CN113797109A - 沙星类药物的抗衰老用途 - Google Patents
沙星类药物的抗衰老用途 Download PDFInfo
- Publication number
- CN113797109A CN113797109A CN202010538207.XA CN202010538207A CN113797109A CN 113797109 A CN113797109 A CN 113797109A CN 202010538207 A CN202010538207 A CN 202010538207A CN 113797109 A CN113797109 A CN 113797109A
- Authority
- CN
- China
- Prior art keywords
- aging
- sarcin
- composition
- pharmaceutically acceptable
- pazufloxacin
- 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
Links
- 239000003814 drug Substances 0.000 title claims abstract description 58
- 230000003712 anti-aging effect Effects 0.000 title claims abstract description 43
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 claims abstract description 63
- 229940079593 drug Drugs 0.000 claims abstract description 43
- XAGMUUZPGZWTRP-ZETCQYMHSA-N LSM-5745 Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1C1(N)CC1 XAGMUUZPGZWTRP-ZETCQYMHSA-N 0.000 claims abstract description 36
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 claims abstract description 36
- 229960003376 levofloxacin Drugs 0.000 claims abstract description 33
- 229960002625 pazufloxacin Drugs 0.000 claims abstract description 33
- BPFYOAJNDMUVBL-UHFFFAOYSA-N LSM-5799 Chemical compound C1CN(C)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN3N(C)COC1=C32 BPFYOAJNDMUVBL-UHFFFAOYSA-N 0.000 claims abstract description 32
- PWNMXPDKBYZCOO-UHFFFAOYSA-N Prulifloxacin Chemical compound C1=C2N3C(C)SC3=C(C(O)=O)C(=O)C2=CC(F)=C1N(CC1)CCN1CC=1OC(=O)OC=1C PWNMXPDKBYZCOO-UHFFFAOYSA-N 0.000 claims abstract description 32
- 229960001224 prulifloxacin Drugs 0.000 claims abstract description 31
- 229960003405 ciprofloxacin Drugs 0.000 claims abstract description 30
- 229960002531 marbofloxacin Drugs 0.000 claims abstract description 29
- 239000000203 mixture Substances 0.000 claims abstract description 28
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- 230000003287 optical effect Effects 0.000 claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 239000004480 active ingredient Substances 0.000 claims description 23
- 230000032683 aging Effects 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 13
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 claims description 8
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- BJRNKVDFDLYUGJ-RMPHRYRLSA-N hydroquinone O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-RMPHRYRLSA-N 0.000 claims description 8
- 239000002537 cosmetic Substances 0.000 claims description 7
- 239000000047 product Substances 0.000 claims description 7
- 238000009472 formulation Methods 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 108010008165 Etanercept Proteins 0.000 claims description 4
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 claims description 4
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 claims description 4
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 claims description 4
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 claims description 4
- 229960000271 arbutin Drugs 0.000 claims description 4
- 235000012754 curcumin Nutrition 0.000 claims description 4
- 229940109262 curcumin Drugs 0.000 claims description 4
- 239000004148 curcumin Substances 0.000 claims description 4
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 claims description 4
- 229960000403 etanercept Drugs 0.000 claims description 4
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 claims description 4
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims description 4
- 229960003105 metformin Drugs 0.000 claims description 4
- BJRNKVDFDLYUGJ-UHFFFAOYSA-N p-hydroxyphenyl beta-D-alloside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-UHFFFAOYSA-N 0.000 claims description 4
- 229960001285 quercetin Drugs 0.000 claims description 4
- 235000005875 quercetin Nutrition 0.000 claims description 4
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 4
- 229940016667 resveratrol Drugs 0.000 claims description 4
- 235000021283 resveratrol Nutrition 0.000 claims description 4
- 229960002930 sirolimus Drugs 0.000 claims description 4
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000002417 nutraceutical Substances 0.000 claims description 3
- 235000021436 nutraceutical agent Nutrition 0.000 claims description 3
- 239000000243 solution Substances 0.000 claims description 3
- 235000015872 dietary supplement Nutrition 0.000 claims description 2
- 235000013305 food Nutrition 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims description 2
- 239000006188 syrup Substances 0.000 claims description 2
- 235000020357 syrup Nutrition 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 241000244206 Nematoda Species 0.000 abstract description 41
- 241000894006 Bacteria Species 0.000 abstract description 30
- DYAHQFWOVKZOOW-UHFFFAOYSA-N Sarin Chemical compound CC(C)OP(C)(F)=O DYAHQFWOVKZOOW-UHFFFAOYSA-N 0.000 abstract description 9
- 230000002035 prolonged effect Effects 0.000 abstract description 9
- 238000004088 simulation Methods 0.000 abstract description 2
- 208000015181 infectious disease Diseases 0.000 description 13
- 230000000844 anti-bacterial effect Effects 0.000 description 11
- 230000000694 effects Effects 0.000 description 8
- 239000000126 substance Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 6
- 108020000946 Bacterial DNA Proteins 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 206010057190 Respiratory tract infections Diseases 0.000 description 4
- 229940124350 antibacterial drug Drugs 0.000 description 4
- 229940124307 fluoroquinolone Drugs 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 102000003844 DNA helicases Human genes 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 3
- 206010062255 Soft tissue infection Diseases 0.000 description 3
- 241000194017 Streptococcus Species 0.000 description 3
- 208000037386 Typhoid Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 210000001074 muscle attachment cell Anatomy 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 206010040872 skin infection Diseases 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 201000008297 typhoid fever Diseases 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 2
- 241000244202 Caenorhabditis Species 0.000 description 2
- 241000244203 Caenorhabditis elegans Species 0.000 description 2
- 206010008631 Cholera Diseases 0.000 description 2
- 208000003322 Coinfection Diseases 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 241000588914 Enterobacter Species 0.000 description 2
- 241000194033 Enterococcus Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000192125 Firmicutes Species 0.000 description 2
- 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 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 241000191940 Staphylococcus Species 0.000 description 2
- 241000191967 Staphylococcus aureus Species 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 201000001352 cholecystitis Diseases 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000005184 irreversible process Methods 0.000 description 2
- 238000001325 log-rank test Methods 0.000 description 2
- 208000004396 mastitis Diseases 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000004576 sand Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 230000001360 synchronised effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 208000019206 urinary tract infection Diseases 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 241001136249 Agriotes lineatus Species 0.000 description 1
- 206010048946 Anal abscess Diseases 0.000 description 1
- 206010060968 Arthritis infective Diseases 0.000 description 1
- 208000004429 Bacillary Dysentery Diseases 0.000 description 1
- 206010005940 Bone and joint infections Diseases 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- 241001647372 Chlamydia pneumoniae Species 0.000 description 1
- 208000014085 Chronic respiratory disease Diseases 0.000 description 1
- 108010054814 DNA Gyrase Proteins 0.000 description 1
- 108010041052 DNA Topoisomerase IV Proteins 0.000 description 1
- 108090000133 DNA helicases Proteins 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- 241000305071 Enterobacterales Species 0.000 description 1
- 241000588921 Enterobacteriaceae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 206010017915 Gastroenteritis shigella Diseases 0.000 description 1
- 206010061977 Genital infection female Diseases 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010022678 Intestinal infections Diseases 0.000 description 1
- 208000036209 Intraabdominal Infections Diseases 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- 241000589248 Legionella Species 0.000 description 1
- 208000007764 Legionnaires' Disease Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 241000588621 Moraxella Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 241000202934 Mycoplasma pneumoniae Species 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 206010036410 Postoperative wound infection Diseases 0.000 description 1
- 241000605861 Prevotella Species 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 241000607720 Serratia Species 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
- 208000031650 Surgical Wound Infection Diseases 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 206010053615 Thermal burn Diseases 0.000 description 1
- 206010046793 Uterine inflammation Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000003679 aging effect Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000003445 biliary tract Anatomy 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000008049 biological aging Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 208000003167 cholangitis Diseases 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000000686 essence Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 229940047650 haemophilus influenzae Drugs 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- GPVRVYYPEHBVLE-UHFFFAOYSA-N methyl 6-amino-5-cyano-4-(2-fluorophenyl)-2-(methoxymethyl)-4h-pyran-3-carboxylate Chemical compound N#CC1=C(N)OC(COC)=C(C(=O)OC)C1C1=CC=CC=C1F GPVRVYYPEHBVLE-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 229940072132 quinolone antibacterials Drugs 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 230000000979 retarding effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000008299 semisolid dosage form Substances 0.000 description 1
- 230000009758 senescence Effects 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 201000005113 shigellosis Diseases 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 210000002229 urogenital system Anatomy 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 238000012070 whole genome sequencing analysis Methods 0.000 description 1
Images
Classifications
-
- 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
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines having two or more nitrogen atoms in the same ring, e.g. oxadiazines
-
- 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
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Birds (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Toxicology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- Organic Chemistry (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供了沙星类药物在抗衰老方面的用途。具体地,本发明提供了以左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星为代表的沙星类药物、或其光学异构体、或其药学上可接受的盐在制备抗衰老制剂或组合物方面的用途。线虫模拟实验验证,左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星在活菌或者死菌喂养的情况下,均能有效延长线虫寿命。因此沙星类药物可有效应用于多种不同的抗衰老场合。
Description
技术领域
本发明涉及医药领域,具体地涉及沙星类药物的抗衰老用途。
背景技术
衰老是机体代谢过程中的一个必然阶段,表现为机体成熟后,随着年龄的增长,自身机能减退、应激能力和内环境的稳定性下降,器官和功能发生退行性改变的不可逆过程。此外,衰老还可导致多种疾病,如冠心病、恶性肿瘤、糖尿病以及脑和内脏的退行性疾病等。衰老及衰老相关疾病严重威胁着人类生命健康和生活质量,并加重社会医疗负担。
虽然衰老是一个不可逆转的过程,但研究表明它具有很大的可塑性,延缓衰老是有可能实现的。通过抗衰老药物来延缓衰老、减轻衰老相关疾病是最有效的干预对策之一。
因此本领域迫切需要开发新的抗衰老功能的活性成分及其应用。
发明内容
本发明的目的是提供一种新的具有抗衰老功能的活性成分及其应用。
具体地,本发明提供了以左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星为代表的沙星类药物安全有效的抗衰老用途。
在本发明的第一发面,提供了一种沙星类药物、或其光学异构体、或其药学上可接受的盐的用途,所述沙星类药物用于制备抗衰老的组合物或制剂。
在另一优选例中,所述组合物或制剂还包括额外的抗衰老活成分
在另一优选例中,所述的额外抗衰老活成分选自下组:二甲双胍、白藜芦醇、雷帕霉素、槲皮素、依那西普、姜黄素、熊果苷。
在另一优选例中,所述沙星类药物包括:左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星或其组合。
在另一优选例中,所述组合物或制剂用于延长寿命和/或延缓衰老。
在另一优选例中,所述组合物为药物组合物、化妆品组合物、膳食补充剂、食品组合物、保健品组合物。
在另一优选例中,所述的药物组合物含有a)沙星类药物、或其光学异构体、或其药学上可接受的盐;b)其他药学上可接受的载体或赋形剂。
在另一优选例中,所述药物组合物为注射用药或口服药物。
在另一优选例中,所述组合物(如药物组合物)的形式选自下组:片剂、胶囊剂、颗粒剂、混悬剂、丸剂、溶液剂、糖浆剂、或注射剂。
在本发明的第二方面,提供了一种化妆品或产品,所述化妆品或产品含有沙星类药物作为抗衰老的有效成分。
在另一优选例中,所述产品为保健品。
在另一优选例中,所述沙星类药物包括但不限于左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星或其组合。
在本发明的第三方面,提供了一种抗衰老方法,包括步骤:给需要的对象施用有效量的沙星类药物、或其光学异构体、或其药学上可接受的盐作为抗衰老活性成分。
在另一优选例中,所述沙星类药物包括但不限于左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星或其组合。
在另一优选例中,所述方法为体外方法。
在另一优选例中,所述方法为非诊断性,非治疗性的。
在本发明的第四方面,提供了一种用于抗衰老的药物组合物,所述的药物组合物含有:
(a1)沙星类药物、或其光学异构体、或其药学上可接受的盐作为活性成分;
(a2)额外的抗衰老活成分,所述的额外抗衰老活成分选自下组:二甲双胍、白藜芦醇、雷帕霉素、槲皮素、依那西普、姜黄素、熊果苷;
(b)药学上可接受的载体或赋形剂。
在另一优选例中,所述沙星类药物包括但不限于左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星或其组合。
应理解,在本发明范围内中,本发明的上述各技术特征和在下文(如实施例)中具体描述的各技术特征之间都可以互相组合,从而构成新的或优选的技术方案。限于篇幅,在此不再一一累述。
附图说明
图1显示了在实施例1中,沙星类药物左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星(100μM)在活菌喂养时均延长线虫寿命(>10%)。
图2显示了在实施例2中,沙星类药物左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星(100μM)在死菌喂养时均延长线虫寿命(>10%)。
具体实施方式
本发明人经过广泛而深入的研究,经过大量筛选,首次意外地发现沙星类药物具有显著的抗衰老活性,因此可应用于各种抗衰老场合,在此基础上完成了本发明。
具体地,线虫模型实验表明,以左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星为代表的沙星类药物能有效延长线虫寿命,从而表明沙星类药物在延缓衰老,延长寿命方面有出乎意料的效果。
术语
如本文所用,术语如“本发明的活性成分”、“本发明的抗衰老的活性成分”、“本发明化合物”、“本发明的抗衰老化合物”指沙星类药物、或其药学上可接受的盐、或其溶剂化物、或其光学异构体、或其外消旋体、或其晶体、或其水合物、或其氘代化合物、或其组合。
衰老和抗衰老
如本文所用,“衰老(aging)”指随时间增加,有机体在构成物质、组织结构、生理功能等方面发生的丧失和退化过程。在本发明中,衰老指生物学衰老。
如本文所用,“抗衰老”是指延缓、阻滞、减少、停止和/或逆转衰老效果或进程。
活性成分
本发明提供了一沙星类药物为活性成分的药物组合或制剂。优选地本发明的活性成分为左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星或其组合。
左氧氟沙星
左氧氟沙星(levofloxacin)为左氧氟沙星的左旋体,其体外抗菌活性约为左氧氟沙星的两倍。其作用机制是通过抑制细菌DNA旋转酶的活性,阻止细菌DNA的合成和复制而导致细菌死亡。左氧氟沙星具有广谱抗菌作用,抗菌作用强,对多数肠杆菌科细菌都有较强的抗菌活性。对金黄色葡萄球菌、肺炎链球菌、化脓性链球菌等革兰氏阳性菌和肺炎支原体、肺炎衣原体也有抗菌作用,但对厌氧菌和肠球菌的作用较差。适用于敏感菌引起的泌尿生殖系统感染,呼吸道感染,胃肠道感染,伤寒,骨和关节感染,皮肤软组织感染,败血症等全身感染,慢性支气管炎等。化学式:C18H20FN3O4,分子量:361.37,CAS号:100986-85-4。结构式如式(Ⅰ)所示:
环丙沙星
环丙沙星(ciprofloxacin)为合成的第三代喹诺酮类抗菌药物,作用于细菌DNA螺旋酶,抑制DNA的合成和复制,促进细菌死亡。环丙沙星的抗菌谱广,杀菌效果好,对肠杆菌、绿脓杆菌、流感嗜血杆菌、淋球菌链球菌、军团菌以及金黄色葡萄球菌等革兰氏阳性和阴性细菌均有很好的效果。临床上主要适用于敏感菌所引起的呼吸道感染、泌尿系感染、肠道感染、胆系感染、腹腔内感染、妇科疾病感染、骨关节感染以及全身严重感染的治疗。化学式:C17H18FN3O3,分子量:331.35,CAS号:85721-33-1。结构式如式(Ⅱ)所示:
马波沙星
马波沙星(marbofloxacin)为一种新型的兽用氟喹诺酮类抗菌药。马波沙星通过抑制细菌的DNA转录酶从而抑制细菌的生长,对革兰氏阴性菌、革兰氏阳性菌和支原体均有抗菌作用。可用于治疗敏感菌所致的牛、猪、犬、猫的呼吸道、消化道、泌尿道及皮肤等感染。对牛、羊乳腺炎及猪乳腺炎-子宫炎-无乳综合征亦有疔效。化学式:C17H19FN4O4,分子量:362.35,CAS号:115550-35-1。结构式如式(Ⅲ)所示:
帕珠沙星
帕珠沙星(pazufloxacin)为第四代氟喹诺酮类抗菌药,它的主要作用机理是通过抑制细菌DNA螺旋酶酶拓扑异构酶Ⅳ的活性,阻碍细菌DNA的复制而达到抗菌作用。帕珠沙星对临床分离的葡萄球菌属、肠杆菌属、铜绿假单孢菌、各种革兰氏阴性菌、拟肝菌及普雷沃氏属细菌有强大的抗菌活性。适用于敏感菌引起的慢性呼吸道疾病继发性感染,肺炎,外科伤口感染,胆囊炎,生殖器官感染,皮肤软组织感染等。化学式:C16H15FN2O4,分子量:318.2997,CAS号:127045-41-4。结构式如式(Ⅳ)所示:
普卢利沙星
普卢利沙星(prulifloxacin)为氟喹诺酮类前体药物,作用机制为其活性代谢物在体内对DNA回旋酶有较强的抑制活性。主要用于治疗对普卢利沙星活性主体敏感的葡萄球菌、链球菌、肺炎球菌、肠球菌、莫拉克斯氏菌、大肠菌、志贺杆菌、沙门氏菌(伤寒菌、副伤寒菌除外)、柠檬酸菌、克雷伯氏菌、肠杆菌、沙雷氏菌属、变形杆菌、霍乱菌、流感菌、绿脓菌、消化链球菌引起的感染。适应症为敏感菌引起的皮肤和软组织感染,肛门周围脓肿,外伤、烫伤、手术等浅表性继发性感染;呼吸系统感染;泌尿生殖系统感染;胆囊炎、胆管炎;感染性肠炎、细菌性痢疾、伤寒、霍乱;眼、耳、鼻感染。化学式:C21H20FN3O6S,分子量:461.463,CAS号:123447-62-1。结构式如式(Ⅴ)所示:
秀丽隐杆线虫
秀丽隐杆线虫作为一个经典的衰老模型已经取得了很多优秀的研究成果,其具有体型小、生命周期短、易于培养与操作、遗传背景清晰等特点。且线虫是第一个完成全基因组测序的模式动物,其基因组很小且与人类同源性较高。这些特点使其在抗衰老药物的高通量筛选上具有得很大的优势。
组合物及施用方法
本发明还提供了含有本发明活性成分的组合物或制剂或产品,所述组合物或制剂或产品可用于抗衰老。代表性的组合物或制剂或产品包括抗衰老的药物、保健品、和化妆品。
一种优选的组合物是药物组合物,它含有有效量的沙星类药物或其药学上可接受的盐和药学上可接受的载体。
如本文所用,术语“有效量”或“有效剂量”是指可对人和/或动物产生功能或活性(即抗衰老功能)的且可被人和/或动物所接受的量。
如本文所用,术语“药学上可接受的”的成分是适用于人和/或哺乳动物而无过度不良副反应(如毒性、刺激和变态反应)的,即具有合理的效益/风险比的物质。术语“药学上可接受的载体”指用于治疗剂给药的载体,包括各种赋形剂和稀释剂。
本发明的药物组合物含有安全有效量的本发明的活性成分以及药学上可接受的载体。这类载体包括(但并不限于):盐水、缓冲液、葡萄糖、水、甘油、乙醇、及其组合。通常药物制剂应与给药方式相匹配,本发明的药物组合物的剂型为注射剂、口服制剂(片剂、胶囊、口服液)、透皮剂、缓释剂。例如用生理盐水或含有葡萄糖和其他辅剂的水溶液通过常规方法进行制备。所述的药物组合物宜在无菌条件下制造。
本发明所述的活性成分的有效量可随给药的模式和待治疗的疾病的严重程度等而变化。优选的有效量的选择可以由本领域普通技术人员根据各种因素来确定(例如通过临床试验)。所述的因素包括但不限于:所述的活性成分的药代动力学参数例如生物利用率、代谢、半衰期等;患者所要治疗的疾病的严重程度、患者的体重、患者的免疫状况、给药的途径等。通常,当本发明的活性成分每天以约0.00001mg-50mg/kg动物体重(较佳的0.0001mg-10mg/kg动物体重)的剂量给予,能得到令人满意的效果。例如,由治疗状况的迫切要求,可每天给予若干次分开的剂量,或将剂量按比例地减少。
典型地,当以口服方式给予沙星类药物时,一个60kg体重的对象(人),日平均剂量通常为10-500mg,较佳地20-300mg,更佳地50-250mg。所述日剂量可以分一次、二次或多次服用。
本发明所述的药学上可接受的载体包括(但不限于):水、盐水、脂质体、脂质、肽类物质、纤维素、纳米凝胶、或其组合。载体的选择应与给药方式相匹配,这些都是本领域的普通技术人员所熟知的。
本发明的药物组合物还包括其他额外的抗衰老活性成分,所述额外的抗衰老活性成分选自下组:二甲双胍、白藜芦醇、雷帕霉素、槲皮素、依那西普、姜黄素、熊果苷。
抗衰老的方法
本发明提供了一种抗衰老方法(包括治疗性方法、或体外非治疗性方法)。
典型地,该方法包括:向培养的细胞体系内加入本发明药物组合物或本发明活性成分,从而延缓衰老进程延长寿命。
本发明还提供了一种抗衰老方法,包括步骤:给需要的对象施用沙星类药物、或其光学异构体、或其药学上可接受的盐作为抗衰老活性成分。
优选地,所述的抗衰老方法为给所述对象的皮肤施用(或施涂)含沙星类药物或其盐的化妆品。
在本发明中,代表性的化妆品的剂型可选自下组(但并不限于):固体剂型、半固体剂型、液体剂型、或其组合,如溶液、凝胶、膏霜、乳液、精华、透皮贴、面膜等。
本发明的主要优点在于:
a)首次证实了沙星类药物尤其是左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星可以有效的延长寿命,延缓衰老。
b)在较低的剂量下(100μM浓度下),以左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星为代表的沙星类药物,活菌条件下可以延长线虫寿命超过10%。其中左氧氟沙星、普卢利沙星延长线虫寿命超过20%。
c)在较低的剂量下(100μM浓度下),以左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星为代表的沙星类药物,死菌条件下可以延长线虫寿命超过10%。其中帕珠沙星延长线虫寿命超过30%。
下面结合具体实施例,进一步阐述本发明。应理解,这些实施例仅用于说明本发明而不用于限制本发明的范围。下列实施例中未注明具体条件的实验方法,通常按照常规条件,例如Sambrook等人,分子克隆:实验室手册(New York:Cold Spring HarborLaboratory Press,1989)中所述的条件,或按照制造厂商所建议的条件。除非另外说明,否则百分比和份数是重量百分比和重量份数。
实施例中的材料购自市场或用常规方法制备。
材料
左氧氟沙星(CAS:100986-85-4),环丙沙星(CAS:85721-33-1)、马波沙星(CAS:115550-35-1)、帕珠沙星(CAS:127045-41-4)、普卢利沙星(CAS:123447-63-2),均购自上海泰坦科技股份有限公司。
野生型秀丽隐杆线虫(N2)购自CAENORHABDITIS GENETICS CENTER(CGC)。
实施例1.沙星类药物左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星在活菌上的线虫寿命实验
同步化后的线虫在L4期转移至空白对照组和沙星类药物给药组(100μM)的线虫生长培养基(NGM)上,每组约15条线虫,每2天更换一次培养基,于20℃条件下培养。每天记录存活线虫数量,将死亡的线虫移出培养皿,直至线虫全部死亡。汇总数据,用Graph Pad绘制生存曲线,并计算显著性差异(Log-rank test)。
实验结果如表1所示,生存曲线如图1所示。
沙星类药物在100μM给药浓度下在活菌上延长线虫寿命大于10%。与对照组相比,100μM浓度下,左氧氟沙星延长线虫寿命29.85%,环丙沙星延长线虫寿命10.45%、马波沙星延长线虫寿命19.11%、帕珠沙星延长线虫寿命17.91%、普卢利沙星延长线虫寿命29.85%。显著性差异相对于对照组:*表示P<0.05。
表1.寿命实验数据
线虫株 | 药物处理 | 平均寿命(天) | 延长寿命 |
N2 | — | 12.07 | — |
N2 | 左氧氟沙星 | 16.40 | 35.87% |
N2 | 环丙沙星 | 13.80 | 14.33% |
N2 | 马波沙星 | 16.20 | 34.22% |
N2 | 帕珠沙星 | 14.80 | 22.62% |
N2 | 普卢利沙星 | 16.40 | 35.87% |
注:“—”代表空白对照组。
实施例2.沙星类药物左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星在死菌上的线虫寿命实验
为排除沙星类药物通过杀菌作用或影响细菌代谢来延长线虫寿命,在死菌上对沙星类药物再次进行寿命实验。
左氧氟沙星(CAS:100986-85-4),环丙沙星(CAS:85721-33-1)、马波沙星(CAS:115550-35-1)、帕珠沙星(CAS:127045-41-4)、普卢利沙星(CAS:123447-63-2),均购自上海泰坦科技股份有限公司;野生型秀丽隐杆线虫(N2)购自CAENORHABDITIS GENETICS CENTER(CGC)。同步化后的线虫在L4期转移至空白对照组和沙星类药物给药组(100μM)的线虫生长培养基(NGM)上,每组约60条线虫,每2天更换一次培养基,于20℃条件下培养。每天记录存活线虫数量,将死亡的线虫移出培养皿,直至线虫全部死亡。汇总数据,用Graph Pad绘制生存曲线,并计算显著性差异(Log-rank test)。
实验结果如表2所示,生存曲线如图2所示。
沙星类药物在100μM给药浓度下在死菌上延长线虫寿命大于10%。与对照组相比,100μM浓度下,左氧氟沙星延长线虫寿命20.89%,环丙沙星延长线虫寿命10.36%、马波沙星延长线虫寿命19.18%、帕珠沙星延长线虫寿命30.98%、普卢利沙星延长线虫寿命14.96%。显著性差异相对于对照组:*表示P<0.05,**表示P<0.01,***表示P<0.001。
表2.寿命实验数据
线虫株 | 药物处理 | 平均寿命(天) | 延长寿命 |
N2 | — | 18.72 | — |
N2 | 左氧氟沙星 | 22.63 | 20.89% |
N2 | 环丙沙星 | 20.66 | 10.36% |
N2 | 马波沙星 | 22.31 | 19.18% |
N2 | 帕珠沙星 | 24.52 | 30.98% |
N2 | 普卢利沙星 | 21.52 | 14.96% |
注:“—”代表空白对照组。
综上所述,本发明经线虫寿命实验,结果表明,本发明所述的沙星类药物左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星在活菌和死菌上均能延长线虫的寿命,在抗衰老领域具有高度利用价值。
讨论
在“人口老龄化”现状及“实施健康中国战略”背景下,抗衰老药物的开发具有重要意义。
而沙星类药物目前多被报道应用于抗菌,是一类化学合成的抗菌药物,又称氟喹诺酮类药物。
目前,一般认为沙星类(喹诺酮类)药物的抗菌机理为,作用于细菌细胞DNA螺旋酶的A亚单位,抑制DNA的合成和复制而导致细菌死亡。有研究表明,沙星类药物会对肌腱细胞和中枢神经细胞产生毒性作用。
近年来很多研究发现沙星类抗菌药导致的毒性作用与氧化应激有关,它们会诱导肌腱细胞中产生过量的ROS,从而激活基质金属蛋白酶,引起肌腱细胞的损伤。
目前,在本发明之前,尚没有文献报道沙星类药物左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星具有抗衰老作用。
出乎意料的是,本发明人通过线虫模拟实验证明,左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星在活菌或者死菌喂养的情况下,均能有效延长线虫寿命。因此沙星类药物可有效应用于多种不同的抗衰老场合。
在本发明提及的所有文献都在本申请中引用作为参考,就如同每一篇文献被单独引用作为参考那样。此外应理解,在阅读了本发明的上述讲授内容之后,本领域技术人员可以对本发明作各种改动或修改,这些等价形式同样落于本申请所附权利要求书所限定的范围。
Claims (10)
1.一种沙星类药物、或其光学异构体、或其药学上可接受的盐的用途,其特征在于,所述沙星类药物用于制备抗衰老的组合物或制剂。
2.如权利要求1所述用途,其特征在于,所述沙星类药物选自下组:左氧氟沙星、环丙沙星、马波沙星、帕珠沙星、普卢利沙星或其组合。
3.如权利要求1所述的用途,其特征在于,所述组合物或制剂用于延长寿命和/或延缓衰老。
4.如权利要求1所述的用途,其特征在于,所述组合物为药物组合物、化妆品组合物、膳食补充剂、食品组合物、保健品组合物。
5.如权利要求4所述的用途,其特征在于,所述的药物组合物含有a)沙星类药物、或其光学异构体、或其药学上可接受的盐;b)其他药学上可接受的载体或赋形剂。
6.如权利要求4所述的用途,其特征在于,所述药物组合物为注射用药或口服药物。
7.如权利要求1所述的用途,其特征在于,所述组合物的形式选自下组:片剂、胶囊剂、颗粒剂、混悬剂、丸剂、溶液剂、糖浆剂、或注射剂。
8.一种化妆品或产品,其特征在于,所述化妆品或产品含有沙星类药物作为抗衰老的有效成分。
9.一种抗衰老方法,其特征在于,包括步骤:给需要的对象施用有效量的沙星类药物、或其光学异构体、或其药学上可接受的盐作为抗衰老活性成分。
10.一种用于抗衰老的药物组合物,其特征在于,所述的药物组合物含有:
(a1)沙星类药物、或其光学异构体、或其药学上可接受的盐作为活性成分;
(a2)额外的抗衰老活成分,所述的额外抗衰老活成分选自下组:二甲双胍、白藜芦醇、雷帕霉素、槲皮素、依那西普、姜黄素、熊果苷;和
(b)药学上可接受的载体或赋形剂。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010538207.XA CN113797109A (zh) | 2020-06-12 | 2020-06-12 | 沙星类药物的抗衰老用途 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010538207.XA CN113797109A (zh) | 2020-06-12 | 2020-06-12 | 沙星类药物的抗衰老用途 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN113797109A true CN113797109A (zh) | 2021-12-17 |
Family
ID=78944130
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010538207.XA Pending CN113797109A (zh) | 2020-06-12 | 2020-06-12 | 沙星类药物的抗衰老用途 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113797109A (zh) |
-
2020
- 2020-06-12 CN CN202010538207.XA patent/CN113797109A/zh active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TWI235060B (en) | Pharmaceutical compositions comprising substituted pyrazolyl benzenesulfonamide derivatives for use in treating or preventing an epithelial cell-derived neoplasia | |
KR20180123475A (ko) | 피부 건강을 촉진하기 위한 조성물 및 방법 | |
WO2020149647A1 (ko) | 페디오코쿠스 이노피나투스를 포함하는 퇴행성 뇌질환의 예방, 개선 또는 치료용 조성물 | |
KR20190080875A (ko) | 모발 성장 자극을 위한 알파-케토부티레이트, 알파-케토글루타레이트, 및 2-하이드록시부티레이트 | |
JP7379152B2 (ja) | 筋線維化抑制用組成物 | |
CN107427697A (zh) | 在非人动物中治疗腹泻和促进肠道健康的方法 | |
EP3190893B1 (en) | Compositions and methods for treating and preventing bacterial infections | |
TWI486162B (zh) | 異類葉升麻苷或其醫藥學上可接受之鹽於抑制澱粉樣β肽生成、累積或聚集、以及製備預防或治療澱粉樣β肽相關疾病或狀況的藥物之用途 | |
JP2005200339A (ja) | 抗菌剤 | |
WO2014030763A1 (ja) | 抗腫瘍剤 | |
ES2973249T3 (es) | Composición que comprende cepa de Agathobaculum sp. como ingrediente efectivo para la prevención, alivio o tratamiento del trastorno del espectro autista | |
CN113797109A (zh) | 沙星类药物的抗衰老用途 | |
JP2010526125A (ja) | ハイビスカスの新規使用、特に製薬的使用 | |
KR20230054431A (ko) | 오토파지 활성화제 | |
US20140186271A1 (en) | Reducing dental caries | |
KR102488864B1 (ko) | 가자 추출물 및 애엽 추출물을 함유하는 피부세균총의 생장 조절 또는 피부 면역 강화용 조성물 | |
CN106102741A (zh) | 包含抗菌剂的药物组合物 | |
KR101764303B1 (ko) | 효소처리된 감초 추출물을 함유하는 바이오필름 형성 방지용 조성물 | |
WO2022139341A1 (ko) | 클레마스틴을 포함하는 강박장애, 틱 장애 또는 뚜렛 증후군 예방 또는 치료용 약학 조성물 | |
WO2024045809A1 (zh) | 用于改善哺乳动物毛囊、头皮或毛发健康的方法和组合物 | |
RU2753606C1 (ru) | Антибактериальное гуминовое средство | |
KR102342160B1 (ko) | 탁시폴린을 포함하는 바이오필름 형성 억제용 조성물 | |
KR102441377B1 (ko) | 펙토리나린을 포함하는 바이오필름 형성 억제용 조성물 | |
US20230303638A1 (en) | Peptide derived from pep27 peptide and uses thereof | |
US20220241356A1 (en) | Composition for preventing, treating, or alleviating viral infection diseases or respiratory diseases comprising vesicle derived from lactobacillus paracasei |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |