HRP20040207A2 - Ascorbic acid derivatives, methods of synthesis and pharmaceutical use thereof - Google Patents
Ascorbic acid derivatives, methods of synthesis and pharmaceutical use thereof Download PDFInfo
- Publication number
- HRP20040207A2 HRP20040207A2 HR20040207A HRP20040207A HRP20040207A2 HR P20040207 A2 HRP20040207 A2 HR P20040207A2 HR 20040207 A HR20040207 A HR 20040207A HR P20040207 A HRP20040207 A HR P20040207A HR P20040207 A2 HRP20040207 A2 HR P20040207A2
- Authority
- HR
- Croatia
- Prior art keywords
- lysine
- proline
- ascorbyl
- ascorbic acid
- polylysine
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 133
- 125000003289 ascorbyl group Chemical class [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 title claims description 7
- 230000015572 biosynthetic process Effects 0.000 title description 24
- 238000003786 synthesis reaction Methods 0.000 title description 22
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 474
- 229960005070 ascorbic acid Drugs 0.000 claims description 228
- 239000002211 L-ascorbic acid Substances 0.000 claims description 212
- 235000000069 L-ascorbic acid Nutrition 0.000 claims description 212
- 239000004472 Lysine Substances 0.000 claims description 176
- 150000000996 L-ascorbic acids Chemical class 0.000 claims description 141
- 235000018977 lysine Nutrition 0.000 claims description 99
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims description 95
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 89
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 87
- 229920000656 polylysine Polymers 0.000 claims description 86
- 235000013930 proline Nutrition 0.000 claims description 80
- 229920000037 Polyproline Polymers 0.000 claims description 78
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 75
- YMOKUFVJGLVTQG-LBNWCAIBSA-N (5S)-5-bromo-3,4-dihydroxy-5-[(1S)-1-hydroxyethyl]furan-2-one Chemical compound C[C@H](O)[C@@]1(Br)OC(=O)C(O)=C1O YMOKUFVJGLVTQG-LBNWCAIBSA-N 0.000 claims description 73
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 58
- 230000008569 process Effects 0.000 claims description 57
- 238000002955 isolation Methods 0.000 claims description 50
- 238000004519 manufacturing process Methods 0.000 claims description 27
- 108010026466 polyproline Proteins 0.000 claims description 20
- 108010039918 Polylysine Proteins 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- LGBPWIAXPVUTMY-JLAZNSOCSA-N (2r)-3,4-dihydroxy-2-[(1s)-1-hydroxyethyl]-2h-furan-5-one Chemical compound C[C@H](O)[C@H]1OC(=O)C(O)=C1O LGBPWIAXPVUTMY-JLAZNSOCSA-N 0.000 claims description 17
- DGQAOZJEDXIMGQ-RAGRJFKESA-N N1[C@@H](CCC1)C(=O)O.N[C@@H](CCCCN)C(=O)O.O=C1C(O)=C(O)[C@H](O1)[C@@H](O)C Chemical compound N1[C@@H](CCC1)C(=O)O.N[C@@H](CCCCN)C(=O)O.O=C1C(O)=C(O)[C@H](O1)[C@@H](O)C DGQAOZJEDXIMGQ-RAGRJFKESA-N 0.000 claims description 14
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
- 239000003937 drug carrier Substances 0.000 claims description 13
- PFTMONKBZOUTNL-LBNWCAIBSA-N (5R)-5-amino-3,4-dihydroxy-5-[(1S)-1-hydroxyethyl]furan-2-one Chemical compound C[C@H](O)[C@@]1(N)OC(=O)C(O)=C1O PFTMONKBZOUTNL-LBNWCAIBSA-N 0.000 claims description 12
- 150000002669 lysines Chemical class 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 7
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 6
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 6
- 210000002744 extracellular matrix Anatomy 0.000 claims description 6
- 150000003148 prolines Chemical class 0.000 claims description 5
- 230000032683 aging Effects 0.000 claims description 4
- 230000015556 catabolic process Effects 0.000 claims description 4
- 210000002808 connective tissue Anatomy 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 230000006378 damage Effects 0.000 claims description 3
- 238000006731 degradation reaction Methods 0.000 claims description 3
- 239000004615 ingredient Substances 0.000 claims description 3
- 230000003647 oxidation Effects 0.000 claims description 3
- 238000007254 oxidation reaction Methods 0.000 claims description 3
- 230000003449 preventive effect Effects 0.000 claims description 3
- 230000000087 stabilizing effect Effects 0.000 claims description 3
- 230000000699 topical effect Effects 0.000 claims description 3
- 229960002429 proline Drugs 0.000 description 130
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 54
- 238000002360 preparation method Methods 0.000 description 24
- 235000010323 ascorbic acid Nutrition 0.000 description 23
- 239000011668 ascorbic acid Substances 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- 150000001875 compounds Chemical class 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 10
- 229940024606 amino acid Drugs 0.000 description 9
- 235000001014 amino acid Nutrition 0.000 description 9
- 150000001413 amino acids Chemical class 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 8
- 229940072107 ascorbate Drugs 0.000 description 7
- 102000008186 Collagen Human genes 0.000 description 5
- 108010035532 Collagen Proteins 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 229920001436 collagen Polymers 0.000 description 5
- VTVJMWZZVJSEMO-BYPYZUCNSA-N (2s)-pyrrolidine-2-carbonyl chloride Chemical compound ClC(=O)[C@@H]1CCCN1 VTVJMWZZVJSEMO-BYPYZUCNSA-N 0.000 description 4
- UHRMWQROTNVNIC-LGASVIGRSA-N N1[C@@H](CCC1)C(=O)O.O=C1C(O)=C(O)[C@H](O1)[C@@H](O)C Chemical compound N1[C@@H](CCC1)C(=O)O.O=C1C(O)=C(O)[C@H](O1)[C@@H](O)C UHRMWQROTNVNIC-LGASVIGRSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 206010047623 Vitamin C deficiency Diseases 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 208000010233 scurvy Diseases 0.000 description 4
- CWPDRBAWZYJDEH-YFKPBYRVSA-N (2s)-2,6-diaminohexanoyl chloride Chemical compound NCCCC[C@H](N)C(Cl)=O CWPDRBAWZYJDEH-YFKPBYRVSA-N 0.000 description 3
- 241000700198 Cavia Species 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 3
- -1 Oxygen radicals Chemical class 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 229960002591 hydroxyproline Drugs 0.000 description 3
- 235000016709 nutrition Nutrition 0.000 description 3
- 230000035764 nutrition Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 102000008490 2-Oxoglutarate 5-Dioxygenase Procollagen-Lysine Human genes 0.000 description 2
- 108010020504 2-Oxoglutarate 5-Dioxygenase Procollagen-Lysine Proteins 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 description 2
- 229930182821 L-proline Natural products 0.000 description 2
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 2
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 2
- OPORUQUGAXTWMO-BHQVQWGSSA-N N[C@@H](CCCCN)C(=O)O.O=C1C(O)=C(O)[C@H](O1)[C@@H](O)C Chemical compound N[C@@H](CCCCN)C(=O)O.O=C1C(O)=C(O)[C@H](O1)[C@@H](O)C OPORUQUGAXTWMO-BHQVQWGSSA-N 0.000 description 2
- 102000004079 Prolyl Hydroxylases Human genes 0.000 description 2
- 108010043005 Prolyl Hydroxylases Proteins 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 2
- 235000019688 fish Nutrition 0.000 description 2
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 229960003646 lysine Drugs 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- PHIQHXFUZVPYII-ZCFIWIBFSA-O (R)-carnitinium Chemical compound C[N+](C)(C)C[C@H](O)CC(O)=O PHIQHXFUZVPYII-ZCFIWIBFSA-O 0.000 description 1
- 208000006770 Ascorbic Acid Deficiency Diseases 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000238424 Crustacea Species 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 206010014080 Ecchymosis Diseases 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 235000019766 L-Lysine Nutrition 0.000 description 1
- MIJPAVRNWPDMOR-ZAFYKAAXSA-N L-ascorbic acid 2-phosphate Chemical compound OC[C@H](O)[C@H]1OC(=O)C(OP(O)(O)=O)=C1O MIJPAVRNWPDMOR-ZAFYKAAXSA-N 0.000 description 1
- XDBMXUKHMOFBPJ-ZAFYKAAXSA-N L-ascorbic acid 2-sulfate Chemical compound OC[C@H](O)[C@H]1OC(=O)C(OS(O)(=O)=O)=C1O XDBMXUKHMOFBPJ-ZAFYKAAXSA-N 0.000 description 1
- 235000000072 L-ascorbyl-6-palmitate Nutrition 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- TWNQRDJRQVTDRR-VQNUYYGJSA-N N1[C@@H](CCC1)C(=O)O.N[C@]1(C(=C(C(=O)O1)O)O)[C@@H](O)C Chemical compound N1[C@@H](CCC1)C(=O)O.N[C@]1(C(=C(C(=O)O1)O)O)[C@@H](O)C TWNQRDJRQVTDRR-VQNUYYGJSA-N 0.000 description 1
- GKKADTUCRPMBOH-ZQLOENRLSA-N N[C@@H](CCCCN)C(=O)O.N[C@]1(C(=C(C(=O)O1)O)O)[C@@H](O)C Chemical compound N[C@@H](CCCCN)C(=O)O.N[C@]1(C(=C(C(=O)O1)O)O)[C@@H](O)C GKKADTUCRPMBOH-ZQLOENRLSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000013566 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 241000277331 Salmonidae Species 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 229960004203 carnitine Drugs 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 241001233037 catfish Species 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000004195 gingiva Anatomy 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 235000008212 improved nutritional status Nutrition 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 210000003041 ligament Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000000955 neuroendocrine Effects 0.000 description 1
- 235000003170 nutritional factors Nutrition 0.000 description 1
- 230000004792 oxidative damage Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000006069 physical mixture Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 210000000515 tooth Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/62—Three oxygen atoms, e.g. ascorbic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
- Furan Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US31485701P | 2001-08-24 | 2001-08-24 | |
| PCT/EP2002/009451 WO2003018568A2 (en) | 2001-08-24 | 2002-08-23 | Ascorbic acid derivatives, methods of synthesis and pharmaceutical use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20040207A2 true HRP20040207A2 (en) | 2005-02-28 |
Family
ID=23221754
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20040207A HRP20040207A2 (en) | 2001-08-24 | 2004-03-02 | Ascorbic acid derivatives, methods of synthesis and pharmaceutical use thereof |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US6864284B2 (no) |
| EP (3) | EP2241559A3 (no) |
| JP (1) | JP4162593B2 (no) |
| KR (1) | KR20040044472A (no) |
| CN (3) | CN100360514C (no) |
| BR (1) | BR0205944A (no) |
| CA (1) | CA2458344A1 (no) |
| HR (1) | HRP20040207A2 (no) |
| HU (1) | HUP0600084A2 (no) |
| IL (4) | IL155578A0 (no) |
| MX (1) | MXPA04001655A (no) |
| NO (1) | NO20031844L (no) |
| NZ (3) | NZ531430A (no) |
| PL (1) | PL373522A1 (no) |
| RU (1) | RU2309152C2 (no) |
| UA (1) | UA78223C2 (no) |
| WO (2) | WO2003018568A2 (no) |
| YU (1) | YU38103A (no) |
| ZA (1) | ZA200304712B (no) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040067890A1 (en) * | 2002-10-04 | 2004-04-08 | Gupta Shyam K. | Ascorbic acid salts of organic bases with enhanced bioavailability for synergictic anti-aging and skin protective cosmetic compositions |
| EP1620419A4 (en) * | 2003-04-21 | 2008-07-23 | Tagra Biotechnologies Ltd | STABILIZED DERIVATIVES OF ASCORBIC ACID |
| CN100346782C (zh) * | 2004-05-21 | 2007-11-07 | 北京京卫信康医药科技发展有限公司 | 一种含氨基酸的维生素c组合物 |
| KR100544159B1 (ko) * | 2004-07-14 | 2006-01-24 | 센양 뉴라이프 인더스트리알 코 엘티디 | 아스코르빌 테트라이소팔미테이트와 디팔미토일하이드록시프롤린을 함유한 나노 에멀젼 및 이를함유하는 화장료 조성물 |
| US20070002866A1 (en) * | 2005-06-29 | 2007-01-04 | Denso Corporation | Receive power priority flooding in mobile ad hoc networks |
| US8865228B2 (en) | 2006-02-21 | 2014-10-21 | Mary Kay Inc. | Stable vitamin C compositions |
| US20080188553A1 (en) * | 2007-02-06 | 2008-08-07 | Waheed M Roomi | Novel ascorbic acid compounds, methods of synthesis and application use thereof |
| FR2913686B1 (fr) * | 2007-03-14 | 2009-05-01 | Oreal | Nouveaux composes carbamates de vitamine c, compositions les comprenant, et utilisations |
| US8828960B2 (en) * | 2007-07-17 | 2014-09-09 | Idexx Laboratories, Inc. | Amino acid vitamin ester compositions for controlled delivery of pharmaceutically active compounds |
| WO2018005762A2 (en) * | 2016-06-29 | 2018-01-04 | Orasis Medical, Inc. | Ascorbic acid-amino acid conjugates and their use in regulation of fluid outflow |
| CA3075607A1 (en) * | 2017-09-15 | 2019-03-21 | Kine Sciences Co., Ltd. | Use of peptides as therapeutic agent for autoimmune diseases and bone diseases |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1273989A (fr) * | 1960-09-09 | 1961-10-20 | Marbou | Procédé de préparation de l'ascorbate de lysine |
| US4424232A (en) * | 1982-05-19 | 1984-01-03 | Parkinson Richard W | Treatment of herpes simplex |
| US4518614A (en) * | 1982-11-04 | 1985-05-21 | Redken Laboratories, Inc. | Cosmetic preparation |
| JPS63190882A (ja) * | 1987-02-03 | 1988-08-08 | Nippon Haipotsukusu:Kk | アスコルビン酸誘導体及びそれを含有する皮膚脱色剤並びにその製造法 |
| FR2650180B1 (fr) * | 1989-07-31 | 1995-03-03 | Chisso Corp | Procede de production d'une feuille facilement soluble dans l'eau a base d'acide hyaluronique ou de hyaluronate et feuille ainsi obtenue |
| EP0532706B1 (en) * | 1990-06-04 | 1995-05-10 | Health Now | REDUCTION OF CARDIOVASCULAR VESSEL OCCLUSIONS WITH ASCORBATE AND LIPOPROTEIN (a) BINDING INHIBITORS |
| JPH04247011A (ja) * | 1991-02-04 | 1992-09-03 | Q P Corp | リン脂質系アスコルビン酸誘導体及び該誘導体を含む皮膚外用剤 |
| US5977073A (en) * | 1991-06-06 | 1999-11-02 | Life Sciences' Technologies, Inc. | Nutrient composition for treatment of immune disorders |
| JPH0666958A (ja) * | 1991-08-29 | 1994-03-11 | Masaki Yoshigaki | 目覚し時計の目覚し設定並びに目覚し音停止機構 |
| JPH0678560A (ja) * | 1992-08-26 | 1994-03-18 | Matsushita Electric Works Ltd | インバータ装置 |
| FR2715156B1 (fr) | 1994-01-20 | 1996-03-01 | Oreal | Mono-esters d'acide cinnamique ou de ses dérivés et de vitamine C, leur procédé de préparation et leur utilisation comme anti-oxydants dans des compositions cosmétiques, pharmaceutiques ou alimentaires. |
| US5626883A (en) * | 1994-04-15 | 1997-05-06 | Metagenics, Inc. | Ascorbic acid compositions providing enhanced human immune system activity |
| US5951990A (en) | 1995-05-15 | 1999-09-14 | Avon Products, Inc. | Ascorbyl-phosphoryl-cholesterol |
| US5607968A (en) | 1995-06-07 | 1997-03-04 | Avon Products, Inc. | Topical alkyl-2-O-L-ascorbyl-phosphates |
| FR2737971B1 (fr) | 1995-08-25 | 1997-11-14 | Lvmh Rech | Utilisation de la vitamine c ou de ses derives ou analogues pour stimuler la synthese de l'elastine cutanee |
| US6162419A (en) | 1996-11-26 | 2000-12-19 | Nicholas V. Perricone | Stabilized ascorbyl compositions |
| US5962517A (en) * | 1997-01-31 | 1999-10-05 | Murad; Howard | Pharmaceutical compositions and methods for treating acne |
| EP0891771A1 (en) * | 1997-07-08 | 1999-01-20 | Health Now, Inc. | Compositions comprising lysine and ascorbate compounds for the treatment and prevention of cardiovascular diseases |
-
2002
- 2002-08-23 NZ NZ531430A patent/NZ531430A/en unknown
- 2002-08-23 PL PL02373522A patent/PL373522A1/xx unknown
- 2002-08-23 CN CNB028030184A patent/CN100360514C/zh not_active Expired - Fee Related
- 2002-08-23 EP EP10006653.9A patent/EP2241559A3/en not_active Withdrawn
- 2002-08-23 WO PCT/EP2002/009451 patent/WO2003018568A2/en active Application Filing
- 2002-08-23 EP EP02772197A patent/EP1423375A2/en not_active Withdrawn
- 2002-08-23 CN CNB2005101136870A patent/CN100378087C/zh not_active Expired - Fee Related
- 2002-08-23 CN CNB2005101136885A patent/CN100361987C/zh not_active Expired - Fee Related
- 2002-08-23 IL IL15557802A patent/IL155578A0/xx not_active IP Right Cessation
- 2002-08-23 NZ NZ542241A patent/NZ542241A/en unknown
- 2002-08-23 EP EP10006654.7A patent/EP2241560A3/en not_active Withdrawn
- 2002-08-23 WO PCT/US2002/027060 patent/WO2003018000A1/en not_active Application Discontinuation
- 2002-08-23 JP JP2003523231A patent/JP4162593B2/ja not_active Expired - Fee Related
- 2002-08-23 BR BR0205944-4A patent/BR0205944A/pt not_active IP Right Cessation
- 2002-08-23 CA CA002458344A patent/CA2458344A1/en not_active Abandoned
- 2002-08-23 NZ NZ542240A patent/NZ542240A/en unknown
- 2002-08-23 US US10/226,588 patent/US6864284B2/en not_active Expired - Fee Related
- 2002-08-23 RU RU2004108687/04A patent/RU2309152C2/ru not_active IP Right Cessation
- 2002-08-23 MX MXPA04001655A patent/MXPA04001655A/es active IP Right Grant
- 2002-08-23 HU HU0600084A patent/HUP0600084A2/hu unknown
- 2002-08-23 UA UA2004032169A patent/UA78223C2/uk unknown
- 2002-08-23 YU YU38103A patent/YU38103A/sh unknown
- 2002-08-23 KR KR10-2004-7002629A patent/KR20040044472A/ko not_active Application Discontinuation
- 2002-08-23 ZA ZA200304712A patent/ZA200304712B/en unknown
-
2003
- 2003-04-24 IL IL176524A patent/IL176524A0/en unknown
- 2003-04-24 NO NO20031844A patent/NO20031844L/no not_active Application Discontinuation
- 2003-04-24 IL IL155578A patent/IL155578A/en unknown
-
2004
- 2004-02-18 US US10/781,296 patent/US7230124B2/en not_active Expired - Fee Related
- 2004-03-02 HR HR20040207A patent/HRP20040207A2/hr not_active Application Discontinuation
-
2006
- 2006-06-22 IL IL176523A patent/IL176523A0/en unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1784388B8 (en) | Biphenyloxyacetic acid derivatives for the treatment of respiratory disease | |
| LT5240B (lt) | Polifenolių turinti maistinė farmacinė kompozicija, skirta vėžio gydymui | |
| HRP20040207A2 (en) | Ascorbic acid derivatives, methods of synthesis and pharmaceutical use thereof | |
| CA2387548A1 (en) | Bioavailable composition of natural and synthetic hca | |
| DE69815750D1 (de) | Verfahren zur Herstellung von Ascorbinsäurederivaten | |
| JP2006282609A (ja) | 安定化αーリポ酸配合化粧料、育毛剤び抗肥満用食品 | |
| US20070167517A1 (en) | Stabilized derivatives of ascorbic aicd | |
| KR970702291A (ko) | 에퀼린의 산 이성질화체로부터 제조된 에퀼린 이중결합 이성질체(Anequilin double bond isomer from the acid isomerization of equilin) | |
| US20080188553A1 (en) | Novel ascorbic acid compounds, methods of synthesis and application use thereof | |
| CA2664982C (en) | Cleavable carnitine compound | |
| AU2002337011A1 (en) | Ascorbic acid derivatives, methods of synthesis and pharmaceutical use thereof | |
| US20030113362A1 (en) | Unique ascorbic acid derivatives with essential amino acids, nonessential amino acid and amino acids that do not occur in protein: the process for their preparation and use in research, medicine, physiology, pharmacology, nutrition, pharmaceuticals, and for cosmetic, commercial and industrial applications | |
| KR20100067260A (ko) | 우수한 안정성을 갖는 항산화제와 히아루론산과의 복합체 | |
| WO2020146635A1 (en) | Water-soluble mineral ferulates and their method of preparation | |
| JP2020029529A (ja) | 抗酸化剤 | |
| KR101123366B1 (ko) | 우수한 안정성을 갖는 항산화제와 키토산과의 복합체 | |
| WO2003074019A1 (en) | Whitening cosmetic composition | |
| JPH09511234A (ja) | アセチル化特性を有するケトパンテノール | |
| JP2002212175A (ja) | 新規化合物 | |
| JP2004521943A (ja) | ビタミンｃ組成物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A1OB | Publication of a patent application | ||
| AIPI | Request for the grant of a patent on the basis of a substantive examination of a patent application | ||
| ODRP | Renewal fee for the maintenance of a patent |
Payment date: 20070820 Year of fee payment: 6 |
|
| OBST | Application withdrawn |