstract description 6
- 125000003729 nucleotide group Chemical group 0.000 claims description 19
- IERHLVCPSMICTF-UHFFFAOYSA-N cytidine monophosphate Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(COP(O)(O)=O)O1 IERHLVCPSMICTF-UHFFFAOYSA-N 0.000 claims description 8
- AEOBEOJCBAYXBA-UHFFFAOYSA-N A2P5P Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1OP(O)(O)=O AEOBEOJCBAYXBA-UHFFFAOYSA-N 0.000 claims description 7
- AANLCWYVVNBGEE-IDIVVRGQSA-L Disodium inosinate Chemical compound [Na+].[Na+].O[C@@H]1[C@H](O)[C@@H](COP([O-])([O-])=O)O[C@H]1N1C(NC=NC2=O)=C2N=C1 AANLCWYVVNBGEE-IDIVVRGQSA-L 0.000 claims description 7
- 235000013890 disodium inosinate Nutrition 0.000 claims description 7
- KURVIXMFFSNONZ-WFIJOQBCSA-L disodium;[(2r,3s,4r,5r)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound [Na+].[Na+].O[C@@H]1[C@H](O)[C@@H](COP([O-])([O-])=O)O[C@H]1N1C(=O)NC(=O)C=C1 KURVIXMFFSNONZ-WFIJOQBCSA-L 0.000 claims description 7
- 159000000000 sodium salts Chemical group 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 4
- 239000003826 tablet Substances 0.000 claims description 4
- PVBRXXAAPNGWGE-LGVAUZIVSA-L disodium 5'-guanylate Chemical compound [Na+].[Na+].C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP([O-])([O-])=O)[C@@H](O)[C@H]1O PVBRXXAAPNGWGE-LGVAUZIVSA-L 0.000 claims description 3
- 235000013896 disodium guanylate Nutrition 0.000 claims description 3
- 239000003655 absorption accelerator Substances 0.000 claims description 2
- 235000013361 beverage Nutrition 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 239000007910 chewable tablet Substances 0.000 claims description 2
- 235000013365 dairy product Nutrition 0.000 claims description 2
- 239000007884 disintegrant Substances 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 239000008298 dragée Substances 0.000 claims description 2
- 239000007938 effervescent tablet Substances 0.000 claims description 2
- 239000000945 filler Substances 0.000 claims description 2
- 239000000796 flavoring agent Substances 0.000 claims description 2
- 235000013355 food flavoring agent Nutrition 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 239000006191 orally-disintegrating tablet Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 238000001179 sorption measurement Methods 0.000 claims description 2
- 239000007940 sugar coated tablet Substances 0.000 claims description 2
- 239000004094 surface-active agent Substances 0.000 claims description 2
- 239000007939 sustained release tablet Substances 0.000 claims description 2
- 239000000080 wetting agent Substances 0.000 claims description 2
- 239000004198 disodium guanylate Substances 0.000 claims 1
- RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical class C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 abstract description 18
- 101001123331 Homo sapiens Peroxisome proliferator-activated receptor gamma coactivator 1-alpha Proteins 0.000 abstract description 12
- 102100028960 Peroxisome proliferator-activated receptor gamma coactivator 1-alpha Human genes 0.000 abstract description 12
- DJJCXFVJDGTHFX-XVFCMESISA-N uridine 5'-monophosphate Chemical class O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 DJJCXFVJDGTHFX-XVFCMESISA-N 0.000 abstract description 9
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 abstract description 7
- 230000037361 pathway Effects 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 102100036009 5'-AMP-activated protein kinase catalytic subunit alpha-2 Human genes 0.000 abstract 1
- 101000783681 Homo sapiens 5'-AMP-activated protein kinase catalytic subunit alpha-2 Proteins 0.000 abstract 1
- 102100029820 Mitochondrial brown fat uncoupling protein 1 Human genes 0.000 abstract 1
- 108050002686 Mitochondrial brown fat uncoupling protein 1 Proteins 0.000 abstract 1
- 150000007513 acids Chemical class 0.000 abstract 1
- 229960003786 inosine Drugs 0.000 abstract 1
- 229940045145 uridine Drugs 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 35
- 230000000694 effects Effects 0.000 description 23
- 102000015494 Mitochondrial Uncoupling Proteins Human genes 0.000 description 12
- 108010050258 Mitochondrial Uncoupling Proteins Proteins 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 210000001789 adipocyte Anatomy 0.000 description 11
- 102000014156 AMP-Activated Protein Kinases Human genes 0.000 description 10
- 108010011376 AMP-Activated Protein Kinases Proteins 0.000 description 10
- 208000008589 Obesity Diseases 0.000 description 10
- 235000020824 obesity Nutrition 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 239000002609 medium Substances 0.000 description 9
- 208000016261 weight loss Diseases 0.000 description 9
- 230000004580 weight loss Effects 0.000 description 9
- 230000006870 function Effects 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 7
- 150000002632 lipids Chemical class 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- 230000000476 thermogenic effect Effects 0.000 description 5
- 210000000593 adipose tissue white Anatomy 0.000 description 4
- 230000036760 body temperature Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 229940029575 guanosine Drugs 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 102000007469 Actins Human genes 0.000 description 3
- 108010085238 Actins Proteins 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 230000035924 thermogenesis Effects 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000004193 disodium 5'-ribonucleotide Substances 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 238000009207 exercise therapy Methods 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 208000030159 metabolic disease Diseases 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 229920002477 rna polymer Polymers 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical group OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 1
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000031636 Body Temperature Changes Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000035484 Cellulite Diseases 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 101000976075 Homo sapiens Insulin Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 101710150697 Inositol monophosphatase 1 Proteins 0.000 description 1
- 102100035679 Inositol monophosphatase 1 Human genes 0.000 description 1
- 102100021608 Inositol monophosphatase 2 Human genes 0.000 description 1
- 101710150707 Inositol monophosphatase 2 Proteins 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 206010025476 Malabsorption Diseases 0.000 description 1
- 208000004155 Malabsorption Syndromes Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102100031455 NAD-dependent protein deacetylase sirtuin-1 Human genes 0.000 description 1
- 206010033307 Overweight Diseases 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 206010049752 Peau d'orange Diseases 0.000 description 1
- 101710137877 Regulatory protein SIR1 Proteins 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 108010041191 Sirtuin 1 Proteins 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- RSSRHKDOIOBLBS-WFIJOQBCSA-N [Na].[Na].[C@@H]1([C@H](O)[C@H](O)[C@@H](COP(=O)(O)O)O1)N1C(=O)NC(=O)C=C1 Chemical compound [Na].[Na].[C@@H]1([C@H](O)[C@H](O)[C@@H](COP(=O)(O)O)O1)N1C(=O)NC(=O)C=C1 RSSRHKDOIOBLBS-WFIJOQBCSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000001593 brown adipocyte Anatomy 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 230000036232 cellulite Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000027288 circadian rhythm Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000030944 contact inhibition Effects 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000001916 dieting Nutrition 0.000 description 1
- 230000037228 dieting effect Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000006996 mental state Effects 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- VOFUROIFQGPCGE-UHFFFAOYSA-N nile red Chemical compound C1=CC=C2C3=NC4=CC=C(N(CC)CC)C=C4OC3=CC(=O)C2=C1 VOFUROIFQGPCGE-UHFFFAOYSA-N 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical group 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—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
- A61K31/7064—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 containing condensed or non-condensed pyrimidines
- A61K31/7076—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 containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- 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
- A61K31/7064—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 containing condensed or non-condensed pyrimidines
- A61K31/7068—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 containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—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 containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- the invention belongs to the technical fields of medicine and health food, and specifically relates to the application of a 5'-monophosphate nucleotide composition in the preparation of fat-reducing and weight-reducing functional foods and medicines.
- Obesity is a chronic metabolic disease in which excessive accumulation of fat in the body threatens health.
- Obesity is related to various factors such as diet, genetics, mental state, and region. With the improvement of residents' living standards, the intake of crude fiber foods has decreased. , increased intake of high-fat, high-calorie foods, lack of physical exercise and other factors have led to an increase in overweight and obesity, and the tendency is to increase and become younger year by year. With the rapid increase in the incidence of obesity, obesity-related diseases are also growing rapidly.
- Obesity-related diseases mainly include hypertension, diabetes, atherosclerosis, and cardiovascular and cerebrovascular diseases.
- the conventional methods for treating obesity mainly include diet control, exercise therapy, drug therapy and surgical treatment. Diet control and exercise therapy are often difficult for obese patients to adhere to and are prone to rebound; most related drugs have side effects and drug resistance. Problem; Surgical treatments such as gastric short-circuit surgery and gastroplasty have the potential risk of complications such as malabsorption, anemia and duct stenosis. Existing treatment methods cannot solve the root cause of obesity.
- White adipose tissue mainly stores ingested rich energy in the form of triglycerides.
- the cells are in the shape of lipid droplets.
- Brown adipose tissue mainly generates heat by oxidizing lipids.
- Activated BAT plays an important role in systemic energy consumption, glucose balance and human insulin sensitivity. Activated BAT can consume excess nutrients in the body. , BAT has gradually become a new target organ for the treatment of obesity and obesity-related metabolic disorders.
- Nucleotides are subunits of nucleic acids.
- the bases composed of cytosine, adenine, guanine, thymine and uracil are attached to the ribose or deoxyribose moiety with a phosphate group.
- NTs are also involved in various cellular processes, including cell signal transduction, participating in enzymatic reactions, and regulating the cell cycle.
- Existing research has found that NTs have many functions such as immune regulation, anti-infection, promoting the growth and development of infants and young children, maintaining gastrointestinal health, protecting liver function, etc.
- nucleotides and their compositions are used to prepare cellulite and weight loss functions. No relevant studies on food and drugs have been reported.
- the object of the present invention is to provide a 5'-monophosphate nucleotide composition for preparing functional foods and medicines for eliminating fat and losing weight. applications in materials.
- the present invention provides the application of 5'-monophosphate nucleotide or a composition in the form of its sodium salt in the preparation of functional foods and/or medicines for eliminating fat and losing weight.
- composition is composed of 5'-adenosine monophosphate (5'-AMP), 5'-cytidine monophosphate (5'-CMP), 5'-guanylate disodium (5'-GMPNa 2 ), disodium 5'-uridylate (5'-UMPNa 2 ) and disodium 5'-inosinate (5'-IMPNa 2 ).
- 5'-AMP 5'-adenosine monophosphate
- 5'-CMP 5'-cytidine monophosphate
- 5'-GMPNa 2 5'-guanylate disodium
- 5'-UMPNa 2 disodium 5'-uridylate
- disodium 5'-IMPNa 2 disodium 5'-inosinate
- the mass ratios of each nucleotide in the composition converted into acid forms of CMP, AMP, UMP, GMP, and IMP are respectively: CMP 23-78%, AMP 6-44%, UMP 7-40%, GMP 7-51%, IMP 0, or greater than 0 and not higher than 2.5%.
- nucleotides in the composition are produced through enzymatic degradation using ribonucleic acid produced by fermentation as raw materials, with a purity of more than 99%.
- the mass ratios of various nucleotides in the composition converted into acid forms of CMP, AMP, UMP, GMP, and IMP are respectively: CMP 23-45%, AMP 15-44%, UMP 20-40%, GMP 7-20%, IMP 0-2%.
- the mass ratios of various nucleotides in the composition converted into acid forms of CMP, AMP, UMP, GMP and IMP are respectively: CMP 40-45%, AMP 15-20%, UMP 20-25% , GMP 15-20%, IMP 0-2%.
- the dosage forms of the drug include tablets, capsules, granules, pills and oral liquid preparations.
- the tablets include sugar-coated tablets, orally disintegrating tablets, effervescent tablets, chewable tablets and sustained-release tablets.
- the functional foods include powders, dairy products, baked products and liquid beverages.
- the functional food and/or medicine contains excipients acceptable in food or medicine.
- auxiliary materials include fillers, binders, wetting agents, disintegrants, absorption accelerators, surfactants, adsorption carriers, lubricants and flavoring agents.
- the functional foods and/or drugs reduce fat and lose weight by improving the heat-generating ability of brown adipose tissue.
- the functional foods and/or drugs can significantly increase the level of UCP-1 in brown adipose tissue, increase AMPK activity, and increase the expression of Sirt-1 and PGC-1 ⁇ .
- the nucleotides in the 5'-monophosphate nucleotide composition of the present application are the basic building blocks of ribonucleic acid and deoxyribonucleic acid.
- the safety of exogenous nucleotides used in the human body has been fully confirmed by scientific tests. It is proved that the 5'-monophosphate nucleotide composition of the present invention is not only safe but also has nutritional and other functions.
- the 5'-monophosphate nucleotide composition of the present invention can significantly increase the level of UCP-1 in brown adipose tissue. Adding AMPK activity and increasing the expression of Sirt-1 and PGC-1 ⁇ can significantly enhance the ability of brown adipose tissue to consume energy, maintain the morphology and function of brown adipocytes, and achieve the purpose of fat elimination and weight loss.
- the 5'-monophosphate nucleotide composition of the present invention has been tested by volunteers and has shown that taking the 5'-monophosphate nucleotide composition of the present invention does not require special dieting, has no side effects such as anorexia and diarrhea, and has good health benefits. It has the effect of thinning waist and losing weight, and has the potential to be used to prepare new fat-reducing and weight-reducing drugs or functional foods.
- Figure 1 shows the effect of the 5'-monophosphate nucleotide composition of the present application on lipid content in adipocytes; # in the figure indicates a statistical difference compared with the general control, * indicates a statistical difference compared with the model control ( P ⁇ 0.05);
- Figure 2 shows the changes in body temperature of mice fed the 5'-monophosphate nucleotide composition of the present application after cold stimulation; # in the figure indicates a statistical difference compared with the general control, * indicates a statistical difference compared with the model control difference in learning (P ⁇ 0.05);
- Figure 3 shows the effect of the 5'-monophosphate nucleotide composition of the present application on the function of brown adipose tissue in each group of SAMP8 mice; A is the Western Blot detection result; B is the effect of the 5'-monophosphate nucleotide composition on each group.
- Figure 4 is an evaluation of the weight loss effect of the 5'-monophosphate nucleotide composition of the present application on volunteers in each group; # in the figure indicates a statistical difference compared with the general control, * indicates a statistical difference compared with the model control ( P ⁇ 0.05).
- the 5'-monophosphate nucleotide composition used in the embodiment includes 5'-adenosine monophosphate (5'-AMP), 5'-cytidine monophosphate (5'-CMP), and 5'-guanosine
- the effective percentage contents of various nucleotides of disodium phosphate (5'-GMPNa 2 ) and 5'-uridylic acid disodium (5'-UMPNa 2 ) based on CMP, AMP, UMP, and GMP are respectively: CMP 43% ,AMP 17%, UMP 22%, GMP 18%.
- the above four kinds of 5'-monophosphate nucleotides or their sodium salts are tested separately. After passing the test, they are passed through a 60-mesh sieve for later use. Weigh the required sample amount of each monophosphate nucleotide according to the above proportion, and mix it. The time should not be less than 40 minutes, and the resulting mixed sample should be stored at room temperature.
- the 5'-monophosphate nucleotide composition used in the embodiment includes 5'-adenosine monophosphate (5'-AMP), 5'-cytidine monophosphate (5'-CMP), and 5'-guanosine Disodium 5'-GMPNa 2 ), disodium 5'-uridylate (5'-UMPNa 2 ) and disodium 5'-inosinate (5'-IMPNa 2 ), various nucleotides are effective
- the content in terms of CMP, AMP, UMP, GMP and IMP is respectively: CMP 23.5%, AMP 44%, UMP 25%, GMP 7% and IMP 0.5%.
- the above five kinds of 5'-monophosphate nucleotides or their sodium salts are tested separately. After passing the test, they are passed through a 60-mesh sieve for later use. Weigh the required sample amount of each monophosphate nucleotide according to the above proportion, and mix it. The time should not be less than 40 minutes, and the resulting mixed sample should be stored at room temperature.
- the 5'-monophosphate nucleotide composition used in the embodiment includes 5'-adenosine monophosphate (5'-AMP), 5'-cytidine monophosphate (5'-CMP), and 5'-guanosine Disodium 5'-GMPNa 2 ), disodium 5'-uridylate (5'-UMPNa 2 ) and disodium 5'-inosinate (5'-IMPNa 2 ), various nucleotides are effective
- the content in terms of CMP, AMP, UMP, GMP and IMP is respectively: CMP 78%, AMP 6%, UMP 8%, GMP 7% and IMP 1%.
- the above five kinds of 5'-monophosphate nucleotides or their sodium salts are tested separately. After passing the test, they are passed through a 60-mesh sieve for later use. Weigh the required sample amount of each monophosphate nucleotide according to the above proportion, and mix it. The time should not be less than 40 minutes, and the resulting mixed sample should be stored at room temperature.
- the 5'-monophosphate nucleotide composition used in the embodiment includes 5'-adenosine monophosphate (5'-AMP), 5'-cytidine monophosphate (5'-CMP), and 5'-guanosine Disodium 5'-GMPNa 2 ), disodium 5'-uridylate (5'-UMPNa 2 ) and disodium 5'-inosinate (5'-IMPNa 2 ), various nucleotides are effective
- the content in terms of CMP, AMP, UMP, GMP and IMP is respectively: CMP 23%, AMP 17%, UMP 40%, GMP 18% and IMP 2%.
- the above five kinds of 5'-monophosphate nucleotides or their sodium salts are tested separately. After passing the test, they are passed through a 60-mesh sieve for later use. Weigh the required sample amount of each monophosphate nucleotide according to the above proportion, and mix it. The time should not be less than 40 minutes, and the resulting mixed sample should be stored at room temperature.
- the 5'-monophosphate nucleotide composition used in the embodiment includes 5'-adenosine monophosphate (5'-AMP), 5'-monophosphate Cytidine monophosphate (5'-CMP), disodium 5'-guanylate (5'-GMPNa 2 ), disodium 5'-uridylate (5'-UMPNa 2 ) and disodium 5'-inosinate (5'-IMPNa 2 ), the effective percentages of various nucleotides based on CMP, AMP, UMP, GMP, and IMP are: CMP 24%, AMP 15.5%, UMP7%, GMP 51%, and IMP 2.5% .
- the above five kinds of 5'-monophosphate nucleotides or their sodium salts are tested separately. After passing the test, they are passed through a 60-mesh sieve for later use. Weigh the required sample amount of each monophosphate nucleotide according to the above proportion, and mix it. The time should not be less than 40 minutes, and the resulting mixed sample should be stored at room temperature.
- This example examines the effect of the 5'-monophosphate nucleotide composition of Examples 1-5 on the lipid content in adipocytes.
- adipocytes differentiated from 3T3-L1 cells as a model, the 5'-monophosphate nucleotide composition of Examples 1-5 is used as a model.
- the fat-reducing effect of the '-monophosphate nucleotide composition was evaluated in an experiment, and experimental group 1 (the 5'-monophosphate nucleotide composition of Example 1) and experimental group 2 (the 5'-monophosphate nucleotide composition of Example 2) were set up.
- 3T3-L1 adipocytes were cultured in DMEM medium (containing 4.5g/l glucose, 2mM glutamine and 10% fetal calf serum). After 2 days when the cells covered more than 90% of the well plate, they were in a contact inhibition state. , replaced with medium containing 4,3-isobutyl-1-methylxanthine solution (IBMX) with a final concentration of 0.5mM, dexamethasone with a final concentration of 1 ⁇ M and insulin with a final concentration of 10 ⁇ g/ml. After two days of culture, replace the culture medium with insulin with a final concentration of 10 ⁇ g/ml and continue culturing. Change the culture medium every 2 days and continue culturing for 6 days. Under the microscope, the cells are basically round, that is, 3T3-L1 is induced. The cells differentiate into fat cells.
- the induced adipocytes were seeded in a 96-well plate at 5 ⁇ 10 4 cells/well. After 24 hours of cell attachment, experimental group 1, experimental group 2, experimental group 3, experimental group 4, experimental group 5, and control were set up respectively. Group 1, control group 2, control group 3, control group 4, control group 5 and positive control (untreated), each group has 6 duplicate wells, and a final concentration of 2.0mg/day is added to the culture medium of the corresponding adipocytes.
- the experimental results are shown in Figure 1.
- the 5'-monophosphate nucleotide composition of Examples 1-5 can significantly reduce the number of adipocytes. It can be used to remove lipids from fat cells.
- Example 6 According to the results of Example 6, it can be seen that the 5'-monophosphate nucleotide composition prepared in Example 1 has the best fat-reducing effect.
- This experiment was conducted using the 5'-monophosphate nucleotide composition prepared in Example 1.
- the brown adipose tissue in the general control group, low-dose group, and medium-dose group mentioned in the following examples are all interscapular brown adipose of aged SAMP8 mice, and the brown adipose tissue in the model control group is the scapular brown fat of aged SAMR1 mice. between brown fat.
- mice used in this example were 3-month-old male SAMP8 and SAMR1 mice, which were raised in an SPF-grade animal room with an environment temperature of 22 ⁇ 2°C and a relative humidity of 50%-60%, with a 12h/12h (8: 00-20:00) lighting mode simulates normal circadian rhythm.
- the SAMP8 mice were randomly divided into a general control group, a low-dose group (NTs-L) and a medium-dose group (NTs-M).
- SAMR1 mice were the model control group, with 8 mice in each group, and were given normal controls.
- mice in the group and model control group were given basal feed, the mice in the low-dose group were given 0.3g/kg of the 5'-monophosphate nucleotide composition prepared in Example 1 + basal feed, and the mice in the medium-dose group were given 0.6g/kg Example 1
- the prepared 5'-monophosphate nucleotide composition + basic feed was fed for 9 months.
- the mice in the general control group, low-dose group, medium-dose group and model control group were continuously exposed to a 4°C environment.
- mice At 0min, 30min, 60min, 90min, 120min and 150min after the start of cold stimulation, insert a paraffin oil-lubricated mouse rectal thermometer about 1.5-2cm into the rectum of mice to measure the rectal temperature of mice in each group; they were sacrificed at 12 months of age.
- Mice isolate the interscapular brown adipose tissue of mice, and use Western Blot to detect the expression of UCP-1, tAMPK, pAMPK, Sirt-1, and PGC-1 ⁇ in brown fat of mice.
- the relative optical density values of UCP-1/ ⁇ -actin, pAMPK/tAMPK, Sirt-1/ ⁇ -actin, and PGC-1 ⁇ / ⁇ -actin were used to express the relative expression of proteins. Data are expressed as mean ⁇ standard deviation.
- mice The body temperature changes of mice in each group after cold stimulation are shown in Figure 2.
- the body temperature of mice in the low-dose group and the medium-dose group was significantly higher than that of mice in the general control group and model control group.
- the gap between the body temperature of the mice in the low-dose group and the middle-dose group and the general control group and the model control group further widened, indicating that the 5'-monophosphate nucleotide composition prepared in the present application can significantly promote
- the mice performed adaptive thermogenesis; when the mice in the low-dose and medium-dose groups were exposed to a cold environment, the body temperature was maintained at a higher temperature by brown adipose tissue producing heat through oxidized lipids.
- Uncoupling protein 1 is the only uncoupling protein expressed in BAT cells. It is mainly involved in the thermogenesis regulation and energy metabolism of BAT. It can complete non-tremor thermogenesis under the stimulation of cold and norepinephrine. It is a marker protein used to reflect the thermogenic function of BAT cells; AMP-activated protein kinase (AMPK) is a key regulator of cell metabolism and energy balance; Silent information regulator-1 (Sirtuin-1, Sirt-1) is involved in regulating the body's glucose and lipid metabolism, oxidative stress, etc., and has important physiological functions; Peroxlsome proliferator-activated receptor- ⁇ coactlvator-1 ⁇ , PGC-1 ⁇ ) can induce the expression of UCP-1 and other thermogenic components in BAT, plays an important role in activating the expression of thermogenic genes, and is the central transcriptional effector of adrenergic activation of thermogenic adipocytes.
- AMPK AMP-activated protein kinase
- the AMPK/Sirt-1/PGC-1 ⁇ pathway plays an important role in maintaining the normal physiological function of BAT. Activating AMPK/Sirt-1/PGC-1 ⁇ signaling can stimulate UCP-1 protein expression, thereby maintaining the thermogenic function of brown fat in aged mice and reducing the production of white fat in mice.
- low-dose (0.3g/kg) 5'-monophosphate nucleotide composition can significantly increase UCP-1 levels in brown adipose tissue, possibly through induction of the AMPK/Sirt-1/PGC-1 ⁇ pathway. , can significantly enhance the ability of brown adipose tissue to consume energy, and has the potential to reduce fat and lose weight.
- 300 volunteers aged 40 to 60 years old with a body mass index (BIM value) greater than 25 were selected to participate in the weight loss effect evaluation experiment of the 5'-monophosphate nucleotide composition of the present application, and were randomly divided into 6 groups , 50 people in each group, 6 groups of volunteers respectively corresponding to the blank group (xylitol), experimental group 1 (5'-monophosphate nucleotide composition of Example 1), experimental group 2 (5'-monophosphate nucleotide composition of Example 2) -monophosphate nucleotide composition), experimental group 3 (5'-monophosphate nucleotide composition of Example 3), experimental group 4 (5'-monophosphate nucleotide composition of Example 4), Experimental group 5 (the 5'-monophosphate nucleotide composition of Example 5), and each group of volunteers used the corresponding test product as the only fat-reducing and weight-loss product.
- BIM value body mass index
- the volunteers ate according to normal habits, and each person took the corresponding test product every day. 0.6g of the nucleotide composition, taken continuously for 30 days. After the test, the volunteers who participated in the test reported back the weight difference and waist circumference difference before and after taking it, to evaluate the weight loss of the 5'-monophosphate nucleotide composition of the present application. Effect.
- the evaluation results of the weight loss effect of the 5'-monophosphate nucleotide composition of the present application are shown in Figure 4.
- the results show that the weight loss effect of the 5'-monophosphate nucleotide composition of the present invention has better weight loss and leanness.
- the waist effect is mainly due to the fact that the 5'-monophosphate nucleotide composition of the present application can improve the heat production level of brown adipose tissue and reduce fat accumulation by activating the AMPK/Sirt-1/PGC-1 ⁇ pathway, thereby reducing body weight and waist circumference. .
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Diabetes (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Child & Adolescent Psychology (AREA)
- Biochemistry (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Saccharide Compounds (AREA)
Abstract
本发明公开了5'-单磷酸核苷酸组合物在制备消脂减肥功能食品和药物中的应用，属于医药和保健食品技术领域。本申请的组合物由5'-单磷酸腺苷、5'-单磷酸胞苷、5'-鸟苷酸二钠、5'-尿苷酸二钠和5'-肌苷酸二钠组成，折合为CMP、AMP、UMP、GMP、IMP酸型的质量比分别为：CMP 23-78％、AMP 6-44％、UMP 7-40％、GMP 7-51％、IMP为0、或大于0且不高于2.5％。本申请的5'-单磷酸核苷酸组合物能够通过AMPK/Sirt-1/PGC-1α通路激活棕色脂肪组织内UCP-1，改善棕色脂肪组织产热水平，显著增强棕色脂肪组织消耗能量的能力，具有用于制备新型的减脂减肥的药物或功能食品的潜力。
Description
本发明属于医药和保健食品技术领域，具体涉及5’-单磷酸核苷酸组合物在制备消脂减肥功能食品和药物中的应用。
肥胖是一种机体内脂肪过度累积以至威胁健康的慢性代谢性疾病，肥胖与饮食、遗传、精神状态及地域等多种因素有关，随着居民生活水平的提高，粗纤维类食物摄入量减少，高脂肪、高热量食物摄入增多，缺乏体育锻炼等因素导致超重和肥胖现象增多，并且呈现逐年增高和年轻化的倾向。随着肥胖发病率的迅速增长，与肥胖相关疾病也呈快速增长趋势，肥胖相关疾病主要包括高血压、糖尿病、动脉粥样硬化以及心脑血管疾病。
目前治疗肥胖的常规方法主要有饮食控制、运动疗法、药物疗法和手术治疗，饮食控制和运动疗法对肥胖患者来说多难以坚持且容易反弹；相关的药物大多存在着药物副作用及耐药性的问题；胃短路手术、胃成形术等手术治疗则存在并发吸收不良、贫血和管路狭窄的潜在危险，现有的治疗方法均无法从根源上解决肥胖问题的发生。
哺乳动物体内主要存在2种重要的脂肪组织：白色脂肪组织(white adipose tissue，WAT)和棕色脂肪组织(Brown adipose tissue，BAT)，白色脂肪组织主要以甘油三酯形式存储摄入的富裕能量，细胞形态呈脂滴状，棕色脂肪组织主要通过氧化脂质来产生热量，被激活的BAT在全身能量消耗、葡萄糖平衡和人胰岛素敏感性方面具有重要作用，由于激活BAT可以消耗体内多余的营养物质，BAT已逐渐成为治疗肥胖及肥胖相关代谢障碍的全新靶点器官。
核苷酸(Nucleotides，NTs)是核酸的亚单位，由胞嘧啶、腺嘌呤、鸟嘌呤、胸腺嘧啶和尿嘧啶组成的碱基附着在核糖或带有磷酸基团的脱氧核糖部分上，除了参与构建DNA和RNA，NTs还参与各种细胞过程，包括细胞信号转导、参与酶促反应，调节细胞周期。现有研究发现NTs具有免疫调节、抗感染、促进婴幼儿生长发育、维持胃肠道健康、保护肝功能等多方面的功能，然而，将核苷酸及其组合物用于制备消脂减肥功能食品和药物的相关研究还未见报道。
发明内容
鉴于此，本发明的目的是提供5’-单磷酸核苷酸组合物在制备消脂减肥功能食品和药
物中的应用。
本发明目的是通过以下方式实现：
本发明提供5’-单磷酸核苷酸或其钠盐形式的组合物在制备消脂减肥功能食品和/或药物中的应用。
进一步的，所述的组合物由5’-单磷酸腺苷(5’-AMP)、5’-单磷酸胞苷(5’-CMP)、5’-鸟苷酸二钠(5’-GMPNa2)、5’-尿苷酸二钠(5’-UMPNa2)和5'-肌苷酸二钠(5’-IMPNa2)组成。
进一步的，所述的组合物中各核苷酸折合为CMP、AMP、UMP、GMP、IMP酸型的质量比分别为：CMP 23-78％、AMP 6-44％、UMP 7-40％、GMP 7-51％、IMP为0、或大于0且不高于2.5％。
进一步地，所述的组合物中的核苷酸是以发酵生产得到的核糖核酸为原料经过酶法降解生产的，纯度在99％以上。
进一步地，所述的组合物中各种核苷酸折合为CMP、AMP、UMP、GMP、IMP酸型的质量比分别为：CMP23-45％、AMP 15-44％、UMP 20-40％、GMP 7-20％、IMP 0-2％。
进一步地，所述的组合物中各种核苷酸折合为CMP、AMP、UMP、GMP、IMP酸型的质量比分别为：CMP 40-45％、AMP 15-20％、UMP 20-25％、GMP 15-20％、IMP为0-2％。
进一步地，所述的药物的剂型包括片剂、胶囊剂、颗粒剂、丸剂和口服液体制剂。
进一步地，所述的片剂包括糖衣片、口腔崩解片、泡腾片、咀嚼片和缓释片。
进一步地，所述的功能食品包括粉剂、乳制品、烘焙制品和液体饮料。
进一步地，所述的功能食品和/或药物中包含有食品或药品中可接受的辅料。
进一步地，所述的辅料包括填充剂、粘合剂、润湿剂、崩解剂、吸收促进剂、表面活性剂、吸附载体、润滑剂和矫味剂。
进一步地，所述的功能食品和/或药物通过改善棕色脂肪组织产热能力来消脂减肥。
进一步地，所述的功能食品和/或药物能够显著升高棕色脂肪组织内UCP-1水平，增加AMPK活性，提高Sirt-1和PGC-1α表达量。
本发明相对于现有技术具有的有益效果如下：
1.本申请的5’-单磷酸核苷酸组合物中的核苷酸是核糖核酸及脱氧核糖核酸的基本组成单位，外源核苷酸在人体中使用的安全性已得到科学试验的充分证明，本发明的5’-单磷酸核苷酸组合物不仅安全还具有营养等功能。
2.本发明的5’-单磷酸核苷酸组合物能够显著升高棕色脂肪组织内UCP-1水平，增
加AMPK活性，提高Sirt-1，PGC-1α表达量，能够显著增强棕色脂肪组织消耗能量的能力，维持棕色脂肪细胞形态和功能，达到消脂减肥的目的。
3.本发明的5’-单磷酸核苷酸组合物经志愿者人群试验表明，服用本发明的5’-单磷酸核苷酸组合物无需特意节食，没有厌食、腹泻等副作用，具有很好的瘦腰围减肥功效，具有用于制备新型的减脂减肥的药物或功能食品的潜力。
为了更清楚地说明本发明实施例，下面将对实施例涉及的附图进行简单地介绍。
图1为本申请的5’-单磷酸核苷酸组合物对脂肪细胞中脂质含量的影响；图中#表示与一般对照比较有统计学差异，*表示与模型对照比较有统计学差异(P<0.05)；
图2为饲喂本申请的5’-单磷酸核苷酸组合物的小鼠在冷刺激后体温变化情况；图中#表示与一般对照比较有统计学差异，*表示与模型对照比较有统计学差异(P<0.05)；
图3为本申请的5’-单磷酸核苷酸组合物对各组SAMP8小鼠棕色脂肪组织功能的影响；A为Western Blot检测结果；B为5’-单磷酸核苷酸组合物对各组小鼠棕色脂肪组织UCP-1表达量的影响；C为5’-单磷酸核苷酸组合物对各组小鼠棕色脂肪组织AMPK活性的影响；D为5’-单磷酸核苷酸组合物对各组小鼠棕色脂肪组织Sirt-1表达量的影响；E为5’-单磷酸核苷酸组合物对各组小鼠棕色脂肪组织PGC-1α表达量的影响；图中#表示与一般对照比较有统计学差异，*表示与模型对照比较有统计学差异(P<0.05)；
图4为本申请的5’-单磷酸核苷酸组合物对各组志愿者的减肥效果评价；图中#表示与一般对照比较有统计学差异，*表示与模型对照比较有统计学差异(P<0.05)。
下面结合实施例对本发明进行详细的说明，但本发明的实施方式不限于此，显而易见地，下面描述中的实施例仅是本发明的部分实施例，对于本领域技术人员来讲，在不付出创造性劳动性的前提下，获得其他的类似的实施例均落入本发明的保护范围。下述实施例中的实验方法，如无特殊说明，均为常规方法，按照本领域内的文献所描述的实验方法或条件或者按照试剂盒说明书进行。下述实施例中所用的材料、试剂、仪器等均可从商业途径得到。
实施例1
实施例中所使用的5’-单磷酸核苷酸组合物包括5’-单磷酸腺苷(5’-AMP)、5’-单磷酸胞苷(5’-CMP)、5’-鸟苷酸二钠(5’-GMPNa2)、5’-尿苷酸二钠(5’-UMPNa2)各种核苷酸有效百分含量以CMP、AMP、UMP、GMP计分别为：CMP 43％、AMP 17％、
UMP 22％、GMP 18％。
上述四种5’-单磷酸核苷酸或者其钠盐分别进行检测，合格后分别过60目筛备用；按上述比例称取所需的各单磷酸核苷酸样品量，进行总混，混合时间不低于40分钟，所得混匀样品常温保存。
实施例2
实施例中所使用的5’-单磷酸核苷酸组合物包括5’-单磷酸腺苷(5’-AMP)、5’-单磷酸胞苷(5’-CMP)、5’-鸟苷酸二钠(5’-GMPNa2)、5’-尿苷酸二钠(5’-UMPNa2)和5'-肌苷酸二钠(5’-IMPNa2)，各种核苷酸有效百分含量以CMP、AMP、UMP、GMP、IMP计分别为：CMP 23.5％、AMP 44％、UMP 25％、GMP 7％、IMP为0.5％。
上述五种5’-单磷酸核苷酸或者其钠盐分别进行检测，合格后分别过60目筛备用；按上述比例称取所需的各单磷酸核苷酸样品量，进行总混，混合时间不低于40分钟，所得混匀样品常温保存。
实施例3
实施例中所使用的5’-单磷酸核苷酸组合物包括5’-单磷酸腺苷(5’-AMP)、5’-单磷酸胞苷(5’-CMP)、5’-鸟苷酸二钠(5’-GMPNa2)、5’-尿苷酸二钠(5’-UMPNa2)和5'-肌苷酸二钠(5’-IMPNa2)，各种核苷酸有效百分含量以CMP、AMP、UMP、GMP、IMP计分别为：CMP 78％、AMP 6％、UMP 8％、GMP 7％、IMP为1％。
上述五种5’-单磷酸核苷酸或者其钠盐分别进行检测，合格后分别过60目筛备用；按上述比例称取所需的各单磷酸核苷酸样品量，进行总混，混合时间不低于40分钟，所得混匀样品常温保存。
实施例4
实施例中所使用的5’-单磷酸核苷酸组合物包括5’-单磷酸腺苷(5’-AMP)、5’-单磷酸胞苷(5’-CMP)、5’-鸟苷酸二钠(5’-GMPNa2)、5’-尿苷酸二钠(5’-UMPNa2)和5'-肌苷酸二钠(5’-IMPNa2)，各种核苷酸有效百分含量以CMP、AMP、UMP、GMP、IMP计分别为：CMP 23％、AMP 17％、UMP 40％、GMP18％、IMP为2％。
上述五种5’-单磷酸核苷酸或者其钠盐分别进行检测，合格后分别过60目筛备用；按上述比例称取所需的各单磷酸核苷酸样品量，进行总混，混合时间不低于40分钟，所得混匀样品常温保存。
实施例5
实施例中所使用的5’-单磷酸核苷酸组合物包括5’-单磷酸腺苷(5’-AMP)、5’-单磷
酸胞苷(5’-CMP)、5’-鸟苷酸二钠(5’-GMPNa2)、5’-尿苷酸二钠(5’-UMPNa2)和5'-肌苷酸二钠(5’-IMPNa2)，各种核苷酸有效百分含量以CMP、AMP、UMP、GMP、IMP计分别为：CMP 24％、AMP 15.5％、UMP7％、GMP 51％、IMP为2.5％。
上述五种5’-单磷酸核苷酸或者其钠盐分别进行检测，合格后分别过60目筛备用；按上述比例称取所需的各单磷酸核苷酸样品量，进行总混，混合时间不低于40分钟，所得混匀样品常温保存。
实施例6
本实施例考察实施例1-5的5’-单磷酸核苷酸组合物对脂肪细胞中脂质含量的影响，以3T3-L1细胞分化的脂肪细胞为模型，对实施例1-5的5’-单磷酸核苷酸组合物的减脂效果进行评价实验，设置实验组1(实施例1的5’-单磷酸核苷酸组合物)、实验组2(实施例2的5’-单磷酸核苷酸组合物)、实验组3(实施例3的5’-单磷酸核苷酸组合物)、实验组4(实施例4的5’-单磷酸核苷酸组合物)、实验组5(实施例5的5’-单磷酸核苷酸组合物)，并以仅含有5’-单磷酸胞苷作为对照组1，以仅含有5’-单磷酸腺苷作为对照组2，以仅含有5’-尿苷酸二钠作为对照组3，以仅5’-鸟苷酸二钠作为对照组4，以仅含有5'-肌苷酸二钠(5’-IMPNa2)作为对照组5。
3T3-L1细胞的培养和分化：
将3T3-L1脂肪细胞在DMEM培养基(包含4.5g/l的葡萄糖、2mM的谷氨酰胺和10％的胎牛血清)中培养，在细胞铺满孔板90％以上呈接触抑制状态2天后，更换为培养基中添加有终浓度为0.5mM的4,3-异丁基-1-甲基黄嘌呤溶液(IBMX)、终浓度为1μM的地塞米松和终浓度为10μg/ml的胰岛素的培养液，培养两天后，更换为终浓度为10μg/ml的胰岛素的培养液继续培养，2天更换一次培养液，继续培养6天，显微镜下观察细胞基本成圆形，即诱导3T3-L1细胞分化成脂肪细胞。
5’-单磷酸核苷酸组合物处理脂肪细胞：
将诱导获得脂肪细胞接种于96孔板中，5×104cells/孔，待24h细胞贴壁后，分别设置实验组1、实验组2、实验组3、实验组4、实验组5、对照组1、对照组2、对照组3、对照组4、对照组5和阳性对照(未处理)，每组6个复孔，每日向对应的脂肪细胞的培养液中添加终浓度为2.0mg/mL的药物，每日更换培养液，持续4天，使用1×PBS缓冲液清洗细胞，然后更换为终浓度为100nM尼罗红的PBS缓冲液，标记10分钟，最后更换为新的PBS缓冲液，将孔板避光放于荧光光谱仪的托架上，于540nm激发，600nm发射条件下进行荧光信号的检测，实验数据以均值±标准偏差表示。
实验结果如图1所示，与阳性对照以及对照组1-5的5’-单磷酸核苷酸相比，实施例1-5的5’-单磷酸核苷酸组合物能够显著降低脂肪细胞内的脂质含量，可用于清除脂肪细胞内的脂质。
实施例7
根据实施例6的结果可知，实施例1制备的5’-单磷酸核苷酸组合物的减脂效果最优，本次实验使用实施例1制备的5’-单磷酸核苷酸组合物进行小鼠实验，下述实施例中所提到的一般对照组、低剂量组、中剂量组棕色脂肪组织均为老年SAMP8小鼠肩胛间棕色脂肪，模型对照组棕色脂肪组织为老年SAMR1小鼠肩胛间棕色脂肪。
本实施例所用的小鼠为3月龄的雄性SAMP8、SAMR1小鼠，饲养于SPF级动物房中，饲养环境温度22±2℃，相对湿度50％-60％，以12h/12h(8:00-20:00)光照模式模拟正常昼夜变化节律。适应喂养一周后，将SAMP8小鼠随机分为一般对照组、低剂量组(NTs-L)和中剂量组(NTs-M)，SAMR1小鼠为模型对照组，每组8只，给予正常对照组、模型对照组小鼠基础饲料，低剂量组小鼠给予0.3g/kg实施例1制备的5’-单磷酸核苷酸组合物+基础饲料、中剂量组给予0.6g/kg实施例1制备的5’-单磷酸核苷酸组合物+基础饲料喂养9个月。实验最后一天早上8:00在喂养5’-单磷酸核苷酸组合物2h后，分别将一般对照组、低剂量组、中剂量组和模型对照组的小鼠持续暴露在4℃环境中，在冷刺激开始后0min，30min，60min，90min，120min和150min时，将石蜡油润滑的小鼠肛温计插入小鼠直肠约1.5-2cm，测定各组小鼠直肠温度；12月龄时处死小鼠，分离小鼠的肩胛间棕色脂肪组织，使用Western Blot检测小鼠棕色脂肪UCP-1、tAMPK、pAMPK、Sirt-1、PGC-1α的表达情况。以UCP-1/β-actin、pAMPK/tAMPK、Sirt-1/β-actin、PGC-1α/β-actin的相对光密度值表示蛋白相对表达量。数据采用均数±标准差表示。
各组小鼠在冷刺激后体温变化情况如图2所示，在冷刺激30min时，低剂量组和中剂量组的小鼠的体温已明显高于一般对照组和模型对照组的小鼠，在冷刺激60min时低剂量组和中剂量组的小鼠的体温与一般对照组和模型对照组的差距进一步拉大，说明本申请制备的5’-单磷酸核苷酸组合物能够明显促进小鼠进行适应性产热；当低剂量组和中剂量组的小鼠暴露于冷环境中，体温保持在较高温度是由棕色脂肪组织通过氧化脂质产生热量来维持的。
本申请的5’-单磷酸核苷酸组合物对小鼠棕色脂肪组织功能的影响的结果如图3所示，可以看出，低剂量组小鼠的棕色脂肪组织内的UCP-1表达量较一般对照组明显升高，低剂量组小鼠的棕色脂肪组织内的AMPK活性显著高于模型对照组(P<0.05)；中剂量组小
鼠的棕色脂肪组织内的的Sirt-1表达量显著高于一般对照组(P<0.05)，中剂量组小鼠的棕色脂肪组织内的PGC-1α表达量显著高于一般对照组(P<0.05)。
Uncoupling protein 1(UCP-1)是唯一在BAT细胞中表达的解偶联蛋白，主要参与BAT的产热调节和能量代谢，在寒冷、去甲肾上腺素刺激作用下可以完成非震颤性产热，是用来反映BAT细胞产热功能的标志蛋白；腺苷酸活化蛋白激酶(AMP-activated protein kinase，AMPK)是细胞代谢和能量平衡的关键调节剂；沉默信息调节因子-1(Sirtuin-1，Sirt-1)参与调节机体糖脂代谢、氧化应激等，具有重要的生理功能；过氧化物酶体增殖物激活受体-γ共激活因子-1α(Peroxlsome proliferator-activated receptor-γcoactlvator-1α，PGC-1α)在BAT中可以诱导UCP-1和其他产热成分的表达，对产热基因激活表达具有重要作用，是产热脂肪细胞肾上腺素能激活的中心转录效应物。AMPK/Sirt-1/PGC-1α通路在维持BAT正常生理功能中发挥着重要作用。激活AMPK/Sirt-1/PGC-1α信号可以刺激UCP-1蛋白表达，从而维持老年小鼠棕色脂肪的产热功能，减少小鼠体内白色脂肪的生成。综上可知，低剂量(0.3g/kg)5’-单磷酸核苷酸组合物可以显著升高棕色脂肪组织内UCP-1水平，可能是通过AMPK/Sirt-1/PGC-1α通路诱导增高，可以显著增强棕色脂肪组织消耗能量的能力，具有潜在减脂减肥作用。
实施例8
本实施例选择300名年龄40～60周岁、身体质量指数(BIM值)大于25的志愿者参加本申请的5’-单磷酸核苷酸组合物的减肥效果评价实验，并随机分为6组，每组50人，6组志愿者分别对应空白组(木糖醇)、实验组1(实施例1的5’-单磷酸核苷酸组合物)、实验组2(实施例2的5’-单磷酸核苷酸组合物)、实验组3(实施例3的5’-单磷酸核苷酸组合物)、实验组4(实施例4的5’-单磷酸核苷酸组合物)、实验组5(实施例5的5’-单磷酸核苷酸组合物)，且每组志愿者均使用对应试验产品作为唯一减脂减肥产品，志愿者按正常习惯进行饮食，每人每天服用对应的核苷酸组合物0.6g，连续服用30天，试验结束后参加试验的志愿者反馈服用前后的体重差值和腰围差值，评价本申请的5’-单磷酸核苷酸组合物的减肥效果。
本申请的5’-单磷酸核苷酸组合物的减肥效果评价结果如图4所示，结果表明本发明的5’-单磷酸核苷酸组合物的减肥效果具有较好的减重和瘦腰功效，主要是由于本申请的5’-单磷酸核苷酸组合物可以通过激活AMPK/Sirt-1/PGC-1α通路改善棕色脂肪组织产热水平，减少脂肪囤积，从而使体重和腰围减少。
最后应说明的是：以上各实施例仅用以说明本发明的技术方案，而非对其限制；尽管参照前述各实施例对本发明进行了详细的说明，本领域的普通技术人员应当理解：其依然可以对前述各实施例所记载的技术方案进行修改，或者对其中部分或者全部技术特征进行等同替换；而这些修改或者替换，并不使相应技术方案的本质脱离本发明各实施例技术方案的范围。
Claims (10)
- 5’-单磷酸核苷酸或其钠盐形式的组合物在制备消脂减肥功能食品和/或药物中的应用。
- 根据权利要求1所述的应用，其特征在于，所述的组合物由5’-单磷酸腺苷(5’-AMP)、5’-单磷酸胞苷(5’-CMP)、5’-鸟苷酸二钠(5’-GMPNa2)、5’-尿苷酸二钠(5’-UMPNa2)和5'-肌苷酸二钠(5’-IMPNa2)组成。
- 根据权利要求2所述的应用，其特征在于，所述的组合物中各核苷酸折合为CMP、AMP、UMP、GMP、IMP酸型的质量比分别为：CMP 23-78％、AMP 6-44％、UMP 7-40％、GMP 7-51％、IMP为0、或大于0且不高于2.5％。
- 根据权利要求3所述的应用，其特征在于，所述的组合物中各种核苷酸折合为CMP、AMP、UMP、GMP、IMP酸型的质量比分别为：CMP 23-45％、AMP 15-44％、UMP 20-40％、GMP 7-20％、IMP 0-2％。
- 根据权利要求2所述的应用，其特征在于，所述的药物的剂型包括片剂、胶囊剂、颗粒剂、丸剂和口服液体制剂。
- 根据权利要求5所述的应用，其特征在于，所述的片剂包括糖衣片、口腔崩解片、泡腾片、咀嚼片和缓释片。
- 根据权利要求2所述的应用，其特征在于，所述的功能食品包括粉剂、乳制品、烘焙制品和液体饮料。
- 根据权利要求2所述的应用，其特征在于，所述的功能食品和/或药物中包含有食品或药品中可接受的辅料。
- 根据权利要求8所述的应用，其特征在于，所述的辅料包括填充剂、粘合剂、润湿剂、崩解剂、吸收促进剂、表面活性剂、吸附载体、润滑剂和矫味剂。
- 根据权利要求2所述的应用，其特征在于，所述的功能食品和/或药物通过改善棕色脂肪组织产热能力来消脂减肥。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210663045.1A CN115227706B (zh) | 2022-06-08 | 2022-06-08 | 5’-单磷酸核苷酸组合物在制备消脂减肥功能食品和药物中的应用 |
| CN202210663045.1 | 2022-06-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2023236740A1 true WO2023236740A1 (zh) | 2023-12-14 |
Family
ID=83669643
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2023/094741 WO2023236740A1 (zh) | 2022-06-08 | 2023-05-17 | 5'-单磷酸核苷酸组合物在制备消脂减肥功能食品和药物中的应用 |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN115227706B (zh) |
| WO (1) | WO2023236740A1 (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115227706B (zh) * | 2022-06-08 | 2023-12-29 | 陈玉松 | 5’-单磷酸核苷酸组合物在制备消脂减肥功能食品和药物中的应用 |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1739555A (zh) * | 2005-09-02 | 2006-03-01 | 颜怀玮 | 防治非胰岛素依赖型高血糖及肥胖和减肥药食兼用营养素及制造方法 |
| CN101559070A (zh) * | 2009-05-27 | 2009-10-21 | 珍奥集团股份有限公司 | 5’核苷酸在制备降血脂药物、保健食品中的用途 |
| CN101559069A (zh) * | 2009-05-27 | 2009-10-21 | 珍奥集团股份有限公司 | 5’核苷酸在制备缓解体力疲劳药物、保健食品中的用途 |
| CN109528748A (zh) * | 2018-12-28 | 2019-03-29 | 广州奕昕生物科技有限公司 | 环磷酸腺苷盐在制备外用消脂减肥产品中的应用 |
| CN113413394A (zh) * | 2021-07-27 | 2021-09-21 | 大连双迪科技股份有限公司 | 5’-单磷酸核苷酸及其混合物在制备改善线粒体功能药物或食品中的应用 |
| CN113616667A (zh) * | 2021-07-27 | 2021-11-09 | 大连珍奥生物技术股份有限公司 | 一种辅助治疗糖尿病的核苷酸组合物及其制备方法和应用 |
| CN115227706A (zh) * | 2022-06-08 | 2022-10-25 | 珍奥集团股份有限公司 | 5’-单磷酸核苷酸组合物在制备消脂减肥功能食品和药物中的应用 |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3173844B2 (ja) * | 1992-03-03 | 2001-06-04 | 雪印乳業株式会社 | 生体組織内ω３系脂肪酸増加剤及びそれを含む栄養組成物 |
| US5700590A (en) * | 1994-01-10 | 1997-12-23 | Abbott Laboratories | Nutritional formula with ribo-nucleotides |
| JP2000319185A (ja) * | 1999-03-10 | 2000-11-21 | Yamasa Shoyu Co Ltd | 脂質代謝調整剤およびその用途 |
| US20030013633A1 (en) * | 1999-06-07 | 2003-01-16 | Rima Kaddurah-Daouk | Use of molecules that modulate an energy related associated state |
| TWI276438B (en) * | 2002-04-25 | 2007-03-21 | Chao-Song Hsue | Weight loss medicine containing adenosine triphosphate (ATP) as active ingredient |
| DE602005012071D1 (de) * | 2004-04-06 | 2009-02-12 | Quest Int Serv Bv | Verfahren zur herstellung von maillard-geschmacks-präparaten |
| CN1264430C (zh) * | 2004-06-14 | 2006-07-19 | 颜怀玮 | 核苷酸氨基酸营养素产品及制造方法 |
| CN1739568A (zh) * | 2005-09-02 | 2006-03-01 | 颜怀玮 | 防治肥胖糖尿病药食兼用营养素及制造方法 |
| JP4723320B2 (ja) * | 2005-09-05 | 2011-07-13 | 明治飼糧株式会社 | 血中レプチン濃度上昇剤 |
| PT1800675E (pt) * | 2005-12-23 | 2011-08-30 | Nutricia Nv | COMPOSIÇÃO CONTENDO ÁCIDOS GORDOS POLI-INSATURADOS, PROTEÍNAS E MANGANjS E/OU MOLIBDÉNIO PARA O MELHORAMENTO DA COMPOSIÇÃO DA MEMBRANA |
| JP2008069126A (ja) * | 2006-09-15 | 2008-03-27 | Meiji Shiryo Kk | 脂肪細胞分化・脂質蓄積調節剤 |
| CN101147779B (zh) * | 2006-09-21 | 2011-04-06 | 珍奥集团股份有限公司 | 一种含有核苷酸的组合物、其制备方法及其用途 |
| WO2010069743A1 (en) * | 2008-12-19 | 2010-06-24 | Unilever Nv | Umami enhancing composition, food product comprising it and method to prepare the same |
| WO2010088375A2 (en) * | 2009-01-28 | 2010-08-05 | Virginia Tech Intellectual Properties, Inc. | Method of synergistically enhancing the therapeutic efficacy and safety of medications through a combination therapy |
| US20130030034A9 (en) * | 2010-09-30 | 2013-01-31 | Quark Pharmaceuticals, Inc. | Modulation of timp1 and timp2 expression |
| WO2013012313A1 (en) * | 2011-07-18 | 2013-01-24 | N.V. Nutricia | Use of a nucleotide for improving the heat stability of an aqueous micellar casein composition |
| MX2014007936A (es) * | 2011-12-27 | 2014-07-30 | Abbott Lab | Uso de una formula para lactantes reducida en calorias que contienen nucleotidos y/o carotenoides para reducir los efectos de salud adversos posteriormente en la vida. |
| US20150282506A1 (en) * | 2012-10-31 | 2015-10-08 | Mars, Incorporated | Flavour additives |
| CN103404827B (zh) * | 2013-07-08 | 2014-12-10 | 北京康比特体育科技股份有限公司 | 一种减肥调味料 |
| CN105533309A (zh) * | 2014-10-29 | 2016-05-04 | 麦亚孙 | 一种辅助减肥的肉味调味粉及其制备方法 |
| KR101604212B1 (ko) * | 2015-07-17 | 2016-03-17 | 울산대학교 산학협력단 | Ｎａｄ를 함유하는 비만 또는 내당능장애의 예방 및 치료용 조성물 |
| US11491175B2 (en) * | 2019-02-25 | 2022-11-08 | Celagenex Research (India) Pvt. Ltd. | Synergistic bioactive compositions for enhancing cellular energy |
| CN111419859B (zh) * | 2020-04-03 | 2021-05-11 | 深圳市仙湖植物园管理处（深圳市园林研究中心） | 化合物compound zz-8在制备治疗肥胖药物中的应用 |
| KR102324725B1 (ko) * | 2020-06-03 | 2021-11-11 | 성균관대학교산학협력단 | 포스포리파아제 d2 억제제를 포함하는 대사성 질환의 예방, 개선 또는 치료용 조성물 |
| CN112961890B (zh) * | 2021-02-05 | 2023-06-27 | 深圳希吉亚生物技术有限公司 | 烟酰胺单核苷酸的酶促合成方法 |
-
2022
- 2022-06-08 CN CN202210663045.1A patent/CN115227706B/zh active Active
-
2023
- 2023-05-17 WO PCT/CN2023/094741 patent/WO2023236740A1/zh unknown
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1739555A (zh) * | 2005-09-02 | 2006-03-01 | 颜怀玮 | 防治非胰岛素依赖型高血糖及肥胖和减肥药食兼用营养素及制造方法 |
| CN101559070A (zh) * | 2009-05-27 | 2009-10-21 | 珍奥集团股份有限公司 | 5’核苷酸在制备降血脂药物、保健食品中的用途 |
| CN101559069A (zh) * | 2009-05-27 | 2009-10-21 | 珍奥集团股份有限公司 | 5’核苷酸在制备缓解体力疲劳药物、保健食品中的用途 |
| CN109528748A (zh) * | 2018-12-28 | 2019-03-29 | 广州奕昕生物科技有限公司 | 环磷酸腺苷盐在制备外用消脂减肥产品中的应用 |
| CN113413394A (zh) * | 2021-07-27 | 2021-09-21 | 大连双迪科技股份有限公司 | 5’-单磷酸核苷酸及其混合物在制备改善线粒体功能药物或食品中的应用 |
| CN113616667A (zh) * | 2021-07-27 | 2021-11-09 | 大连珍奥生物技术股份有限公司 | 一种辅助治疗糖尿病的核苷酸组合物及其制备方法和应用 |
| CN115227706A (zh) * | 2022-06-08 | 2022-10-25 | 珍奥集团股份有限公司 | 5’-单磷酸核苷酸组合物在制备消脂减肥功能食品和药物中的应用 |
Non-Patent Citations (1)
| Title |
|---|
| LEVINE, A.S. ; MORLEY, J.E.: "Effect of intraventricular adenosine on food intake in rats", PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR., ELSEVIER., US, vol. 19, no. 1, 1 July 1983 (1983-07-01), US , pages 23 - 26, XP025886209, ISSN: 0091-3057, DOI: 10.1016/0091-3057(83)90305-2 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115227706A (zh) | 2022-10-25 |
| CN115227706B (zh) | 2023-12-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Sjoerdsma et al. | Serotonin and histamine in mast cells | |
| US5814078A (en) | Method and apparatus for regulating and improving the status of development and survival of living organisms | |
| Lonsdale | Thiamin | |
| WO2023236740A1 (zh) | 5'-单磷酸核苷酸组合物在制备消脂减肥功能食品和药物中的应用 | |
| US20050261239A1 (en) | Use of ATP for the manufacture of a medicament for treating certain inflammatory conditions, oxidative stress and fatigue | |
| Baugh et al. | Human biotin deficiency: a case history of biotin deficiency induced by raw egg consumption in a cirrhotic patient | |
| CN113398144B (zh) | 核苷酸混合物在制备预防或缓解老年肌少症制剂中的应用 | |
| CN112206237A (zh) | 一种含有牛磺酸锌的抗衰老组合物、制备方法及其应用 | |
| Kaparianos et al. | Obstructive sleep apnoea syndrome and genes | |
| BR112012006872B1 (pt) | Composição, promotor de lipólise oral, inibidor de enzima de conversão de angiotensina oral, e, alimento ou bebida | |
| Cheek et al. | Cellular growth, nutrition and development | |
| WO2023236739A1 (zh) | 核苷酸混合物在用于防治阿尔茨海默症制剂中的应用 | |
| CN108478582A (zh) | 桦木酸作为脂肪酸合酶抑制剂的应用 | |
| WO2022077276A1 (zh) | 烟酰胺单核苷酸与发酵乳杆菌联合在制备缓解皮肤光老化制剂中的应用 | |
| Kotler et al. | Refeeding after a fast in rats: effects on small intestinal enzymes | |
| CN107927790A (zh) | 一种组合物及其应用 | |
| CN101559069A (zh) | 5’核苷酸在制备缓解体力疲劳药物、保健食品中的用途 | |
| CN105663900B (zh) | 一种用于改善肝硬化营养状态的药膳 | |
| CN114631629A (zh) | 一种低蛋白治疗肥胖的方法 | |
| CN105982921A (zh) | 一种治疗痛风的组合物及其应用 | |
| CN111840278A (zh) | 化合物与微生素e的组合在制备抗衰老药物或者化妆品中的用途 | |
| Eskin | New Research and Developments of Water-Soluble Vitamins | |
| CN1602959B (zh) | 一种组合物在制备提高免疫力广谱性防癌与延长癌症患者生命营养素产品中的应用 | |
| JP2007506645A (ja) | 抗腫瘍および抗転移のための製剤の製造におけるｎ−アセチル−ｄ−グルコサミンの使用 | |
| BR112015023730B1 (pt) | produto alimentício |
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: 23818905 Country of ref document: EP Kind code of ref document: A1 |