KR102049233B1 - Composition for treating and preventing of chronic allograft dysfuction comprising bisphosphonate - Google Patents
Composition for treating and preventing of chronic allograft dysfuction comprising bisphosphonate Download PDFInfo
- Publication number
- KR102049233B1 KR102049233B1 KR1020190004444A KR20190004444A KR102049233B1 KR 102049233 B1 KR102049233 B1 KR 102049233B1 KR 1020190004444 A KR1020190004444 A KR 1020190004444A KR 20190004444 A KR20190004444 A KR 20190004444A KR 102049233 B1 KR102049233 B1 KR 102049233B1
- Authority
- KR
- South Korea
- Prior art keywords
- acid
- long term
- bisphosphonate
- present
- organ
- Prior art date
Links
- 229940122361 Bisphosphonate Drugs 0.000 title claims abstract description 32
- 150000004663 bisphosphonates Chemical class 0.000 title claims abstract description 32
- 239000000203 mixture Substances 0.000 title claims abstract description 26
- 230000001684 chronic effect Effects 0.000 title abstract description 17
- 230000004083 survival effect Effects 0.000 claims abstract description 31
- 210000000056 organ Anatomy 0.000 claims abstract description 19
- 230000007774 longterm Effects 0.000 claims description 19
- MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 claims description 15
- IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 claims description 15
- 235000013305 food Nutrition 0.000 claims description 14
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 claims description 12
- 210000003734 kidney Anatomy 0.000 claims description 12
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 claims description 12
- 210000001519 tissue Anatomy 0.000 claims description 12
- 229950006971 incadronic acid Drugs 0.000 claims description 11
- LWRDQHOZTAOILO-UHFFFAOYSA-N incadronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)NC1CCCCCC1 LWRDQHOZTAOILO-UHFFFAOYSA-N 0.000 claims description 11
- UGEPSJNLORCRBO-UHFFFAOYSA-N [3-(dimethylamino)-1-hydroxy-1-phosphonopropyl]phosphonic acid Chemical compound CN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O UGEPSJNLORCRBO-UHFFFAOYSA-N 0.000 claims description 10
- 229960005236 ibandronic acid Drugs 0.000 claims description 10
- DKJJVAGXPKPDRL-UHFFFAOYSA-N Tiludronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)SC1=CC=C(Cl)C=C1 DKJJVAGXPKPDRL-UHFFFAOYSA-N 0.000 claims description 9
- 229960004585 etidronic acid Drugs 0.000 claims description 9
- PUUSSSIBPPTKTP-UHFFFAOYSA-N neridronic acid Chemical compound NCCCCCC(O)(P(O)(O)=O)P(O)(O)=O PUUSSSIBPPTKTP-UHFFFAOYSA-N 0.000 claims description 9
- 229950010733 neridronic acid Drugs 0.000 claims description 9
- 239000000843 powder Substances 0.000 claims description 9
- 229940089617 risedronate Drugs 0.000 claims description 9
- 239000002775 capsule Substances 0.000 claims description 8
- 229960002286 clodronic acid Drugs 0.000 claims description 8
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 229950011129 minodronic acid Drugs 0.000 claims description 8
- VMMKGHQPQIEGSQ-UHFFFAOYSA-N minodronic acid Chemical compound C1=CC=CN2C(CC(O)(P(O)(O)=O)P(O)(O)=O)=CN=C21 VMMKGHQPQIEGSQ-UHFFFAOYSA-N 0.000 claims description 8
- 239000003826 tablet Substances 0.000 claims description 8
- 229940062527 alendronate Drugs 0.000 claims description 7
- 235000013361 beverage Nutrition 0.000 claims description 7
- 239000008187 granular material Substances 0.000 claims description 7
- 229940015872 ibandronate Drugs 0.000 claims description 7
- 229940009626 etidronate Drugs 0.000 claims description 6
- 229940046231 pamidronate Drugs 0.000 claims description 6
- 229960003978 pamidronic acid Drugs 0.000 claims description 6
- 229960000759 risedronic acid Drugs 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 5
- 229960004343 alendronic acid Drugs 0.000 claims description 5
- 210000001185 bone marrow Anatomy 0.000 claims description 5
- 210000004087 cornea Anatomy 0.000 claims description 5
- 238000009472 formulation Methods 0.000 claims description 5
- 210000002216 heart Anatomy 0.000 claims description 5
- 210000000936 intestine Anatomy 0.000 claims description 5
- 210000004185 liver Anatomy 0.000 claims description 5
- 210000004072 lung Anatomy 0.000 claims description 5
- 210000000496 pancreas Anatomy 0.000 claims description 5
- 210000003491 skin Anatomy 0.000 claims description 5
- 239000000725 suspension Substances 0.000 claims description 5
- 229940019375 tiludronate Drugs 0.000 claims description 5
- 229950004969 olpadronic acid Drugs 0.000 claims description 4
- 229960005324 tiludronic acid Drugs 0.000 claims description 4
- 239000002674 ointment Substances 0.000 claims description 3
- 239000003889 eye drop Substances 0.000 claims description 2
- 229940012356 eye drops Drugs 0.000 claims description 2
- -1 injectables Substances 0.000 claims description 2
- 238000013268 sustained release Methods 0.000 claims description 2
- 239000012730 sustained-release form Substances 0.000 claims description 2
- 238000002054 transplantation Methods 0.000 abstract description 13
- 230000008085 renal dysfunction Effects 0.000 abstract description 9
- 238000001356 surgical procedure Methods 0.000 abstract description 9
- 208000001132 Osteoporosis Diseases 0.000 abstract description 8
- 230000000069 prophylactic effect Effects 0.000 abstract description 3
- 230000001225 therapeutic effect Effects 0.000 abstract description 3
- 230000003466 anti-cipated effect Effects 0.000 abstract 1
- 239000000796 flavoring agent Substances 0.000 description 9
- 208000001647 Renal Insufficiency Diseases 0.000 description 7
- 201000006370 kidney failure Diseases 0.000 description 7
- 230000006870 function Effects 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- 235000013355 food flavoring agent Nutrition 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 235000019634 flavors Nutrition 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 230000003907 kidney function Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 239000004386 Erythritol Substances 0.000 description 2
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 208000020832 chronic kidney disease Diseases 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 2
- 235000019414 erythritol Nutrition 0.000 description 2
- 229940009714 erythritol Drugs 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 238000001631 haemodialysis Methods 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000000322 hemodialysis Effects 0.000 description 2
- 229940125721 immunosuppressive agent Drugs 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 239000001512 FEMA 4601 Substances 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 208000034706 Graft dysfunction Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- HELXLJCILKEWJH-SEAGSNCFSA-N Rebaudioside A Natural products O=C(O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@]1(C)[C@@H]2[C@](C)([C@H]3[C@@]4(CC(=C)[C@@](O[C@H]5[C@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@H](O)[C@@H](CO)O5)(C4)CC3)CC2)CCC1 HELXLJCILKEWJH-SEAGSNCFSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 208000004608 Ureteral Obstruction Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- IWLDTXOHXPDPQG-UHFFFAOYSA-L disodium;hydroxy-[1-hydroxy-1-[hydroxy(oxido)phosphoryl]-3-pyrrolidin-1-ylpropyl]phosphinate Chemical compound [Na+].[Na+].OP(=O)(O)C(P([O-])([O-])=O)(O)CCN1CCCC1 IWLDTXOHXPDPQG-UHFFFAOYSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- HELXLJCILKEWJH-UHFFFAOYSA-N entered according to Sigma 01432 Natural products C1CC2C3(C)CCCC(C)(C(=O)OC4C(C(O)C(O)C(CO)O4)O)C3CCC2(C2)CC(=C)C21OC(C1OC2C(C(O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1O HELXLJCILKEWJH-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000019203 rebaudioside A Nutrition 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000003860 topical agent Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
- A61K31/663—Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- 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
-
- 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
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/306—Foods, ingredients or supplements having a functional effect on health having an effect on bone mass, e.g. osteoporosis prevention
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (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
본 발명은 골다공증 치료제로 사용되고 있는 비스포스포네이트를 포함하는 만성 이식신 기능부전 예방 또는 치료용 조성물에 관한 것으로, 본 발명에 따른 비스포스포네이트를 포함하는 만성 이식신 기능부전 예방 또는 치료용 조성물은 조직 또는 장기 이식 수술 이후에 서서히 이식된 조직 또는 장기의 기능이 감소되는 만성 이식신 기능부전의 예방 및/또는 치료 효과가 뛰어나며 이로 인하여 이식 수술 이후 장기의 생존율을 현저히 증가시킬 수 있을 것으로 기대된다.The present invention relates to a composition for preventing or treating chronic transplant renal dysfunction, including bisphosphonate, which is used as an agent for treating osteoporosis, and the composition for preventing or treating chronic transplant renal dysfunction including bisphosphonate according to the present invention is tissue or organ transplant surgery. It is anticipated that the prophylactic and / or therapeutic effects of chronic transplant renal dysfunction in which the function of the transplanted tissues or organs is gradually reduced afterwards will significantly increase the survival rate of organs after transplantation.
Description
본 발명은 골다공증 치료제로 사용되고 있는 비스포스포네이트를 포함하는 만성 이식신 기능부전 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing or treating chronic transplant renal dysfunction, including bisphosphonate, which is used as an agent for treating osteoporosis.
신장의 손상이나 신장의 기능이 저하된 상태가 3개월 이상 지속되는 것을 만성 신장병이라고 하며, 이러한 경우 지속적으로 혈액 투석이나 복막 투석을 해야 하고, 치료를 위해서는 신장 이식을 필요로 한다. 이러한 장기 이식의 경우 이식 수술 후 이식신 기능부전(allograft dysfuction)으로 인하여 신장 기능이 다시 악화되는 경우가 종종 발생한다. 이식신 기능부전이란, 장기이식에서의 거절 반응의 일종으로 이식 후 수개월부터 발명할 수 있으며, 이식신 기능부전이 발생하면 이식되었던 신장의 기능이 저하되어 다시 복막 투석 또는 혈액 투석을 지속적으로 받아야 한다.Kidney damage or kidney function deterioration that lasts more than three months is called chronic kidney disease, in which case hemodialysis or peritoneal dialysis is required, and treatment requires a kidney transplant. In the case of such organ transplantation, renal function is often deteriorated again due to postoperative graft renal dysfunction. Transplant renal insufficiency is a type of rejection response in organ transplantation, which can be invented from several months after transplantation. When renal insufficiency occurs, the function of the transplanted kidney is degraded and the patient must undergo continuous peritoneal dialysis or hemodialysis. .
이러한 이식신 기능부전의 경우 급성 이식신 기능부전(acute allograft dysfunction)과 만성 이식신 기능부전(chronic allograft dysfunction)으로 크게 나뉘어진다(Ryan J. G. et. al., Med . Cli . N. Am. (2016) 100: 487-503). 급성 이식신 기능부전의 경우, 수술 후 6개월 이내에 발생하며 초급성 거절반응(hyperacute rejection), 혈전증(thrombosis), 소변누출(urine leak), 요관폐쇄(ureteral obstruction) 등의 증상이 나타나며, 치료 방법으로는 부신피질호르몬 등의 면역억제제의 대량 투여가 사용되고 있다. 그러나 수개월에서부터 수년 이후에 서서히 발생하게 되는 만성 이식신 기능부전의 경우에는 면역억제제의 대량 투여로는 거의 치료가 되지 않으며, 이로 인하여 미국에서 신장 이식 후 1년 생존율은 96%이나, 5년 생존율은 81%, 10년 생존율은 59%로 신장 이식 후에 장기간 생존율은 급격히 감소하고 있으나, 이에 대한 효과적인 치료제의 개발은 미비한 상태이다(2009년도 미국 USRDS 자료). 따라서, 만성 이식신 기능부전에 대한 효과적인 치료제 또는 예방제제의 개발은 신장 이식 환자들의 장기간 생존율을 현저히 증가시킬 수 있을 것으로 기대되고 있다(Leonardo V. R. et. al., Transplantation Rev. (2016) in press).These graft dysfunctions are largely divided into acute allograft dysfunction and chronic allograft dysfunction (Ryan JG et. Al. , Med . Cli . N. Am. (2016) . ) 100: 487-503). Acute graft renal failure occurs within 6 months after surgery, with symptoms such as hyperacute rejection, thrombosis, urine leak, and ureteral obstruction. A large amount of immunosuppressive agents such as corticosteroids are used. However, chronic transplant renal dysfunction, which occurs slowly from months to years, is rarely treated with high doses of immunosuppressive agents. Thus, in the US, one-year survival rate is 96%, but five-year survival The long-term survival rate after renal transplantation is 81%, and the 10-year survival rate is 59%. However, the development of effective treatments for this is insufficient (2009 USRDS data). Therefore, the development of effective therapeutic or prophylactic agents for chronic renal failure is expected to significantly increase the long-term survival rate of kidney transplant patients (Leonardo VR et. Al. , Transplantation Rev. (2016) in press ). .
본 발명은 상기와 같은 종래 기술상의 문제점을 해결하기 위해 안출된 것으로, 비스포스포네이트를 유효성분으로 포함하는, 만성 이식신 기능부전 예방 또는 치료용 약학 조성물을 제공하는 것을 그 목적으로 한다.The present invention has been made to solve the above-mentioned problems in the prior art, and it is an object of the present invention to provide a pharmaceutical composition for preventing or treating chronic transplant renal dysfunction, including bisphosphonate as an active ingredient.
그러나 본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 과제에 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 당업계에서 통상의 지식을 가진 자에게 명확하게 이해될 수 있을 것이다.However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problem, another task that is not mentioned will be clearly understood by those skilled in the art from the following description.
이하, 본원에 기재된 다양한 구체예가 도면을 참조로 기재된다. 하기 설명에서, 본 발명의 완전한 이해를 위해서, 다양한 특이적 상세사항, 예컨대, 특이적 형태, 조성물, 및 공정 등이 기재되어 있다. 그러나 특정의 구체예는 이들 특이적 상세 사항 중 하나 이상 없이, 또는 다른 공지된 방법 및 형태와 함께 실행될 수 있다. 다른 예에서, 공지된 공정 및 제조 기술은 본 발명을 불필요하게 모호하게 하지 않게 하기 위해서, 특정의 상세사항으로 기재되지 않는다. "한 가지 구체예" 또는 "구체예"에 대한 본 명세서 전체를 통한 참조는 구체예와 결부되어 기재된 특별한 특징, 형태, 조성 또는 특성이 본 발명의 하나 이상의 구체예에 포함됨을 의미한다. 따라서, 본 명세서 전체에 걸친 다양한 위치에서 표현된 "한 가지 구체예에서" 또는 "구체예"의 상황은 반드시 본 발명의 동일한 구체예를 나타내지는 않는다. 추가로, 특별한 특징, 형태, 조성, 또는 특성은 하나 이상의 구체예에서 어떠한 적합한 방법으로 조합될 수 있다.Hereinafter, various embodiments described herein are described with reference to the drawings. In the following description, for a thorough understanding of the present invention, various specific details are described, such as specific forms, compositions, processes and the like. However, certain embodiments may be practiced without one or more of these specific details, or in conjunction with other known methods and forms. In other instances, well known processes and manufacturing techniques have not been described in particular detail in order to not unnecessarily obscure the present invention. Reference throughout this specification to "one embodiment" or "embodiment" means that a particular feature, form, composition or characteristic described in connection with the embodiment is included in one or more embodiments of the invention. Thus, the context of “in one embodiment” or “embodiment” expressed at various places throughout this specification does not necessarily represent the same embodiment of the invention. In addition, particular features, forms, compositions, or properties may be combined in any suitable manner in one or more embodiments.
명세서에서 특별한 정의가 없으면 본 명세서에 사용된 모든 과학적 및 기술적인 용어는 본 발명이 속하는 기술분야에서 당업자에 의하여 통상적으로 이해되는 것과 동일한 의미를 가진다.Unless otherwise defined, all scientific and technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
본 명세서에 있어서, "만성 이식신 기능부전(chronic allograft dysfuction)"이란 조직 또는 장기 이식 수술 후에 서서히 이식된 조직 또는 장기의 기능이 감소되는 것을 총칭하며, 바람직하게는 이식 수술 후 6개월 이상이 지난 후에 발병되는 것을 의미하나, 급성으로 기능이 감소되는 것이 아니라면 이에 제한되지 않는다. 상기 조직 또는 장기는 바람직하게는 신장, 골수, 심장, 각막, 장, 간, 폐, 췌장, 피부 등 일 수 있으며, 더욱 바람직하게는 신장이나, 이식이 가능한 조직 또는 장기라면 이에 제한되지 않는다.In the present specification, "chronic allograft dysfuction" refers to a decrease in the function of a tissue or an organ transplanted slowly after a tissue or organ transplant surgery, preferably 6 months or more after the transplant surgery. Means later onset, but is not limited to, unless acutely reduced function. The tissue or organ is preferably kidney, bone marrow, heart, cornea, intestine, liver, lung, pancreas, skin and the like, and more preferably, if the kidney or transplantable tissue or organ is not limited thereto.
본 명세서에 있어서, "비스포스포네이트(bisphosphonate)"란 피로포스페이트의 구조적 유사체로서 피로포스페이트의 P-O-P-그룹이 효소적으로 안정한 P-C-P-그룹으로 대체되어 있는 화합물을 총칭하며, P-C-P-그룹의 C-원자에서 수소 원자들을 치환함으로써 다양한 구조적 요소 및 특성을 가진 비스포스포네이트들을 제조 가능하다. 임상적 사용이 승인된 공지 비스포스포네이트로는 미드로네이트, 알렌드로네이트, 에티드로네이트, 클로드로네이트, 리세드로네이트, 틸루드로네이트, 이반드로네이트, 인카드로네이트, 미노드로네이트, 올파드로네이트, 네리드로네이트, EB-1053 등이 있으며, 이러한 비스포스포네이트는 골다공증 치료제로서 널리 알려져 있고 사용되어지고 있다.As used herein, the term "bisphosphonate" refers to a compound in which the POP-group of pyrophosphate is replaced by an enzymatically stable PCP-group as a structural analogue of pyrophosphate, and hydrogen at the C-atom of the PCP-group. By substituting atoms, bisphosphonates having various structural elements and properties can be prepared. Known bisphosphonates approved for clinical use include midronate, alendronate, ethedronate, clathronate, risedronate, tiludronate, ibandronate, incadronate, minodronate, olpadronate , Neridronate, EB-1053, and the like, and such bisphosphonates are widely known and used as therapeutic agents for osteoporosis.
본 발명은 비스포스포네이트(bisphosphonate)를 유효성분으로 포함하는 만성 이식신 기능부전(chronic allograft dysfuction) 예방 또는 치료용 약학 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating chronic allograft dysfuction including bisphosphonate as an active ingredient.
본 발명의 일 구체예에 있어서, 상기 비스포스포네이트는 바람직하게는 골다공증 치료 용도로 사용되는 것이며, 더욱 바람직하게는 리세드로네이트(risedronate; risedronic acid), 이반드로네이트(Ibandronate; ibandronic acid), 에티드로네이트(Etidronate; etidronic acid), 알렌드로네이트(Alendronate; alendronic acid), 파미드로네이트(Pamidronate; pamidronic acid), 클로드로네이트(Clodronate; clodronic acid), 틸루드로네이트(Tiludronate; tiludronic acid), 인카드로네이트(Incadronate; incadronic acid), 미노드로네이트(Minodronate; minodronic acid), 올파드로네이트(Olpadronate; olpadronic acid), 네리드로데이트(Neridronate; neridronic acid), EB-1053 등이며, 더욱 바람직하게는 리세드로네이트(risedronate; risedronic acid), 이반드로네이트(Ibandronate; ibandronic acid), 에티드로네이트(Etidronate; etidronic acid), 알렌드로네이트(Alendronate; alendronic acid), 파미드로네이트(Pamidronate; pamidronic acid)이나, 골다공증 치료 용도로 사용되고 있는 비스포스포네이트라면 이에 제한되지 않는다.In one embodiment of the present invention, the bisphosphonate is preferably used for the treatment of osteoporosis, more preferably risedronate (risedronic acid), ibandronic acid (Ibandronate; ibandronic acid), ethidro Etidronate (etidronic acid), Alendronate (alendronic acid), Pamideronate (Pamidronic acid), Clodronate (clodronic acid), Tiludronate (tiludronic acid), Incadronate (Incadronate; incadronic acid), Minodronate (minodronic acid), Olpadronate (Olpadronate; olpadronic acid), Neridronate (neridronic acid), EB-1053, and the like. Risedronate (risedronic acid), ibandronic acid (ibandronic acid), etidronate (etidronic acid), alendronate (alendronate) ic acid), pamidronate (pamidronic acid), or bisphosphonates used for the treatment of osteoporosis are not limited thereto.
본 발명의 다른 구체예에 있어서, 상기 이식신 기능부전은 신장, 골수, 심장, 각막, 장, 간, 폐, 췌장, 피부 등으로 이루어진 군으로부터 선택된 어느 하나의 조직 또는 장기 이식으로 인한 부작용이며, 이식수술 후 이식된 조직 또는 장기의 기능이 서서히 감소되는 것을 의미한다.In another embodiment of the present invention, the transplant renal dysfunction is a side effect of any tissue or organ transplant selected from the group consisting of kidney, bone marrow, heart, cornea, intestine, liver, lung, pancreas, skin, and the like, This means that after transplantation, the function of transplanted tissues or organs is gradually decreased.
본 발명의 또다른 구체예에 있어서, 상기 약학 조성물은 이식 수술 후 10년 이상의 장기간 생존율(long-term survival)을 증가시키며, 상기 약학 조성물은 현탁액, 산제, 분말제, 과립제, 정제, 서방형 제제, 주사제, 연고제, 점안제 등 다양한 형태로 제조될 수 있다.In another embodiment of the present invention, the pharmaceutical composition increases the long-term survival of more than 10 years after transplantation surgery, the pharmaceutical composition is a suspension, powder, powder, granules, tablets, sustained release formulation Injectables, ointments, eye drops and the like can be prepared in various forms.
본 발명에 있어서 상기 약학 조성물은 캡슐, 정제, 과립, 주사제, 연고제, 분말 또는 음료 형태임을 특징으로 할 수 있으며, 상기 약학 조성물은 인간을 대상으로 하는 것을 특징으로 할 수 있다. 상기 약학 조성물은 이들로 한정되는 것은 아니지만, 각각 통상의 방법에 따라 산제, 과립제, 캡슐, 정제, 수성 현탁액 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 본 발명의 약학 조성물은 약제적으로 허용가능한 담체를 포함할 수 있다. 약제학적으로 허용되는 담체는 경구투여시에는 결합제, 활탁제, 붕해제, 부형제, 가용화제, 분산제, 안정화제, 현탁화제, 색소, 향료 등을 사용할 수 있으며, 주사제의 경우에는 완충제, 보존제, 무통화제, 가용화제, 등장제, 안정화제 등을 혼합하여 사용할 수 있으며, 국소투여용의 경우에는 기제, 부형제, 윤활제, 보존제 등을 사용할 수 있다. 본 발명의 약제학적 조성물의 제형은 상술한 바와 같은 약제학적으로 허용되는 담체와 혼합하여 다양하게 제조될 수 있다. 예를 들어, 경구투여시에는 정제, 트로키, 캡슐, 엘릭서(elixir), 서스펜션, 시럽, 웨이퍼 등의 형태로 제조할 수 있으며, 주사제의 경우에는 단위 투약 앰플 또는 다수회 투약 형태로 제조할 수 있다. 기타, 용액, 현탁액, 정제, 캡슐, 서방형 제제 등으로 제형할 수 있다.In the present invention, the pharmaceutical composition may be characterized in that the capsule, tablets, granules, injections, ointments, powder or beverage form, the pharmaceutical composition may be characterized in that it is intended for humans. The pharmaceutical composition is not limited to these, but can be used in the form of oral dosage forms such as powders, granules, capsules, tablets, aqueous suspensions, external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods. The pharmaceutical composition of the present invention may comprise a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers can be used as oral administration binders, suspending agents, disintegrants, excipients, solubilizers, dispersants, stabilizers, suspending agents, pigments, fragrances, etc. In the case of injections, buffers, preservatives, analgesic Topical agents, solubilizers, isotonic agents, stabilizers and the like can be mixed and used, and for topical administration, bases, excipients, lubricants, preservatives and the like can be used. The formulation of the pharmaceutical composition of the present invention may be prepared in various ways by mixing with a pharmaceutically acceptable carrier as described above. For example, oral administration may be in the form of tablets, troches, capsules, elixirs, suspensions, syrups, wafers, and the like, in the case of injections, in unit dosage ampoules or multiple dosage forms. have. And others, solutions, suspensions, tablets, capsules, sustained release preparations and the like.
한편, 제제화에 적합한 담체, 부형제 및 희석제의 예로는, 락토즈, 덱스트로즈, 수크로즈, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말디톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로즈, 폴리비닐피롤리돈, 물, 메틸하이드록시벤조에이트, 프로필하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 또는 광물유 등이 사용될 수 있다. 또한, 충진제, 항응집제, 윤활제, 습윤제, 향료, 유화제, 방부제 등을 추가로 포함할 수 있다.Examples of suitable carriers, excipients and diluents suitable for formulation include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, malditol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil and the like can be used. In addition, fillers, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers, preservatives and the like may be further included.
본 발명에 따른 약학 조성물의 투여 경로는 이들로 한정되는 것은 아니지만 구강, 정맥내, 근육내, 동맥내, 골수내, 경막내, 심장내, 경피, 피하, 복강내, 비강내, 장관, 국소, 설하 또는 직장이 포함된다. 경구 또는 비경구 투하가 바람직하다. 본원에 사용된 용어 "비경구"는 피하, 피내, 정맥내, 근육내, 관절내, 활액낭내, 흉골내, 경막내, 병소내 및 두개골내 주사 또는 주입기술을 포함한다. 본 발명의 약학 조성물은 또한 직장 투여를 위한 좌제의 형태로 투여될 수 있다.Routes of administration of the pharmaceutical compositions according to the invention are not limited to these, but are oral, intravenous, intramuscular, intraarterial, intramedullary, intradural, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal, topical, Sublingual or rectal. Oral or parenteral release is preferred. As used herein, the term “parenteral” includes subcutaneous, intradermal, intravenous, intramuscular, intraarticular, intramuscular, intrasternal, intradural, intralesional and intracranial injection or infusion techniques. The pharmaceutical compositions of the invention may also be administered in the form of suppositories for rectal administration.
본 발명의 약학 조성물은 사용된 특정 화합물의 활성, 연령, 체중, 일반적인 건강, 성별, 정식, 투여시간, 투여경로, 배출율, 약물 배합 및 예방 또는 치료될 특정 질환의 중증을 포함한 여러 요인에 따라 다양하게 변할 수 있고, 상기 약학 조성물의 투여량은 환자의 상태, 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만 당업자에 의해 적절하게 선택될 수 있고, 1일 0.0001 내지 50mg/kg 또는 0.001 내지 50mg/kg으로 투여할 수 있다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. 본 발명에 따른 의약 조성물은 환제, 당의정, 캡슐, 액제, 겔, 시럽, 슬러리, 현탁제로 제형화될 수 있다.The pharmaceutical compositions of the present invention vary depending on a number of factors, including the activity, age, weight, general health, sex, formulation, time of administration, route of administration, rate of release, drug combination and severity of the particular disease to be prevented or treated, of the specific compound employed. The dosage of the pharmaceutical composition may be appropriately selected by those skilled in the art depending on the patient's condition, weight, degree of disease, drug form, route of administration and duration, and 0.0001 to 50 mg / kg or It may be administered at 0.001 to 50 mg / kg. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect. The pharmaceutical composition according to the present invention may be formulated as pills, dragees, capsules, solutions, gels, syrups, slurries, suspensions.
또한, 본 발명은 비스포스포네이트(bisphosphonate)를 유효성분으로 포함하는 만성 이식신 기능부전(chronic allograft dysfuction) 예방 또는 개선용 식품 조성물을 제공한다.In addition, the present invention provides a food composition for preventing or improving chronic allograft dysfuction including bisphosphonate as an active ingredient.
본 발명의 일 구체예에 있어서, 상기 비스포스포네이트는 바람직하게는 골다공증 치료 용도로 사용되는 것이며, 더욱 바람직하게는 리세드로네이트(risedronate; risedronic acid), 이반드로네이트(Ibandronate; ibandronic acid), 에티드로네이트(Etidronate; etidronic acid), 알렌드로네이트(Alendronate; alendronic acid), 파미드로네이트(Pamidronate; pamidronic acid), 클로드로네이트(Clodronate; clodronic acid), 틸루드로네이트(Tiludronate; tiludronic acid), 인카드로네이트(Incadronate; incadronic acid), 미노드로네이트(Minodronate; minodronic acid), 올파드로네이트(Olpadronate; olpadronic acid), 네리드로데이트(Neridronate; neridronic acid), EB-1053 등으로 이루어진 군으로부터 선택된 어느 하나 이상이나, 골다공증 치료제로 사용되고 있는 비스포스포네이트라면 이에 제한되지 않는다.In one embodiment of the present invention, the bisphosphonate is preferably used for the treatment of osteoporosis, more preferably risedronate (risedronic acid), ibandronic acid (Ibandronate; ibandronic acid), ethidro Etidronate (etidronic acid), Alendronate (alendronic acid), Pamideronate (Pamidronic acid), Clodronate (clodronic acid), Tiludronate (tiludronic acid), Incadronate At least one selected from the group consisting of (Incadronate; incadronic acid), Minordronate (minodronic acid), Olpadronate (olpadronic acid), Neridronate (neridronic acid), EB-1053, and the like. However, bisphosphonates used as therapeutic agents for osteoporosis are not limited thereto.
본 발명의 다른 구체예에서, 상기 이식신 기능부전은 신장, 골수, 심장, 각막, 장, 간, 폐, 췌장, 피부 등으로 이루어진 군으로부터 선택된 어느 하나의 조직 또는 장기 이식으로 인한 부작용이며, 이식 수술 이후 서서히 이식된 조직 또는 장기의 기능이 감소되는 것을 의미한다.In another embodiment of the present invention, the transplant renal failure is a side effect of any tissue or organ transplant selected from the group consisting of kidney, bone marrow, heart, cornea, intestine, liver, lung, pancreas, skin, and the like, and transplantation This means that after surgery the function of the transplanted tissues or organs is reduced.
본 발명의 또다른 구체예에서, 상기 식품 조성물은 이식 수술 후 장기간 생존율(long-term survival)을 증가시키며, 캡슐제, 정제, 과립제, 분말제, 음료 형태 등으로 제조될 수 있다.In another embodiment of the present invention, the food composition increases long-term survival after transplant surgery, and may be prepared in capsules, tablets, granules, powders, beverage forms, and the like.
본 발명에 있어서 상기 식품 조성물은, 각종 식품류, 예를 들어, 음료, 껌, 차, 비타민 복합제, 건강보조 식품류 등에 사용할 수 있으며, 환제, 분말, 과립, 침제, 정제, 캡슐 또는 음료의 형태로 사용할 수 있다. 이때, 식품 또는 음료 중의 상기 비스포스포네이트의 양은, 일반적으로 본 발명의 식품 조성물의 경우 전체 식품 중량의 0.01 내지 15 중량%로 가할 수 있으며, 건강 음료 조성물의 경우 100mL를 기준으로 0.02 내지 10g, 바람직하게는 0.3 내지 1g의 비율로 가할 수 있다.In the present invention, the food composition may be used in various foods, for example, beverages, gums, teas, vitamin complexes, health supplements, and the like, and may be used in the form of pills, powders, granules, tablets, capsules, or beverages. Can be. At this time, the amount of the bisphosphonate in the food or beverage may be added in general from 0.01 to 15% by weight of the total food weight in the case of the food composition of the present invention, 0.02 to 10g based on 100mL for the health beverage composition, preferably It can be added at a ratio of 0.3 to 1 g.
본 발명의 식품 조성물은 당업계에 통상적인 식품첨가제, 예를 들어 향미제, 풍미제, 착색제, 충진제, 안정화제 등을 포함할 수 있다. 본 발명에 따른 식품 조성물은 필수 성분으로서, 상기 비스포스포네이트 외에 첨가되는 성분에는 특별한 제한은 없으며 통상의 식품과 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상기 천연 탄수화물의 예로는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린; 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물 (예를 들어 레바우디오시드 A, 글리시르히진 등)) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100mL당 일반적으로 약 1 내지 20g, 바람직하게는 약 5 내지 12g이다.The food composition of the present invention may include food additives conventional in the art, such as flavoring agents, flavoring agents, coloring agents, fillers, stabilizers, and the like. The food composition according to the present invention is an essential ingredient, and there are no particular restrictions on the ingredients added in addition to the bisphosphonate, and may include various flavors or natural carbohydrates as additional ingredients, as in general foods. Examples of the natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; Polysaccharides such as dextrin, cyclodextrin; Conventional sugars such as and the like and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. have. The proportion of said natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 mL of the composition of the present invention.
상기 외에 본 발명의 식품 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the food composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, alginic acid and Salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
본 발명에 따른 비스포스포네이트를 포함하는 만성 이식신 기능부전 예방 또는 치료용 조성물은 조직 또는 장기 이식 수술 이후에 서서히 이식된 조직 또는 장기의 기능이 감소되는 만성 이식신 기능부전의 예방 및/또는 치료 효과가 뛰어나며 이로 인하여 이식 수술 이후 장기간의 생존율을 현저히 증가시킬 수 있을 것으로 기대된다.The composition for preventing or treating chronic transplant renal failure including the bisphosphonate according to the present invention has a prophylactic and / or therapeutic effect of chronic transplant renal dysfunction in which the function of a tissue or organ which is gradually transplanted after tissue or organ transplant surgery is reduced. It is expected that the long-term survival after transplantation can be significantly increased.
도 1은 본 발명의 일 실시예에 따른 비스포스포네이트 실험군 전체에 대한 평균 생존률(~300month)을 확인한 결과를 나타낸 도면이다.
도 2는 본 발명의 일 실시예에 따른 알레드로네이트 투여군에 대한 장기간 생존률을 확인한 결과를 나타낸 도면이다.
도 3은 본 발명의 일 실시예에 따른 에티드로네이트 투여군에 대한 장기간 생존률을 확인한 결과를 나타낸 도면이다.
도 4는 본 발명의 일 실시예에 따른 파미드로네이트 투여군에 대한 장기간 생존률을 확인한 결과를 나타낸 도면이다.
도 5는 본 발명의 일 실시예에 따른 리세드로네이트 투여군에 대한 장기간 생존률을 확인한 결과를 나타낸 도면이다.
도 6은 본 발명의 일 실시예에 따른, 에티드로네이트, 이반드로네이트, 및 파미드로네이트 투여군에 대한 평균 생존률을 확인한 결과를 나타낸 도면이다.1 is a view showing the results of confirming the average survival rate (~ 300month) for the entire bisphosphonate experimental group according to an embodiment of the present invention.
2 is a view showing the results of confirming the long-term survival rate for the alledronate administration group according to an embodiment of the present invention.
3 is a view showing the results of confirming the long-term survival rate for the ethidronate administration group according to an embodiment of the present invention.
Figure 4 is a view showing the results of confirming the long-term survival rate for the administration of pamideronate group according to an embodiment of the present invention.
5 is a view showing the results of confirming long-term survival rate for risedronate administration group according to an embodiment of the present invention.
6 is a view showing the results of confirming the average survival rate for the ethidronate, ibandronate, and pamidronate administration group according to an embodiment of the present invention.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로서, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .
실시예Example
실시예Example 1: 만성 1: chronic 이식신Transplant 기능부전에서의 In malfunction 비스포스포네이트Bisphosphonates 역할 확인 Check role
만성 이식신 기능부전에서의 비스포스포네이트(bisphosphonate)의 역할을 확인하기 위하여, 1979년 04월부터 2016년 06월까지 연세대학교 의료원에서 신장이식(kidney transplantation; KT)을 받은 4,000명의 환자 중에서 이식수술 전에 비스포스포네이트를 사용했던 환자들과 데이터가 소실된 환자들을 제외한 3,939명을 대상으로 하여 연구를 진행하였다. 대상 환자 중 비스포스포네이트를 사용하지 않은 환자는 3,022명(대조군)이었고, 나머지 917명은 수술 후 1년이 지난 후에 비스포스포네이트를 사용하였다. 비스포스포네이트를 사용하는 시점에서 환자들의 신장기능검사(renal function test; glomerular filtration rate; GFR)를 시행하였고, 검사 결과값이 30mL/min/1.73m2 이상인 환자 866명을 실험군으로 지정하였다. 대조군과 실험군의 이식편 생존율(graft survival)을 성향점수 매칭법(propensity score matching; PSM)을 이용하여 분석하였다, 실시예의 모든 통계분석은 IBM PSS statistics ver. 21(IBM Korea corporation, Seoul, Korea) 및 MedCalc Ver. 11.6(MedCalc Software)을 이용하여 실시하였다. "p<0.05"이면 유의성이 있는 것으로 분석하였다. 비스포스포네이트로는 리세드로네이트(Risedronate; risedronic acid), 이반드로네이트(Ibandronate; ibandronic acid), 에티드로네이트(Etidronate; etidronic acid), 알레드로네이트(Alendronate; alendronic acid), 및 파미드로네이트(Pamidronate; pamidronic acid)를 사용하였고, 리세드로네이트는 559명, 이반드로네이트는 16명, 에티드로네이트는 13명, 알레드로네이트는 245명, 그리고 파미드로네이트는 33명에게 사용하였고, 투여용량 및 횟수는 각각의 기존 투여방법에 따라 사용하였다. 그 결과는 도 1 내지 도 6에 나타내었다.To determine the role of bisphosphonates in chronic graft renal insufficiency, bisphosphonates prior to transplantation among 4,000 patients undergoing kidney transplantation (KT) at Yonsei University Medical Center from April 1979 to June 2016 The study was conducted on 3,939 patients, except for those who used and who had lost data. 3,022 patients (control group) did not use bisphosphonates, and the remaining 917 patients used bisphosphonates one year after surgery. At the time of using bisphosphonate, a renal function test (GFR) was performed. 866 patients with a test result of 30 mL / min / 1.73 m 2 or more were designated as an experimental group. Graft survival of the control and experimental groups was analyzed using propensity score matching (PSM). 21 (IBM Korea corporation, Seoul, Korea) and MedCalc Ver. It was carried out using 11.6 (MedCalc Software). "p <0.05" was analyzed as significant. Bisphosphonates include risedronate (risedronic acid), ibandronic acid (Ibandronate; ibandronic acid), etidronate (etidronic acid), allendronate (alendronic acid), and pamidronate. pamidronic acid), risedronate (559), ivandronate (16), ethidronate (13), alledronate (245), and pamidronate (33). And the number of times was used according to each existing administration method. The results are shown in FIGS. 1 to 6.
도 1에 나타난 바와 같이, 비스포스포네이트를 투여한 실험군과 투여하지 않은 대조군 사이의 생존률은 100개월(month)까지 크게 차이가 나지 않는 것을 확인하였으며, 이 후 서서히 생존률의 차이가 벌어지는 것을 확인하였다. 이를 통하여 비스포스포네이트의 투여가 단기 생존률에는 거의 영향을 미치지 않지만, 장기간으로 갈수록 생존률이 현저히 증가되는 것을 확인할 수 있었다.As shown in Figure 1, the survival rate between the experimental group and the non-phosphonate-administered control group was confirmed that the difference does not significantly up to 100 months (month), after which it was confirmed that the difference in survival rate gradually spreads. Through this, the administration of bisphosphonate has little effect on the short-term survival rate, but it was confirmed that the survival rate increased significantly over the long term.
또한, 도 2 내지 도 6에 나타난 바와 같이, 각각의 비스포스포네이트 투여시의 장기간 생존률을 확인한 결과에서도 단기 생존률에서는 차이가 나지 않았지만 장기 생존률에서는 현저한 차이를 나타내는 것을 확인하였다.In addition, as shown in Figures 2 to 6, even in the results of confirming the long-term survival rate at each bisphosphonate administration, it was confirmed that there was no difference in the short-term survival rate, but a significant difference in the long-term survival rate.
상기 결과들을 통하여, 기존에 골다공증 치료제로 사용되고 있는 비스포스포네이트를 신장 이식 수술을 시행한 환자에게 투여하면, 만성 이식신 기능부전(chronic allograft dysfunction)의 발병률을 현저히 감소시켜 신장 이식 환자들의 장기 생존율(long-term survival)을 현저히 증가시킬 수 있다는 것을 확인할 수 있었으며, 이를 통하여 비스포스포네이트를 만성 이식신 기능부전의 예방 또는 치료 용도로 사용가능하다는 것을 확인할 수 있었다. Based on the above results, the administration of bisphosphonates, which have been previously used for treating osteoporosis, to patients undergoing renal transplantation, significantly reduces the incidence of chronic allograft dysfunction and results in long-term survival of kidney transplant patients. term survival) can be significantly increased, and it was confirmed that bisphosphonate can be used for the prevention or treatment of chronic graft renal failure.
이상으로 본 발명의 특정한 부분을 상세히 기술하였는바, 당업계의 통상의 지식을 가진 자에게 있어서 이러한 구체적인 기술은 단지 바람직한 구현 예일 뿐이며, 이에 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 따라서 본 발명의 실질적인 범위는 첨부된 청구항과 그의 등가물에 의하여 정의된다고 할 것이다.Having described the specific part of the present invention in detail, it is apparent to those skilled in the art that the specific technology is only a preferred embodiment, and the scope of the present invention is not limited thereto. Therefore, the substantial scope of the present invention will be defined by the appended claims and equivalents thereof.
Claims (8)
상기 약학 조성물은 현탁액, 산제, 분말제, 과립제, 정제, 서방형 제제, 주사제, 연고제, 또는 점안제 형태인, 장기 이식편 생존율(long term graft survival)을 증가시키는 약학 조성물.The method of claim 1,
Wherein said pharmaceutical composition is in the form of a suspension, powder, powder, granules, tablets, sustained release formulations, injectables, ointments, or eye drops, for increasing long term graft survival.
상기 식품 조성물은 캡슐제, 정제, 과립제, 분말제 또는 음료 형태인, 장기 이식편 생존율(long term graft survival)을 증가시키는 식품 조성물.The method of claim 5,
Wherein said food composition is a capsule, tablet, granule, powder or beverage form, wherein said food composition increases long term graft survival.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020190004444A KR102049233B1 (en) | 2019-01-14 | 2019-01-14 | Composition for treating and preventing of chronic allograft dysfuction comprising bisphosphonate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020190004444A KR102049233B1 (en) | 2019-01-14 | 2019-01-14 | Composition for treating and preventing of chronic allograft dysfuction comprising bisphosphonate |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020170048564A Division KR20180115979A (en) | 2017-04-14 | 2017-04-14 | Composition for treating and preventing of chronic allograft dysfuction comprising bisphosphonate |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020190147587A Division KR20190131465A (en) | 2019-11-18 | 2019-11-18 | Composition for treating and preventing of chronic allograft dysfuction comprising bisphosphonate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20190007082A KR20190007082A (en) | 2019-01-21 |
| KR102049233B1 true KR102049233B1 (en) | 2019-11-28 |
Family
ID=65277477
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020190004444A KR102049233B1 (en) | 2019-01-14 | 2019-01-14 | Composition for treating and preventing of chronic allograft dysfuction comprising bisphosphonate |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR102049233B1 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100864743B1 (en) | 2000-06-20 | 2008-10-22 | 노파르티스 아게 | Method of administering bisphosphonates |
-
2019
- 2019-01-14 KR KR1020190004444A patent/KR102049233B1/en active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100864743B1 (en) | 2000-06-20 | 2008-10-22 | 노파르티스 아게 | Method of administering bisphosphonates |
Non-Patent Citations (3)
| Title |
|---|
| Clinical Journal of American Society of Nephrology. 2009. Vol.4, pp.221-233. |
| Clinical Transplantation. 2016. Vol.30, pp.1090-1096. |
| Journal of the American Society of Nephrology. 2001. Vol.12, pp.1530-1537.* |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20190007082A (en) | 2019-01-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CZ301701B6 (en) | Medicament containing zoledronic acid for treating pain | |
| EP2478909B1 (en) | Pharmaceutical compositions comprising bisphosphonate derivatives and high-dose cholecalciferol | |
| AU775079B2 (en) | Pharmaceutical compositions and uses | |
| CZ389897A3 (en) | Use of biphosphonates for preparing a pharmaceutical preparation | |
| US9949992B2 (en) | Bisphosphonate compositions and methods for treating and\or reducing cardiac dysfunction | |
| AU2001261283B2 (en) | Use of Zolendronate for the manufacture of a medicament for the treatment of bone metabolism diseases | |
| CN103202816B (en) | Pantoprazole sodium freeze-dried powder injection | |
| KR102049233B1 (en) | Composition for treating and preventing of chronic allograft dysfuction comprising bisphosphonate | |
| AU2001261283A1 (en) | Use of zolendronate for the manufacture of a medicament for the treatment of bone metabolism diseases | |
| KR20190131465A (en) | Composition for treating and preventing of chronic allograft dysfuction comprising bisphosphonate | |
| US11554129B2 (en) | Composition for treating chronic renal transplant dysfunction comprising bisphosphonate | |
| US8324189B2 (en) | Use of zolendronate for the manufacture of a medicament for the treatment of bone metabolism diseases | |
| US20100179110A1 (en) | Composition Containing a Bisphosphonic Acid in Combination with Vitamin D | |
| US10286025B2 (en) | Composition comprising combined extracts of Schisandra fructus, Eucommiae cortex and Lycii fructus for preventing or treating metabolic bone diseases | |
| KR20200016640A (en) | Composition for inhibiting osteoclast differentiation comprising gold compound as an active ingredient | |
| EP2389165A2 (en) | Pharmaceutical composition of ibandronate sodium salt or a hydrate thereof | |
| US20090170815A1 (en) | Alendronate oral liquid formulations | |
| Marcucci | Antiresorptive Drugs’ Role in Management of Postmenopausal Osteoporosis | |
| KR20110088474A (en) | Pharmaceutical composition comprising bisphosphonate derivative and high amount of cholecalciferol | |
| MX2011013867A (en) | Biophosphonates useful for preventing and treating abnormal bone resorption. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A107 | Divisional application of patent | ||
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| E701 | Decision to grant or registration of patent right | ||
| A107 | Divisional application of patent |