JP2005508297A - Ｐ２ｙプリン受容体作用物質による関節潤滑 - Google Patents
Ｐ２ｙプリン受容体作用物質による関節潤滑 Download PDFInfo
- Publication number
- JP2005508297A JP2005508297A JP2003506510A JP2003506510A JP2005508297A JP 2005508297 A JP2005508297 A JP 2005508297A JP 2003506510 A JP2003506510 A JP 2003506510A JP 2003506510 A JP2003506510 A JP 2003506510A JP 2005508297 A JP2005508297 A JP 2005508297A
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- JP
- Japan
- Prior art keywords
- uridine
- triphosphate
- tetraphosphates
- adenosine
- alkyl
- 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.)
- Withdrawn
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- 238000005461 lubrication Methods 0.000 title claims abstract description 19
- 239000003227 purinergic agonist Substances 0.000 title claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 59
- 150000001875 compounds Chemical class 0.000 claims abstract description 50
- 239000001226 triphosphate Substances 0.000 claims abstract description 44
- 235000011178 triphosphate Nutrition 0.000 claims abstract description 40
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 claims abstract description 33
- 210000001179 synovial fluid Anatomy 0.000 claims abstract description 28
- 201000008482 osteoarthritis Diseases 0.000 claims abstract description 26
- 229920000388 Polyphosphate Polymers 0.000 claims abstract description 25
- 239000001205 polyphosphate Substances 0.000 claims abstract description 25
- 235000011176 polyphosphates Nutrition 0.000 claims abstract description 25
- 239000000203 mixture Substances 0.000 claims abstract description 20
- 238000011282 treatment Methods 0.000 claims abstract description 19
- 229920002674 hyaluronan Polymers 0.000 claims abstract description 18
- 230000028327 secretion Effects 0.000 claims abstract description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims abstract description 10
- 229960003160 hyaluronic acid Drugs 0.000 claims abstract description 10
- 230000002708 enhancing effect Effects 0.000 claims abstract description 8
- 102000000033 Purinergic Receptors Human genes 0.000 claims abstract description 7
- 108010080192 Purinergic Receptors Proteins 0.000 claims abstract description 7
- 150000003904 phospholipids Chemical class 0.000 claims abstract description 7
- 108010009030 lubricin Proteins 0.000 claims abstract description 5
- 102100028965 Proteoglycan 4 Human genes 0.000 claims abstract description 4
- ZWIADYZPOWUWEW-ZAKLUEHWSA-N cytidine-5'-diphosphate Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO[P@](O)(=O)OP(O)(O)=O)O1 ZWIADYZPOWUWEW-ZAKLUEHWSA-N 0.000 claims abstract 2
- -1 methylene, monochloromethylene Chemical group 0.000 claims description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 31
- 125000003118 aryl group Chemical group 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- 239000002777 nucleoside Substances 0.000 claims description 24
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 150000002431 hydrogen Chemical class 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- YDHWWBZFRZWVHO-UHFFFAOYSA-H [oxido-[oxido(phosphonatooxy)phosphoryl]oxyphosphoryl] phosphate Chemical class [O-]P([O-])(=O)OP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O YDHWWBZFRZWVHO-UHFFFAOYSA-H 0.000 claims description 14
- 125000004104 aryloxy group Chemical group 0.000 claims description 14
- 239000001301 oxygen Substances 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
- 239000012530 fluid Substances 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 239000011593 sulfur Substances 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 10
- 238000009472 formulation Methods 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- PGAVKCOVUIYSFO-UHFFFAOYSA-N uridine-triphosphate Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-UHFFFAOYSA-N 0.000 claims description 10
- PGAVKCOVUIYSFO-XVFCMESISA-N UTP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-XVFCMESISA-N 0.000 claims description 9
- 239000001177 diphosphate Substances 0.000 claims description 9
- 235000011180 diphosphates Nutrition 0.000 claims description 9
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 9
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 8
- 229910019142 PO4 Inorganic materials 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 206010003246 arthritis Diseases 0.000 claims description 8
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 8
- ZLOIGESWDJYCTF-XVFCMESISA-N 4-thiouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-XVFCMESISA-N 0.000 claims description 7
- PCDQPRRSZKQHHS-UHFFFAOYSA-N Cytidine 5'-triphosphate Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 PCDQPRRSZKQHHS-UHFFFAOYSA-N 0.000 claims description 7
- 125000003282 alkyl amino group Chemical group 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 7
- 210000005222 synovial tissue Anatomy 0.000 claims description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- 125000004442 acylamino group Chemical group 0.000 claims description 6
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 6
- 125000001769 aryl amino group Chemical group 0.000 claims description 6
- 125000005110 aryl thio group Chemical group 0.000 claims description 6
- 239000006071 cream Substances 0.000 claims description 6
- 125000004986 diarylamino group Chemical group 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- 239000007922 nasal spray Substances 0.000 claims description 6
- 239000002245 particle Substances 0.000 claims description 6
- 239000010452 phosphate Substances 0.000 claims description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 6
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 5
- XCCTYIAWTASOJW-UHFFFAOYSA-N UDP-Glc Natural products OC1C(O)C(COP(O)(=O)OP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 XCCTYIAWTASOJW-UHFFFAOYSA-N 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 5
- PCDQPRRSZKQHHS-ZAKLUEHWSA-N cytidine-5'-triphosphate Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO[P@](O)(=O)O[P@@](O)(=O)OP(O)(O)=O)O1 PCDQPRRSZKQHHS-ZAKLUEHWSA-N 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 239000007924 injection Substances 0.000 claims description 5
- 238000002347 injection Methods 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000003107 substituted aryl group Chemical group 0.000 claims description 5
- 238000007910 systemic administration Methods 0.000 claims description 5
- 230000009885 systemic effect Effects 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- GNVMUORYQLCPJZ-UHFFFAOYSA-M Thiocarbamate Chemical compound NC([S-])=O GNVMUORYQLCPJZ-UHFFFAOYSA-M 0.000 claims description 4
- 239000000730 antalgic agent Substances 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000006260 foam Substances 0.000 claims description 4
- 125000003843 furanosyl group Chemical group 0.000 claims description 4
- 239000000499 gel Substances 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 239000002674 ointment Substances 0.000 claims description 4
- 239000000243 solution Substances 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical group NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 4
- 238000011200 topical administration Methods 0.000 claims description 4
- XCCTYIAWTASOJW-XVFCMESISA-N Uridine-5'-Diphosphate Chemical group O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 XCCTYIAWTASOJW-XVFCMESISA-N 0.000 claims description 3
- 238000010521 absorption reaction Methods 0.000 claims description 3
- 239000000443 aerosol Substances 0.000 claims description 3
- 150000001408 amides Chemical group 0.000 claims description 3
- 229940035676 analgesics Drugs 0.000 claims description 3
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 3
- 125000000328 arabinofuranosyl group Chemical group C1([C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 125000001369 canonical nucleoside group Chemical group 0.000 claims description 3
- 150000001721 carbon Chemical group 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 3
- 150000003949 imides Chemical class 0.000 claims description 3
- 239000006194 liquid suspension Substances 0.000 claims description 3
- 229940035363 muscle relaxants Drugs 0.000 claims description 3
- 239000003158 myorelaxant agent Substances 0.000 claims description 3
- 229940097496 nasal spray Drugs 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 230000029058 respiratory gaseous exchange Effects 0.000 claims description 3
- 230000004044 response Effects 0.000 claims description 3
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims description 3
- 230000004936 stimulating effect Effects 0.000 claims description 3
- 239000000829 suppository Substances 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 2
- 239000000935 antidepressant agent Substances 0.000 claims description 2
- 229940005513 antidepressants Drugs 0.000 claims description 2
- 150000001540 azides Chemical class 0.000 claims description 2
- 239000004202 carbamide Substances 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 2
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 2
- PFBUKDPBVNJDEW-UHFFFAOYSA-N dichlorocarbene Chemical group Cl[C]Cl PFBUKDPBVNJDEW-UHFFFAOYSA-N 0.000 claims description 2
- LTVOKYUPTHZZQH-UHFFFAOYSA-N difluoromethane Chemical group F[C]F LTVOKYUPTHZZQH-UHFFFAOYSA-N 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical group CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 2
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 2
- 150000007970 thio esters Chemical class 0.000 claims description 2
- 125000002264 triphosphate group Chemical class [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 claims description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims 66
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 claims 33
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims 33
- 229940045145 uridine Drugs 0.000 claims 33
- MWEQTWJABOLLOS-UHFFFAOYSA-L disodium;[[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-oxidophosphoryl] hydrogen phosphate;trihydrate Chemical compound O.O.O.[Na+].[Na+].C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP([O-])(=O)OP(O)([O-])=O)C(O)C1O MWEQTWJABOLLOS-UHFFFAOYSA-L 0.000 claims 11
- ZLOIGESWDJYCTF-UHFFFAOYSA-N 4-Thiouridine Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-UHFFFAOYSA-N 0.000 claims 6
- OLXZPDWKRNYJJZ-UHFFFAOYSA-N 5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol Chemical compound C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(CO)O1 OLXZPDWKRNYJJZ-UHFFFAOYSA-N 0.000 claims 4
- HAEJPQIATWHALX-KQYNXXCUSA-N ITP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(N=CNC2=O)=C2N=C1 HAEJPQIATWHALX-KQYNXXCUSA-N 0.000 claims 4
- NKGPJODWTZCHGF-UHFFFAOYSA-N 9-[3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound OC1C(O)C(CO)OC1N1C(NC=NC2=S)=C2N=C1 NKGPJODWTZCHGF-UHFFFAOYSA-N 0.000 claims 3
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims 3
- VGONTNSXDCQUGY-UHFFFAOYSA-N desoxyinosine Natural products C1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 VGONTNSXDCQUGY-UHFFFAOYSA-N 0.000 claims 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 3
- AHOIUDITWFBFQU-MCDZGGTQSA-N (2R,3R,4S,5R)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol ethanol Chemical compound CCO.C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O AHOIUDITWFBFQU-MCDZGGTQSA-N 0.000 claims 2
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 claims 2
- VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 claims 2
- MXHRCPNRJAMMIM-SHYZEUOFSA-N 2'-deoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-SHYZEUOFSA-N 0.000 claims 2
- CKTSBUTUHBMZGZ-SHYZEUOFSA-N 2'‐deoxycytidine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-SHYZEUOFSA-N 0.000 claims 2
- OAUKGFJQZRGECT-UUOKFMHZSA-N 8-Azaadenosine Chemical compound N1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OAUKGFJQZRGECT-UUOKFMHZSA-N 0.000 claims 2
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 claims 2
- CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 claims 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 claims 2
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 claims 2
- MXHRCPNRJAMMIM-UHFFFAOYSA-N desoxyuridine Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-UHFFFAOYSA-N 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- PQWQQQGKMHENOC-UHFFFAOYSA-N imidazo[1,2-c]pyrimidine Chemical compound C1=NC=CC2=NC=CN21 PQWQQQGKMHENOC-UHFFFAOYSA-N 0.000 claims 2
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims 2
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 claims 2
- YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 claims 1
- YKBGVTZYEHREMT-UHFFFAOYSA-N 2'-deoxyguanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1CC(O)C(CO)O1 YKBGVTZYEHREMT-UHFFFAOYSA-N 0.000 claims 1
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 claims 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 claims 1
- CIVASUFDJVIXRU-UHFFFAOYSA-N C1(OP(=O)(O1)OP2(=O)OC(OP(=O)(O2)OP(=O)(O)O)F)F Chemical compound C1(OP(=O)(O1)OP2(=O)OC(OP(=O)(O2)OP(=O)(O)O)F)F CIVASUFDJVIXRU-UHFFFAOYSA-N 0.000 claims 1
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- 239000001993 wax Substances 0.000 description 1
Images
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
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- 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
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- 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
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30094201P | 2001-06-25 | 2001-06-25 | |
| PCT/US2002/020703 WO2003000056A1 (en) | 2001-06-25 | 2002-06-25 | Joint lubrication with p2y purinergic receptor agonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005508297A true JP2005508297A (ja) | 2005-03-31 |
| JP2005508297A5 JP2005508297A5 (https=) | 2006-01-05 |
Family
ID=23161253
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003506510A Withdrawn JP2005508297A (ja) | 2001-06-25 | 2002-06-25 | Ｐ２ｙプリン受容体作用物質による関節潤滑 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US7109181B2 (https=) |
| JP (1) | JP2005508297A (https=) |
| AR (1) | AR034635A1 (https=) |
| GB (1) | GB2394419B (https=) |
| WO (1) | WO2003000056A1 (https=) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US6743774B1 (en) * | 1999-04-23 | 2004-06-01 | Rhode Island Hospital | Tribonectins |
| WO2003028712A2 (en) * | 2001-09-28 | 2003-04-10 | Universite Libre De Bruxelles | Purinergic and pyrimidinergic receptor agonists for the treatment of activated cd4+ t lymphocyte-mediated immune diseases |
| EP1348466A3 (en) | 2002-02-01 | 2003-10-29 | Inspire Pharmaceuticals, Inc. | Method for treating pain with adenosine-tetraphosphates |
| WO2003072757A2 (en) * | 2002-02-28 | 2003-09-04 | Biota, Inc. | Nucleotide mimics and their prodrugs |
| US20060240037A1 (en) * | 2003-06-04 | 2006-10-26 | Edward Fey | Methods and compositions for the treatment and prevention of degenerative joint disorders |
| GB0502250D0 (en) * | 2005-02-03 | 2005-03-09 | Ic Vec Ltd | Use |
| ITRM20050391A1 (it) | 2005-07-22 | 2007-01-23 | Giuliani Spa | Composti analoghi della 6-tioguanosina trifosfato, loro uso in campo medico e procedimento per la loro preparazione. |
| US20080177389A1 (en) * | 2006-12-21 | 2008-07-24 | Rob Gene Parrish | Intervertebral disc spacer |
| US7947081B2 (en) * | 2007-07-11 | 2011-05-24 | Linares Medical Devices, Llc | Skeletal implant for replacing a human bone |
| EP2209443A4 (en) * | 2007-09-17 | 2012-08-29 | Linares Medical Devices Llc | ARTIFICIAL JOINT SUPPORT BETWEEN A FIRST AND A SECOND BONE |
| US8979938B2 (en) * | 2007-11-08 | 2015-03-17 | Linares Medical Devices, Llc | Artificial knee implant including liquid ballast supporting / rotating surfaces and incorporating flexible multi-material and natural lubricant retaining matrix applied to a joint surface |
| US9539097B2 (en) | 2007-11-08 | 2017-01-10 | Linares Medical Devices, Llc | Hip and knee joint assemblies incorporating debris collection architecture between the ball and seat interface |
| US8828088B2 (en) * | 2007-11-08 | 2014-09-09 | Linares Medical Devices, Llc | Joint assembly incorporating undercut surface design to entrap accumulating wear debris from plastic joint assembly |
| CN102026591A (zh) * | 2008-02-25 | 2011-04-20 | 利纳雷斯医疗设备有限责任公司 | 用于安装至原有关节骨骼的人造耐磨栓 |
| WO2009120776A2 (en) * | 2008-03-26 | 2009-10-01 | Linares Medical Devices, Llc | Joint construction, such as for use by athletes |
| US8926705B2 (en) | 2010-05-10 | 2015-01-06 | Linares Medical Devices, Llc | Implantable joint assembly featuring debris entrapment chamber subassemblies along with opposing magnetic fields generated between articulating implant components in order to minimize frictional force and associated wear |
| WO2012032513A1 (en) * | 2010-09-07 | 2012-03-15 | Bar-Ilan University | Boranophosphate derivatives for the treatment of osteoarthritis |
| MX368764B (es) | 2011-06-03 | 2019-10-15 | Maguire Abbey Llc | Método, composición, y artículos para mejorar la lubricación de articulación. |
| GB201209244D0 (en) * | 2012-05-25 | 2012-07-04 | Globalacorn Ltd | Compositions |
| AU2014305843B2 (en) | 2013-08-09 | 2019-08-29 | Ardelyx, Inc. | Compounds and methods for inhibiting phosphate transport |
| MX2021002878A (es) | 2018-09-11 | 2021-08-16 | Risen Suzhou Pharma Tech Co Ltd | Inhibidores de cd73 y usos farmaceuticos de los mismos. |
| US11530234B2 (en) | 2018-09-11 | 2022-12-20 | Risen (Suzhou) Pharma Tech Co., Ltd. | CD73 inhibitors and pharmaceutical uses thereof |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO1991016056A1 (en) * | 1990-04-16 | 1991-10-31 | The United States Of America, As Represented By The Secretary, U.S. Department Of Commerce | Use of purinergic receptor agonists as antineoplastic agents |
| US5292498A (en) | 1991-06-19 | 1994-03-08 | The University Of North Carolina At Chapel Hill | Method of treating lung disease with uridine triphosphates |
| US5656256A (en) | 1994-12-14 | 1997-08-12 | The University Of North Carolina At Chapel Hill | Methods of treating lung disease by an aerosol containing benzamil or phenamil |
| US5635160A (en) | 1995-06-07 | 1997-06-03 | The University Of North Carolina At Chapel Hill | Dinucleotides useful for the treatment of cystic fibrosis and for hydrating mucus secretions |
| US5628984A (en) | 1995-07-31 | 1997-05-13 | University Of North Carolina At Chapel Hill | Method of detecting lung disease |
| US6423694B1 (en) | 1996-02-21 | 2002-07-23 | Inspire Pharmaceuticals, Inc. | Method of treating otitis media with uridine triphosphates and related compounds |
| US5837861A (en) | 1997-02-10 | 1998-11-17 | Inspire Pharmaceuticals, Inc. | Dinucleotides and their use as modulators of mucociliary clearance and ciliary beat frequency |
| US5900407A (en) | 1997-02-06 | 1999-05-04 | Inspire Pharmaceuticals, Inc. | Method of treating dry eye disease with uridine triphosphates and related compounds |
| EP0889728B1 (en) | 1996-03-27 | 2006-08-09 | Inspire Pharmaceuticals, Inc. | Method of treating ciliary dyskinesia with uridine triphosphates and related compounds |
| US5789391A (en) | 1996-07-03 | 1998-08-04 | Inspire Pharmaceuticals, Inc. | Method of treating sinusitis with uridine triphosphates and related compounds |
| US5968913A (en) | 1996-07-03 | 1999-10-19 | Inspire Pharmaceuticals, Inc. | Pharmaceutical compositions of uridine triphosphate |
| US5763447C1 (en) | 1996-07-23 | 2002-05-07 | Inspire Pharmaceuticals | Method of preventing or treating pneumonia in immobilized patients with uridine triphosphates and related compounds |
| AU4978897A (en) | 1996-10-08 | 1998-05-05 | Inspire Pharmaceuticals, Inc. | Method of early lung cancer detection via sputum induction and analysis of sputum to detect cancer associated substances |
| US6159952A (en) | 1996-11-07 | 2000-12-12 | Inspire Pharmaceuticals, Inc. | Method of treating bronchitis with uridine triphosphate and related compounds |
| CN1262556C (zh) | 1997-02-06 | 2006-07-05 | 印斯拜尔药品股份有限公司 | 特定的二核苷酸和它们作为粘膜纤毛清除和纤毛颤动频率调节剂的应用 |
| SE9701219D0 (sv) * | 1997-04-04 | 1997-04-04 | Astra Pharma Prod | New compounds |
| US6133434A (en) * | 1997-04-28 | 2000-10-17 | Glaxo Group Limited | Purinergic receptor |
| US6462028B2 (en) | 1997-07-25 | 2002-10-08 | Inspire Pharmaceuticals, Inc. | Method of promoting cervical and vaginal secretions |
| EP1011688B1 (en) | 1997-08-29 | 2005-02-02 | The University of North Carolina at Chapel Hill | Use of uridine 5'-diphosphate and analogs thereof for the treatment of lung diseases |
| JP4633927B2 (ja) | 1998-05-22 | 2011-02-16 | インスパイアー ファーマシューティカルズ，インコーポレイティド | 治療用ジヌクレオチドおよび誘導体 |
| DE60015734D1 (de) | 1999-02-26 | 2004-12-16 | Inspire Pharmaceuticals Durham | Verwendung von dinukleotidtriphosphaten, cytidindiphosphaten und adenindiphosphaten zur herstellung einer pharmazeutischen zubereitung zur förderung der schleimauthydratation |
-
2002
- 2002-06-25 JP JP2003506510A patent/JP2005508297A/ja not_active Withdrawn
- 2002-06-25 AR ARP020102395A patent/AR034635A1/es unknown
- 2002-06-25 WO PCT/US2002/020703 patent/WO2003000056A1/en not_active Ceased
- 2002-06-25 US US10/183,320 patent/US7109181B2/en not_active Expired - Fee Related
- 2002-06-25 GB GB0401471A patent/GB2394419B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AR034635A1 (es) | 2004-03-03 |
| US7109181B2 (en) | 2006-09-19 |
| US20030027785A1 (en) | 2003-02-06 |
| GB2394419B (en) | 2005-09-07 |
| GB2394419A (en) | 2004-04-28 |
| GB0401471D0 (en) | 2004-02-25 |
| WO2003000056A1 (en) | 2003-01-03 |
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